Important Note: The following information is provided for your education. It should not be relied upon for personal diagnosis or treatment. If you believe that a particular therapy applies to you or someone you care about, be sure to consult a doctor before trying it.
   

Bronchitis Research: 2002-2006
     
Respir Med. 2006 Sep;100(9):1504-11. Epub 2006 Feb 28.
Moxifloxacin versus levofloxacin against acute exacerbations of chronic bronchitis: The Latin American Cohort.
Urueta-Robledo J, Ariza H, Jardim JR, Caballero A, Garcia-Calderon A, Amabile-Cuevas CF, Hernandez-Oliva G, Vivar-Orozco R; the MOX-CB Study Group.
Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.

We compared the efficacy and safety of moxifloxacin and levofloxacin for the treatment of patients with acute exacerbations of chronic bronchitis (AECB) using a prospective, randomized, double blind, parallel-group clinical trial design. A total of 563 patients with AECB were enrolled (437 efficacy-valid) at 34 centers in Mexico, Argentina, Brazil, Colombia, and Peru. Patients were randomized to oral therapy with either moxifloxacin 400mg once daily for 5 days or levofloxacin 500mg once daily for 7 days. Clinical success was achieved in 201 out of 221 (91.0%) patients in the moxifloxacin group, and in 203 out of 216 (94.0%) in the levofloxacin group, indicating that moxifloxacin is equivalently effective to levofloxacin. Bacteriologic eradication or presumed eradication was also similar in the two treatment groups: 92.8% in the moxifloxacin group and 93.8% in the levofloxacin group. Nausea was the most common drug-related adverse event in each treatment group. The rate of discontinuation because of adverse events was very low (2%). In conclusion, a 5-day course of moxifloxacin is clinically and bacteriologically equivalent to a 7-day course of levofloxacin in the treatment of patients with AECB. The short treatment duration with moxifloxacin may have compliance advantages over other currently used therapies in the 'real-life' clinical setting.

-----

Cochrane Database Syst Rev. 2006 Jul 19;3:CD001287.
Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease.
Poole P, Black P.

BACKGROUND: Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume and/or purulence of sputum. Because of the personal and healthcare costs associated with exacerbations, any therapy that reduces the number of exacerbations is useful. There is a marked difference between countries in terms of prescribing of mucolytics depending on whether or not they are perceived to be effective. OBJECTIVES: To assess the effects of oral mucolytics in adults with stable chronic bronchitis or COPD. SEARCH STRATEGY: We have searched the Cochrane Airways Group Specialised Register and reference lists of articles on four separate occasions, the most recent being in June 2005. This is the third major update. SELECTION CRITERIA: Randomised trials that compared oral mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. Studies of people with asthma and cystic fibrosis were excluded. DATA COLLECTION AND ANALYSIS: One reviewer extracted data. Study authors and drug companies were contacted for missing information. MAIN RESULTS: Twenty six trials were included (7335 participants). Compared with placebo, there was a significant reduction in the number of exacerbations per patient with oral mucolytics (weighted mean difference (WMD) -0.05 per month, 95% confidence interval -0.05, -0.04). Using the annualised rate of exacerbations in the control patients of 2.6 per year, this is a 20% reduction. The number of days of disability also fell (WMD -0.56, 95% confidence interval -0.77, -0.35). A recent study has shown that the benefit may apply only to those patients not already receiving inhaled corticosteroids. The number of patients who remained exacerbation-free was greater in the mucolytic group (OR 2.13 (95% CI 1.86 to 2.42)). There was no difference in lung function or in adverse effects reported between the treatments. AUTHORS' CONCLUSIONS: In subjects with chronic bronchitis or COPD, treatment with mucolytics was associated with a small reduction in acute exacerbations and a reduction in total number of days of disability. Benefit may be greater in individuals who have frequent or prolonged exacerbations, or those who are repeatedly admitted to hospital with exacerbations with COPD. They should be considered for use, through the winter months at least, in patients with moderate or severe COPD in whom inhaled corticosteroids (ICS) are not prescribed.

-----

Internist (Berl). 2006 Jul 20; [Epub ahead of print]
[Antibiotic therapy for exacerbation.]
[Article in German]
Dalhoff K, Kothe H.
Medizinische Klinik III, Universitatsklinikum Schleswig-Holstein - Campus Lubeck, Ratzeburger Allee 160, 23538 , Lubeck, klaus.dalhoff@uni-luebeck.de.

Bacterial infections are involved in approximately 50% of acute exacerbations of chronic bronchitis (AECB). Pneumococci, Haemophilus influenzae and Moraxella catarrhalis are the main pathogens. Studies using quantitative cultures and molecular typing suggest a causal relationship between bacterial infection and exacerbation. Furthermore, an association between infection and bronchial inflammation has been demonstrated. In contrast to steroid therapy and non-invasive ventilation, the benefits of antibiotic treatment are not well established. Current guidelines recommend antimicrobial therapy for AECB in type I exacerbations, for patients needing ventilatory support and for patients with cardiac comorbidity. Bacterial eradication is able to prolong the infection free interval.

-----

Clin Microbiol Infect. 2006 May;12 Suppl 3:42-54.
Should patients with acute exacerbation of chronic bronchitis be treated with antibiotics? Advantages of the use of fluoroquinolones.
Mensa J, Trilla A.
Infectious Diseases Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain. jmensa@clinic.ub.es

The pathological changes in chronic bronchitis (CB) produce airflow obstruction, reduce the effectiveness of the mucocilliary drainage system and lead to bacterial colonisation of bronchial secretion. The presence of bacteria induces an inflammatory response mediated by leukocytes. There is a direct relationship between the degree of impairment of the mucocilliary drainage system, the density of bacteria in mucus and the number of leukocytes in the sputum. Purulent sputum is a good marker of a high bacterial load. Eventually, if the number of leukocytes is high, their normal activity could decrease the effectiveness of the drainage system, increase the bronchial obstruction and probably damage the lung parenchyma. Whenever the density of bacteria in the bronchial lumen is >or=10(6) CFU/mL, there is a high probability that the degree of inflammatory response will lead to a vicious cycle which in turn tends to sustain the process. This situation can arise during the clinical course of any acute exacerbation of CB, independently of its aetiology, provided the episode is sufficiently severe and/or prolonged. Fluoroquinolones of the third and fourth generation are bactericidal against most microorganisms usually related to acute exacerbations of CB. Their diffusion to bronchial mucus is adequate. When used in short (5-day) treatment they reduce the bacterial load in a higher proportion than is achieved by beta-lactam or macrolide antibiotics given orally. Although the clinical cure rate is similar to that obtained with other antibiotics, the time between exacerbations could be increased.

-----

Antimicrob Agents Chemother. 2006 May;50(5):1762-7.
Clinical and bacteriological efficacy in treatment of acute exacerbations of chronic bronchitis with cefditoren-pivoxil versus cefuroxime-axetil.
Alvarez-Sala JL, Kardos P, Martinez-Beltran J, Coronel P, Aguilar L.
Microbiology Department, School of Medicine, Universidad Complutense, Avda. Complutense s/n, 28040 Madrid, Spain.

A randomized, double-blind, double-dummy trial was performed comparing 200 mg of cefditoren-pivoxil twice daily for 5 days versus standard cefuroxime-axetil treatment (250 mg twice daily for 10 days) of Anthonisen type I or II acute exacerbations of chronic bronchitis. The modified intention-to-treat population included 541 patients. Patients were assessed during therapy, at the end of therapy (visit 3; primary evaluation time point), and at follow-up. Clinical success was obtained in 79.9% of the 264 patients included in the cefditoren-pivoxil group and in 82.7% of the 277 patients in the cefuroxime-axetil group (treatment difference, 95% confidence interval [CI]: -2.8, -9.7 to 3.6%). Treatment clinical effects were more clearly seen in sputum signs (decreasing volume and purulence from approximately 80% to approximately 10% of the patients). At the end of treatment, exploratory analysis of the per-pathogen bacteriological response showed 72.8% (of 103 isolates) in the cefditoren-pivoxil arm versus 67.0% (of 94 isolates) in the cefuroxime-axetil group (treatment difference; 95% CI: 5.8, -7.0 to 18.6%). Globally, the per-pathogen bacteriological response correlated well with clinical success: 83.5% of 164 baseline isolates from patients with a clinical success were eradicated or presumably eradicated, in contrast to only 3% of 33 isolates from patients with a clinical failure. Clinical success in patients infected with Haemophilus influenzae, the most frequent isolate, was 84% (of 50) and 82.5% (of 40) (treatment difference; 95% CI: 1.5, -14 to 17%) in the cefditoren-pivoxil versus the cefuroxime-axetil group. Although this study does not prove that either drug is better than a placebo, cefditoren-pivoxil and the standard 10-day cefuroxime-axetil course had similar point estimates of success in acute exacerbations of chronic bronchitis.

-----

Arzneimittelforschung. 2006;56(3):249-57.
[Efficacy and safety profile of a herbal drug containing nasturtium herb and horseradish root in acute sinusitis, acute bronchitis and acute urinary tract infection in comparison with other treatments in the daily practice/results of a prospective cohort study]
[Article in German]
Goos KH, Albrecht U, Schneider B.
Repha GmbH, Biologische Arzneimittel, Langenhagen.

PATIENTS AND METHODS: In a prospective cohort study from 251 centers in Germany patients with age of 4 years or above who were treated due to acute sinusitis, bronchitis or urinary tract infections (UTI) in the period from 1st March 2004 - 30th July 2005, were elected. They were included in the study analysis, if they had no exclusion criteria (severe diseases, need for antibiotic therapy, participation in another trial) and came to the final investigation. The patients were treated either with the nasturtium herb and horseradish root containing herbal drug Angocin Anti-Infekt N (test group, n = 1223) or with standard antibiotic therapy (control group, n = 426). Treatment, dosage and treatment duration were determined by the physician in accordance with the patient. 536 subjects (408 test, 128 control patients) suffered from acute sinusitis, 634 subjects (469 test, 165 control patients) from acute bronchitis and 479 subjects (346 test, 133 control patients) from UTI. At study start and end the severity of the symptoms were judged by the investigator and quantified with 4 scores (0 = no symptom, 3 severe symptom). During the treatment information on use of medication, concomitant procedures and adverse events (AEs) in a patient diary. At the end of the study (disease free or after 7-14 days) the patient returned to the investigator, who recorded the vital parameters, finally judged the treatment efficacy and potential persisting symptoms on the basis of score values. Primary efficacy criterion was the change of the complaints quantified by the change of the relative symptom score averaged over all symptoms and related to the baseline value. RESULTS: In patients with acute sinusitis the mean relative reduction of the averaged symptom score was 81.3% for the test group and 84.6% for the control group, in patients with acute bronchitis the mean reduction was 78.3% for the test group and 80.3% for the control group, in patients with UTI 81.2% for the test group and 87.9% for the control group. The 95% confidence interval for the difference of the expected reductions between test and control group was -8.5% to 1.8% for acute sinusitis, 7.6% to 3.6% for acute bronchitis and -13.1% to -0.1% for UTI. Non-inferiority of the test treatment, i.e. if the lower limit of the 95% confidence interval is greater than 10%, could be stated for acute sinusitis and bronchitis. In UTI the non-inferiority level was exceeded only by 3%. Complementary procedures were less in the test group than in the control group. For 1.5 % of test patients and 6.8% of control patients AEs were observed CONCLUSION: Therapy with the herbal drug in the indications acute sinusitis, acute bronchitis und acute urinary tract infection is - with regard to its efficacy comparable to the treatment with standard antibiotics. The application of supportive procedures and the administration of concurrent medication were less expressed in the group treated with the herbal drug. In the above mentioned indications the group treated with the herbal drug displayed a clear advantageous safety profile compared to the group treated with standard antibiotics.

-----

Pediatrics. 2006 Mar;117(3):633-40.
A randomized trial of home oxygen therapy from the emergency department for acute bronchiolitis.
Bajaj L, Turner CG, Bothner J.
Department of Pediatrics, University of Colorado Health Sciences Center/Children's Hospital, Denver, CO 80218, USA. bajaj.lalit@tchden.org

OBJECTIVE: Hypoxia is a common reason for hospital admission in infants and children with acute bronchiolitis. No study has evaluated discharge from the emergency department (ED) on home oxygen. This study evaluated the feasibility and safety of ED discharge on home oxygen in the treatment of acute bronchiolitis. METHODS: This was a prospective, randomized trial of infants and children with acute bronchiolitis and hypoxia (room-air saturations of < or =87%) aged 2 to 24 months presenting to an urban, academic, tertiary care children's hospital ED from December 1998 to April 2001. Subjects received inpatient admission or home oxygen after an 8-hour observation period in the ED. We measured the failure to meet discharge criteria during the observation period, return for hospital admission, and incidence of serious complications. RESULTS: Ninety-two patients were enrolled. Fifty three (58%) were randomly assigned to home and 39 (42%) to inpatient admission. There were no differences between the groups in age, initial room-air saturation, and respiratory distress severity score. Of 53 patients, 37 (70%) randomly assigned to home oxygen completed the observation period and were discharged from the hospital. The remaining 16 patients were excluded from the study (6), resolved their oxygen requirement (5), or failed to meet the discharge criteria and were admitted (5). One discharged patient (2.7%) returned to the hospital and was admitted for a cyanotic spell at home after the 24-hour follow-up appointment. The patient had an uncomplicated hospital course with a length of stay of 45 hours. The remaining 36 patients (97%) were treated successfully as outpatients with home oxygen. Satisfaction with home oxygen was high from the caregiver and the primary care provider. CONCLUSIONS: Discharge from the ED on home oxygen after a period of observation is an option for patients with acute bronchiolitis. Secondary to the low incidence of complications, the safety of this practice will require a larger study.

-----

Respir Med. 2006 Mar 10; [Epub ahead of print]
Eradication of H. influenzae in AECB: A pooled analysis of moxifloxacin phase III trials compared with macrolide agents.
Niederman MS, Anzueto A, Sethi S, Choudhri S, Kureishi A, Haverstock D, Perroncel R.
Department of Medicine, Winthrop-University Hospital, 222 Station Plaza North, Suite 509, Mineola, NY 11501, USA; State University of New York at Stony Brook, 222 Station Plaza North, Suite 509, Mineola, NY 11501, USA.

Haemophilus influenzae is the most common bacterial pathogen associated with acute exacerbations of chronic bronchitis (AECB). This study determined the rate of bacterial eradication of H. influenzae during AECB treated with either macrolides or moxifloxacin. Adult AECB patients with H. influenzae were included in a pooled analysis of four double-blind, multicentre, randomised trials. Patients received either moxifloxacin (400mgqd for 5-10 days) or macrolides (azithromycin 500mg/250mgqd for 5 days or clarithromycin 500mgbid for 5-10 days). Bacterial eradication and clinical success were recorded at the test-of-cure visit (7-37 days post-therapy). Of 2555 patients in the intent-to-treat population, 910 were microbiologically valid and 292 (32%) had H. influenzae cultured at baseline. Bacterial eradication of H. influenzae was significantly higher with moxifloxacin vs. macrolide-treated patients (93.0% [133/143] vs. 73.2% [109/149], respectively, P=0.001). Moxifloxacin also demonstrated higher eradication rates compared with azithromycin (96.8% vs. 84.6%, P=0.019) and clarithromycin (90.1% vs. 64.2%, P=0.001) analysed separately. Clinical success was 89.5% (128/143) for moxifloxacin vs. 85.2% (127/149) for the macrolide group (P=0.278); similar results were found when moxifloxacin was compared individually with each macrolide. For patients with AECB due to H. influenzae, moxifloxacin provided superior bacterial eradication rates than macrolide therapy.

-----

Expert Rev Anti Infect Ther. 2006 Feb;4(1):27-41.
Prulifloxacin: a new antibacterial fluoroquinolone.
Prats G, Rossi V, Salvatori E, Mirelis B.
Microbiology Departament, Hospital Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona 08035, Spain. gprats@cs.vhebron.es

In the last few years, the antimicrobial activity, efficacy and relative safety of fluoroquinolones have made them attractive for the treatment of community-acquired and nosocomial infections. Prulifloxacin is a new fluoroquinolone antibacterial agent with a broad spectrum of activity against Gram-positive and -negative bacteria. Prulifloxacin is available for oral use, and after absorption is metabolized in to the active form, ulifloxacin. It exhibits good penetration in target tissues and a long elimination half-life, allowing once-daily administration. A number of randomized, controlled clinical trials carried out in Europe demonstrated the efficacy of prulifloxacin in the treatment of urinary tract (acute uncomplicated and complicated) and respiratory tract infections (acute exacerbations of chronic bronchitis), in comparison with the most widely used drugs such as ciprofloxacin, co-amoxiclav and pefloxacin. Prulifloxacin was generally well tolerated. The most frequent adverse reactions observed in clinical trials were gastric pain, diarrhea, nausea and skin rash. This review focuses on the characteristics of prulifloxacin, summarizing the relevant preclinical and clinical data.

-----

Respir Med. 2006 Feb 24; [Epub ahead of print]
Moxifloxacin versus levofloxacin against acute exacerbations of chronic bronchitis: The Latin American Cohort.
Urueta-Robledo J, Ariza H, Jardim JR, Caballero A, Garcia-Calderon A, Amabile-Cuevas CF, Hernandez-Oliva G, Vivar-Orozco R; the MOX-CB Study Group.
Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.

We compared the efficacy and safety of moxifloxacin and levofloxacin for the treatment of patients with acute exacerbations of chronic bronchitis (AECB) using a prospective, randomized, double blind, parallel-group clinical trial design. A total of 563 patients with AECB were enrolled (437 efficacy-valid) at 34 centers in Mexico, Argentina, Brazil, Colombia, and Peru. Patients were randomized to oral therapy with either moxifloxacin 400mg once daily for 5 days or levofloxacin 500mg once daily for 7 days. Clinical success was achieved in 201 out of 221 (91.0%) patients in the moxifloxacin group, and in 203 out of 216 (94.0%) in the levofloxacin group, indicating that moxifloxacin is equivalently effective to levofloxacin. Bacteriologic eradication or presumed eradication was also similar in the two treatment groups: 92.8% in the moxifloxacin group and 93.8% in the levofloxacin group. Nausea was the most common drug-related adverse event in each treatment group. The rate of discontinuation because of adverse events was very low (2%). In conclusion, a 5-day course of moxifloxacin is clinically and bacteriologically equivalent to a 7-day course of levofloxacin in the treatment of patients with AECB. The short treatment duration with moxifloxacin may have compliance advantages over other currently used therapies in the 'real-life' clinical setting.

-----

Chest. 2006 Jan;129(1 Suppl):238S-249S.
Cough suppressant and pharmacologic protussive therapy: ACCP evidence-based clinical practice guidelines.
Bolser DC.
Department of Physiological Sciences, University of Florida, Gainesville, FL 32610-0144, USA. bolserd@mail.vetmed.ufl.edu

BACKGROUND: Cough-suppressant therapy, previously termed nonspecific antitussive therapy, incorporates the use of pharmacologic agents with mucolytic effects and/or inhibitory effects on the cough reflex itself. The intent of this type of therapy is to reduce the frequency and/or intensity of coughing on a short-term basis. METHODS: Data for this review were obtained from several National Library of Medicine (PubMed) searches (from 1960 to 2004), which were performed between May and September 2004, of the literature published in the English language, limited to human studies, using combinations of the search terms "cough," "double-blind placebo-controlled," "antitussive," "mucolytic," "cough clearance," "common cold," "protussive," "guaifenesin," "glycerol," and "zinc." RESULTS: Mucolytic agents are not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Peripheral and central antitussive agents can be useful in patients with chronic bronchitis, but can have little efficacy in patients with cough due to upper respiratory infection. Some protussive agents are effective in increasing cough clearance, but their long-term effectiveness has not been established. DNase is not effective as a protussive agent in patients with cystic fibrosis. Inhaled mannitol is acutely effective in this patient population, but its therapeutic potential must be investigated further. CONCLUSIONS: These findings suggest that suppressant therapy is most effective when used for the short-term reduction of coughing. Relatively few drugs are effective as cough suppressants.

-----

Thorax. 2006 Jan 31; [Epub ahead of print]
Antibiotic treatment and factors influencing short and long-term outcomes of acute exacerbations of chronic bronchitis.
Wilson R, Jones P, Schaberg T, Arvis P, Duprat-Lomon I, Sagnier P.
Royal Brompton Hospital, London, United Kingdom.

