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.
   

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Previous Bronchitis Research: 2002-2006   
The Bronchitis File also contains summaries of past research that has shown promise and may still be standard practice among many physicians. To download earlier research findings on Bronchitis, click HERE.
 

Latest Research on Bronchitis
     
Crit Care Med. 2008 Jul;36(7):2008-13. Comment in: Crit Care Med. 2008 Jul;36(7):2191-2.
Aerosolized antibiotics and ventilator-associated tracheobronchitis in the intensive care unit.
Palmer LB, Smaldone GC, Chen JJ, Baram D, Duan T, Monteforte M, Varela M, Tempone AK, O'Riordan T, Daroowalla F, Richman P.
Department of Medicine, Pulmonary/Critical Care Division, University Hospital, State University of New York at Stony Brook, Stony Brook, New York, USA. Lucy.B.Palmer@Stonybrook.edu

CONTEXT: In critically ill intubated patients, signs of respiratory infection often persist despite treatment with potent systemic antibiotics. OBJECTIVE: The purpose of this study was to determine whether aerosolized antibiotics, which achieve high drug concentrations in the target organ, would more effectively treat respiratory infection and decrease the need for systemic antibiotics. DESIGN: Double-blind, randomized, placebo-controlled study performed from 2003 through 2004. SETTING: The medical and surgical intensive care units of a university hospital. PATIENTS: Critically ill intubated patients were randomized if: 1) > or = 18 yrs of age, intubated for a minimum of 3 days, and expected to survive at least 14 days; and 2) had ventilator-associated tracheobronchitis defined as the production of purulent secretions (> or = 2 mL during 4 hrs) with organism(s) on Gram stain. Of 104 patients monitored, 43 consented for treatment and completed the study. No patients were withdrawn from the study for adverse events. INTERVENTION: Aerosol antibiotic (AA) or aerosol saline placebo was given for 14 days or until extubation. The responsible clinician determined the administration of systemic antibiotics (SA). Patients were followed for 28 days. MAIN OUTCOME MEASURES: Primary: Centers for Disease Control National Nosocomial Infection Survey diagnostic criteria for ventilator-associated pneumonia (VAP) and clinical pulmonary infection score. Secondary: white blood cell count, SA use, acquired antibiotic resistance, and weaning from mechanical ventilation. RESULTS: Most patients had VAP at randomization. With treatment, the AA group had reduced signs of respiratory infection: reduced Centers for Disease Control National Nosocomial Infection Survey VAP (14/19; 73.6%) to (5/14; 35.7%) vs. placebo (18/24; 75%) to (11/14; 78.6%), reduction in clinical pulmonary infection score, lower white blood cell count at day 14, reduced bacterial resistance, reduced use of SA, and increased weaning (all p < or = .05). CONCLUSIONS: In critically ill patients with ventilator-associated tracheobronchitis, AA decrease VAP and other signs and symptoms of respiratory infection, facilitate weaning, and reduce bacterial resistance and use of systemic antibiotics.

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Expert Opin Pharmacother. 2008 Jul;9(10):1755-72.
Moxifloxacin: a respiratory fluoroquinolone.
Miravitlles M, Anzueto A.
Servei de Pneumologia, Institut Clínic del Tòrax (IDIBAPS), Ciber de Enfermedades Respiratorias (CIBERES), Hospital Clínic, Barcelona, Spain. marcm@clinic.ub.es

BACKGROUND: Respiratory quinolones are a class of antimicrobials with a high activity against most respiratory pathogens. Moxifloxacin is a fourth-generation fluoroquinolone that has been shown to be effective against Gram-positive, Gram-negative, and atypical strains, as well as multi-drug resistant Streptococcus pneumoniae. OBJECTIVE: To review and update the clinical efficacy of moxifloxacin in the treatment of respiratory infections. METHOD: To perform a systematic review of publications on the clinical efficacy of moxifloxacin in respiratory infections. RESULTS: The clinical efficacy of moxifloxacin has been shown in controlled studies of community-acquired pneumonia, exacerbations of chronic bronchitis and acute bacterial rhinosinusitis. Moxifloxacin has demonstrated a faster resolution of symptoms in community-acquired pneumonia and exacerbations of chronic bronchitis patients compared with first-line therapy together with excellent eradication rates. CONCLUSIONS: The use of moxifloxacin as first-line therapy for moderate to severe respiratory infections in the community and the hospital has been recognized in international guidelines.

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Expert Opin Pharmacother. 2008 Jul;9(10):1735-44.
A pharmacoeconomic review of the management of respiratory tract infections with moxifloxacin.
Simoens S, Decramer M.
Katholieke Universiteit Leuven, Research Centre for Pharmaceutical Care and Pharmaco-economics, Faculty of Pharmaceutical Sciences, Onderwijs en Navorsing 2, Herestraat 49, PO Box 521, 3000 Leuven, Belgium. steven.simoens@pharm.kuleuven.be

BACKGROUND: Moxifloxacin, a fluoroquinolone, has demonstrated its safety and effectiveness in the management of community-acquired pneumonia, acute exacerbations of chronic bronchitis and acute bacterial sinusitis. OBJECTIVE: The aim of this article was to provide a synthesis and critical appraisal of economic evaluations of the management of respiratory tract infections with moxifloxacin. METHODS: Studies were included if they assessed the costs and consequences of moxifloxacin as compared with an alternative antimicrobial in the management of community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute bacterial sinusitis. RESULTS/CONCLUSIONS: Treatment of community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute bacterial sinusitis with moxifloxacin is equally or more effective and less expensive than treatment with other antimicrobials.