Background: The MOSAIC study compared moxifloxacin to 3 standard antibiotic regimens in Anthonisen type 1 acute exacerbations of chronic bronchitis (AECB). Further exploratory analyses were performed to identify prognostic factors of short and long term clinical outcomes, and their value for clinical research. Methods: Outpatients >/=45 years were screened between AECB episodes, randomized to treatment upon presenting with an AECB, assessed 7-10 days after study treatment, and followed monthly until a new AECB or up to 9 months. Logistic regression assessed the predictive factors for clinical cure (return to pre-AECB status) and clinical success (cure or improvement), and a stepwise Cox regression model time to a composite event (failure of study treatment, new AECB, or further antibiotic treatment for AECB). Results: In multivariate analyses, clinical cure was positively influenced by treatment with moxifloxacin (Odds Ratio=1.499), while cardiopulmonary disease (OR=0.58), FEV1 <50% predicted (OR=0.48) and >4 AECB in previous year (OR=0.68) predicted poorer outcome. For clinical success, treatment with moxifloxacin had a positive influence (OR=1.57), while cardiopulmonary disease (OR: 0.41) and use of acute bronchodilatators (OR; 0.50) predicted poorer outcome. The occurrence of the composite event was influenced by antibiotic treatment (Hazard Ratio=0.82), age >65 years (HR=1.22), FEV1<50% predicted (HR=1.27), >4 AECB in previous year (HR=1.63) and acute bronchodilator use (HR=1.48). For the composite event the beneficial effect of moxifloxacin was primarily seen in patients aged >65 years. Conclusion: Despite selection of a homogeneous population of chronic bronchitis patients between group differences relating to antibiotic treatment could still be confounded by factors related to medical history, severity of disease and use of concomitant medicators. Design of future clinical trials should take these factors into account.

-----

Chest. 2006 Jan;129(1 Suppl):104S-115S.
Chronic cough due to chronic bronchitis: ACCP evidence-based clinical practice guidelines.
Braman SS.
Division of Pulmonary and Critical Care Medicine, Rhode Island Hospital, 595 Eddy St, Providence, RI 02903, USA. sidney_braman@brown.edu

BACKGROUND: Chronic bronchitis is a disease of the bronchi that is manifested by cough and sputum expectoration occurring on most days for at least 3 months of the year and for at least 2 consecutive years when other respiratory or cardiac causes for the chronic productive cough are excluded. The disease is caused by an interaction between noxious inhaled agents (eg, cigarette smoke, industrial pollutants, and other environmental pollutants) and host factors (eg, genetic and respiratory infections) that results in chronic inflammation in the walls and lumen of the airways. As the disease advances, progressive airflow limitation occurs, usually in association with pathologic changes of emphysema. This condition is called COPD. When a stable patient experiences a sudden clinical deterioration with increased sputum volume, sputum purulence, and/or worsening of shortness of breath, this is referred to as an acute exacerbation of chronic bronchitis as long as conditions other than acute tracheobronchitis are ruled out. The purpose of this review is to present the evidence for the diagnosis and treatment of cough due to chronic bronchitis, and to make recommendations that will be useful for clinical practice. METHODS: Recommendations for this section of the review were obtained from data using a National Library of Medicine (PubMed) search dating back to 1950, performed in August 2004, of the literature published in the English language. The search was limited to human studies, using the search terms "cough," "chronic bronchitis," and "COPD." RESULTS: The most effective way to reduce or eliminate cough in patients with chronic bronchitis and persistent exposure to respiratory irritants, such as personal tobacco use, passive smoke exposure, and workplace hazards is avoidance. Therapy with a short-acting inhaled beta-agonist, inhaled ipratropium bromide, and oral theophylline, and a combined regimen of inhaled long-acting beta-agonist and an inhaled corticosteroid may improve cough in patients with chronic bronchitis, but there is no proven benefit for the use of prophylactic antibiotics, oral corticosteroids, expectorants, postural drainage, or chest physiotherapy. For the treatment of an acute exacerbation of chronic bronchitis, there is evidence that inhaled bronchodilators, oral antibiotics, and oral corticosteroids (or in severe cases IV corticosteroids) are useful, but their effects on cough have not been systematically evaluated. Therapy with expectorants, postural drainage, chest physiotherapy, and theophylline is not recommended. Central cough suppressants such as codeine and dextromethorphan are recommended for short-term symptomatic relief of coughing. CONCLUSIONS: Chronic bronchitis due to cigarette smoking or other exposures to inhaled noxious agents is one of the most common causes of chronic cough in the general population. The most effective way to eliminate cough is the avoidance of all respiratory irritants. When cough persists despite the removal of these inciting agents, there are effective agents to reduce or eliminate cough.

-----

Chest. 2006 Jan;129(1 Suppl):95S-103S.
Chronic cough due to acute bronchitis: ACCP evidence-based clinical practice guidelines.
Braman SS.
Division of Pulmonary and Critical Care Medicine, Rhode Island Hospital, 595 Eddy St, Providence, RI 02903, USA. sidney_braman@brown.edu

BACKGROUND: The purpose of this review is to present the evidence for the diagnosis and treatment of cough due to acute bronchitis and make recommendations that will be useful for clinical practice. Acute bronchitis is one of the most common diagnoses made by primary care clinicians and emergency department physicians. It is an acute respiratory infection with a normal chest radiograph that is manifested by cough with or without phlegm production that lasts for up to 3 weeks. Respiratory viruses appear to be the most common cause of acute bronchitis; however, the organism responsible is rarely identified in clinical practice because viral cultures and serologic assays are not routinely performed. Fewer than 10% of patients will have a bacterial infection diagnosed as the cause of bronchitis. The diagnosis of acute bronchitis should be made only when there is no clinical or radiographic evidence of pneumonia, and the common cold, acute asthma, or an exacerbation of COPD have been ruled out as the cause of cough. Acute bronchitis is a self-limited respiratory disorder, and when the cough persists for >3 weeks, other diagnoses must be considered. METHODS: Recommendations for this review were obtained from data using a National Library of Medicine (PubMed) search dating back to 1950, which was performed in August 2004. The search was limited to literature published in the English language and human studies, using search terms such as "cough," "acute bronchitis," and "acute viral respiratory infection." RESULTS: Unfortunately, most previous controlled trials guiding the treatment of acute bronchitis have not vigorously differentiated acute bronchitis and the common cold, and also have not distinguished between an acute exacerbation of chronic bronchitis and acute asthma as a cause of acute cough. For patients with the putative diagnosis of acute bronchitis, routine treatment with antibiotics is not justified and should not be offered. Antitussive agents are occasionally useful and can be offered as therapy for short-term symptomatic relief of coughing, but there is no role for inhaled bronchodilator or expectorant therapy. Children and adult patients with confirmed and probable whooping cough should receive a macrolide antibiotic and should be isolated for 5 days from the start of treatment; early treatment within the first few weeks will diminish the coughing paroxysms and prevent spread of the disease; the patient is unlikely to respond to treatment beyond this period. CONCLUSION: Acute bronchitis is an acute respiratory infection that is manifested by cough and, at times, sputum production that lasts for no more than 3 weeks. This syndrome should be distinguished from the common cold, an acute exacerbation of chronic bronchitis, and acute asthma as the cause of acute cough. The widespread use of antibiotics for the treatment of acute bronchitis is not justified, and vigorous efforts to curtail their use should be encouraged.

-----

Int J Antimicrob Agents. 2005 Dec;26 Suppl 3:S156-63.
Acute exacerbation of chronic bronchitis: expanding short-course therapy.
Martinez FJ.
Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor, USA. fmartine@med.umich.edu

Recent management guidelines for acute exacerbation of chronic bronchitis (AECB) have provided antimicrobial options for different classes of patients according to varying disease severity or risk of treatment failure. In a pivotal, double-blind, double-dummy study comparing azithromycin microspheres (2 g single dose) with the respiratory quinolone levofloxacin (500 mg once daily x 7 days) for the treatment of AECB, the two regimens were equally effective and well tolerated in patients with mild-to-moderate disease (clinical cure rate 93.6% vs. 92.7%, respectively [95% confidence interval (CI) for difference, -3.4, 5.5] and overall bacteriological eradication rate 91.9% vs. 94.4%, respectively (95% CI for difference, -8.8, 3.8). Interestingly, additional post hoc analyses suggest that a single dose of azithromycin also provides comparable clinical efficacy to levofloxacin in patients with a forced expiratory volume in 1 s (FEV1) of less than 70% of the predicted value, a risk factor that would place them in a more severe stratum. These data support azithromycin microspheres as an appropriate option in patients with mild-to-moderate AECB. The potential role of this preparation and other macrolides in patients at higher risk of therapeutic failure requires additional prospective data.

-----

Arzneimittelforschung. 2005;55(11):669-76.
Efficacy and tolerability of a fixed combination of thyme and primrose root in patients with acute bronchitis. A double-blind, randomized, placebo-controlled clinical trial.
Gruenwald J, Graubaum HJ, Busch R.
Analyze & realize ag / Phytopharm Research, Berlin, Germany. jgruenwald@phytopharm.org

In a double-blind, randomized, placebo-controlled, multicenter, prospective study, the clinical efficacy and tolerability of a fixed combination of thyme fluid extract and primose root tincture (Bronchicum Tropfen) was investigated at a dosage of 30 drops (1 ml), taken orally five times daily. 150 outpatients (97 women, 53 men) suffering from acute, not previously treated bronchitis, lasting for less than 48 h, were randomized and treated with either verum (75 patients: 45 women, 30 men) or placebo (75 patients: 52 women, 23 men) over a time period of 7-9 days. 17 patients were excluded from the per-protocol (PP) collective because of either withdrawal from the trial (n = 2) or violations regarding examination time points and/or intake of the study medication (n = 15). The primary outcome criterion for efficacy assessment was the decrease of the Bronchitis Severity Score (BSS) at the end of the study compared to baseline. In the verum group, the BSS decreased from 12.0 +/- 4.4 points at baseline to 1.0 +/- 2.1 at study end compared to a decrease from 11.7 +/- 4.3 points at baseline to 6.5 +/- 4.8 at study end in the placebo group. The inter-group difference of 5.8 points was highly significant (p < or = 10(-3)) in favour of the verum medication [Intention-to-treat (ITT) analysis]. At the end of the study, significantly more patients were symptom free in the verum group (58.7%) than in the placebo group (5.3%) as compared by the ITT analysis (secondary outcome criterion). For both parameters, the PP analysis showed comparable results. The results for the concomitant variables of efficacy support the high superiority of the verum medication compared to placebo. The therapeutic effect was more pronounced the stronger the severity of the acute bronchitis was (as proofed by a stratified evaluation based on severity grade). The tolerability was very good in both groups; neither serious adverse events nor clinically relevant findings in the safety parameters were observed. A total of 7 adverse events occurred, 2 in the verum group and 5 in the placebo group. One of the two adverse events in the verum group was considered to be possibly related to the intake of the study medication. Neither serious nor unknown adverse drug reactions were observed. Two drop-outs occurred during the study related to adverse events, both in the placebo group. In the global safety assessment, the tolerability of both medications was rated as "good" or "very good" by more than 90% of the patients and physicians. In the present study, the fixed combination of thyme fluid extract and primrose root tincture was well tolerated and resulted in a clinically relevant and more pronounced decrease of the bronchitis symptoms (primary outcome criterion) and in shortening the duration of acute bronchitis (secondary outcome criterion) when compared to placebo.

-----

Pulm Pharmacol Ther. 2005 Dec 13; [Epub ahead of print]
Prulifloxacin: A new fluoroquinolone for the treatment of acute exacerbation of chronic bronchitis.
Cazzola M, Salvatori E, Dionisio P, Allegra L.
Department of Pneumology, Unit of Pneumology and Allergology, A. Cardarelli Hospital, Naples, Italy.

Empiric therapy with oral antibiotics is normal practice in the treatment of acute exacerbations of chronic bronchitis (AECB), but there is growing concern regarding efficacy of the currently available antimicrobials. Prulifloxacin, the lipophilic prodrug of ulifloxacin, is an oral fluoroquinolone antibacterial agent with a broad-spectrum in vitro activity against Gram-negative and -positive bacteria, and a long elimination half-life, which allows the once-daily administration. In addition, it penetrates extensively into lung tissues. Statistical analyses indicated a significant linear trend between the prulifloxacin 300, 450, and 600mg doses, which would point to an interesting relationship between dose employed and response obtained. The 600mg once-daily dose showed the best risk/benefit ratio, and was selected for use in the pivotal clinical trials. In well-designed clinical trials, prulifloxacin 600mg administered once daily for 10 days in patients with AECB showed good clinical and bacteriological efficacy (similar to that of ciprofloxacin or co-amoxiclav). In particular, the clinical response rates were favourable in all clinical trials, with eradication rates in patients with pneumococcal infections at least as high as the comparators. It can be concluded that prulifloxacin 600mg once daily is a new therapeutic prospect in the antimicrobial therapy of AECB. In particular, since good patient compliance is a key factor in the successful treatment of any infection, the once daily treatment with prulifloxacin may have some compliance advantages compared to the twice-daily treatment with agents such as ciprofloxacin or co-amoxiclav.

-----

Pulm Pharmacol Ther. 2005 Dec 9; [Epub ahead of print]
Acute exacerbation of chronic bronchitis: Need for an evidence-based approach.
Donner CF.
Division of Pulmonary Disease, Fondazione Salvatore Maugeri IRCCS, Scientific Institute of Veruno, Veruno NO, Italy.

Acute exacerbations of chronic bronchitis (AECB) can be classified into three levels according to severity: (1) home treatment sufficient; (2) hospitalisation required; (3) hospitalisation in the presence of respiratory failure. This evidence-based classification is useful in ranking the clinical relevance of the episode and its outcome, and makes it possible to define the clinical history, clinical evaluation and diagnostic procedures of an exacerbation. Treatment guidelines vary according to severity, but they are essentially based on appropriate bronchodilator therapy (beta(2) agonists and/or anticholinergics, corticosteroids and antibiotics selected according to the local bacterial resistance pattern). It is important that cases requiring management in an intermediate/special respiratory care unit or intensive care unit (ICU) be identified. This is the stage where oxygen therapy and ventilatory support become particularly important. As first choice, they should be non-invasive, saving intubation and invasive ventilatory support for most severe cases characterised by severe acidemia and hypercapnia. We identify the optimal criteria for hospital discharge and follow-up of patients with AECB. In view of the chronic nature of the underlying disease, a correct follow-up is essential to avoid frequent and repeated relapses.

-----

Expert Opin Pharmacother. 2005 Dec;6(16):2867-76.
Clarithromycin extended-release in community-acquired respiratory tract infections.
Williams KN, Bishai WR.
Division of Infectious Diseases, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21231-1001, USA.

Clarithromycin extended-release (ER) is a second-generation macrolide with bactericidal activity against a broad group of pathogens. It allows for convenient once-daily dosing (2 x 500 mg/day), and has less severe adverse effects than the immediate-release (IR) formulation of the drug, which may result in improved patient compliance. Clarithromycin ER has been approved for the treatment of community-acquired pneumonia, acute maxillary sinusitis and acute bacterial exacerbation of chronic bronchitis. In comparison to the IR formulation, clarithromycin ER demonstrates prolonged absorption from the gastrointestinal tract, allowing for once-daily dosing with improved gastrointestinal tolerability. Various double-blind, randomised clinical trials and group studies have found clarithromycin ER to be an efficacious treatment option, comparable with clarithromycin IR, or its other competitors.

-----

Med Mal Infect. 2005 Oct;35(10):507-15. Epub 2005 Oct 18.
[Efficacy and safety of extended-release clarithromycin (5-day short-course) vs telithromycin, in acute bacterial exacerbation of chronic bronchitis.]
[Article in French]
Perronne C, Drugeon H, Zuck P, Filipecki J, Vincent-Lacaze N, Goldfarb G, Leophonte P.
Service des maladies infectieuses et tropicales, hopital Raymond-Poincare, 104, boulevard Raymond-Poincare, 92380 Garches, France.

Background. - The extended-release formulation of clarithromycin (CLA-ER) allows using this macrolide as a single daily dose. The purpose of this study was to evaluate the efficacy and safety of the CLA-ER formulation (500 mgx2) vs telithromycin (TELI) (400 mgx2) as a short course 5-day treatment, once a day, in patients with AECB. Method. - This randomized double-blind study was conducted in patients with AECB without severe airflow limitation (FEV1>35%), with sputum purulence (mandatory criterion), and with either increased sputum volume or increased dyspnea, or both (Anthonisen criteria I or II). Results. - Three hundred sixty-two patients were assessed (62.6 years of age+/-12.9, men: 58.8%) positive culture on inclusion for 53.8%, with Haemophilus influenzae (N=57), Moraxella catarrhalis (N=42), and Streptococcus pneumoniae (N=41). In the per protocol population, the clinical success rate at day 8 was 97% (161/166) vs 97% (146/151), 97.5% CI=[-4.12 -4.71], the clinical cure rate at day 30 was 78% (129/166) versus 77% (116/151), P=0.85, and mean time without recurrence was 62 days versus 61 days (P=0.51), in CLA-ER and TELI groups, respectively. Fourteen patients in the CLA-ER group (8.2%) and 20 patients in the TELI group (12.4%) experienced at least one treatment-related adverse event (P=0.21), upon which gastrointestinal events were the most commonly reported treatment-related ones. Conclusion. - CLA-ER (1000 mg once a day) for 5 days is at least as effective as telithromycin in the treatment of AECB without severe airflow limitation and is well tolerated.

-----

Chest. 2005 Oct;128(4):1980-8.
Five-day telithromycin once daily is as effective as 10-day clarithromycin twice daily for the treatment of acute exacerbations of chronic bronchitis and is associated with reduced health-care resource utilization.
Fogarty C, de Wet R, Mandell L, Chang J, Rangaraju M, Nusrat R.
Spartanburg Pharmaceutical Research, 126 Dillon St, Spartanburg, SC 29307, USA. cmf@bonetesting.com

STUDY OBJECTIVES: To demonstrate equivalence in the clinical efficacy of telithromycin vs clarithromycin treatment of outpatients with acute exacerbations of chronic bronchitis (AECB), and to compare the tolerability and respiratory-related health-care resource utilization associated with these treatment regimens. DESIGN AND PATIENTS: A randomized, double-blind, multicenter, clinical study was conducted at 105 centers in 14 countries. Adult outpatients (age > or = 30 years) received oral telithromycin, 800 mg qd for 5 days (n = 270), or oral clarithromycin, 500 mg bid for 10 days (n = 282), for the treatment of AECB. Clinical and bacteriologic outcomes were assessed at the posttherapy/test-of-cure (TOC) visit (days 17 to 24; per-protocol population). Health-care resource utilization data were collected for each patient by investigators blinded to study medication up to the late posttherapy visit (days 31 to 36). RESULTS: Clinical cure rates at the posttherapy/TOC visit were comparable between the groups (telithromycin, 193 of 225 patients [85.8%]; clarithromycin, 206 of 231 patients [89.2%]); bacteriologic outcome was satisfactory for 59 of 72 telithromycin-treated patients (81.9%) vs 63 of 76 clarithromycin-treated patients (82.9%). Health-care resource utilization assessed up to the late posttherapy visit was lower in the telithromycin treatment group than the clarithromycin treatment group, with significantly fewer hospitalizations for respiratory-related causes (one hospitalization vs eight hospitalizations for a total of 4 inpatient days vs 39 inpatient days, respectively), significantly fewer AECB-related emergency department visits (0 vs 8), and fewer unscheduled outpatient visits (11 vs 18). Fewer telithromycin-treated patients reported days lost from work (21 of 91 patients [23.1%]; 133 days) compared with those receiving clarithromycin (30 of 98 patients [30.6%]; 141 days). Telithromycin was well tolerated; adverse events considered possibly related to study medication were reported by 61 of 269 patients (22.7%) and 100 of 280 patients (35.7%) receiving telithromycin and clarithromycin, respectively. CONCLUSIONS: In this study, 5-day telithromycin treatment was as effective and well tolerated as 10-day clarithromycin treatment for patients with AECB, and was associated with a reduced utilization of health-care resources.

-----

Expert Opin Pharmacother. 2005 Oct;6(13):2335-51.
Azithromycin and lower respiratory tract infections.
Blasi F, Cazzola M, Tarsia P, Cosentini R, Aliberti S, Santus P, Allegra L.
Institute of Respiratory Diseases, University of Milan, IRCCS Fondazione Policlinico-Mangiagalli-Regina Elena, Milan, Italy. francesco.blasi@unimi.it

Azithromycin is a macrolide antibiotic that has been structurally modified from erythromycin with an expanded spectrum of activity and improved tissue pharmacokinetic characteristics relative to erythromycin. This allows once-daily administration for 3-5 days of treatment compared with traditional multi dosing 7-10-day treatment regimens. It has been successfully employed in lower respiratory tract infections. Recent data indicate that azithromycin may exert anti-inflammatory/immunomodulatory effects that may be of use in the treatment of both acute and chronic airway diseases. This review examines the role of azithromycin in lower respiratory tract infections analysing published data on exacerbations of chronic bronchitis, community-acquired pneumonia and cystic fibrosis both in adults and children. In addition, pharmacokinetic and pharmacodynamic properties of the drug are also considered.

-----

Proc (Bayl Univ Med Cent). 2004 Oct;17(4):475-9.
Telithromycin: a novel agent for the treatment of community-acquired upper respiratory infections.
Tran MP.
Department of Pharmacy Services, Baylor University Medical Center, Dallas, Texas.

The ketolides are a new subclass of macrolides, and telithromycin is the first of these agents to be approved. Modifications to the basic macrolide structure result in enhanced activity against penicillin- and erythromycin resistant respiratory pathogens. It is therefore an option in the treatment of mild to moderate community-acquired respiratory infections, such as pneumonia, acute exacerbations of chronic bronchitis, pharyngitis/tonsillitis, and sinusitis. Telithromycin also offers the advantages of once-daily dosing and a shorter course of therapy in certain infections. Comparative clinical trials, although limited and involving only a small number of resistant organisms, showed the equivalence of telithromycin to existing therapies, although telithromycin generally had a higher frequency of mild to moderate gastrointestinal adverse effects. Further clinical and safety data, especially in patients with resistant organisms, are needed.

-----

Int J Infect Dis. 2005 Sep 21; [Epub ahead of print]
Telithromycin in the treatment of pneumococcal community-acquired respiratory tract infections: a review.
Fogarty CM, Buchanan P, Aubier M, Baz M, van Rensburg D, Rangaraju M, Nusrat R.
Spartanburg Pharmaceutical Research, 126 Dillon Street, Spartanburg, SC 29307 USA.

OBJECTIVES:: A pooled analysis of 14 Phase III studies was performed to establish the clinical and bacteriologic efficacy of telithromycin 800mg once daily in the treatment of pneumococcal community-acquired respiratory tract infections (RTIs). METHODS:: Data were examined from 5534adult/adolescent patients with community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB), or acute bacterial sinusitis, who had received telithromycin for 5-10 days or a comparator antibacterial. RESULTS:: Streptococcus pneumoniae was identified in 704/2060 (34.2%) bacteriologically evaluable patients. The respective per-protocol clinical cure rates for telithromycin and comparators were 94.3% and 90.0% (CAP); 81.5% and 78.9% (AECB); 90.1% and 87.5% (acute sinusitis); 92.7% and 87.6% (all indications). Clinical cure rates were 28/34 (82.4%) and 5/7, respectively, for penicillin-resistant infections, and 44/52 (84.6%) and 11/14, respectively, for erythromycin-resistant infections. Of 82 patients with pneumococcal bacteremia, 74 (90.2%) were clinically cured after telithromycin treatment, including 5/7 and 8/10 with penicillin- or erythromycin-resistant strains, respectively. Adverse events considered possibly related to study medication were reported by 1071/4045 (26.5%) telithromycin and 505/1715 (29.4%) comparator recipients. These events were generally of mild/moderate severity, and mainly gastrointestinal in nature. CONCLUSIONS:: As S. pneumoniae is the leading bacterial cause of community-acquired RTIs, and antibacterial resistance is increasing among this species, these findings support the use of telithromycin as first-line therapy in this setting.

-----

Paediatr Respir Rev. 2005 Sep;6(3):227-35.
Macrolides and airway inflammation in children.
Shinkai M, Rubin BK.
Department of Pediatrics, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1081 USA.

For more than 20 years macrolide antibiotics have been used to treat chronic inflammatory airway diseases based on their immunomodulatory activity. Macrolide antibiotics down-regulate damaging prolonged inflammation as well as increase mucus clearance, decrease bacterial virulence and prevent biofilm formation. Initially shown to decrease morbidity and mortality in diffuse panbronchiolitis and in steroid-dependent asthma, long-term macrolide therapy has now been shown to significantly reduce exacerbations and improve lung function and quality of life in children with cystic fibrosis. They have also proven beneficial in Japanese children and adults with chronic sinobronchitis especially when there is nasal polyposis. Long-term macrolides have also proven clinically beneficial in some patients with plastic bronchitis. Adverse reactions are few and generally self-limited when used at the recommended dosage for immunomodulation.

-----

Clin Ther. 2005 Aug;27(8):1144-63.
Telithromycin: The first ketolide antimicrobial.
Nguyen M, Chung EP.
Western University of Health Sciences, College of Pharmacy, Pomona, California, USA; St. Mary Medical Center, Long Beach, California, USA.

Abstract BACKGROUND:: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration (FDA) approval for clinical use. It is approved for the treatment of community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB), and acute maxillary sinusitis (AMS) in adults. OBJECTIVE:: This article reviews the mechanism of action, in vitro antimicrobial activity, pharmacokinetics and pharmacodynamics, clinical efficacy, safety, and drug-interaction profile of telithromycin. METHODS:: Relevant studies were identified through a search of the English-language literature indexed on MEDLINE (1990-March 2005) using the terms telithromycin and HMR 3647, a review of the reference lists of identified articles, and a review of the briefing document prepared by the manufacturer of telithromycin for presentation to the FDA Anti-infective Drugs Advisory Committee. A search of abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy (2001-2004) also was performed. RESULTS:: The results of in vitro susceptibility studies suggest that telithromycin provides coverage against the key respiratory pathogens, both typical and atypical. In addition, telithromycin may be useful against multidrug-resistant strains of Streptococcus pneumoniae and against Haemophilus influenzae, irrespective of beta-lactamase production. In randomized, double-blind, comparative trials (against amoxicillin, amoxicillin/clavulanate, cefuroxime axetil, clarithromycin, moxifloxacin, or trovafloxacin), telithromycin had comparable efficacy to its comparators in the empiric treatment of CAP (4 studies), AECB (3 studies), and AMS (3 studies). Telithromycin is dosed at 800 mg (two 400-mg tablets) QD in community-acquired respiratory tract infections (RTIs). No dose adjustment is required in the elderly, patients with mild to moderate renal insufficiency, or patients with hepatic insufficiency. The majority of adverse events associated with telithromycin were mild to moderate, with gastrointestinal effects (diarrhea, nausea, vomiting) being the most commonly reported, followed by headache and dizziness. Telithromycin has been associated with elevations in hepatic transaminases and prolongation of the electrocardiographic QTc interval, although the significance of these findings is not known. Telithromycin is also a strong inhibitor of and substrate for the cytochrome P450 (CYP) 3A4 isozyme. Therefore, it is important to monitor for potential drug interactions with medications that prolong the QTc interval or are metabolized by the CYP system. CONCLUSIONS:: Telithromycin appears to be a useful option for the empiric treatment of community-acquired RTIs in adults. It may be particularly useful in the outpatient setting in areas with high rates of penicillin- and macrolide-resistant S pneumoniae; it may also be an alternative agent for patients who are allergic to beta-lactams and live in areas with a high prevalence of multidrug-resistant S pneumoniae or for those who have failed to respond to beta-lactam- or macrolide-based therapy.

-----

Clin Ther. 2005 Jun;27(6):926-39.
Prospective observational study of patient-reported outcomes for azithromycin versus usual care in the treatment of bacterial acute exacerbation of chronic bronchitis.
Milstone A, Patsimas J, Farzan D, Castaldo R, Singh H, Feurer I, Harnett J, Luke DR; the PROPeR Use Study Group.
Pulmonary Division, Vanderbilt University Medical Center, Nashville, TN 37232, USA. aaron.milstone@vanderbilt.edu

BACKGROUND: The 3-day course of azithromycin (AZM) 500 mg/d was introduced to the US market in June 2002. OBJECTIVE: The objective of this study was to evaluate changes in health-related quality of life (HRQOL) as measured by the St. George's Respiratory Questionnaire (SGRQ) over a 1-month period in patients receiving a 3-day course of AZM for bacterial acute exacerbation of chronic bronchitis (AECB). METHODS: This was a prospective, multicenter, observational study evaluating outpatient adults with AECB who received either 3 days of AZM 500 mg/d or 5- to 14-day courses of other antibiotics (usual care [UC]) as directed by the clinician. Patients completed 2 HRQOL instruments-the SGRQ and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)-at baseline, day 14, and end of study (EOS) at days 24 to 28. In addition, patients kept a diary for the first 14 days after initiating antibiotic therapy. RESULTS: One hundred twenty-eight patients (57 AZM, 71 UC) were clinically evaluable. There were no significant differences between treatment groups in clinical presentation or baseline demographics, with the exception of a higher percentage of patients with diabetes mellitus in the UC group compared with the AZM group (16.9% vs 3.5%; P = 0.02). Both groups reported similar improvements in signs and symptoms, absenteeism, concomitant respiratory medication use, resource utilization, compliance, and treatment satisfaction as reported in the patient diary. The AZM group reported statistically significant improvement (simple contrasts for end of study vs baseline) in SGRQ measures (total score, P < 0.001; symptoms, P = 0.031; activity, P < 0.001; impacts, P < 0.001) and the SF-36 mental and physical summary components, compared with baseline (both, P < 0.001). Similarly, the UC group reported significant improvement in all SGRQ measures and in the SF-36 physical component score (P < 0.01), but not in the SF-36 mental component score, compared with baseline. At EOS, 80.0% of AZM patients and 59.0% of UC patients had a > or =4-point improvement on the SGRQ total score; however, this difference was not statistically significant in the multivariate analysis. In addition, 89.5% of AZM patients and 89.9% of UC patients were satisfied or very satisfied with their treatment (P = NS). Resource utilization was similar between the groups. CONCLUSIONS: In this observational study, patients with AECB treated with a 3-day course of AZM experienced significant improvements in HRQOL as measured by a change of > or =4 points on the SGRQ and SF-36 physical and mental component scores versus baseline.

-----

Cochrane Database Syst Rev. 2005 Jul 20;(3):CD004560.
Chinese medicinal herbs for acute bronchitis.
Wu T, Chen X, Duan X, Juan N, Liu G, Qiao J, Wang Q, Wei J, Zhen J, Zhou L.
Chinese Cochrane Centre, Chinese Evidence-Based Medicine Centre & Regional Clinical Epidemiology Resource & Training Centre, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan, CHINA, 610041.

BACKGROUND: Acute bronchitis is one of the most common diagnoses made by primary-care physicians. It is traditionally treated with antibiotics, (although the evidence for their effectiveness is weak and modest at best), and other even less effective treatments. Chinese medicinal herbs have been also used as treatment. OBJECTIVES: This review aims to summarise the existing evidence on the comparative effectiveness and safety of Chinese medicinal herbs for treating uncomplicated acute bronchitis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2005), which includes the Cochrane Acute Respiratory Infections Group's specialised register; The Chinese Cochrane Centre's Controlled Trials Register (up to December 2004); MEDLINE (1966 to March Week 1, 2005); EMBASE (1988 to December 2004); and the Chinese Biomedical Database (CBM) (1980 to December 2004). SELECTION CRITERIA: Randomised controlled trials comparing Chinese medicinal herbs with placebo, antibiotics or other Western medicines for the treatment of uncomplicated acute bronchitis. DATA COLLECTION AND ANALYSIS: At least two authors extracted data and assessed trial quality. MAIN RESULTS: Four trials reported the time to improvement of cough, fever, and rales associated with bronchitis and showed that patients treated with Chinese herbs had a shorter duration of signs and symptoms. Two trials reported the proportion of patients with improved signs and symptoms at follow up and showed that Chinese herbs were beneficial in terms of relief of signs and symptoms. Thirteen trials analysed the data on physician global assessment of improvement at follow up. Nine of thirteen trials showed that Chinese herbs were superior to routine treatment and the other four trials showed a similar effect to routine treatment. In general, Chinese herbs appeared beneficial. Only one trial reported on adverse effects during treatment. AUTHORS' CONCLUSIONS: There is insufficient quality data to recommend the routine use of Chinese herbs for acute bronchitis. The benefit found in this systematic review could be due to publication bias and study-design limitations of the individual studies. In addition, the safety of Chinese herbs is unknown due to the lack of toxicological evidence on these Chinese herbs, though adverse events are rarely reported. Chinese herbs should be used carefully.

-----

Am J Med. 2005 Jul;118(Suppl 7A):39S-44S.
Appropriate outpatient treatment of acute bacterial exacerbations of chronic bronchitis.
Martinez FJ, Anzueto A.
University of Michigan Health System, Ann Arbor, Michigan, USA.

Acute exacerbations of chronic bronchitis (AECB), which are characteristic of chronic obstructive pulmonary disease (COPD), contribute to morbidity and decreased quality of life for patients with COPD. A significant proportion of these exacerbations are due to bacterial infections. The Council for Appropriate and Rational Antibiotic Therapy (CARAT) criteria provide guidance for choosing the optimal drug at its optimal dose and duration for antimicrobial treatment of AECB due to bacterial infection. Evidence-based guidelines recommend stratifying patients according to risk factors to improve selection of targeted antimicrobial therapy. With increasing rates of resistance to some antimicrobials, resistance is also an important consideration for reducing treatment failures and decreasing the need for further pharmacologic treatment. Fluoroquinolones are recommended as first-line therapy for patients with chronic bronchitis who have risk factors; gatifloxacin, gemifloxacin, and levofloxacin are highly active against commonly encountered pathogens. Safety profiles are an important consideration because adverse events and poor tolerability can reduce patient adherence rates, which in turn can lead to poorer outcomes. Safety profiles also become an important consideration as shorter-course, higher-dose therapies become more prevalent. First-line therapy with a well-tolerated antibiotic that is active against the predominant pathogens, combined with low resistance rates and a convenient once-a-day dosing regimen, may reduce overall costs. Fluoroquinolones exhibit low resistance, good activity levels, and high respiratory penetration, and they are particularly well suited for shorter-course, higher-dose regimens in selected patients. Shorter-course, higher dose regimens, in turn, may be more effective, cost-efficient, and appropriate for controlling the rise of resistance than standard regimens.

-----

Am J Med. 2005 Jul;118(Suppl 7A):29S-38S.
Antimicrobial treatment of lower respiratory tract infections in the hospital setting.
Grossman RF, Rotschafer JC, Tan JS.
University of Toronto, Toronto, Ontario, Canada.

Respiratory tract infections (RTIs) that may require hospitalization include acute exacerbations of chronic bronchitis (AECB), community-acquired pneumonia (CAP), and hospital-acquired pneumonia (HAP), which includes ventilator-associated pneumonia (VAP). Healthcare-associated pneumonia (HCAP) is treated similar to HAP and may be considered with HAP. For CAP requiring hospitalization, the current guidelines for the treatments of RTIs generally recommend either a beta-lactam and macrolide combination or a fluoroquinolone. The respiratory fluoroquinolones (levofloxacin, gatifloxacin, moxifloxacin, and gemifloxacin) are excellent antibiotics due to high levels of susceptibility among gram-negative, gram-positive, and atypical pathogens. The fluoroquinolones are active against > 98% of Streptococcus pneumoniae, including penicillin-resistant strains. Fluoroquinolones are also recommended for AECB requiring hospitalization. Evidence from clinical trials suggests that levofloxacin monotherapy is as efficacious as combination ceftriaxone-erythromycin therapy in the treatment of patients hospitalized with CAP. For early-onset HAP, VAP, and HCAP without the risk of multidrug resistance, ceftriaxone, ampicillin-sulbactam, ertapenem, or one of the fluoroquinolones is recommended. High-dose, short-course therapy regimens may offer improved treatment due to higher drug concentrations, more rapid killing, increased adherence, and the potential to reduce development of resistance. Recent studies have shown that short-course therapy with levofloxacin, azithromycin, or telithromycin in patients with CAP was effective, safe, and tolerable and may control the rate of resistance.

-----

Pulm Pharmacol Ther. 2005 Jun 18; [Epub ahead of print]
Effect of salmeterol on mucociliary and cough clearance in chronic bronchitis.
Bennett WD, Almond MA, Zeman KL, Johnson JG, Donohue JF.
Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina at Chapel Hill, CB 7310, 104 Mason Farm Road, Chapel Hill, NC 27599, USA.

The effect of long acting beta(2)-adrenergic bronchodilators on impaired mucociliary clearance in chronic bronchitis is unknown. Using a radiolabeled aerosol (technetium-99m-labeled sulfur colloid) and gamma camera analysis, we measured the acute effect of salmeterol vs. placebo on mucociliary and cough clearance in mild-moderate chronic bronchitics (n=14) over a 2h period. During the 1-1(1/2)h period of observation patients performed 60 controlled coughs on each study day. Average whole lung clearance through 1 and 2h after administration of salmeterol (42mug) or placebo via metered dose inhaler (double-blinded, crossover design study) showed no significant difference between treatments. Similarly, for the specific period when cough was added to mucociliary clearance, there was no difference on whole lung clearance between treatments. However, when clearance from the peripheral region of the lung was assessed over the entire 2h period of observation, salmeterol provided a 30% enhancement of airway clearance compared to placebo, average peripheral 2h clearance (%)=22+/-9 vs. 17+/-10 for salmeterol vs. placebo (P=0.05 by paired analysis). Thus, in addition to its bronchodilating effects, salmeterol acutely enhances peripheral airway clearance of secretions in mild-moderate chronic bronchitis.

-----

Eur Respir J. 2005 Jun;25(6):1001-10.
Patient stratification in the management of acute bacterial exacerbation of chronic bronchitis: the role of levofloxacin 750 mg.
Martinez FJ, Grossman RF, Zadeikis N, Fisher AC, Walker K, Ambruzs ME, Tennenberg AM.
The University of Michigan Health System, 1500 East Medical Center Drive, 3916 Taubman Center, Box 0360, Ann Arbor, MI 48109, USA. fmartine@umich.edu

This is the first prospective clinical trial in which patients with acute bacterial exacerbation of chronic bronchitis have been stratified by degree of underlying illness. Uncomplicated patients were randomised to levofloxacin 750 mg once daily (q.d.) for 3 days or azithromycin q.d. for 5 days. Complicated patients were randomised to levofloxacin 750 mg q.d. for 5 days or amoxicillin 875 mg/clavulanate 125 mg twice daily for 10 days. Regardless of therapy, complicated patients demonstrated lower clinical and microbiological success than uncomplicated patients. Clinical success for clinically evaluable patients was similar for levofloxacin and azithromycin (93.0 versus 90.1%, respectively), and levofloxacin and amoxicillin/clavulanate (79.2 versus 81.7%, respectively). For microbiologically evaluable patients, clinical response to levofloxacin for 3 days was superior to azithromycin for 5 days (96.3 versus 87.4%, respectively), and levofloxacin for 5 days was similar to amoxicillin/clavulanate for 10 days (81.4 versus 80.9%, respectively). Microbiological eradication was superior for levofloxacin for 3 days compared with azithromycin for 5 days (93.8 versus 82.8%, respectively), and similar for levofloxacin and amoxicillin/clavulanate for 10 days (81.4 versus 79.8%, respectively). In conclusion, levofloxacin 750 mg for 3 days was comparable to azithromycin for 5 days for uncomplicated patients with acute bacterial exacerbation of chronic bronchitis, while 5 days of 750 mg levofloxacin was comparable to 10 days of amoxicillin/clavulanate for complicated acute bacterial exacerbation of chronic bronchitis.

-----

Clin Infect Dis. 2005 Jun 1;40(11):1657-64. Epub 2005 Apr 22.
Telithromycin: a ketolide antibiotic for treatment of respiratory tract infections.
Lonks JR, Goldmann DA.
Division of Infectious Diseases, Brown Medical School and Miriam Hospital, Providence, RI 02912, USA. John_Lonks@brown.edu

Telithromycin, a recently approved ketolide antibiotic derived from 14-membered macrolides, is active against erythromycin-resistant pneumococci. Telithromycin has enhanced activity in vitro because it binds not only to domain V of ribosomal RNA (like macrolides do) but also to domain II. However, it is not active against streptococci and staphylococci with constitutive macrolide, lincosamide, and streptogramin B resistance. Telithromycin, available in an oral formulation, is approved by the US Food and Drug Administration for use in adults for treatment of (1) community-acquired pneumonia due to Streptococcus pneumoniae (including multidrug-resistant isolates), Haemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniae, or Mycoplasma pneumoniae; (2) acute exacerbation of chronic bronchitis due to S. pneumoniae, H. influenzae, or M. catarrhalis; or (3) acute bacterial sinusitis due to S. pneumoniae, H. influenzae, M. catarrhalis, or methicillin- and erythromycin-susceptible Streptococcus aureus. It is not approved for treatment of tonsillitis, pharyngitis, or severe pneumococcal pneumonia. Unique visual adverse effects occurred in 0.27%-2.1% of patients receiving telithromycin therapy. Its enhanced activity against some common respiratory pathogens makes it a valuable addition to the available macrolides.