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Altern Ther Health Med. 2008 May-Jun;14(3):42-4.
Inhaled glutathione for the prevention of air pollution-related health effects: a brief review.
Allen J.
University of Washington School of Public Health and Community Medicine, Department of Environmental and Occupational Health Sciences, Seattle, USA.

Exposure to air pollution is associated with significant adverse health effects, such as cardiovascular disease and asthma. Most current research trends focus on quantifying illnesses or deaths attributable to air pollutants, but limited research has examined potential methods of preventing these effects. The mainstay of conventional therapies lies in the treatment of exposure-related diseases, not prevention strategies. Few medical interventions seek to protect the lungs directly. Complementary and alternative medicine (CAM) practitioners are widely recognized, and often criticized, for administering therapeutic substances based on biochemical plausibility or pre-clinical studies. One widely used CAM intervention that specifically targets the Slung is inhalation of the antioxidant glutathione. Inhaled glutathione is commonly used in the CAM community to treat a number of conditions, such as asthma, chronic obstructive pulmonary disease, bronchitis, sinusitis, and chemical sensitivity. Evidence suggests that inhaled glutathione rapidly increases pulmonary glutathione levels, providing a potential preventive intervention in the presence of environmental oxidants (eg, air pollutants). Enhancing pulmonary glutathione levels may reduce or eliminate systemic effects of air pollutants; however, no controlled studies have evaluated this potential. This article briefly reviews a major air pollutant (particulate matter) and the natural defense system against its toxicity and propose a pilot study to investigate the potential of inhaled glutathione to blunt its adverse effects.

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Expert Opin Investig Drugs. 2008 Mar;17(3):387-400.
Use of cethromycin, a new ketolide, for treatment of community-acquired respiratory infections.
Hammerschlag MR, Sharma R.
State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203-2098, USA. mhammerschlag@downstate.edu

BACKGROUND: The ketolides are a subclass of macrolides, which were designed specifically to overcome macrolide-resistant respiratory pathogens. Ketolides lack the cladinose sugar, which is replaced with a 3-ketone group. Ketolides bind to a secondary region on domain II of the 23S rRNA subunit. Telithromycin was the first ketolide to be approved by the FDA in 2004 for treatment of community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB) and sinusitis. However, in 2006, after reports of serious hepatotoxicity, the FDA issued a public health advisory followed by a warning. In 2007 the indications for treatment of AECB and sinusitis were removed from the labeling. Cethromycin (ABT-773) is the only other ketolide currently under clinical development. OBJECTIVE: To review currently available data on cethromycin, including chemistry, in vitro activity, pharmacokinetics, pharmacodynamics, in vivo activity and results of treatment studies in humans. METHOD
S: A search was made in PubMed, pharmaceutical databases and meeting abstracts using the terms ketolides, ABT-773 and cethromycin. RESULTS/CONCLUSIONS: Cethromycin has comparable tissue penetration, pharmacokinetics and in vitro activity compared with telithromycin to Streptococcus pneumoniae, including multidrug-resistant isolates, Haemophilus influenzae, Moraxella catarrhalis, Chlamydophila pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila. There is only one published CAP treatment study that compared cethromycin 150 mg q.d. with 150 mg b.i.d. One Phase II and a Phase II/III study have been presented in abstract form, both were non-comparative, dose-ranging studies, which suggested that 150 mg q.d. or 300 mg q.d. were comparable in terms of clinical response and bacterial eradication, although data on the latter are limited. Data on side effects are limited and appear to be mainly gastrointestinal. There have been no reports of serious hepatotoxicity at the time of this writing. Cethromycin may have other uses in addition to treatment of CAP respiratory infections, including treatment of infections due to Neisseria gonorrhoeae and Chlamydia trachomatis and bioterrorism agents including Bacillus anthracis, Yersinia pestis and Francisella tularensis.

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Curr Opin Pulm Med. 2008 Mar;14(2):105-9.
Smoking: relationship to chronic bronchitis, chronic obstructive pulmonary disease and mortality.
Pelkonen M.
Department of Pulmonary Diseases, Kuopio University Hospital, Kuopio, Finland.

PURPOSE OF REVIEW: To describe the recent findings concerning the relationship between smoking, chronic bronchitis, chronic obstructive pulmonary disease and mortality. RECENT FINDINGS: During their lifetime, over 40% of smokers develop chronic bronchitis. Chronic bronchitis is associated with an accelerated decline in lung function - a risk of developing chronic obstructive pulmonary disease and mortality. Approximately one-quarter of smokers can be affected by clinically significant chronic obstructive pulmonary disease. The incidence of chronic obstructive pulmonary disease is also substantial in young adults. Smokers may reduce their risk of developing chronic obstructive pulmonary disease by physical activity and increase their survival by smoking reduction. In adults and the elderly population, severe chronic obstructive pulmonary disease is associated with the most rapid decline in lung function, which is, in turn, associated with chronic obstructive pulmonary disease-related hospitalization and mortality. Using a fixed forced expiratory volume in 1 s/force vital capacity ratio (0.7) to define obstruction in chronic obstructive pulmonary disease at old age is acceptable. In chronic obstructive pulmonary disease patients, the disease is still underreported on death certificates. Chronic mucus production and being a female are associated with chronic obstructive pulmonary disease mentioned on death certificates. SUMMARY: Chronic bronchitis is a marker identifying high-risk individuals. With respect to chronic obstructive pulmonary disease and mortality, interventions to promote smoking cessation are important to reduce these risks.

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Pediatr Allergy Immunol. 2008 Feb 11 [Epub ahead of print]
Children with absent surfactant protein D in bronchoalveolar lavage have more frequently pneumonia.
Griese M, Steinecker M, Schumacher S, Braun A, Lohse P, Heinrich S.
Children’s Hospital, University of Munich, Munich, Germany.