-----

Pharmacotherapy. 2005 May;25(5):717-40.
Gemifloxacin for the treatment of respiratory tract infections: in vitro susceptibility, pharmacokinetics and pharmacodynamics, clinical efficacy, and safety.
Bhavnani SM, Andes DR.
Institute for Clinical Pharmacodynamics, Ordway Research Institute, Albany, NY 12208, USA. SBhavnani-ICPD@ordway.research.org

Gemifloxacin is a synthetic fluoroquinolone antimicrobial agent exhibiting potent activity against most gram-negative and gram-positive organisms, such as the important community-acquired respiratory pathogens Streptococcus pneumoniae (including multidrug-resistant S. pneumoniae), Haemophilus influenzae , and Moraxella catarrhalis . The agent's mechanism of action involves dual targeting of two essential bacterial enzymes: DNA gyrase and topoisomerase IV. Gemifloxacin was approved by the Food and Drug Administration in April 2003 for treatment of community-acquired pneumonia and acute bacterial exacerbation of chronic bronchitis. The drug has an oral bioavailability of approximately 71%. Approximately 20-35% of gemifloxacin is excreted unchanged in the urine after 24 hours. The elimination half-life of gemifloxacin is 6-8 hours in patients with normal renal function, supporting once-daily dosing. The 24-hour free-drug area under the plasma concentration-time curve:minimum inhibitory concentration ratio (fAUC(0-24):MIC) associated with efficacy, based on results from in vitro and animal models of infection, is approximately 30. With a mean fAUC(0-24) of approximately 3 microg*hour/ml (35% of total AUC(0-24) of 8.4) and a median S. pneumoniae MIC for 90% of tested strains of 0.03, a fAUC(0-24):MIC ratio of 100 would be expected after standard dosing (320 mg once/day). In clinical studies involving both hospitalized and outpatient populations, gemifloxacin has been highly effective in the treatment of community-acquired pneumonia and acute exacerbation of chronic bronchitis. Clinical success rates ranged from 93.9-95.9% in patients with community-acquired pneumonia and 96.1-97.5% in those with acute exacerbation of chronic bronchitis. Gemifloxacin is well tolerated; the frequency of adverse events with this agent is low. Most adverse events are mild-to-moderate in severity, with diarrhea (< 4%), nausea and rash (< 3%), and headache (< 2%) most commonly reported. Drug interactions with gemifloxacin are not common, although absorption is greatly reduced when given with divalent and trivalent cation-containing compounds, such as antacids. Due to its potent activity against many common gram-positive and gram-negative respiratory pathogens, its proven clinical efficacy, and its favorable safety profile, gemifloxacin is a highly effective empiric treatment for community-acquired lower respiratory tract infections.

-----

Am J Health Syst Pharm. 2005 May 1;62(9):905-16.
Telithromycin: the first ketolide for the treatment of respiratory infections.
Kasbekar N, Acharya PS.
Department of Pharmacy, University of Pennsylvania Medical Center-Presbyterian, Philadelphia, PA 19104, USA. kasbekar@uphs.upenn.edu

PURPOSE: The pharmacology, mechanisms of resistance, in vitro activity, clinical efficacy, pharmacokinetics, indications, adverse effects, dosage and administration, and place in therapy of telithromycin in the treatment of respiratory infections are reviewed. SUMMARY: Telithromycin is the first ketolide to be approved in the United States for use against common respiratory pathogens. The unique structure of telithromycin allows for enhanced binding to bacterial ribosomal RNA, thereby blocking protein synthesis. Its spectrum of activity includes pathogens implicated in common respiratory infections (Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumonia, and Chlamydia pneumoniae) and multidrug-resistant isolates of pneumococcus. Clinical efficacy has been documented in several multicenter, comparative trials for the treatment of community-acquired pneumonia, acute exacerbation of chronic bronchitis, acute maxillary sinusitis, and pharyngitis tonsillitis. Although studies have demonstrated that the clinical efficacy of telithromycin is comparable to macrolides, telithromycin is unique in that it provides activity against penicillin- and macrolide-resistant respiratory pathogens. The recommended dosage of telithromycin is 800 mg p.o. once daily. The most common adverse events resulting from telithromycin use include diarrhea, nausea, headache, dizziness, vomiting, loose stools, dysgeusia, and dyspepsia. The drug's adverse-event profile is comparable to that of similar agents. Telithromycin is a strong inhibitor of cytochrome P-450 isoenzyme 3A4; therefore, it can affect the efficacy and toxicity profile of medications that are metabolized by this isoenzyme. CONCLUSION: Telithromycin is a reasonable addition to the current treatment options for upper-respiratory-tract infections. Its use should be restricted to infections caused by penicillin- and macrolide-resistant pathogens.

-----

Dtsch Med Wochenschr. 2005 Mar 18;130(11):563-7.
[Antioxidant treatment with N-acetylcysteine and vitamin C in patients with chronic bronchitis]
[Article in German]
Lukas R, Scharling B, Schultze-Werninghaus G, Gillissen A.
Abteilung fur Pneumologie, Allergologie und Schlafmedizin, Berufsgenossenschaftliche Kliniken Bergmannsheil, Universitatsklinik der Ruhr-Universitat Bochum.

BACKGROUND AND OBJECTIVE: N-acetylcysteine (NAC) is known to have direct antioxidant properties due to its thiol-group on the one hand as well as indirect antioxidant capacity as cysteine-donor to cellular glutathione-synthesis on the other hand. Therefore NAC appears to be attractive in antioxidant therapy of inflammatory disorders of the lung. This study aimed to investigate the use of antioxidant therapy with NAC in chronic bronchitis. PATIENTS AND METHODS: In this randomized, double-blinded and placebo-controlled trial 100 patients divided into four groups were observed over a period of 3 months. The treatment consisted of either 600 mg NAC bid, 500 mg Vitamin C bid, a combination of those two substances using the same dosage or a placebo-preparation. The release of reactive oxygen species from isolated neutrophilic granulocytes and mononuclear cells was quantified before treatment and after three months using chemiluminescence (primary outcome parameter). Furthermore cellular glutathione content of these inflammatory cells was quantified spectrometrically. In addition, leukocyte-count and erythrocyte sedimentation rate as well as spirometry and a standardized symptom-based questionnaire were used to monitor the clinical efficacy. RESULTS: None of the above substances were able to significantly reduce the release of reactive oxygen species from the examined population of inflammatory cells. They also failed to increase intracellular glutathione-levels. Concordantly, no changes in spirometry and the results of the symptom-based questionnaire were found. CONCLUSION: In summary NAC, Vitamin C and the NAC/ Vitamin C-combination did neither enhance antioxidant protection in the blood nor is it of any clinical benefit in chronic bronchitis. Possible reasons may be a lack of antioxidant deficiency in these patients and negative feedback mechanisms of the glutathione-system.

-----

Ann Clin Microbiol Antimicrob. 2005 Mar 8;4(1):5.
Antibiotic activity of telithromycin and comparators against bacterial pathogens isolated from 3,043 patients with acute exacerbation of chronic bronchitis.
Sethi S, Anzueto A, Farrell DJ.
University at Buffalo SUNY, Buffalo NY, USA. ssethi@buffalo.edu.

BACKGROUND: Antimicrobial therapy is considered an important component in the medical management of most patients with acute exacerbation of chronic bronchitis (AECB). The three predominant bacterial species isolated are nontypeable Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Staphylococcus aureus is also frequently isolated while atypical bacteria are thought to cause up to 10% of exacerbations. Antibacterial resistance is increasing worldwide and little surveillance data exist concerning pathogens isolated from patients with AECB. METHODS: This study examines the prevalence of antibacterial resistance in isolates obtained from patients with clinically diagnosed AECB. A total of 3043 isolates were obtained from 85 centres in 29 countries, between 1999-2003, and were tested against the new ketolide telithromycin and a panel of commonly used antibiotics. RESULTS AND DISCUSSION: Of the S. pneumoniae isolates, 99.9% were susceptible to telithromycin, but only 71% were susceptible to erythromycin and 75.3% to penicillin. Of the H. influenzae isolates, 99.6% were susceptible to telithromycin. 11.7% of these isolates produced beta-lactamase. Almost 10% of S. pneumoniae were multidrug-resistant; 99.0% of these isolates were susceptible to telithromycin. Telithromycin also demonstrated good in vitro activity against M. catarrhalis (MIC90 = 0.12 mg/L) and was the most active compound against methicillin-susceptible S. aureus (98.9% susceptible). CONCLUSION: Telithromycin demonstrated similar or better activity against the bacterial species investigated than the other agents, with the most complete coverage overall. These species are the predominant causative bacterial pathogens in AECB and thus the spectrum of activity of telithromycin makes it a potential alternative for the empirical treatment of AECB.

-----

Drugs. 2005;65(5):695-724.
Gatifloxacin: A Review of its Use in the Treatment of Bacterial Infections in the US.
Keam SJ, Croom KF, Keating GM.
Adis International Limited, Auckland, New Zealand.

Gatifloxacin (Tequin((R))) is an 8-methoxy fluoroquinolone approved in the US for use in the treatment of community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB), acute sinusitis, uncomplicated and complicated urinary tract infections (UTIs), pyelonephritis, gonorrhoea and uncomplicated skin and skin structure infections.Gatifloxacin has a broad spectrum of antibacterial activity in vitro and good clinical and bacteriological efficacy in patients with indicated infections following once-daily administration by the intravenous or oral routes. It is generally well tolerated; the most common adverse events are associated with the gastrointestinal tract and CNS. Recent approvals for the use of gatifloxacin in the treatment of CAP due to multidrug-resistant Streptococcus pneumoniae (MDRSP) and in uncomplicated skin and skin structure infections extend the role of this drug in the treatment of bacterial infections in the US.

-----

Dtsch Med Wochenschr. 2005 Mar 18;130(11):563-7.
[Administration of N-acetylcysteine and Vitamin C to augment antioxidant protection in patients with chronic bronchitis.]
[Article in German]
Lukas R, Scharling B, Schultze-Werninghaus G, Gillissen A.
Abteilung fur Pneumologie, Allergologie und Schlafmedizin, Berufsgenossenschaftliche Kliniken Bergmannsheil, Universitatsklinik der Ruhr-Universitat Bochum.

Summary. BACKGROUND AND OBJECTIVE: N-acetylcysteine (NAC) is known to have direct antioxidant properties due to its thiole-group on the one hand as well as indirect antioxidant capacity as cysteine-donor to cellular glutathione-synthesis on the other hand. Therefore NAC appears to be attractive in antioxidant therapy of inflammatory disorders of the lung. This study aimed to investigate the use of antioxidant therapy with NAC in chronic bronchitis. PATIENTS AND METHODS: In this randomized, double-blinded and placebo-controlled trial100 patients divided into four groups were observed over a period of 3 months. The treatment consistet of either 600 mg NAC bid, 500 mg Vitamin C bid, a combination of those two substances using the same dosage or a placebo-preparation. The release of reactive oxygen species from isolated neutrophilic granulocytes and mononuclear cells was quantified before treatment and after three months using chemiluminescence (primary outcome parameter). Furthermore cellular glutathione content of these inflammatory cells was quantified spectrometrically. In addition, leukocyte-count and erythrocyte sedimentation rate as well as spirometry and a standardized symptom-based questionnaire were used to monitor the clinical efficacy. RESULTS: None of the above substances were able to significantly reduce the release of reactive oxygen species from the examined population of inflammatory cells. They also failed to increase intracellular glutathione-levels. Concordantly, no changes in spirometry and the results of the symptom-based questionnaire were found. CONCLUSION: In summary NAC, Vitamin C and the NAC/ Vitamin C-combination did neither enhance antioxidant protection in the blood nor is it of any clinical benefit in chronic bronchitis. Possible reasons may be a lack of antioxidant defficiency in these patients and negative feedback mechanisms of the glutathione-system.

-----

Expert Opin Pharmacother. 2005 Feb;6(2):283-93.
Moxifloxacin in respiratory tract infections.
Miravitlles M.
Servei de Pneumologia i Allergia Respiratoria (IDIBAPS), Red Respira RTIC 03/11, ISCIII, Hospital Clinic, Barcelona, Spain. marcm@clinic.ub.es.

Moxifloxacin is a fourth-generation fluoroquinolone that has been shown to be effective against respiratory pathogens, including Gram-positive (Streptococcus pneumoniae), Gram-negative (Haemophilus influenzae, Moraxella catarrhalis), and atypical strains (Chlamydia pneumoniae, Mycoplasma pneumoniae), as well as multi-drug resistant S. pneumoniae, including strains resistant to penicillin, macrolides, tetracyclines, trimethoprim/sulfamethoxazole and some fluoroquinolones. Moxifloxacin is highly concentrated in lung tissue, and has demonstrated rapid eradication rates. The bioavailability and half-life of moxifloxacin provides potent bactericidal effects at a dose of 400mg/day. The ratio of the area under the concentration-time curve to MIC of moxifloxacin is the highest among the fluoroquinolones against S. pneumoniae. The clinical efficacy of moxifloxacin has been shown in controlled studies of community-acquired pneumonia (CAP), exacerbations of chronic bronchitis (CB) and acute bacterial rhinosinusitis. Moxifloxacin has demonstrated a faster resolution of symptoms in CAP and exacerbations of CB patients compared with first-line therapy. It has also demonstrated better eradication in exacerbations of CB compared with standard therapy, in particular the macrolides. Treatment guidelines should take into account the results of clinical trials with moxifloxacin in order to establish the role of this antimicrobial in the therapeutic arsenal against respiratory tract infections.

-----

Treat Respir Med. 2005;4(1):31-9.
Once-daily azithromycin for 3 days compared with clarithromycin for 10 days for acute exacerbation of chronic bronchitis: a multicenter, double-blind, randomized study.
Swanson RN, Lainez-Ventosilla A, De Salvo MC, Dunne MW, Amsden GW.
Pfizer Global Research & Development, Groton, Connecticut, USA.

STUDY OBJECTIVES: To compare the efficacy and safety of oral azithromycin 500 mg once daily for 3 days with those of oral clarithromycin 500 mg twice daily for 10 days. DESIGN: Randomized, double-blind, double-dummy, multicenter study. SETTING: Seventy-six study centers in eight countries (Argentina, Brazil, Canada, Chile, Costa Rica, India, South Africa, and USA). PATIENTS: Three hundred and twenty-two adult outpatients with acute exacerbation of chronic bronchitis (AECB) as documented by increased cough or sputum production, worsening dyspnea, and purulent sputum production. INTERVENTIONS: Randomization 1 : 1 to azithromycin 500 mg once daily for 3 days or clarithromycin 500 mg twice daily for 10 days. RESULTS: The primary efficacy endpoint was clinical response at day 21-24, or test of cure (TOC) visit in the modified intent-to-treat (MITT) analysis (n = 318 patients). The TOC clinical cure rates in the MITT population were equivalent in the two treatment groups at 85% with azithromycin and 82% with clarithromycin (95% CI -5.9%, 12.0%). Clinical success rates on day 10-12 were also equivalent at 93% with azithromycin and 94% with clarithromycin (95% CI -7.9%, 4.4%). Clinical cure rates at TOC by pathogen were equivalent for the two treatment groups for Haemophilus influenzae (azithromycin, 85.7%; clarithromycin, 87.5%), Moraxella catarrhalis (91.7% and 80.0%, respectively) and Streptococcus pneumoniae (90.6% and 77.8%, respectively). Bacteriologic success rates were also equivalent between the azithromycin and clarithromycin treatment groups at TOC for S. pneumoniae (90.6% and 85.2%, respectively), H. influenzae (71.4% and 81.3%, respectively) and M. catarrhalis (100% and 86.7%, respectively). The overall incidence of treatment-related adverse events was similar in the azithromycin and clarithromycin groups (20.9% and 26.8%, respectively), with the most common being abdominal pain (6.3% and 6.1%, respectively), diarrhea (4.4% and 5.5%, respectively), and nausea (4.4% and 3.7%, respectively). CONCLUSIONS: Three-day treatment with azithromycin 500 mg once daily is equivalent to a 10-day treatment with clarithromycin 500 mg twice daily in adult patients with AECB.

-----

J Allergy Clin Immunol. 2005 Feb;115(2):S1-13.
Telithromycin new product overview.
File TM.
Department of Medicine, College of Medicine, Northeastern Ohio University, Rootstown, OH, USA. filet@summa-health.org

Community-acquired respiratory tract infections (CARTIs), including community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute bacterial sinusitis, contribute substantially to health care costs in the United States. Although many prescriptions for antibiotics are written each year for the treatment of CARTIs, most are prescribed on an empiric basis. Concerns about the increasing prevalence of antimicrobial resistance and the changing pattern of pathogens isolated from subjects with CARTIs have raised questions about the empiric treatment paradigm. When choosing appropriate antimicrobial therapy for CARTIs, physicians must consider not only the spectrum of activity of antibiotics but also the potential risk of resistance. Telithromycin is the first member of the ketolide class, a new family of antimicrobials structurally related to the macrolides, to be approved by the US Food and Drug Administration for the treatment of CARTIs. The spectrum of activity of telithromycin includes common typical and atypical causative pathogens associated with community-acquired respiratory tract infections, including antibiotic-resistant strains of Streptococcus pneumoniae. Clinical trials have shown that telithromycin is as effective as traditionally used antimicrobial agents in the treatment of mild-to-moderate community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute bacterial sinusitis.

-----

Expert Rev Anti Infect Ther. 2004 Dec;2(6):831-43.
Gemifloxacin: a new, potent fluoroquinolone for the therapy of lower respiratory tract infections.
File TM Jr, Tillotson GS.
Northeastern Ohio Universities, College of Medicine and Summa Health System, 75 Arch St. Suite 105, Akron, OH 44304, USA. filet@summahealth.org

The fluoroquinolone gemifloxacin has recently been approved for the treatment of acute bacterial exacerbations of chronic bronchitis and mild community acquired pneumonia, including that caused by multidrug-resistant Streptococcus pneumoniae. Owing to the increasing prevalence of multidrug-resistant S. pneumoniae, as well as resistance to other common pathogens of acute bacterial exacerbations of chronic bronchitis and community acquired pneumonia, it is important to have new, potent antimicrobial agents for the treatment of these infections. Gemifloxacin is the most potent antimicrobial agent in vitro for S. pneumoniae, and has excellent activity against the other key pathogens of acute bacterial exacerbations of chronic bronchitis and community acquired pneumonia, including the atypical microorganisms. The clinical trial outcomes of several studies that have evaluated gemifloxacin show a range of superior clinical or bacteriologic outcomes against several current antimicrobials, including levofloxacin, clarithromycin, trovafloxacin and ceftriaxone. The safety profile of gemifloxacin is similar to that of approved agents to treat acute bacterial exacerbations of chronic bronchitis and community acquired pneumonia, with a low discontinuation rate of 2.2%. A nonphototoxic rash (usually a mild, maculopapular rash) was observed in 2.8% of patients in clinical studies.

-----

Cochrane Database Syst Rev. 2004 Oct 18;(4):CD001954.
Azithromycin for acute lower respiratory tract infections.
Panpanich R, Lerttrakarnnon P; Laopaiboon; M.
Community Medicine, Faculty of Medicine, Chiang Mai University, 110 Intawaroros Road, Chiang Mai, THAILAND, 50200.

BACKGROUND: The spectrum of acute lower respiratory tract infection ranges from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia. Annually approximately five million people die of acute respiratory tract infections. Among these, pneumonia represents the most frequent cause of mortality, hospitalization and medical consultation. Azithromycin is a new macrolide antibiotic, structurally modified from erythromycin and is noted for its activity against some gram-negative organisms associated with respiratory tract infections, particularly Haemophilus influenzae (H. influenzae). OBJECTIVES: To compare the effectiveness of azithromycin to amoxycillin or amoxycillin/clavulanic acid (amoxyclav) in the treatment of LRTI, in terms of clinical failure, incidence of adverse events and microbial eradication. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2003), MEDLINE (January 1966 to January Week 3, 2004), and EMBASE (January 1988 to 2003). SELECTION CRITERIA: Randomised and quasi-randomised controlled trials, which compared azithromycin to amoxycillin or amoxycillin/clavulanic acid in patients with clinical evidence of acute LRTI: acute bronchitis, pneumonia, and acute exacerbation of chronic bronchitis were studied. DATA COLLECTION AND ANALYSIS: The criteria for assessing study quality were generation of allocation sequence, concealment of treatment allocation, blinding, and completeness of the trial. All types of acute lower respiratory tract infections were initially pooled in the meta-analyses. Funnel plot was used to examine publication bias. The heterogeneity of results was investigated by the forest plot and Chi-square test. Index of I(2) was also used to measure inconsistency results among trials. Subgroup analysis was conducted for age, types of respiratory tract infection and types of antibiotic in control groups. Sensitivity analysis was conducted under the condition of trial size and concealment of treatment allocation. MAIN RESULTS: Fourteen trials with 2,521 enrolled patients used 2,416 patients in the analysis. A total of 1,350 patients received azithromycin and 1,066 received amoxicillin or amoxicillin-clavulanic acid. The pooled analysis of all trials showed that there was no significant difference in the incidence of clinical failure on about day 10 to 14 after therapy started between the two groups (relative risk (RR) (random effects) 0.96; 95% CI 0.58 to 1.57). Sensitivity analysis showed that a reduction of clinical failure in azithromycin-treated patients (RR 0.52; 95% CI 0.24 to 1.12) in three adequately concealed studies, compared to RR 1.14 (95% CI 0.62 to 2.08) in eleven studies with inadequate concealment. Eleven trials reported the incidence of microbial eradication and there was no significant difference between the two groups (RR 0.98; 95% CI 0.91 to 1.07). The reduction of adverse events in azithromycin group was RR 0.75 (95% CI 0.56 to 1.00). REVIEWERS' CONCLUSIONS: There is unclear evidence that azithromycin is superior to amoxicillin or amoxicillin-clavulanic acid in treating acute LRTI. Future trials with high methodological quality are needed.