Surfactant protein D (SP-D) is an important component of the pulmonary host defense system. We hypothesized that bronchoalveolar lavage (BAL) SP-D levels are lower in children presenting with recurrent bronchitis, providing evidence for a role of SP-D in human respiratory diseases. SP-D levels in BAL were measured in 45 children, who suffered from recurrent bronchitis for an average of 2-3 yr. Clinical outcome was assessed 2 yr after BAL. For comparison, BAL fluids from 15 control children without respiratory symptoms were evaluated. Among the 45 children with recurrent bronchitis, 12 had no SP-D in their BAL at the time of investigation. These SP-D-deficient patients had more frequently pneumonias and their long-term outcome was worse than that of the children with detectable SP-D. No genetic cause could be identified for the SP-D deficiency. Among the children with recurrent bronchitis and SP-D clearly detectable in BAL, those with the diagnosis of allergic asthma had threefold elevated levels compared with controls. In accordance with animal and in vitro data, elevated SP-D concentrations in BAL may represent an up-regulation due to allergic airway inflammation. In contrast, SP-D deficiency due to consumption or failure to up-regulate SP-D may be linked to pulmonary morbidity in children.

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Cochrane Database Syst Rev. 2008 Jan 23;(1):CD001954.
Azithromycin for acute lower respiratory tract infections.
Panpanich R, Lerttrakarnnon P, Laopaiboon M.

BACKGROUND: Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia. Approximately five million people die of acute respiratory tract infections annually. 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 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 2007 Issue 2), MEDLINE (January 1966 to July 2007), and EMBASE (January 1974 to July 2007). SELECTION CRITERIA: Randomized and quasi-randomized controlled trials, comparing azithromycin to amoxycillin or amoxycillin/clavulanic acid in participants 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 LRTI were initially pooled in the meta-analyses. The heterogeneity of results was investigated by the forest plot and Chi-square test. Index of I-square (I(2)) was also used to measure inconsistent results among trials. Subgroup and sensitivity analyses were conducted. MAIN RESULTS: Fifteen trials were analysed. 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 between the two groups (relative risk (RR), random-effects 1.09; 95% confidence interval (CI) 0.64 to 1.85). Sensitivity analysis showed a reduction of clinical failure in azithromycin-treated participants (RR 0.55; 95% CI 0.25 to 1.21) in three adequately concealed studies, compared to RR 1.32; 95% CI 0.70 to 2.49 in 12 studies with inadequate concealment. Twelve trials reported the incidence of microbial eradication and there was no significant difference between the two groups (RR 0.95; 95% CI 0.87 to 1.03). The reduction of adverse events in the azithromycin group was RR 0.76 (95% CI 0.57 to 1.00). AUTHORS' CONCLUSIONS: There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI. In patients with acute bronchitis of a suspected bacterial cause, azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav. Future trials of high methodological quality are needed.

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Thorax. 2008 Jan 30 [Epub ahead of print]
Short course antibiotic treatment in acute exacerbations of chronic bronchitis and COPD: a meta-analysis of double-blind studies.
El Moussaoui R, Roede BM, Speelman P, Bresser P, Prins JM, Bossuyt PM.
Academical Medical Center, Netherlands.

OBJECTIVE: To determine whether a short course of antibiotic treatment (up to 5 days) is as effective as the conventional longer treatment in acute exacerbations of chronic bronchitis and COPD. METHODS: MEDLINE, EMBASE and the Cochrane central register of controlled trials were searched to July 2006. Eligible were double-blind randomized clinical trials including adult patients >/= 18 years of age with clinical diagnosis of exacerbation of COPD or chronic bronchitis, no antimicrobial therapy at the time of diagnosis and random assignment to antibiotic treatment up to 5 days versus longer than 5 days. Primary outcome measure was clinical cure at early follow-up, on intention to treat basis. RESULTS: 21 studies with a total of 10698 patients were included. The average quality of the studies was high: the mean Jadad score was 3.9 (SD 0.9). At early follow-up (<25 days) the summary odds ratio (OR) for clinical cure with short treatment versus conventional treatment was 0.99 (95% CI 0.90 to 1.08). At late follow-up the summary OR was 1.0 (95% CI 0.91 to 1.10) and the summary OR for bacteriological cure was 1.05 (95% CI 0.87 to 1.26). Similar summary ORs were observed for early cure in trials with the same antibiotic in both arms and in studies grouped by the antibiotic class used in the short-course arm. CONCLUSIONS: A short course of antibiotic treatment is as effective as the traditional longer treatment in patients with mild to moderate exacerbations of chronic bronchitis and COPD.

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Phytomedicine. 2008 Jan 25 [Epub ahead of print]
Pelargonium sidoides for acute bronchitis: A systematic review and meta-analysis.
Agbabiaka TB, Guo R, Ernst E.
Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, 25 Victoria Park Road, Exeter EX2 4NT, UK.

OBJECTIVE: To critically assess the efficacy of Pelargonium sidoides for treating acute bronchitis. DATA SOURCES: Systematic literature searches were performed in 5 electronic databases: (Medline (1950 - July 2007), Amed (1985 - July 2007), Embase (1974 - July 2007), CINAHL (1982 - July 2007), and The Cochrane Library (Issue 3, 2007) without language restrictions. Reference lists of retrieved articles were searched, and manufacturers contacted for published and unpublished materials. REVIEW METHODS: Study selection was done according to predefined criteria. All randomized clinical trials (RCTs) testing P. sidoides extracts (mono preparations) against placebo or standard treatment in patients with acute bronchitis and assessing clinically relevant outcomes were included. Two reviewers independently selected studies, extracted and validated relevant data. Methodological quality was evaluated using the Jadad score. Meta-analysis was performed using a fixed-effect model for continuous data, reported as weighted mean difference with 95% confidence intervals. RESULTS: Six RCTs met the inclusion criteria, of which 4 were suitable for statistical pooling. Methodological quality of most trials was good. One study compared an extract of P. sidoides, EPs((R))7630, against conventional non-antibiotic treatment (acetylcysteine); the other five studies tested EPs((R))7630 against placebo. All RCTs reported findings suggesting the effectiveness of P. sidoides in treating acute bronchitis. Meta-analysis of the four placebo-controlled RCTs suggested that EPs((R))7630 significantly reduced bronchitis symptom scores in patients with acute bronchitis by day 7. No serious adverse events were reported. CONCLUSION: There is encouraging evidence from currently available data that P. sidoides is effective compared to placebo for patients with acute bronchitis.