-----

Cochrane Database Syst Rev. 2004 Oct 18;(4):CD004417.
Delayed antibiotics for symptoms and complications of respiratory infections.
Spurling G, Mar C, Dooley L, Foxlee R.
Discipline of General Practice, University of Queensland, Level 2, Edith Cavell Building, Royal Brisbane Hospital, Brisbane, Queensland, AUSTRALIA, 4029.

BACKGROUND: The use of antibiotics for upper respiratory tract infections is controversial. Any benefits have to be weighed against common adverse reactions (including rash, abdominal pain, diarrhoea and vomiting), cost and antibacterial resistance. There has been interest in ways to reduce antibiotic prescribing for acute respiratory infections. One is delaying the use of prescribed antibiotics by more than 48 hours for acute upper respiratory tract infections. Such methods have been shown to reduce prescribing. This review asks what effect this practice has on the clinical course of the illness. OBJECTIVES: To evaluate the clinical effect of delayed antibiotic use in acute upper respiratory tract infections compared to immediate use of antibiotics SEARCH STRATEGY: The following electronic databases were searched: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2004) which includes the Acute Respiratory Infection Groups' specialised register; MEDLINE (January 1966 to January Week 1 2004), EMBASE (1990 to September 2003) and Current Contents (1998 to 2003). The search was carried out by an expert librarian. Abstracts of identified articles were used to determine which studies were trials. SELECTION CRITERIA: Randomised controlled trials involving patients of all ages defined as having acute otitis media, acute pharyngitis, sore throat, common cold, a viral upper respiratory tract infection, acute sinusitis, and acute bronchitis were included in which delayed antibiotics are compared to antibiotics used immediately. Delayed antibiotic use was defined as the use of or advice to use antibiotics more than 48 hours after the initial consultation. 'Immediate antibiotic use' was defined as the immediate use of oral antibiotics given at the initial consultation. Clinical outcomes measured included: the presence or absence of fever, cough, pain, duration and severity of illness, complications of the disease, adverse effects from the antibiotics. Trial quality was assessed independently by two reviewers who were blinded to the author, journal and results of each study. DATA COLLECTION AND ANALYSIS: Data was collected by two reviewers who were blinded to the author and journal. Data were analysed and reported using RevMan. MAIN RESULTS: Seven trials were eligible on the basis of design and all reported patient-centred outcomes. Methodological quality of included trials was generally high. There was no difference between immediate and delayed antibiotic groups for symptoms on day one and day seven. For most symptom measures there was no significant difference between the immediate and delayed antibiotic groups. Missing data and marked heterogeneity between study outcomes prevented pooling of results as a meta-analysis. Three studies out of six reporting fever, all involving patients with sore throat, indicated that there was more fever in the delayed antibiotic group. The remaining three studies showed no difference. There was no significant symptom difference for patients with cough or the common cold between the two intervention groups. Pain and malaise severity scores at day three significantly favoured the immediate antibiotic group in children with acute otitis media (Little 2001). In this study by Little 2001 of children with otitis media proxies for other malaise related outcomes were reported, including 'last day of crying' which favoured the immediate antibiotic group by approximately 16 hours (0.69 days; 95% CI 0.31 to 1.07). In the same study, just over half a spoon of paracetamol a day less was used in the immediate antibiotic group (0.59; 95% CI 0.25 to 0.93). There was no significant difference between the intervention groups for the adverse outcome of rash. Two studies reported the outcome of vomiting which was reduced in the immediate antibiotic group in children with suspected streptococcal pharyngitis in El-Daher 1991 but there was no difference in children with sore throat in Little 1997. Diarrhoea was reported by three studies of which two showed no difference Little 1997; Arroll 2002a while Little 2001reported less diarrhoea in the delayed antibiotic group in children with otitis media. REVIEWERS' CONCLUSIONS: When considering treatment options for upper respiratory tract infections, the option of delayed antibiotics has been used in an attempt to reduce the use of antibiotic prescriptions. This review shows that for all symptom scores the evidence varies between trials. Most symptom outcomes show no difference between immediate and delayed antibiotic groups. Three of the six studies, all involving patients with sore throat, indicated that patients in the delayed antibiotic group had significantly more fever that their counterparts in the immediate antibiotic group. The other three showed no difference for the outcome of fever. There is evidence indicating that for children with otitis media, pain and malaise scores are worse in the delayed antibiotic group compared to the immediate antibiotic group. This price must be weighed up against the benefits of reduced antibiotic prescribing. Future randomised controlled trials of delaying antibiotics as an intervention should fully report symptoms as well as changes of prescription rates.

-----

Cochrane Database Syst Rev. 2004 Oct 18;(4):CD000245
Antibiotics for acute bronchitis.
Smucny J, Fahey T, Becker L, Glazier R.

BACKGROUND: Antibiotic treatment of acute bronchitis, which is one of the most common illnesses seen in primary care, is controversial. Most clinicians prescribe antibiotics in spite of expert recommendations against this practice. OBJECTIVES: The objective of this review was to assess the effects of antibiotic treatment for patients with a clinical diagnosis of acute bronchitis. SEARCH STRATEGY: In this updated review, we searched the Cochrane Central Register of Controlled trials (CENTRAL) (The Cochrane Library Issue 2, 2004); MEDLINE (January 1966 to March 2004); EMBASE (January 2000 to December 2003); SciSearch from 1989 to 2004; reference lists of articles and the authors' personal collections up to 1996, and also wrote to study authors and drug manufacturers. EMBASE has previously been searched from 1974 to 2000). SELECTION CRITERIA: Randomised controlled trials comparing any antibiotic therapy with placebo in acute bronchitis or acute productive cough without other obvious cause in patients without underlying pulmonary disease. DATA COLLECTION AND ANALYSIS: At least two reviewers extracted data and assessed trial quality. Authors were contacted for missing data. MAIN RESULTS: Nine trials involving over 750 patients aged eight to over 65 and including smokers and non-smokers were included in the primary analysis. The quality of the trials was variable. A variety of outcome measures were assessed. Overall, patients receiving antibiotics had better outcomes than did those receiving placebo. At a follow-up visit, they were less likely to have a cough (relative risk (RR) 0.64, 95% confidence interval (CI) 0.49 to 0.85; number-needed-to-treat (NNT) 5; 95% CI 3 to 14), show no improvement on physician assessment (RR 0.52; 95% CI 0.31 to 0.87; NNT 14; 95% CI 8 to 50), or have abnormal lung findings (RR 0.48; 95% CI 0.26 to 0.89; NNT 11; 95% CI 6 to 50); and had shorter durations of cough (weighted mean difference 0.58 days; 95% CI 0.01 to 1.16 days), productive cough (weighted mean difference (WMD) 0.52 days; 95% CI 0.01 to 1.03 days), and feeling ill (WMD 0.58 days; 95% CI 0.00 to 1.16 days). There were no significant differences regarding the presence of night cough, productive cough, or activity limitations at follow up, or in the mean duration of activity limitations. The benefits of antibiotics were less apparent in a sensitivity analysis that included data from two other studies of patients with upper respiratory tract infections with productive cough. There was a non significant trend towards an increase in adverse effects in the antibiotic group, relative risk (RR) 1.22 (95% CI 0.94 to 1.58). REVIEWERS' CONCLUSIONS: Overall, antibiotics appear to have a modest beneficial effect in patients who are diagnosed with acute bronchitis. The magnitude of this benefit, however, is similar to that of the detriment from potential adverse effects.

-----

Am J Manag Care. 2004 Oct;10(10):689-96.
Acute exacerbation of chronic bronchitis: a primary care consensus guideline.
Brunton S, Carmichael BP, Colgan R, Feeney AS, Fendrick AM, Quintiliani R, Scott G.
Department of Family Medicine, University of California, Irvine, Calif, USA.

OBJECTIVE: To develop consensus on appropriate treatment for acute exacerbation of chronic bronchitis (AECB). CHARACTERISTICS AND ETIOLOGY: Patients with chronic bronchitis have an irreversible reduction in maximal airflow velocity and a productive cough on most days of the month for 3 months over 2 consecutive years. An AECB is characterized by a period of unstable lung function with worsening airflow and other symptoms. Most (80%) cases of AECB are due to infection, with half due to aerobic bacteria. The remaining 20% are due to noninfectious causes such as environmental factors or medication nonadherence. MANAGEMENT: Supportive care should be provided to all patients, which might include removal of irritants, use of a bronchodilator, oxygen, hydration, use of a systemic corticosteroid, and chest physical therapy. Antibacterial treatment should be reserved for patients with at least 1 key symptom (ie, increased dyspnea, sputum production, sputum purulence) and 1 risk factor (ie, age > or = 65 years, forced expiratory volume in 1 second < 50% of the predicted value, > or = 4 AECBs in 12 months, 1 or more comorbidities). A newer macrolide, extended-spectrum cephalosporin, or doxycycline is appropriate for an exacerbation of moderate severity, and high-dose amoxicillin/clavulanate or a respiratory fluoroquinolone should be used for a severe exacerbation. There has been increasing antibacterial resistance by the 3 most prevalent pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis). CONCLUSION: Although all AECB patients should receive supportive care, only patients with at least 1 key symptom and 1 risk factor should receive antibiotic therapy.

-----

Drugs Exp Clin Res. 2004;30(4):133-41.
Levocloperastine in the treatment of chronic nonproductive cough: comparative efficacy versus standard antitussive agents.
Aliprandi P, Castelli C, Bernorio S, Dell'Abate E, Carrara M.
Division of Rehabilitation Pneumatology, Rho Hospital, Rho, Italy.

The medical and social impact of cough is substantial. Current antitussive agents at effective doses have adverse events such as drowsiness, nausea and constipation that limit their use. There is also recent evidence that standard antitussive agents, such as codeine, may not reduce cough during upper respiratory infections. Therefore, there is a need for more effective and better-tolerated agents. The efficacy of levocloperastine, a novel antitussive, which acts both centrally on the cough center and on peripheral receptors in the tracheobronchial tree in treating chronic cough, was compared with that of other standard antitussive agents (codeine, levodropropizine and DL-cloperastine) in six open clinical trials. The studies enrolled patients of all ages with cough associated with various respiratory disorders including bronchitis, asthma, pneumonia and chronic obstructive pulmonary disease. Levocloperastine significantly improved cough symptoms (intensity and frequency of cough) in all trials, and improvements were observed after the first day of treatment. In children, levocloperastine reduced nighttime awakenings and irritability, and in adults it was effective in treating cough induced by angiotensin-converting enzyme inhibitors. When compared with other antitussive agents, levocloperastine had improved or comparable efficacy, with a more rapid onset of action. Importantly, no evidence of central adverse events was recorded with levocloperastine, whereas drowsiness was reported by a significant number of patients receiving codeine. Levocloperastine is an effective antitussive agent for the treatment of cough in patients of all ages. It has a more rapid onset of action than standard agents with an improved tolerability profile.

-----

Ter Arkh. 2004;76(8):51-6.
[Efficacy of a complementary antiinflammatory treatment with erespal in chronic obstructive and nonobstructive bronchitis]
[Article in Russian]
[No authors listed]

AIM: To compare efficacy of atrovent alone and in combination with erespal in patients with chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS: Of 80 participants of the trial (51 male and 29 female--63.75 and 36.25%, respectively) who had CB or COPD, 39 patients (28 with CB and 11 with COPD) received 6-month combined treatment with erespal (160 mg/day) and atrovent (160 mcg/day) and 41 patients (32 with CB and 9 with COPD) received atrovent monotherapy in the same dosage. RESULTS: Combined therapy produced positive changes in dyspnea, sputum characteristics and its discharge, cough, monotherapy improved sputum discharge and relieved cough; pulmonary ventilation improved in both groups especially in those on monotherapy. CB patients showed low cytosis, percentage and absolute count of neutrophils, absolute count of lymphocytes and eosinophils in induced sputum. In CB patients percentage of lymphocytes reduced while count of macrophages went up. Combined treatment including erespal also promoted a significant fall of serum and sputum TNFalpha and IL-8 reduction in the sputum. CONCLUSION: Erespal+atrovent treatment proved more effective than atrovent alone. It is recommended for both CB and COPD patients without marked disorders of external respiration function.

-----

Respir Med. 2004 Aug;98(8):697-707.
A randomized, double-blind study comparing 5 days oral gemifloxacin with 7 days oral levofloxacin in patients with acute exacerbation of chronic bronchitis.
Sethi S, Fogarty C, Fulambarker A.
Pulmonary and Critical Care Medicine, University at Buffalo, State University of New York, Buffalo, NY, USA. ssethi@buffalo.edu

OBJECTIVE: To demonstrate that 5 days of treatment with a new fluoroquinolone, gemifloxacin, is at least as effective as 7 days of treatment with levofloxacin in adult patients with acute exacerbation of chronic bronchitis (AECB). DESIGN: Randomized, double-blind, double dummy, multicentre, parallel group study SETTING: Sixty different medical centers in US, UK and Germany. MATERIAL AND METHODS: A total of 360 adults (>40 years of age) with AECB were randomly assigned to receive gemifloxacin 320 mg once daily for 5 days or levofloxacin 500mg once daily for 7 days. The primary efficacy parameter was a clinical response at follow-up (Days 14-21). RESULTS: In total, 335/360 patients completed the study (93.1%). Seven patients receiving gemifloxacin withdrew from the study compared to 18 patients receiving levofloxacin; this difference was statistically significant (Fisher's exact test: p=0.02). In the intent-to-treat (ITT) population, the clinical success rate at follow-up (Days 14-21) was 85.2% (155/182) with gemifloxacin and 78.1% (139/178) with levofloxacin. Clinical success rate in the per-protocol (PP) population was 88.2% (134/152) with gemifloxacin and 85.1% (126/148) with levofloxacin. At long-term follow-up (Days 28-35), the clinical success rates in the PP population were 83.7% (123/147) with gemifloxacin and 78.4% (109/139) with levofloxacin. The difference in success rates was 5.26% (95% CI: -3.83, 14.34). CONCLUSION: The clinical efficacy of gemifloxacin 320 mg once daily for 5 days in AECB was at least as good as levofloxacin 500 mg once daily for 7 days. Fewer withdrawals and superior clinical efficacy at long-term follow-up were also seen with gemifloxacin.

-----

Chemotherapy. 2004;50 Suppl 1:22-8.
New insights in the treatment by levofloxacin.
File TM Jr.
Infectious Disease Service, Summa Health System, Akron, Ohio 44304, USA. FileT@summa-health.org

Levofloxacin is widely regarded as one of the most important fluoroquinolones available today. It possesses excellent activity against a wide range of important pathogens, including those resistant to many other antimicrobials. While rates of resistance to other previously useful antimicrobial classes has grown, levofloxacin has maintained its efficacy, with generally very low rates of resistance around the world. It is indicated for a wide range of infections including community-acquired respiratory infections in adults, particularly community-acquired pneumonia (CAP), acute bacterial exacerbations of chronic bronchitis (AECB), and acute sinusitis. In addition, it is recommended for infections of skin and soft tissue, and the urinary tract. With postmarketing surveillance data available for the last decade, levofloxacin possesses an unparalleled database to demonstrate its clinical efficacy and safety. Remarkably, levofloxacin continues to expand its list of indications. The development of a new high-dose 750-mg schedule has the potential to decrease the duration of treatment as well as reduce the emergence of resistance.

-----

Drugs. 2004;64(15):1683-94; discussion 1695-6.
Telithromycin.
Wellington K, Noble S.
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz

Telithromycin, the first member of the ketolide antibacterials, has good activity against community-acquired respiratory pathogens, including multiple-drug-resistant strains of Streptococcus pneumoniae. Telithromycin 800 mg once daily has been US FDA approved for the treatment of acute bacterial sinusitis (ABS; treatment duration 5 days), acute bacterial exacerbations of chronic bronchitis (AECB; 5 days) and mild-to-moderate community-acquired pneumonia (CAP; 7-10 days). In patients with CAP, telithromycin was as effective as amoxicillin 1000 mg three times daily for 10 days, clarithromycin 500 mg twice daily for 10 days or trovafloxacin 200 mg once daily for 7-10 days. In patients with AECB, telithromycin was as effective as a 10-day regimen of amoxicillin/clavulanic acid 500/125 mg three times daily, cefuroxime axetil 500 mg twice daily or clarithromycin 500 mg twice daily. In patients with ABS, telithromycin was as effective as a 10-day course of amoxicillin/clavulanic acid 500/125 mg three times daily or cefuroxime axetil 250 mg twice daily. Telithromycin was generally well tolerated and most adverse events were of mild-to-moderate severity and transitory. The most common adverse events with telithromycin were diarrhoea and nausea (10.8% and 7.9% of 2702 patients in clinical trials); these events occurred in 8.6% and 4.6% of 2139 comparator-treated patients.

-----

Drugs. 2004;64(13):1433-64.
Cefdinir: a review of its use in the management of mild-to-moderate bacterial infections.
Perry CM, Scott LJ.
Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 1311, New Zealand. demail@adis.cm.nz

Cefdinir (Omnicef) is an oral third-generation cephalosporin with good in vitro activity against many pathogens commonly causative in community-acquired infections. The drug provides good coverage against Haemophilus influenzae, Moraxella catarrhalis and penicillin-susceptible Streptococcus pneumoniae, the most common respiratory tract pathogens. Cefdinir is stable to hydrolysis by commonly occurring plasmid-mediated beta-lactamases and retains good activity against beta-lactamase-producing strains of H. influenzae and M. catarrhalis. The drug distributes into various tissues (e.g. sinus and tonsil) and fluids (e.g. middle ear), and has a pharmacokinetic profile that allows for once- or twice-daily administration.Cefdinir, administered for 5 or 10 days, has shown good clinical and bacteriological efficacy in the treatment of a wide range of mild-to-moderate infections of the respiratory tract and skin in adults, adolescents and paediatric patients in randomised, controlled trials. In adults and adolescents, cefdinir is an effective treatment for both lower (acute bacterial exacerbations of chronic bronchitis [ABECB], community-acquired pneumonia) and upper (acute bacterial rhinosinusitis, streptococcal pharyngitis) respiratory tract infections, and uncomplicated skin infections. Its bacteriological and clinical efficacy in patients with lower respiratory tract infections was equivalent to that of comparator agents (cefprozil [bacteriological only], loracarbef, cefuroxime axetil and cefaclor). In one trial in patients with ABECB, cefdinir produced a higher rate of clinical cure than cefprozil (95% CIs indicated nonequivalence). Cefdinir also produced good clinical and bacteriological responses equivalent to responses with amoxicillin/clavulanic acid in patients with acute bacterial rhinosinusitis. In addition, it was at least as effective as penicillin V (phenoxymethylpenicillin) in streptococcal pharyngitis/tonsillitis and as effective as cefalexin in uncomplicated skin infections. In paediatric patients aged > or =6 months, cefdinir showed similar efficacy to that of amoxicillin/clavulanic acid or cefprozil in acute otitis media, and cefalexin in uncomplicated skin infections. Cefdinir given for 5 or 10 days was at least as effective as penicillin V for 10 days in patients with streptococcal pharyngitis/tonsillitis. Cefdinir is usually well tolerated. Diarrhoea was the most common adverse event in trials in all age groups. Although the incidence of diarrhoea in cefdinir recipients was generally higher than in adults and adolescents treated with comparators, discontinuation rates due to adverse events were generally similar for cefdinir and comparator groups.In conclusion, cefdinir is a third-generation cephalosporin with a broad spectrum of antibacterial activity encompassing pathogens that are commonly causative in infections of the respiratory tract or skin and skin structure. Depending on the infection being treated, cefdinir can be administered as a convenient once- or twice-daily 5- or 10-day regimen. Clinical evidence indicates that cefdinir is an effective and generally well tolerated drug with superior taste over comparator antibacterial agents and is therefore a good option for the treatment of adults, adolescents and paediatric patients with specific mild-to-moderate respiratory tract or skin infections, particularly in areas where beta-lactamase-mediated resistance among common community-acquired pathogens is a concern.

-----

Expert Opin Pharmacother. 2004 May;5(5):1117-52.
Gemifloxacin: a new fluoroquinolone.
Blondeau JM, Missaghi B.
Department of Microbiology, Royal University Hospital, Saskatoon, Saschatchewan, Canada. joseph.blondeau@saskatoonhealthregion.ca

Gemifloxacin is a dual targeted fluoroquinolone with potent in vitro activity against Gram-positive, -negative and atypical human pathogens--pathogens considered to be important causes of community-acquired respiratory tract infections. Gemifloxacin demonstrates impressive minimal inhibitory concentrations (MIC 90 ) values against clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniae and Legionella spp., with MIC 90 values reported to be 0.016-0.06, < 0.0008-0.06, 0.008-0.3, 0.25, 0.125 and 0.016-0.07 microg/ml, respectively. Gemifloxacin is also active in vitro against a broad range of Gram-negative bacilli with MIC 90 values against the Enterobacteriaceae in the range of 0.016 to > 16 microg/ml ( Escherichia coli and Providencia stuartii, respectively), with the majority of the genus having MIC 90 drug concentrations < 0.5 microg/ml. The in vitro activity of gemifloxacin against anaerobic organisms is variable. The MIC values for gemifloxacin are not affected by beta-lactamase production nor by penicillin or macrolide resistance in S. pneumoniae. Gemifloxacin is approved by the FDA to be clinically efficacious against multi-drug resistant S. pneumoniae. The pharmacokinetics of gemifloxacin are such that the drug can be administered orally once-daily to yield or achieve sustainable drug concentrations exceeding the MIC values of clinically important organisms. Gemifloxacin has been shown to target both DNA gyrase (preferred target) and topoisomerase IV (secondary target) - enzymes critical for DNA replication and organism survival - against clinical isolates of S. pneumoniae. This dual targeting activity is thought to be important for reducing the likelihood for selecting for quinolone resistance. Gemifloxacin has been investigated and approved for therapy in patients with community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis. In one study, more patients receiving gemifloxacin compared to clarithromycin remained free of exacerbations for longer periods of time (p < 0.016) and gemifloxacin had a shorter time to eradication of H. influenzae than did clarithromycin (p < 0.02). From efficacy studies, gemifloxacin was found to have an adverse profile that was comparable with other compounds. The most frequent side effects were diarrhoea, abdominal pain and headache. Gemifloxacin is a welcomed addition to currently available agents for the treatment of community-acquired lower respiratory tract infections. Other potential indications appear to be within the spectrum of this compound.

-----

Rev Mal Respir. 2004 Apr;21(2 Pt 1):261-71.
[Treatment of exacerbations of chronic obstructive pulmonary disease with pristinamycin]
[Article in French]
Leophonte P, Chidiac C, Drugeon HB, Strabach S, Cabrillac-Rives S, Chone C, Dellatolas F, Safran C.
Service de Pneumologie, Hopital Larrey, Cliniques des voies respiratoires, Toulouse, France. leophonte.p@chu-toulouse.fr

BACKGROUND: Pristinamycin is a bactericidal antibiotic whose spectrum covers the main respiratory pathogens including S. pneumoniae poorly sensitive to penicillin. It has not yet been evaluated in short course treatment of acute exacerbations of chronic obstructive bronchitis (AECB). METHODS: 476 patients suffering from an AECB were randomised to either a short course of pristinamycin, 3 G daily for 4 days, or conventional treatment with co-amoxiclav (AAC) 2G daily for 8 days. The duration of follow-up was 6 months. RESULTS: The clinical success rate at 21 days was the same in both groups at 87.2% and 87.9%, CI95% [-7.0%, 6.0%], in the protocol population (FEV1<80%). Among the 120 patients in whom a bacterial pathogen was isolated at the time of inclusion a satisfactory bacteriological response was obtained in 84.6% of the PRI patients against 78.2% of the AAC patients. The time to relapse was comparable with a relapse rate of 25% reached in 128 days in the PRI group and 125 days in the AAC group. Treatment related side effects occurred in 9.2% of the PRI group and in 10.6% of the AAC group. CONCLUSION: Pristinamycin 3 G daily for 4 days is as effective and well tolerated as co-amoxiclav 2G daily for 8 days in the treatment of AECB.

-----

Chest. 2004 Mar;125(3):953-64.
Short-term and Long-term Outcomes of Moxifloxacin Compared to Standard Antibiotic Treatment in Acute Exacerbations of Chronic Bronchitis.
Wilson R, Allegra L, Huchon G, Izquierdo JL, Jones P, Schaberg T, Sagnier PP.
Royal Brompton Hospital (Dr. Wilson), London, UK.

STUDY OBJECTIVE:s: To compare the effectiveness of oral moxifloxacin with standard antibiotic therapy in acute exacerbation of chronic bronchitis (AECB). DESIGN: Multicenter, multinational, randomized, double-blind study of two parallel treatment arms. PATIENTS: Outpatients >/==" BORDER="0"> 45 years old with stable chronic bronchitis, smoking history of >/==" BORDER="0"> 20 pack-years, two or more AECBs in the previous year, and FEV(1) < 85% of predicted value. Patients were enrolled when in a stable condition, and patients with exacerbations within 12 months of enrollment were randomized. INTERVENTIONS: Randomization (stratified on steroid use) between moxifloxacin (400 mg qd for 5 days) and standard therapy (amoxicillin [500 mg tid for 7 days], clarithromycin [500 mg bid for 7 days], or cefuroxime-axetil [250 mg bid for 7 days]). MEASUREMENTS: Assessment at enrollment, randomization (Anthonisen type 1 exacerbation), 7 to 10 days after treatment, and monthly until next AECB or up to 9 months. The primary efficacy variable was clinical success (sufficient improvement, no alternative antimicrobial therapy required) 7 to 10 days after therapy. Secondary predefined end points were clinical cure (return to pre-exacerbation status), further antimicrobial use, time to next AECB, and bacteriologic success. RESULTS: Three hundred fifty-four patients received moxifloxacin, and 376 patients received standard therapy. At 7 to 10 days after therapy, clinical success rates were similar in intention-to-treat (ITT) patients (95% confidence interval [CI], - 0.7 to 9.5) and per-protocol (PP) patients (95% CI, - 3.0 to 8.5). Moxifloxacin showed superior clinical cure rates over standard therapy in both ITT patients (95% CI, 1.4 to 14.9) and PP patients (95% CI, 0.3 to 15.6), and higher bacteriologic success in microbiologically valid patients (95% CI, 0.4 to 22.1). Fewer ITT patients required antimicrobials after treatment with moxifloxacin than standard therapy (p < 0.01). Time to next exacerbation was longer with moxifloxacin; median and mean times to new AECBs in ITT patients who did not require any further antibiotics were 131.0 days and 132.8 days in moxifloxacin, and 103.5 days and 118.0 days in standard therapy, respectively (p = 0.03). The occurrence of failure, new exacerbation, or any further antibiotic was less frequent in moxifloxacin-treated patients for up to 5 months of follow-up (p = 0.03). CONCLUSIONS: Moxifloxacin was equivalent to standard therapy for clinical success and showed superiority over standard therapy in clinical cure, bacteriologic eradication, and long-term outcomes.

-----

Int J Antimicrob Agents. 2004 Feb;23(2):129-37.
Five-day moxifloxacin therapy compared with 7-day co-amoxiclav therapy for the treatment of acute exacerbation of chronic bronchitis.
Starakis I, Gogos CA, Bassaris H.
Department of Internal Medicine, Infectious Diseases Section, University Hospital, 26500 Rion Patras, Greece.

In this randomized, non-blinded study, the efficacy and safety of a 5-day course of moxifloxacin (one 400mg tablet daily) was compared with that of co-amoxiclav (one 625mg tablet every 8h) for 7 days, for the treatment of acute exacerbations of chronic bronchitis (AECB). A total of 162 patients with clear signs of an acute exacerbation of chronic bronchitis were enrolled. Of these, 153 could be studied. Seventy-nine patients were randomized in the moxifloxacin arm and 74 in the co-amoxiclav arm of the study. The primary efficacy parameter was clinical response at 14 days in the evaluable population. A clinical success was classified as resolution or improvement of symptoms. Variables used to assess clinical response included wheeze, cough, dyspnoea, sputum volume, rales and ronchi. The success rate in the moxifloxacin group was 88.6% (70 of 79) and that for co-amoxiclav group was 89.2% (66 of 74). At follow-up (28-35 days post-treatment), the continued clinical cure rates were 90.0% (63 of 70) for moxifloxacin and 89.4% (59 of 66) for co-amoxiclav. No significant differences were detected between the two groups. A total of 78 pathogenic bacteria were isolated from the sputum samples of the patients, with Moraxella catarrhalis, Haemophilus influenzae and Streptococcus pneumoniae being the most frequently isolated pathogens. The eradication rate at 14 days in the valid patients was similar for both groups, 90.9% (20 of 22) for the moxifloxacin group and 90.0% (18 of 20) for the co-amoxiclav group. Both drugs were well tolerated with no differences in the drug-related adverse effects or the patients withdrawing because of an adverse event. These results and the good spectrum of antibacterial activity make moxifloxacin a promising and also safe alternative for the empirical treatment of AECB.

-----

J Int Med Res. 2003 May-Jun;31(3):157-69.
Oral telithromycin 800 mg once daily for 5 days versus cefuroxime axetil 500 mg twice daily for 10 days in adults with acute exacerbations of chronic bronchitis.
Zervos MJ, Heyder AM, Leroy B.
William Beaumont Hospital, Royal Oak, MI, USA. mzervos@beaumont.edu

The efficacy and safety of a 5-day regimen of 800 mg telithromycin once daily was compared with a standard 10-day regimen of 500 mg cefuroxime axetil twice daily in a multicentre, randomized, double-blind, parallel-group trial involving 376 patients with acute exacerbations of chronic bronchitis (AECB). In clinically evaluable patients (n = 282), post-therapy clinical cure rates were 86.4% with telithromycin and 83.1% with cefuroxime axetil. In bacteriologically evaluable patients (n = 53), eradication or presumed eradication of the pathogen was achieved in 76.0% and 78.6% of telithromycin and cefuroxime axetil patients, respectively. Adverse events were mostly mild; the most common were diarrhoea (12.8% versus 11.8%) and nausea (8.9% versus 3.2%) in telithromycin and cefuroxime axetil patients, respectively. The 5-day regimen of 800 mg telithromycin once daily was similar in efficacy and equally well tolerated as a 10-day regimen of 500 mg cefuroxime axetil twice daily in adults with AECB.

-----

Indian J Pediatr. 2003 May;70(5):395-400.
Cefprozil: a review.
Bhargava S, Lodha R, Kabra SK.
Department of Paediatrics, All India Insitute of Medical Sciences, Ansari Nagar, New Delhi 110029. skkabra@hotmail.com

Cefprozil is a novel third generation, broad-spectrum oral cephalosporin with activity against a spectrum of aerobic gram-negative and positive bacteria, as well as certain anaerobes. The beta-lactamase stability of cefprozil may exceed that of other oral cephalosporins for some important pathogens. Cefprozil may be a suitable alternative to several other commonly used beta-lactams and cephalosporins in the treatment of mild to moderate upper and lower respiratory tract infections including sinusitis, otitis media, pharyngitis/tonsillitis, secondary bacterial infection of acute bronchitis, and acute bacterial exacerbations of chronic bronchitis, and skin and skin structure infections in children. Available data indicate the safety of cefprozil in both pediatric and adult population.

-----

Medicina (Kaunas). 2003;39(3):217-20.
[Current treatment options for acute bronchiolitis in children]
[Article in Lithuanian]
Miseviciene V, Bojarskas J.
Clinic of Children Diseases, Kaunas University of Medicine Hospital, Lithuania. valdonemis@takas.lt

Bronchiolitis is the most common lower respiratory tract infection in infants and is responsible for the majority of pediatric hospital admissions in winter. Respiratory syncytial virus has been identified as the main causative agent, causing 50-90% of the cases of bronchiolitis. Despite significant advances in pharmacotherapy, the management of infants with bronchiolitis has changed little over the years from supplemental oxygen and good fluid management. Approaches to therapy vary widely all over the world and are controversial. This paper reviews current treatment options for bronchiolitis, including the use of bronchodilators, epinephrine, steroids and ribavirin. Most recent advances, including immunotherapy and intensive care, are discussed.

-----

Med Tr Prom Ekol. 2003;(1):16-9.
[Efficiency of medication nebulizers in the treatment of dust obstructive bronchitis]
[Article in Russian]
Kravchenko EA, Gorblianskii IuIu, Krutikova AE.

The clinical and functional study was aimed to evaluate efficiency of nebulized 2-agonists in miners suffering from moderate dust obstructive bronchitis. The nebulizers were used if conventional therapy appeared ineffective. The authors proved Berodual and Atrovent in nebulizers to be effective against dust obstructive bronchitis. Nebulizers enable to successfully cope with bronchial obstruction and occur to positively influence minor circulation hemodynamics.

-----

Eur J Clin Microbiol Infect Dis. 2003 Mar;22(3):144-50. Epub 2003 Mar 05.
Randomised double-blind comparison of oral gatifloxacin and co-amoxiclav for acute exacerbation of chronic Bronchitis.
Soler M, Lode H, Baldwin R, Levine JH, Schreurs AJ, van Noord JA, Maesen FP, Zehrer M; European Gatifloxacin Study group.
Department of Chest Diseases, Kantonsspital Basel, Petersgraben 4, 4031, Basel, Switzerland. markus.soler@claraspital.ch

Antimicrobial therapy can have a significant impact in the treatment of acute infectious exacerbations in patients with chronic bronchitis, in whom repeated episodes are common. The aim of this randomised, double-blind, double-dummy, parallel group study was to compare the efficacy and safety of oral gatifloxacin (200 and 400 mg once daily) administered for 5 days with co-amoxiclav (500 mg amoxicillin/125 mg clavulanic acid t.i.d.) administered for 10 days in 414 adult patients with acute exacerbation of chronic bronchitis. Overall clinical response rates (cure plus improvement) were 86.2%, 79.4% and 81.7% in the gatifloxacin 200 mg, gatifloxacin 400 mg and co-amoxiclav groups, respectively, and the equivalence hypothesis used for statistical analysis showed equivalent efficacy for both gatifloxacin 200 and 400 mg compared to co-amoxiclav. The same was true for rates of bacterial response, with eradication or presumed eradication of causative pathogens achieved in 87.5%, 87.3% and 79.1% of cases in the gatifloxacin 200 mg, gatifloxacin 400 mg and co-amoxiclav groups, respectively. All treatments were well tolerated, with the nature and frequency of treatment-related adverse events similar in all groups. The results of the study show that gatifloxacin is a safe and effective agent for the treatment of patients with chronic bronchitis experiencing an acute infectious exacerbation.

-----

Cochrane Database Syst Rev. 2003;(1):CD004105.
Prophylactic antibiotic therapy for chronic bronchitis.
Black P, Staykova T, Chacko E, Ram FS, Poole P.
Dept of Medicine, University of Auckland, New Zealand. pn.black@auckland.ac.nz

BACKGROUND: The use of prophylactic antibiotics to reduce the frequency and severity of acute exacerbations of chronic bronchitis is controversial. OBJECTIVES: To determine if prophylactic antibiotics reduce the frequency of exacerbations and/or days of disability in subjects with chronic bronchitis. SEARCH STRATEGY: We searched the Cochrane Airways Group Register of Clinical Trials and the bibliographies of relevant articles. SELECTION CRITERIA: Randomised controlled trials of prophylactic antibiotics in patients with chronic bronchitis and/or COPD were selected. DATA COLLECTION AND ANALYSIS: The eligibility of studies for inclusion was evaluated by three independent reviewers. MAIN RESULTS: Nine trials involving 1055 subjects were included in the analysis. All were performed before 1970. Concealment of allocation was assessed as clearly adequate in only 3 studies. The likelihood of having a exacerbation at any time during the course of the study was decreased with treatment (Relative Risk 0.91, 95% Confidence Intervals (CI) 0.84, 0.99). There was a small reduction in the number of exacerbations per patient per year with prophylactic antibiotics but this was not statistically significant ( Weighted Mean Difference (WMD) -0.15, 95%CI -0.34, 0.04 ). There was a modest but significant reduction of 22% in the number of days of disability per patient per month treated ( WMD -0.95, 95%CI -1.89 to - 0.01 ). A parallel reduction in the days of disability for each exacerbation (WMD -2.08, 95% CI -4.08 to -0.07) was seen. There was a small increase in adverse effects with antibiotics. REVIEWER'S CONCLUSIONS: Prophylactic antibiotics in chronic bronchitis / COPD have a small but statistically significant effect in reducing the days of illness due to exacerbations of chronic bronchitis. They do not have a place in routine treatment because of concerns about the development of antibiotic resistance and the possibility of adverse effects. The available data are over 30 years old, so the pattern of antibiotic sensitivity may have changed and there is a wider range of antibiotics in use.

-----

Respir Med. 2003 Mar;97(3):242-9.
Oral gemifloxacin once daily for 5 days compared with sequential therapy with i.v. ceftriaxone/oral cefuroxime (maximum of 10 days) in the treatment of hospitalized patients with acute exacerbations of chronic bronchitis.
Wilson R, Langan C, Ball P, Bateman K, Pypstra R; Gemifloxacin 207 Clinical Study Group.
Royal Brompton Hospital, London, U.K. r.wilson@rbh.nthames.nhs.uk

In a randomized, open-label, controlled, multicentre study, the clinical and bacteriological efficacy, safety and tolerability of oral gemifloxacin (320 mg once daily, 5 days) was compared with sequential intravenous (i.v.) ceftriaxone (1 g once daily, maximum 3 days) followed by oral cefuroxime axetil (500 mg twice daily, maximum 7 days) in adult hospitalized patients with acute exacerbations of chronic bronchitis (AECB) (n = 274). The clinical success rates at follow-up (21-28 days post-therapy) in the clinical per-protocol population (the primary endpoint) were 86.8% (105/121) for gemifloxacin vs. 81.3% (91/112) for ceftriaxone/cefuroxime (treatment difference = 5.5,95% CI -3.9,14.9). The corresponding clinical results in the clinical intention-to-treat (ITT) population were 82.6% (114/138) vs. 72.1% (98/136), respectively (treatment difference = 10.5,95% CI 0.7, 20.4).Thus, gemifloxacin had significantly higher clinical success rates than ceftriaxone/cefuroxime.The median time to discharge was 9 days in the gemifloxacin group vs. 11 days in the ceftriaxone/cefuroxime group (P = 0.04, Wilcoxon test). At follow-up, 120/138 (87.0%) gemifloxacin-treated patients had been discharged from hospital, compared with 111/136 (81.6%) ceftriaxone/cefuroxime-treated patients in the clinical ITT population. Both treatments were generally well tolerated and there was no significant difference between the treatment groups in the incidence or type of adverse events reported. A 5-day course of oral gemifloxacin was shown by this study to be at least equivalent to sequential i.v. ceftriaxone/cefuroxime axetil (for up to 10 days) in patients with AECB who require hospital treatment.

-----

J Chemother. 2002 Dec;14(6):597-608.
Efficacy and safety of short course (5-day) moxifloxacin vs 7-day ceftriaxone in the treatment of acute exacerbations of chronic bronchitis (AECB).
Grassi C, Casali L, Curti E, Tellarini M, Lazzaro C, Schito G; SMART Study Group. Studio Multicentrico con Moxifloxacina nel Trattamento delle Riacutizzazioni de Bronchite Cronica.
Pneumology Department, University of Pavia, Italy. grassicarlo@tiscali.it

The aim of this multicenter, open, randomized study was to compare the efficacy and tolerability of a 5-day treatment course with oral moxifloxacin (MXF) vs a 7-day course with i.m. ceftriaxone (CRO) in 476 patients with acute exacerbations of chronic bronchitis (AECB), and to conduct a cost minimization analysis of the two treatments from the perspectives of both the Italian National Health Service (INHS) and society. The study was conducted in Italy. Clinical success rates at test-of-cure in the 423 patients of the PP (Per Protocol) population (primary efficacy parameter) were 90.6% and 89.0% for MXF and CRO, respectively. Statistical non-inferiority of MXF vs CRO was confirmed. Similar results were found between study drugs on the secondary efficacy parameters, including success at end-of-treatment (95.3% for MXF vs 92.9% for CRO), success at test-of-cure in bacteriologically-positive patients (94.1% vs 90.7%) and eradication/presumed eradication rates (91.7% vs 93.3%). ITT (Intention-to-Treat) analysis confirmed these data. There was a low incidence of adverse events (10.8% vs 9.1%). During a 6-month follow-up period, relapse rates were lower for MXF vs CRO (23.3% vs 28.3%; p > .05). Compared with CRO, MXF was associated with cost savings per patient ranging from Euro226.57 (INHS perspective) to Euro448.23 (societal perspective), with lower hospitalization rate the major variable contributing to reduced costs. MXF appears to be an ideal candidate for AECB treatment.