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Int J Chron Obstruct Pulmon Dis. 2007;2(3):191-204.
Moxifloxacin in the management of exacerbations of chronic bronchitis and COPD.
Miravitlles M.
Servei de Pneumologia, Institut Clínic del Tòrax (IDIBAPS), Hospital Clínic, Barcelona, Spain. marcm@clinic.ub.es

Bacteria are isolated in more than 50% of exacerbations of chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD). The most prevalent respiratory pathogens include Gram-positive (Streptococcus pneumoniae) and Gram-negative (Haemophilus influenzae, Moraxella catarrhalis) microorganims. Moxifloxacin is a fourth-generation fluoroquinolone that has been shown to be effective against respiratory pathogens, including atypicals and those resistant to most common antibiotics. The bioavailability and half-life ofmoxifloxacin provides potent bactericidal effects at a dose of 400 mg once daily. Among the fluoroquinolones, the ratio of the area under the concentration-time curve (AUC) to minimal inhibitory concentration of moxifloxacin is the highest against S. pneumoniae. Moxifloxacin has demonstrated better eradication in exacerbations of CB and COPD compared with standard therapy, in particular, with macrolides. Patients treated with moxifloxacin showed a prolonged time to the next exacerbation and observational studies suggest that moxifloxacin induces a faster release of symptoms of exacerbation. Some guidelines recommend the use of moxifloxacin as first-line therapy in bacterial exacerbations in patients with moderate to severe COPD and in patients with mild COPD with risk factors. The current article reviews the use of moxifloxacin in bacterial exacerbations of CB and COPD.

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Int J Nanomedicine. 2007;2(4):551-9.
Clinical applications of azithromycin microspheres in respiratory tract infections.
Blasi F, Aliberti S, Tarsia P.
Institute of Respiratory Diseases, University of Milan, IRCCS Fondazione Policlinico-Mangiagalli-Regina Elena Milano, Italy. francesco.blasi@unimi.it

Few adequately designed clinical trials have addressed optimal treatment duration in lower respiratory tract infections. Drugs possessing favourable pharmacokinetic and pharmacodynamic profiles may obtain early bacterial eradication allowing shorter treatment duration. This may be associated with a number of advantages including reduced resistance induction, increased compliance, lesser adverse events, and cost containment. Recently, a novel 2.0 g single dose of azithromycin microspheres has been compared with 7-day levofloxacin 500 mg or extended release clarithromycin in over 400 patients with community-acquired pneumonia. Clinical cure and bacteriological eradication rates, hospitalizations, and deaths were similar between azithromycin and comparators. Azithromycin 2.0 g microspheres proved as effective as 7 days of levofloxacin 500 mg in acute exacerbation of chronic bronchitis patients across all degrees of obstruction severity. In both settings Azithromycin microspheres obtained clinical cure in most patients harbouring macrolide-resistant Streptococcus pneumoniae strains. The drug was well tolerated in clinical studies and in healthy volunteers with modest and transitory adverse events. An undoubted advantage of single-dose azithromycin administration is the facility in ensuring that patients complete their prescribed course of therapy. A further advantage of single-dose therapy is the potential for use as directly-observed therapy, which may be useful in specific clinical conditions.

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Int J Antimicrob Agents. 2007 Dec;30 Suppl 2:113-7. Epub 2007 Nov 7.
The clinical development and launch of amoxicillin/clavulanate for the treatment of a range of community-acquired infections.
Ball P.
School of Biomedical Sciences, St Andrews University, St Andrews, Fife, UK.

By the 1960s and 1970s, problems in the antibacterial treatment of infections had begun to emerge. Previously active antibacterials were being compromised by the development of resistance. Beta-lactamase production was identified in isolates of staphylococci, and, amongst others, in Escherichia coli, Proteus mirabilis, Haemophilus influenzae and Moraxella catarrhalis. The discovery of the potent beta-lactamase inhibitor clavulanic acid, and its protective effect on amoxicillin, a semi-synthetic penicillin with good oral absorption and potent broad-spectrum antimicrobial activity, was thus of great importance in the treatment of bacterial disease. Following preliminary clinical studies in bronchitis and urinary tract infections, amoxicillin/clavulanate therapy was investigated in a wide range of infections and proved to demonstrate a high level of clinical efficacy. These results supported the launch of amoxicillin/clavulanate (Augmentin) in 1981 for use in upper and lower respiratory tract infections, urinary tract infections, skin and soft tissue infections and obstetric, gynaecological and intra-abdominal infections.