-----

Clin Ther. 2002 Dec;24(12):2105-22.
An open-label, randomized, multicenter, comparative study of the efficacy and safety of 7 days of treatment with clarithromycin extended-release tablets versus clarithromycin immediate-release tablets for the treatment of patients with acute bacterial exacerbation of chronic bronchitis.
Weiss K, Vanjaka A; Canadian Clarithromycin Study Group on Bronchitis.
Department of Infectious Diseases and Microbiology, Hopital Maisonneuve-Rosemont, University of Montreal, Montreal, Quebec, Canada. weisscan@aol.com

OBJECTIVE: The aim of this study was to compare the efficacy and safety of clarithromycin extended-release (ER) tablets and immediate-release (IR) tablets. METHODS: This was a Phase III, open-label, randomized, multicenter, comparative study in ambulatory patients with a diagnosis of acute exacerbation of chronic bronchitis (AECB). Eligible patients were randomized 1:1 to receive either 1 clarithromycin ER 500-mg tablet QD for 7 days or 1 clarithromycin IR 250-mg tablet BID for 7 days. Clinical and bacteriologic responses were assessed within 48 hours after the last dose of study drug and at a test-of-cure visit 21 +/- 2 days posttreatment. RESULTS: Of 233 patients randomized, 162 (86/117 [73.5%] in the ER group and 76/115 [66.1%] in the IR group) completed the study protocol. Compliance did not differ significantly between the treatment groups; however, significantly fewer patients in the ER group reported missing doses of study medication than in the IR group (7/118 [5.9%] vs 16/115 [13.9%]; P = 0.04). The clinical cure rates for the clarithromycin ER and IR groups were 81.0% (68/84) and 82.1% (64/78) and the clinical success (clinical cure plus clinical improvement) rates were 94.0% [79/84] and 89.7% [70/78], respectively. There were insufficient data for analysis of bacteriologic efficacy. However, bacteria were eradicated or presumed eradicated in 71.4% (10/14) and 79.2% (19/24) of patients in the ER and IR groups, respectively. The number of adverse events (AEs) considered to be possibly or probably related to study drug (23.4% [52/222] of patients receiving clarithromycin ER and 24.4% [43/176] of patients receiving clarithromycin IR) was similar between groups, as was the severity of these events (94.2% [49/52] in the ER group classified as mild or moderate vs 93.0% [40/43] in the IR group). Overall, the most commonly reported AEs were diarrhea, nausea, abdominal pain, headache, and taste disturbance. CONCLUSION: Clarithromycin ER 500-mg tablets QD for 7 days were as effective and well tolerated as clarithromycin IR 250-mg tablets BID for 7 days in treating adults with AECB.

-----

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2002 Aug;22(8):597-8.
[Clinical observation on effect of kesuning granule in treating acute onset of chronic bronchitis]
[Article in Chinese]
Mao B, Zhang RM, Li TQ.
West China Hospital, Sichuan University, Chengdu 610041.

OBJECTIVE: To prove the effect of Kesuning Granule (KSNG) in treating chronic bronchitis in exacerbation (Phlegm-Heat syndrome) and objectively evaluate its safety. METHODS: The double-blinded, double-dummy and randomized controlled method was adopted to observe 120 patients, who were divided into the treated group (n = 60, treated with KSNG 8 g, three times a day) and the control group (n = 60, treated with Jinbei Tankeqing Granule (JBTKQ) 7 g, three times a day). The therapeutic course for both groups was 6 days. RESULTS: In the treated group, the markedly effective rate was 58.33% and effective rate was 93.33%, while in the control group, they were 51.67% and 91.67% respectively, no significant difference was found between the two groups. For therapeutic effects on TCM syndromes, the markedly effective rate and effective rate in the treated group was 68.33% and 93.33% respectively and in the control group, 66.67% and 90.00% respectively, also showed insignificant difference. The effect initiative time was earlier in the treated group than that in the control group significantly (P < 0.05). No adverse effect was found in the observation. CONCLUSION: KSNG shows a definite clinical effect with no obvious toxic-adverse effects.

-----

Antibiot Khimioter. 2002;47(8):16-9.
[Current possibilities and perspectives of the combined treatment of patients with severe bronchopulmonary diseases]
[Article in Russian]
Sokolova VI, Shenderovich VA, Orlov VA, Elagina LV.
Russian Medical Academy of Post-Graduated Education, Moscow.

Complex treatment with ceftriaxone (or ceftazidime) and intravenous immunoglobulin G (Biaven V. I.) was performed at 21 patients with severe pneumonia and tracheobronchitis complicated by immunedeficient status (myasthenia, diabetes mellitus etc). The results of the treatment proves strong tendency to normalization of the immune system (ceruloplasmin level, CIC, catalase, immunoglobulins) along with clinical signs regression.

-----

Pneumologie. 2002 Dec;56(12):793-7.
[N-acetylcystein in the therapy of chronic bronchitis]
[Article in German]
Reichenberger F, Tamm M.
Pneumologie, Departement Innere Medizin, Universitatskliniken Basel, Schweiz, Germany.

Chronic bronchitis (CB) shows an increasing global morbidity and mortality with major impact on socioeconomics. N-Acetylcysteine (NAC), previously used as a mucolytic compound in CB, has also antioxidative effects. Furthermore it influences intrabronchial bacterial colonisation. In a randomised pilot study of 24 patients (16-male, 8 female, mean age 66 +/- 10 years) with acute exacerbation of CB and positive bacterial culture in the sputum, the addition of twice daily 600 mg NAC to standard antibiotic therapy lead to a significantly higher bacterial eradication rate (70 % versus 36 %, p < 0.03). Clinical studies suggest that treatment with NAC has different effects in CB including a reduction of the number and duration of acute exacerbation episodes and possibly influences lung function. The improvement of symptoms and quality of life also has an impact on socio-economic costs. The use of NAC in CB as an antioxidative rather than a mucolytic compound should be considered. However, further placebo controlled studies are undergoing to definitively establish the role of NAC for the treatment of CB and COPD.

-----

Chemotherapy. 2002 Dec;48(5):259-66.
Esberitox N as supportive therapy when providing standard antibiotic treatment in subjects with a severe bacterial infection (acute exacerbation of chronic bronchitis). A multicentric, prospective, double-blind, placebo-controlled study.
Hauke W, Kohler G, Henneicke-Von Zepelin HH, Freudenstein J.
EPA-Europharma Auftragsforschung, Kronberg, Germany.

53 patients with planned antibiotic therapy for the treatment of acute exacerbation of chronic bronchitis as an example of a severe bacterial infection requiring antibiotics were included in a prospective, multicentre, double-blind, placebo-controlled study. The chronic bronchitis was staged by forced expiratory volume of the 1st second (FEV(1)) measured in the infection-free interval prior to the current episode and had to be between 35 and 75% for the predicted value. Patients were randomly assigned to receive newer macrolide antibiotics plus either Esberitox N or placebo. Antibiotic therapy was administered according to generally accepted guidelines and Esberitox N or placebo was given for 28 days. The baseline-adjusted means for FEV(1) (%) on day 10 were 68.7 points for the Esberitox N group and 59.2 points for the placebo group (p = 0.0303). For FEV(1) the difference between the two treatment groups was 267 ml (p = 0.0499). The time to half maximal improvement was 5.7 days in the Esberitox N group compared to 12.8 days in the placebo group. The treatment was well tolerated; no serious adverse events were documented. In conclusion, comedication of antibiotics with Esberitox N in subjects with acute exacerbation of chronic bronchitis seems to be of benefit for the patient. Apparently, therapy with Esberitox N leads to a faster recovery from this severe bacterial infection, possibly via preventing an impairment of the host's immune system which might otherwise occur as a consequence of aggressive antimicrobial therapeutics. Copyright 2002 S. Karger AG, Basel

-----

Chest. 2002 Dec;122(6):2021-9.
Improved sputum expectoration following a single dose of INS316 in patients with chronic bronchitis.
Johnson FL, Donohue JF, Shaffer CL.
Inspire Pharmaceuticals, Inc., 4222 Emperor Boulevard, Suite 470, Durham, NC 27703-8466, USA. FJohnson@inspirepharm.com

Uridine 5'-triphosphate (UTP) is a naturally occurring agonist for P2Y(2) receptors on the apical surface of ciliated respiratory epithelium. UTP stimulates salt and water transport and cilia beat frequency in human airway epithelium in vitro. Single, inhaled doses of UTP stimulate mucociliary clearance in conscious, intubated sheep and in patients with mild chronic bronchitis (smokers and former smokers), suggesting that UTP may be useful for obtaining deep-lung sputum specimens suitable for diagnostic purposes. STUDY OBJECTIVE: UTP is being developed for the cytologic diagnosis of lung cancer under the compound number INS316 Solution for Inhalation (Inspire Pharmaceuticals; Durham, NC). Its ability to improve the quality of expectorated sputum was tested in the current study. DESIGN: Placebo-controlled, double-blind, escalating two-period cross-over study. SETTING: Outpatient volunteers. Patients or participants: Twenty-six patients with mild chronic bronchitis. INTERVENTION: Patients attempted to expectorate a specimen spontaneously, following a single inhaled dose of INS316 (10 to 180 mg), and following placebo. Measurements and results: Sputum weight, sputum cell content, spirometry, and oxyhemoglobin saturation. Only 28% of these patients were able to expectorate a macrophage-containing, deep-lung specimen spontaneously or following inhalation of placebo. In contrast, 85% of the patients were able to produce a specimen following inhalation of INS316. The average weight of the sputum expectorated was increased fourfold by placebo and 10-fold by INS316. A mild transient decrease in pulmonary function was observed following INS316 administration. CONCLUSION: A single dose of INS316 safely improves the ability of patients with mild chronic bronchitis to expectorate a deep-lung sputum specimen suitable for cytologic evaluation.

-----

Swiss Med Wkly. 2002 Jul 27;132(29-30):414-22.
Inhibition of the TNF-pathway: use of infliximab and etanercept as remission-inducing agents in cases of therapy-resistant chronic inflammatory disorders.
Aeberli D, Oertle S, Mauron H, Reichenbach S, Jordi B, Villiger PM.
Department of Rheumatology and Clinical Immunology/Allergology, University Hospital (Inselspital), Bern, Switzerland.

OBJECTIVE: To examine the potential of the two tumour necrosis factor (TNF) inhibitors infliximab and etanercept as remission-inducing agents in chronic therapy-resistant inflammatory disorders of immune or non-immune pathogenesis. METHODS: 14 patients with adult Still's disease/macrophage activation syndrome (4), Wegener's disease (3), Behcet's disease (3), keratoscleritis (1), lymphomatous tracheo-bronchitis (1) Cogan's syndrome (1), and rapidly destructive crystal arthropathy (1) were treated with infliximab (n = 10) and etanercept (n = 4). All patients showed organ-threatening progression of their diseases with resistance to conventional immunosuppressive medication. Therapeutic benefit was assessed clinically and by documenting organ-specific functional and morphological alterations. Side effects were compared with the data of our clinic's rheumatoid arthritis (RA) patients treated by TNF inhibitors. RESULTS: A rapid and dramatic beneficial effect was documented in 9 patients and a moderate one in 5. Best responses (clinical and laboratory parameters) were seen in patients with macrophage activation syndrome/adult Still's disease and Behcet's disease, while the results were less impressive in those with Wegener's disease, Cogan's syndrome, idiopathic cerato-scleritis and lymphomatous tracheobronchitis. In all cases immunosuppressive agents and systemic glucocorticoids could be reduced or discontinued. CONCLUSIONS: TNF inhibition may be highly effective in patients with severe, therapy-resistant chronic inflammatory disorders.

-----

Respirology. 2002 Dec;7(4):317-24.
Addition of a 2-month low-dose course of levofloxacin to long-term erythromycin therapy in
sinobronchial syndrome.
Fujimura M, Mizuguchi M, Nakatsumi Y, Mizuhashi K, Sasaki S, Yasui M; Kanazawa Asthma Research Group.
The Third Department of Internal Medicine, Kanazawa University Hospital, Kanazawa, Japan. fujimura@med3.m.kanazawa-u.ac.jp

BACKGROUND: We previously reported that a 6-month low-dose course of ofloxacin combined with long-term low-dose erythromycin therapy (EM therapy) was superior to EM therapy alone for sinobronchial syndrome (SBS), especially during the initial 2 months of treatment. However, there was no data as to whether discontinuation of low-dose ofloxacin after 2 months results in symptom relapse. This study was designed to clarify this issue. METHODOLOGY: Twenty-three patients with SBS received a 2-month course of levofloxacin (LVFX) therapy (100 mg once a day) concurrent with a 6-month course of EM therapy (200 mg three times a day) (group A). Eighteen other patients were given the EM therapy alone (group B). Clinical parameters, including quantity of morning sputum, were recorded in a daily symptom diary, and reviewed by each doctor in charge at 2-4 week intervals. RESULTS: The quantity of morning sputum decreased more rapidly in group A than in group B. No relapse of symptoms was recognized after discontinuation of LVFX in group A. CONCLUSIONS: A 2-month low-dose course of LVFX in conjunction with long-term EM therapy may be efficacious for the treatment of SBS, as evidenced by rapid improvement of expectoration without any relapse after LVFX discontinuation.

-----

Respir Med. 2002 Nov;96(11):862-71.
Telithromycin is as effective as amoxicillin/clavulanate in acute exacerbations of chronic bronchitis.
Aubier M, Aldons PM, Leak A, McKeith DD, Leroy B, Rangaraju M, Bienfait-Beuzon C.
Xavier Bichat School of Medicine, Paris, France. michel.aubier@bch.ap-hop-paris.fr

This randomized, double-blind study evaluated the efficacy and safety of a short, 5-day course of telithromycin, a new ketolide antibacterial, compared with a standard 10-day course of amoxicillin/clavulanate, in the treatment of acute exacerbations of chronic bronchitis (AECB). The study enrolled 325 adult patients with AECB and a history of chronic obstructive pulmonary disease (COPD). Patients received either telithromycin 800 mg once daily (qd) for 5 days (followed by placebo for 5 days) or amoxicillin/clavulanate 500/125 mg three times daily (tid) for 10 days. Clinical cure rates for telithromycin post-therapy (Days 17-21, test-of-cure) and late post-therapy (Days 31-36) were 86.1 and 78.1%, respectively; 82.1 and 75.0% for amoxicillin/clavulanate. Excellent clinical cure rates were also observed for high-risk patients. Bacteriologic outcome was satisfactory for 69.2% of telithromycin recipients vs 70.0% for amoxicillin/clavulanate recipients. Both treatments were generally well tolerated, although the frequency of drug-related adverse events was almost two-fold higher for amoxicillin/clavulanate (25.0 vs. 13.1%). Thus, a 5-day course of telithromycin 800 mg qd is an effective and well-tolerated alternative to a standard 10-day course of amoxicillin/clavulanate 500/125 mg tid for first-line empiric treatment of AECB in adults with COPD.

-----

Pharmacotherapy. 2002 Oct;22(10):1278-93.
Cefditoren, a new aminothiazolyl cephalosporin.
Balbisi EA.
College of Pharmacy and Allied Health Professions, St John's University, and Queens Hospital Center, Jamaica, New York 11439, USA. balbisie@stjohns.edu

Cefditoren pivoxil, an oral third-generation cephalosporin, was approved by the Food and Drug Administration in September 2001. It has been used in Japan for several years. The greatest therapeutic potential of cefditoren appears to be its activity against gram-positive and gram-negative organisms causing respiratory tract infections and skin and skin-structure infections, such as Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Cefditoren is also effective against methicillin-susceptible strains of Staphylococcus aureus. Nevertheless, cefditoren has no activity against atypical pathogens, including Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella sp. Moreover, cefditoren does not inhibit Pseudomonas aeruginosa or Bacteroides fragilis. In virtually all studies, cefditoren has compared favorably against other orally administered antibiotics used against the most commonly isolated respiratory tract pathogens. Its side effect profile includes diarrhea, nausea, vomiting, headache, and dyspepsia. Cefditoren is indicated for treatment of mild-to-moderate acute exacerbations of chronic bronchitis, pharyngitis-tonsillitis, and uncomplicated skin and skin-structure infections caused by susceptible strains of organisms in adults and adolescents (> or = 12 yrs of age). Based on its reported antimicrobial activity, cefditoren has potential for empiric management of most commonly encountered respiratory tract infections. Additional studies will further define its role in clinical practice.

-----

Clin Ther. 2002 Sep;24(9):1414-25.
Open-label, randomized comparison of the efficacy and tolerability of clarithromycin, levofloxacin, and cefuroxime axetil in the treatment of adults with acute bacterial exacerbations of chronic bronchitis.
Weiss LR.
Department of Emergency Medicine, Knox Community Hospital, Mount Vernon, Ohio 43050, USA. Weiss@whiteflower.net

BACKGROUND: In the absence of a confirmed pathogen, empiric antimicrobial treatment of patients with acute exacerbations of chronic bronchitis and acute bacterial exacerbations of chronic bronchitis (ABECB) is accepted as standard practice and recommended in treatment guidelines. OBJECTIVE: This study compared the efficacy and tolerability of a 10-day course of 3 antimicrobial regimens commonly used to treat adults with ABECB. METHODS: This prospective, open-label, randomized study assessed clarithromycin 500 mg twice daily, levofloxacin 500 mg once daily, and cefuroxime axetil 250 mg twice daily, each administered for 10 days with food, in patients with ABECB. Efficacy was determined on the basis of the clinical response to treatment and need for hospitalization and/or further antimicrobial therapy. RESULTS: A total of 283 patients (150 men, 133 women) with a mean age of 55 years (range, 29 to 86 years) were randomized to receive clarithromycin (n = 97), levofloxacin (n = 94), or cefuroxime axetil (n = 92). Of 262 clinically assessable patients, clinical cure or improvement occurred in 87.9% (80/91) of those treated with clarithromycin, 87.4% (76/87) of those treated with levofloxacin, and 79.8% (67/84) of those treated with cefuroxime axetil. Eight (8.8%) clarithromycin-treated patients, 6 (6.9%) levofloxacin-treated patients, and 12 (14.3%) cefuroxime axetil-treated patients required a change in antimicrobial therapy to achieve clinical cure/improvement; between-group differences were not significant. No patients treated with clarithromycin required hospitalization for further antimicrobial treatment, compared with 3.4% (3/87) of levofloxacin-treated and 3.6% (3/84) of cefuroxime axetil-treated patients (P = NS). A total of 6.2% (6/97) of clarithromycin-treated patients were prematurely discontinued from treatment due to adverse events, compared with 7.4% (7/94) and 8.7% (8/92) of levofloxacin- and cefuroxime axetil-treated patients, respectively. CONCLUSION: A high rate of clinical efficacy and tolerability was observed in this population of patients with ABECB treated with clarithromycin 500 mg twice daily, levofloxacin 500 mg once daily, or cefuroxime axetil 250 mg twice daily for 10 days.

-----

Vopr Kurortol Fizioter Lech Fiz Kult. 2002 Jul-Aug;(4):18-21.
[Pelotherapy in combined aftertreatment of patients with chronic bronchitis]
[Article in Russian]
Ivanov EM, Shakirova OV, Zhuravskaia NS.

A therapeutic complex based on pelotherapy given as mud applications or electrophoresis of squeezed mud on the area of lung root projection (a total of 10-12 procedures, each other day) was tested in 99 patients with chronic bronchitis (CB). 68 CB controls received the above complex but no peloids. The results were assessed by clinical changes, clinical biochemical indices, immunograms, changes in external respiration function. The pelotherapy was found to have a corrective effect on CB pathogenesis and a stimulating action on sanogenic mechanisms of the body.

-----

Presse Med. 2002 Sep;31 Spec No 1:HS11-5.
[Bronchial inflammation during chronic bronchitis, importance of fenspiride]
[Article in French]
Melloni B.
Service de Pneumologie, Hopital du Cluzeau, CHU Limoges (87).