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Int J Chron Obstruct Pulmon Dis. 2007;2(1):27-31.
Prulifloxacin: a brief review of its potential in the treatment of acute exacerbation of chronic bronchitis.
Blasi F, Aliberti S, Tarsia P, Santus P, Centanni S, Allegra L.
Institute of Respiratory Diseases, University of Milan, Fondazione IRCCS Policlinico-Mangiagalli-Regina Elena, Milano, Italy. francesco.blasi@unimi.it

Exacerbations of chronic bronchitis (AECB) are a major cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), and their impact on public health is increasing. The new fluoroquinolones have an excellent spectrum providing cover for the most important respiratory pathogens, including atypical and "typical" pathogens. Not surprisingly, different guidelines have inserted these agents among the drugs of choice in the empirical therapy of AECB. The pharmacokinetic and dynamic properties of the new fluoroquinolones have a significant impact on their clinical and bacteriological efficacy. They cause a concentration-dependent killing with a sustained post-antibiotic effect. This review discusses the most recent data on the new fluoroquinolone prulifloxacin and critically analyses its activity and safety in the management of AECB.

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Phytomedicine. 2007 Dec;14(12):787-91.
Pinimenthol ointment in patients suffering from upper respiratory tract infections—a post-marketing observational study.
Kamin W, Kieser M.
Children's Hospital, University of Mainz, Langenbeckstr. 1, D-55101 Mainz, Germany. kamin@kinder.klinik.uni-mainz.de

In order to gain further experience regarding the tolerability of Pinimenthol ointment(1) in adolescents (> or = 12 years) and adults suffering from upper respiratory tract infections, a post-marketing observational study was performed. In this study, data of 3060 patients were collected (64.9% prospectively over an individual observation period of 5-14 days, 35.1% retrospectively). The prospective documentation also comprised data concerning treatment effects. Sample size of the post-marketing observational study was calculated in the way that adverse drug reactions with an event probability of at least 1:1000 would occur within the study at least once with a probability of 95%. Most patients suffered from cold, acute or chronic bronchitis, bronchial catarrh or hoarseness. Pinimenthol ointment was prescribed to inunction (29.6%), inhalation (17.3%) or inunction and inhalation (53.1%), respectively. The mean duration of study participation was 8.0 +/- 3.4 days. The tolerability was rated as excellent or good by 96.7% of physicians and 95.7% of patients. A total of 22 patients (0.7%) reported adverse drug reactions which mostly affected the skin or mucus membrane and therefore correspond to the expected adverse effects profile of Pinimenthol ointment. The treatment effect was mostly judged as excellent or good (physicians: 88.3%; patients: 88.1%). In conclusion, the study confirms Pinimenthol ointment as a well tolerated therapy option for upper respiratory tract infections in both adolescents and adults.

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Arzneimittelforschung. 2007;57(9):607-15.
Evaluation of efficacy and tolerability of a fixed combination of dry extracts of thyme herb and primrose root in adults suffering from acute bronchitis with productive cough. A prospective, double-blind, placebo-controlled multicentre clinical trial.
Kemmerich B.
bernd.kemmerich@web.de

STUDY OBJECTIVE: The objective of the study was to assess the efficacy and tolerability of a fixed combination of dry extracts of thyme herb and primrose root (thyme-primrose combination) and matched placebo in patients suffering from acute bronchitis with productive cough. METHODS: In a double-blind, placebo-controlled, multicentre Phase IV study, 361 outpatients with acute bronchitis and > or = 10 coughing fits during the day, onset of bronchial mucus production with impaired ability to cough up at a maximum of 2 days prior to recruitment, and a Bronchitis Severity Score (BSS) > or = 5 score points were randomly assigned to an 11-day treatment (1 tablet three times daily) with either thyme-primrose combination (Bronchipret TP FCT; N = 183) or placebo (N = 178). After the baseline examination (Visit 1 = Day 0), 2 control examinations were scheduled (Visit 2 = Day 4; Visit 3 = Day 10/end of treatment). The efficacy of the study treatment on acute bronchitis was evaluated by the patient's daily counting of coughing fits during the daytime (manual counter), assessment of acute bronchitis related symptoms and by the investigator's assessment of the most important symptoms of acute bronchitis using the BSS. Evaluation of tolerability was based upon adverse event (AE) monitoring, measurement of vital signs as well as the patient's and investigator's global judgement of tolerability at study end. Primary outcome was the change in frequency of coughing fits during daytime on days 7-9 according to patient's accurate daily recording with a manual counter and documentation in the diary. Treatment effects were analysed by analysis of variance (ANOVA) adjusted for centre effects. Due to significant deviation from the "preconditions" of the ANOVA, the Mann-Whitney-Wilcoxon test (stratified by centre) was carried out additionally. RESULTS: The mean reduction in coughing fits on days 7 to 9 relative to baseline (primary endpoint) was 67.1% under thyme-primrose combination compared to 51.3% under placebo (p < 0.0001). In the thyme-primrose combination group, a 50% reduction in coughing fits from baseline was reached about 2 days earlier compared to the placebo group. The symptoms of acute bronchitis (BSS) improved rapidly in both groups, but regression was faster and the responder rates compared to placebo were higher at Visit 2 (77.5% vs 60.1%; p = 0.0006) and Visit 3 (92.9% vs 75.8%; p < 0.0001) under the treatment of thyme-primrose combination. Treatment was well tolerated with no difference in the frequency or severity of AE between thyme-primrose combination and placebo groups. Severe or serious AE were not reported. CONCLUSION: Oral treatment of acute bronchitis with thyme-primrose combination for about 11 days was superior to placebo in terms of efficacy. The treatment was safe and well tolerated.

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Lung. 2007 Oct 2 [Epub ahead of print]
Currently Available Cough Suppressants for Chronic Cough.
Chung KF.
National Heart & Lung Institute, Imperial College London, and Royal Brompton & Harefield NHS Trust, Dovehouse Street, London, SW3 6LY, UK, f.chung@imperial.ac.uk.

Chronic cough is a common symptom but only a fraction of patients seek medical attention. Addressing the causes of chronic cough may lead to control of cough; however, this approach is not always successful since there is a certain degree of failure even when the cause(s) of cough are adequately treated; in idiopathic cough, there is no cause to treat. Persistent cough may be associated with deterioration of quality of life, and treatment with cough suppressants is indicated. Currently available cough suppressants include the centrally acting opioids such as morphine, codeine, and dextromethorphan. Peripherally acting antitussives include moguisteine and levodropropizine. Early studies report success in reducing cough in patients with chronic bronchitis or COPD; however, a carefully conducted study showed no effect of codeine on cough of COPD. Success with these cough suppressants can be achieved at high doses that are associated with side effects. Slow-release morphine has been reported to be useful in controlling intractable cough with good tolerance to constipation and drowsiness. There have been case reports of the success of centrally acting drugs such as amitryptiline, paroxetine, gabapentin, and carbamezepine in chronic cough. New opioids such as nociceptin or antagonists of TRPV1 may turn out to be more effective. Efficacy of cough suppressants must be tested in double-blind randomised trials using validated measures of cough in patients with chronic cough not responding to specific treatments. Patients with chronic cough are in desperate need of effective antitussives that can be used either on demand or on a long-term basis.

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Drugs Aging. 2007;24(7):555-72.
Acute exacerbations of chronic bronchitis in elderly patients: pathogenesis, diagnosis and management.
Hayes D, Meyer KC.
Departments of Pediatrics and Internal Medicine, University of Kentucky College of Medicine, Lexington, Kentucky, USA.

Chronic bronchitis (CB) is a disorder that is characterised by chronic mucus production. This disorder is called chronic obstructive pulmonary disease (COPD) when airflow obstruction is present. The majority of patients with COPD, which often goes undiagnosed or inadequately treated in the elderly, have symptoms consistent with CB. The clinical course of CB is usually punctuated by periodic acute exacerbations linked to infections caused by viral and typical or atypical bacterial pathogens. Acute exacerbations of chronic bronchitis (AECB) often lead to a decline in lung function and poor quality of life in association with increased risk of mortality and a significant economic impact on the healthcare system and society because of the direct costs of hospitalisations. In elderly individuals with COPD, co-morbidities play a vital role as determinants of health status and prognosis. Failure to eradicate infecting pathogens contributes to persistence of infection and inflammation that requires repeated courses of therapy and hospitalisation. Stratifying patients with AECB according to symptoms, degree of pulmonary function impairment and risk factors for poor outcome can help clinicians choose empirical antimicrobial chemotherapy regimens that are most likely to result in treatment success. Failure to cover likely pathogens associated with episodes of AECB can lead to lengthy hospital admissions and significant declines in functional status for elderly patients. Fluoroquinolones may provide the best therapeutic option for elderly patients with COPD who have complicated underlying CB but who are sufficiently stable to be treated in the outpatient setting. Optimised treatment for stable outpatients with CB may diminish the frequency of AECB, and effective antimicrobial therapy for AECB episodes can significantly diminish healthcare costs and maintain quality of life in the elderly patient.

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N Engl J Med. 2007 Jul 26;357(4):331-9. Comment in: N Engl J Med. 2007 Jul 26;357(4):402-4.
A multicenter, randomized, controlled trial of dexamethasone for bronchiolitis.
Corneli HM, Zorc JJ, Majahan P, Shaw KN, Holubkov R, Reeves SD, Ruddy RM, Malik B, Nelson KA, Bregstein JS, Brown KM, Denenberg MN, Lillis KA, Cimpello LB, Tsung JW, Borgialli DA, Baskin MN, Teshome G, Goldstein MA, Monroe D, Dean JM, Kuppermann N; Bronchiolitis Study Group of the Pediatric Emergency Care Applied Research Network (PECARN).
University of Utah, Salt Lake City, USA.

BACKGROUND: Bronchiolitis, the most common infection of the lower respiratory tract in infants, is a leading cause of hospitalization in childhood. Corticosteroids are commonly used to treat bronchiolitis, but evidence of their effectiveness is limited. METHODS: We conducted a double-blind, randomized trial comparing a single dose of oral dexamethasone (1 mg per kilogram of body weight) with placebo in 600 children (age range, 2 to 12 months) with a first episode of wheezing diagnosed in the emergency department as moderate-to-severe bronchiolitis (defined by a Respiratory Distress Assessment Instrument score > or =6). We enrolled patients at 20 emergency departments during the months of November through April over a 3-year period. The primary outcome was hospital admission after 4 hours of emergency department observation. The secondary outcome was the Respiratory Assessment Change Score (RACS). We also evaluated later outcomes: length of hospital stay, later medical visits or admissions, and adverse events. RESULTS: Baseline characteristics were similar in the two groups. The admission rate was 39.7% for children assigned to dexamethasone, as compared with 41.0% for those assigned to placebo (absolute difference, -1.3%; 95% confidence interval [CI], -9.2 to 6.5). Both groups had respiratory improvement during observation; the mean 4-hour RACS was -5.3 for dexamethasone, as compared with -4.8 for placebo (absolute difference, -0.5; 95% CI, -1.3 to 0.3). Multivariate adjustment did not significantly alter the results, nor were differences detected in later outcomes. CONCLUSIONS: In infants with acute moderate-to-severe bronchiolitis who were treated in the emergency department, a single dose of 1 mg of oral dexamethasone per kilogram did not significantly alter the rate of hospital admission, the respiratory status after 4 hours of observation, or later outcomes. (ClinicalTrials.gov number, NCT00119002 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.

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Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004417.
Delayed antibiotics for respiratory infections.
Spurling G, Del Mar C, Dooley L, Foxlee R.