PATHOPHYSIOLOGY OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD): Chronic inflammation of the upper airways, pulmonary parenchyma and pulmonary vasculature is the characteristic feature of COPD. Two mechanisms besides inflammation are also involved: oxidative stress and imbalance between proteinases and antiproteinases. Cellular infiltration of the upper airways involved neutrophils, macrophages, T lymphocytes and eosinophils. Inflammatory mediators appear to play a crucial role in the interaction between inflammation and obstruction. PROPERTIES OF FENSPIRIDE: A nonsteroidal drug, fenspiride, exhibits interesting properties documented in vitro: anti-bronchoconstriction activity, anti-secretory activity, and anti-inflammatory activity (reduction in the activity of phospholipase A2 and release of proinflammatory leukotriens). Two french clinical trials have studied the efficacy of fenspiride in patients with acute excerbation or stable COPD and have demonstrated an improvement in the group treated with fenspiride compared with the placebo group.

-----

Ter Arkh. 2002;74(8):52-5.
[Experience in treating patients with chronic obstructive bronchitis with fenspirid]
[Article in Russian]
Kirichenko AA, Shabanova TM.

AIM: To study a clinical effect of fenspirid and its impact on external respiration function in patients with chronic obstructive bronchitis (COB) in the exacerbation phase. MATERIAL AND METHODS: 30 COB patients participated in the trial (20 males, 10 females, age 39-80 years). The severity of clinical symptoms (cough, sputum, dyspnea) was studied using special scales. External respiration function was examined by a spirometric system "Tamrac system spiro sense Y2 14". Fenspirid treatment was conducted in a dose 80 mg twice a day for 3 months. Control examinations were made 2 weeks, 1 and 3 months after the treatment start. RESULTS: A 3-month treatment with fenspirid resulted in regression of COB symptoms: cough and sputum ceased, dyspnea decreased. This led to improvement in external respiration function, especially in patients with mixed ventilatory disorders with prevailing restriction. CONCLUSION: Fenspirid is an effective and well tolerated treatment of chronic obstructive bronchitis.

-----

Ter Arkh. 2002;74(8):49-52.
[Comparison of acute bronchiolytic effect of inhaling solutions of berodual vs salgim using a nebulizer in patients with chronic obstructive bronchitis and bronchial asthma]
[Article in Russian]
Vizel' AA, Gil'manov AA, Samerkhanova AE, Gizatullina ED, Buniatin AA.

AIM: Comparison of acute response to nebulizer inhalation of therapeutic doses of combined broncholitic berodual and domestic bronchoselective adrenomimetic salgim in patients with bronchial asthma (BA) and chronic obstructive bronchitis (COB). MATERIAL AND METHODS: The trial included 17 COB and 15 BA patients who for two consecutive days inhaled berodual and salgim solutions. Before and after the inhalations, subjective condition of the patients and parameters of the forced expiration were recorded. The sequence of the solutions use was determined randomly. RESULTS: Nebulizer inhalations of berodual and salgim relieved respiration subjectively in 83.9 and 93.5% patients, respectively. Significant bronchodilation was registered 30 min after inhalation of each of the solutions both in BA and COB. Berodual caused no side effects, salgim provoked short-term cough in 6(19.4%) patients. CONCLUSION: Nebulizer therapy of berodual or salgim is clinically and cost effective in moderate and severe obstruction in BA and COB patients.

-----

Presse Med. 2002 Jun 15;31(21 Pt 2):S15-8.
[Update on the use of levofloxacin in the management of acute exacerbations of chronic bronchitis
with risk factors]
[Article in French]
Zuck P.
Service de Pneumologie, CHR de Metz-Thionville 57038 Metz.

INDICATIONS FOR ANTIBIOTICS: In patients with acute exacerbation of chronic bronchitis depend on the stage of the chronic disease. Theoretically, antibiotics are not necessary for acute exacerbation of simple chronic bronchitis, but may be needed to reinforce bronchodilatation therapy and respiratory physical therapy. If fever persists for more than three days, group 1 antibiotics can be prescribed. In a second stage (obstructive chronic bronchitis), antibiotic therapy can be useful for patients with two or three Anthonisen criteria: group 1 antibiotics for occasional exacerbation, group 2 antibiotics in case of failure or as first line treatment for patients with frequent exacerbations; anti-pneumococcal fluoroquinolones are a possible alternative. At a third stage (chronic respiratory failure), first line therapy should include group 2 antibiotics. THE BRONCHEA STUDY: Was designed to search for risk factors favoring frequent acute exacerbation of chronic bronchitis in adults. The findings suggest that certain classical risk factors such as age should be revisited. This study demonstrated the crucial need for rigorous surveillance by a lung specialist, the importance of not smoking, and the beneficial effect of optimized treatment. It was also found that earlier initiation of group 2 antibiotic therapy may be useful for patients with a high risk of exacerbation.

-----

Klin Med (Mosk). 2002;80(6):21-5.
[Use of autotransfusion of UV-irradiated blood in chronic bronchitis]
[Article in Russian]
Ivanov EM, Shakirova OV, Zhuravskaia NS.

Effectiveness of rehabilitation with therapeutic complex based on autotransfusion of UV-radiated blood (ATUVRB) was studied in 81 patients with chronic bronchitis (CB). The course consisted of 5 procedures with interval 2-3 days. The first procedure was exploratory with irradiated blood 0.5-0.8 ml/kg body weight. Control group comprised 48 CB patients getting conventional complex of rehabilitation measures. As shown by clinical criteria, clinico-biochemical indices, immunograms, external respiration function, ATUVRB-based rehabilitation corrects main pathogenetic mechanisms of CB.

-----

J Chemother. 2002 Jun;14(3):279-84.
Recent clinical evidence of the efficacy and safety of thiamphenicol glycinate acetylcysteinate and thiamphenicol glycinate.
Grassi C, De Benedetto F.
Postgraduate School for Respiratory Diseases-University of Pavia, Italy. tisiolmm@ipv36.unipv.it

Thiamphenicol is a broad-spectrum antimicrobial agent active against penicillin-resistant Streptococcus pneumoniae, Staphylococcus aureus VISA strains, most methicillin-resistant isolates and atypical pathogens such as Mycoplasma pneumoniae and Chlamydia pneumoniae). Thiamphenicol is present as glycinate hydrochloride (TG) and glycinate acetylcysteinate (TGA) esters in the parenteral and aerosol dosage form. This multicenter, double-blind, randomized clinical trial aimed to evaluate the efficacy and tolerability of aerosol administration of TGA, compared to TG, in the treatment of acute and/or exacerbated infections of the respiratory tract. Results showed that both treatments ameliorated the symptoms (frequency and severity of cough, difficulty in expectoration) associated with the evaluated pathologies, i.e. tracheobronchitis, acute and exacerbated chronic bronchitis. The investigators rated both treatments Good or Very Good in 90% of patients at the end of treatment, with "Very Good" for patients treated with TGA (37%) compared to 28% of patients treated with TG. Both treatments were well tolerated with fewer than 5% of patients experiencing an adverse event.

-----

Chest. 2002 Jul;122(1):289-94.
A randomized, placebo-controlled trial of a leukotriene synthesis inhibitor in patients with COPD.
Gompertz S, Stockley RA.
Department of Respiratory Medicine, Queen Elizabeth Hospital, Birmingham, UK. sgomp@doctors.org.uk

STUDY OBJECTIVE: Patients with COPD classically have neutrophilic bronchial inflammation and raised airway concentrations of the neutrophil chemoattractant leukotriene B(4) (LTB(4)). A small phase II trial was conducted to assess the effects of a leukotriene synthesis inhibitor on bronchial inflammation in patients with stable COPD. DESIGN: A randomized, double-blind, placebo-controlled, parallel-group study. SETTING: Respiratory medicine department of a university hospital. PATIENTS AND INTERVENTION: Seventeen patients with chronic bronchitis and COPD (mean FEV(1), 35.5% predicted; SD, 14.8% predicted) were randomized to receive 14 days of the oral leukotriene synthesis inhibitor BAYx1005 (500 mg bid) or placebo. MEASUREMENTS AND RESULTS: Spontaneous sputum samples obtained at baseline and at the end of treatment were assayed for LTB(4), myeloperoxidase (an indirect marker of neutrophil numbers and/or activation), and chemotactic activity (Boyden chamber). After 14 days, there were no significant differences (p > 0.05) in absolute LTB(4) concentrations between the two treatment groups. However, BAYx1005 treatment produced a significantly greater median reduction in LTB(4) of - 3.1 nM (interquartile range [IQR], - 9.6 to - 0.2 nM) vs 3.0 nM (IQR, - 0.3 to 8.5 nM) [p = 0.001], with concentrations decreasing from 8.0 nM (IQR, 4.3 to 24.4 nM) at baseline to 4.2 nM (IQR, 1.9 to 11.9 nM) at the end of treatment (p = 0.03). There were no changes in the placebo group and no differences in sputum myeloperoxidase concentration or chemotaxis between the two treatment arms (p > 0.05). CONCLUSIONS: This small study suggests that a leukotriene synthesis inhibitor can produce modest reductions in some measures of neutrophilic bronchial inflammation in patients with COPD. This class of anti-inflammatory agent requires further study in larger numbers of patients to determine clinical benefit.

-----

Respiration. 2002;69(3):217-22.
Randomized, double-blind study of prulifloxacin versus ciprofloxacin in patients with acute exacerbations of chronic bronchitis.
Grassi C, Salvatori E, Rosignoli MT, Dionisio P; Prulifloxacin Study Group.
Institute of Phthisiology and Respiratory Diseases, University of Pavia, Italy.

BACKGROUND: Recently the role of bacteria in acute exacerbations of chronic bronchitis (AECB) as well as antibiotic treatment with selected drugs, especially fluoroquinolones, have been better defined. OBJECTIVE: To assess the efficacy and safety in patients with AECB of prulifloxacin in comparison with ciprofloxacin. METHODS: AECB was defined according to the guidelines for the evaluation of new anti-infective drugs for the treatment of respiratory tract infections (1992). 235 patients took part in the trial; 117 (88 males and 29 females, mean age 64.8 years) received 600 mg prulifloxacin once daily and 118 (91 males and 27 females, mean age 64.5 years) 500 mg ciprofloxacin twice a day, for a duration of 10 days. The study design was randomized, multicenter, double-blind, double-dummy. Efficacy evaluations were performed by comparing pretreatment and posttreatment assessments. The clinical response was determined by 4-point rating scores on cough, dyspnea, and expectoration (volume and appearance). The microbiological response was assessed on sputum specimen. RESULTS: Clinical success was observed in 84.7 and 85% of patients in the prulifloxacin and ciprofloxacin groups, respectively. The 95% confidence interval proved the equivalence of treatments. Both drugs successfully eradicated the most commonly isolated strains, including Haemophilus influenzae, Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa. Both treatments were well tolerated. Adverse drug reactions were always of mild or moderate intensity. CONCLUSION: The study showed that a 10-day course of prulifloxacin is as effective and safe as ciprofloxacin in the treatment of patients with AECB. Copyright 2002 S. Karger AG, Basel

-----

Expert Opin Investig Drugs. 2002 Jul;11(7):911-25.
Antibiotics in the treatment of acute exacerbations of chronic bronchitis.
Dever LL, Shashikumar K, Johanson WG Jr.
Medical Service 111-ID, VA New Jersey Health Care System, 385 Tremont Avenue, East Orange, NJ 07018 USA. Lisa.Dever@med.va.gov

The benefit of antimicrobial therapy for patients with an acute exacerbation of chronic bronchitis (AECB) remains controversial for two main reasons. First, the distal airways of patients with chronic bronchitis are persistently colonised, even during clinically stable periods, with the same bacteria that have been associated with AECB. Second, bacterial infection is only one of several causes of AECB. These factors have led to conflicting analyses on the role of bacterial agents and the response to antimicrobial therapy of patients with AECB. An episode of AECB is said to be present when a patient with chronic obstructive pulmonary disease (COPD) experiences some combination of increased dyspnoea, increased sputum volume, increased sputum purulence and worsening lung function. While the average COPD patient experiences 2 - 4 episodes of AECB per year, some patients, particularly those with more severe airway obstruction, are more susceptible to these attacks than others. Bacterial agents appear to be particularly associated with AECB in patients with low lung function and those with frequent episodes accompanied by purulent sputum. Non-typeable Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis account for up to 50% of episodes of AECB. Gram-negative bacilli are more likely to occur in patients with more severe lung disease. Antibiotics have been used to ameliorate AECB, to prevent AECB and to prevent the long-term loss of lung function that characterises COPD. Numerous prevention trials have been conducted with fairly consistent results; antibiotics do not lessen the number of episodes of AECB but do reduce the number of days lost from work. Most antibiotic trials have studied the impact of treatment on episodes of AECB and results have been inconsistent, largely due to patient selection and end point definition. In patients with severe airway obstruction, especially in the presence of purulent sputum, antibiotic therapy significantly shortens the duration of symptoms and can be cost-effective. Over the past 50 years, virtually all classes of antimicrobial agents have been studied in AECB. Important considerations include penetration into respiratory secretions, spectrum of activity and antimicrobial resistance. These factors limit the usefulness of drugs such as amoxicillin, erythromycin and trimethoprim-sulfamethoxazole. Extended-spectrum oral cephalosporins, newer macrolides and doxycycline have demonstrated efficacy in clinical trials. Amoxicillin-clavulanate and flouoroquinolones should generally be reserved for patients with more severe disease. A number of investigational agents, including ketolides and newer quinolones, hold promise for treatment of AECB.

-----

Am Fam Physician. 2002 May 15;65(10):2039-44.
Diagnosis and management of acute bronchitis.
Knutson D, Braun C.
Department of Family Medicine, Ohio State University School of Medicine and Public Health, Columbus 43201, USA.

Acute bronchitis is one of the top 10 conditions for which patients seek medical care. Physicians show considerable variability in describing the signs and symptoms necessary to its diagnosis. Because acute bronchitis most often has a viral cause, symptomatic treatment with protussives, antitussives, or bronchodilators is appropriate. However, studies indicate that many physicians treat bronchitis with antibiotics. These drugs have generally been shown to be ineffective in patients with uncomplicated acute bronchitis. Furthermore, antibiotics often have detrimental side effects, and their overuse contributes to the increasing problem of antibiotic resistance. Patient satisfaction with the treatment of acute bronchitis is related to the quality of the physician-patient interaction rather than to prescription of an antibiotic.

-----

Clin Ther. 2002 Apr;24(4):639-52.
A comparison of gemifloxacin and clarithromycin in acute exacerbations of chronic bronchitis and long-term clinical outcomes.
Wilson R, Schentag JJ, Ball P, Mandell L; 068 Study Group.
Royal Brompton Hospital, London, England. r.wilson@rbh.nthames.nhs.uk

BACKGROUND: Gemifloxacin is an enhanced-affinity quinolone with potent activity against lower respiratory tract pathogens. OBJECTIVE: The efficacy and safety of a 5-day course of gemifloxacin were compared with those of a standard 7-day regimen of clarithromycin in patients with an acute exacerbation of chronic bronchitis (AECB). The impact of treatment on the long-term (26 weeks) clinical outcome was also assessed. METHODS: The acute phase of this randomized, double-blind study was performed in 93 centers in 7 countries. Adult patients (age >40 years) with a history of chronic bronchitis and an Anthonisen type 1 acute exacerbation (increased dyspnea, cough, and sputum purulence) were eligible. Patients receiving systemic steroids at a dose of >10 mg prednisone or the equivalent were excluded. Patients were randomized to receive gemifloxacin 320 mg once daily for 5 days or clarithromycin 500 mg twice daily for 7 days. Clinical and bacteriologic response rates were assessed at the end-of-therapy visit (days 8-12), the week 2-3 follow-up visit (days 13-24), and the week 4-5 follow-up visit (days 25-38). The long-term phase (26 weeks), which included US and Canadian participants only, evaluated the proportion of patients who remained free of a recurrence of AECB requiring additional antimicrobial therapy after resolution of the initial episode. RESULTS: Seven hundred twelve patients were randomized to treatment, 351 to gemifloxacin and 361 to clarithromycin. The long-term study included 438 patients, 214 receiving gemifloxacin and 224 receiving clarithromycin. Clinical success rates at the 2-3 week follow-up visit were 85.4% for gemifloxacin and 84.6% for clarithromycin. Bacteriologic success rates were 86.7% for gemifloxacin and 73.1% for clarithromycin. Significantly more patients receiving gemifloxacin than clarithromycin remained free of AECB recurrences (71.0% vs 58.5%, respectively; P = 0.016). Both treatments were well tolerated. CONCLUSIONS: In the acute treatment of Anthonisen type 1 AECB, a 5-day course of gemifloxacin was at least as effective as a 7-day regimen of clarithromycin. In this population, significantly more patients receiving gemifloxacin remained free of AECB recurrence after 26 weeks compared with those receiving clarithromycin.

-----

Lancet. 2002 May 11;359(9318):1648-54.
Azithromycin for acute bronchitis: a randomised, double-blind, controlled trial.
Evans AT, Husain S, Durairaj L, Sadowski LS, Charles-Damte M, Wang Y.
Collaborative Research Unit, Department of Medicine, Cook County Hospital and Rush Medical College, Chicago, IL 60612, USA. aevans@cchil.org

BACKGROUND: The value of azithromycin for treatment of acute bronchitis is unknown, even though this drug is commonly prescribed. We have investigated this question in a randomised, double-blind, controlled trial. METHODS: Adults diagnosed with acute bronchitis, without evidence of underlying lung disease, were randomly assigned azithromycin (n=112) or vitamin C (n=108) for 5 days (total dose for each 1.5 g). All individuals were also given liquid dextromethorphan and albuterol inhaler with a spacer. The primary outcome was improvement in health-related quality of life at 7 days; an important difference was defined as 0.5 or greater. Analysis was by intention to treat. FINDINGS: The study was stopped by the data-monitoring and safety committee when 220 patients had been recruited. On day 7, the adjusted difference in health-related quality of life was small and not significant (difference 0.03 [95% CI -0.20 to 0.26], p=0.8). 86 (89%) of 97 patients in the azithromycin group and 82 (89%) of 92 in the vitamin C group had returned to their usual activities by day 7 (difference 0.5% [-10% to 9%], p>0.9). There were no differences in the frequency of adverse effects; three patients in the vitamin C group discontinued the study medicine because of perceived adverse effects, compared with none in the azithromycin group. Most patients (81%) reported benefit from the albuterol inhaler. INTERPRETATION: Azithromycin is no better than low-dose vitamin C for acute bronchitis. Further studies are needed to identify the best treatment for this disorder.

-----

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2001 Nov;21(11):816-8.
[Clinical study on treatment of chronic bronchitis by tracheitis plaster]
[Article in Chinese]
Huo GR, Ma LQ, Huang CH.
Lanzhou Second People's Hospital, Lanzhou 730046.

OBJECTIVE: To study the clinical effect and mechanism of Tracheitis Plaster (TP) in treating chronic bronchitis. METHODS: TP is consisted of ephedra, almond, pinellia tuber, earthworm and white mustard seed. Patients were randomly divided into two groups, 59 patients in the treated group were treated with TP sticking on acupoints Dingchuan, Dashu, Fengmen, Feishu and Xinshu at back along both sides of thoracic vertebrae 1-6 and the 25 patients in the control group were treated with intramuscular injection of Siqikang. The times of treatment for both groups were 20. Clinical symptoms, X-ray chest film, level of immunoglobulin and T-lymphocyte subsets were recorded before and after treatment, and follow-up were carried out 0.5-1 year later. RESULTS: The clinical total effective rate was 93.2% and the X-ray improvement rate was 40.7% in the treated group, while in the control group, 80.0% and 20.0% respectively. Half and 1 year follow-up studies showed the total effective rate in the treated group was 91.5% and 89.8% respectively, which was significantly higher than that in the control group (80.0% and 76.0%) respectively (P < 0.05). The improvement in levels of IgG and CD8 in the treated group was also superior to those in the control group (P < 0.05). CONCLUSION: TP is a highly effective transcutaneous absorbent with promising long-term effect, it could regulate the immune function.

The Bronchitis FileSM Compiled and Maintained by    The Center for Current Research, Inc. 708 Aubrey Avenue • Ardmore PA USA 19003 Phone: 610-649-3165 Email: customerservice@lifestages.com Website: www.lifestages.com

©Copyright 1992-date by The Center for Current Research. The Bronchitis File is a proprietary compilation of the Center for Current Research. The information in the File is solely for your use, and the use of your family, friends, and doctors. The information is the property of the individual researchers and institutions that produced it. It is an infringement of copyright law to attempt to "resell" the information as it is presented here.