BACKGROUND: Modest benefits of antibiotics for acute upper respiratory tract infections have to be weighed against common adverse reactions, cost and antibacterial resistance. There has been interest in ways to reduce antibiotic prescribing. One strategy is to provide the prescription, but advise delay of more than 48 hours before use, in the hope symptoms resolve first. Advocates suggest this will preserve patient satisfaction. This review asks what effect delayed antibiotics have on clinical outcomes of respiratory infections, antibiotic use and patient satisfaction. OBJECTIVES: To evaluate the prescribing strategy of delayed antibiotics for acute respiratory tract infections compared to immediate or no antibiotics for clinical outcomes, antibiotic use and patient satisfaction. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2006); MEDLINE (January 1966 to January Week 2, 2007), EMBASE (1990 to Week 2, 2007) and Current Contents - ISI Web of Knowledge (1998 to January 2007). SELECTION CRITERIA: Randomised controlled trials (RCTs) involving patients of all ages defined as having an acute respiratory infection were included in which delayed antibiotics were compared to antibiotics used immediately or no antibiotics. Outcomes measured included clinical outcomes, antibiotic use and patient satisfaction. DATA COLLECTION AND ANALYSIS: Data were collected and analysed by three review authors. MAIN RESULTS: Nine trials were eligible on the basis of design and relevant outcomes. For most clinical outcomes there was no difference between delayed, immediate and no antibiotics. Antibiotics prescribed immediately were more effective than delayed for fever, pain and malaise in some studies of patients with acute otitis media and sore throat but for other studies there was no difference. There was no difference for the common cold and bronchitis. Delaying antibiotic prescriptions reduced antibiotic use, and in three studies, reduced patient satisfaction compared to immediate antibiotics. In the other two studies comparing delayed and immediate antibiotics measuring satisfaction, there was no difference. Two studies also included a 'no antibiotics' arm for bronchitis and sore throat: there was no difference in symptom resolution nor patient satisfaction from antibiotic delay. In one study, but not the other, antibiotic use was significantly decreased with no, rather than delayed, antibiotics. AUTHORS' CONCLUSIONS: For most clinical outcomes there is no difference between the strategies. Immediate antibiotics was the strategy most likely to provide the best clinical outcomes in patients with sore throat and otitis media. Delaying or avoiding antibiotics, rather than providing them immediately, reduces antibiotic use for acute respiratory infections. Delay also reduced patient satisfaction in three trials, compared to immediate antibiotics with no difference in two other trials. Delaying antibiotics seems to have little advantage over avoiding them altogether where it is safe to do so.

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Int J Antimicrob Agents. 2007 Jul;30(1):52-9. Epub 2007 May 18.
Levofloxacin 500 mg once daily versus cefuroxime 250 mg twice daily in patients with acute exacerbations of chronic obstructive bronchitis: clinical efficacy and exacerbation-free interval.
Petitpretz P, Choné C, Trémolières F; Investigator Study Group.
Hôpital André Mignot, Le Chesnay, France. ppetitpretz@ch-versailles.fr

The long-term outcome time to relapse determined as the exacerbation-free interval (EFI) has been proposed as a standard measure for comparing the efficacy of antimicrobial therapies in acute exacerbation of chronic obstructive bronchitis (AECOB). In this 6-month, randomised, open-label study, the efficacy of 10 days of oral levofloxacin 500 mg once daily or cefuroxime 250 mg twice daily was evaluated in 689 well-defined patients experiencing AECOB episodes. In the clinically evaluable per-protocol (PPc) population and the modified intent-to-treat population, the clinical cure rates at test of cure were, respectively, 94.6% for levofloxacin versus 93.8% for cefuroxime (0.8% difference, 95% confidence interval (CI) -3.2 to 4.8) and 94.5% for levofloxacin versus 92.2% for cefuroxime (2.3% difference, 95% CI -1.8 to 6.2), whilst the probability that 25% of patients would relapse during follow-up was reached within 93 days for levofloxacin compared with 81 days for cefuroxime in the PPc population (P=0.756). A multivariate analysis revealed that only congestive heart failure and number of AECOB episodes in the previous 12 months were predictive of relapse. Safety was comparable in the two treatment groups, with possibly related treatment-emergent adverse events occurring in 5.0% and 2.9% of subjects in the levofloxacin and cefuroxime groups, respectively. In addition to demonstrating the non-inferiority of levofloxacin compared with cefuroxime in AECOB, the data from this study raise the question of whether EFI is a useful discriminative endpoint for comparing antimicrobial therapies.

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MMW Fortschr Med. 2007 Jun 28;149(11):69-74.
[Treatment of acute bronchitis in children and adolescents. Non-interventional postmarketing surveillance study confirms the benefit and safety of a syrup made of extracts from thyme and ivy leaves]
[Article in German]
Marzian O.
Facharzt für Kinderheilkunde, Hannover.

OBJECTIVE: For the investigation of the benefits and tolerability of a syrup made of extracts from thyme and ivy (Bronchipret Saft) in children and adolescents (ages: 2-17 years) with acute bronchitis and productive cough, a non-interventional postmarketing surveillance study was carried out. METHODS: Prerequisites for participation in the surveillance study were productive cough for a maximum of two days, at least ten coughing fits per day prior to the initiation of treatment (estimation of the parents or adolescent) and a Bronchitis Severity Score (BSS) of at least five points. The primary outcome measure was the change in the clinical symptoms based on the BSS. Treatment was carried out using age-appropriate dosages prescribed by the doctor on a case-by-case basis in accordance with the summary of product characteristics. Documentation of the course of treatment for the surveillance study was to be taken on treatment days 0, 4 and 10. RESULTS: For the descriptive, statistical evaluation of the surveillance study, the data from 1234 children and adolescents (623 boys and 611 girls) in the age groups < 2 years (N = 12), 2-5 years (N = 372), 6-11 years (N = 438) and 12-17 years (N = 412) were available. The correspondence of the dosages to the age-specific recommendations of the valid summary of product characteristics varied from 81.7% to 93.9% in the different age groups. The average BSS value decreased from 8.8 points to 4.8 on treatment day 4 and to 1.3 points after about ten days of treatment. Compared to that of the initial examination, the number of documented coughing fits had decreased on the average by 18.7 (81.3%) on day 10. The responder rates of the various age groups were 92.0% to 96.5%. The tolerability was rated as very good to good by the physicians in 96.5% of the cases. Two female patients had temporary, not serious adverse drug reactions (stomache ache, mild nausea). CONCLUSION: Acute bronchitis with productive cough in (young) children and adolescents can be treated safely and effectively with the thyme and ivy syrup. A ten-day treatment using age-appropriate dosages led to a clear improvement in the symptoms or cure with very good tolerability.

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Expert Rev Anti Infect Ther. 2007 Apr;5(2):185-98.
Faropenem: review of a new oral penem.
Schurek KN, Wiebe R, Karlowsky JA, Rubinstein E, Hoban DJ, Zhanel GG.
Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada. kristen@cmdr.ubc.ca

Faropenem medoxomil is a new orally administered penem antibiotic. Its chiral tetrahydrofuran substituent at position C2 is responsible for its improved chemical stability and reduced CNS effects, compared with imipenem. Faropenem demonstrates broad-spectrum in vitro antimicrobial activity against many Gram-positive and -negative aerobes and anaerobes, and is resistant to hydrolysis by nearly all beta-lactamases, including extended-spectrum beta-lactamases and AmpC beta-lactamases. However, faropenem is not active against methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, Pseudomonas aeruginosa or Stenotrophomonas maltophilia. Prospective, multicenter, randomized, double-blind, comparative (not vs placebo) clinical trials of acute bacterial sinusitis (ABS), acute exacerbations of chronic bronchitis (AECB), community-acquired pneumonia (CAP) and uncomplicated skin and skin structure infections (uSSSIs) have demonstrated that faropenem medoxomil has equivalent efficacy and safety compared with cefuroxime, clarithromycin, azithromycin, amoxicillin, cefpodoxime and amoxicillin-clavulanate. The evidence supports faropenem medoxomil as a promising new oral beta-lactam with proven efficacy and safety for the treatment of a variety of community-acquired infections. However, the US FDA recently rejected faropenem for all four indications stating that the clinical trials in ABS and AECB should have been performed versus a placebo. In the CAP studies, the FDA stated that they could not be certain of the validity of the study population actually having the disease and for uSSSI, the FDA stated that only a single trial was not adequate evidence of efficacy for this indication.

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Diagn Microbiol Infect Dis. 2007 Mar;57(3 Suppl):S31-8.
Role of oral extended-spectrum cephems in the treatment of acute exacerbation of chronic bronchitis.
Anzueto A, Bishai WR, Pottumarthy S.
University of Texas Health Science Center and South Texas Veterans Healthcare System, San Antonio, TX 78284, USA.

Risk stratification is the recommended approach for treatment of acute exacerbation of chronic bronchitis (AECB) to optimize the chances of clinical success. The suggested oral therapy for "simple or uncomplicated" AECB, which is predominantly a result of infection due to Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae, includes advanced macrolides and 2nd- or 3rd-generation cephalosporins, in addition to the older 1st-line agents (aminopenicillins, doxycycline, trimethoprim/sulfamethoxazole, and erythromycin). In light of increasing resistance of H. influenzae and S. pneumoniae to the older agents, the specific directed structural modification of the cephalosporin nucleus resulted in the development of extended-spectrum 3rd-generation oral cephems with enhanced beta-lactamase stability and improved activity against Gram-positive pathogens (penicillin-susceptible S. pneumoniae and oxacillin-susceptible Staphylococcus aureus). Analysis of results of double-blind randomized clinical trials assessing efficacy of the extended-spectrum oral cephems published since 2000 demonstrates that both cefdinir and cefditoren have similar point estimates of success in comparison to their comparators (cefuroxime, cefprozil, or Locarbacef), when either the clinical cure or the bacteriologic response was analyzed. Thus, oral extended-spectrum 3rd-generation cephems, which retain antimicrobial efficacy against the traditional respiratory pathogens despite changing resistance patterns, offer excellent coverage against the key pathogens involved in simple or uncomplicated AECB.

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Curr Med Res Opin. 2007 Feb;23(2):459-66.
Role for 5-day, once-daily extended-release clarithromycin in acute bacterial exacerbation of chronic bronchitis.
Gotfried M, Busman TA, Norris S, Notario GF.
University of Arizona, Pulmonary Associates, Phoenix, AZ 85020, USA. mgotfried@aol.com

BACKGROUND: Clarithromycin is commonly dosed for 7 or more days in patients with acute bacterial exacerbation of chronic bronchitis (ABECB). Studies with other antibiotics have shown equivalent efficacy, reduced/similar frequency of adverse events, improved adherence and patient satisfaction, and lower treatment costs with a shorter treatment course. PATIENTS AND METHODS: The study population was derived from two multicenter, randomized, double-blind (North America)/single-blind (France) comparative trials in which outpatients at least 35 years old with a presumptive diagnosis of obstructive ABECB were randomized to receive clarithromycin extended-release (ER) 1000 mg once daily for 5 days or a comparator agent--clarithromycin immediate-release (IR) 500 mg twice daily for 7 days (in North America) or telithromycin 800 mg once daily for 5 days (in France). RESULTS: A total of 818 patients were randomized (411 to clarithromycin ER and 407 to a comparator agent). The clinical cure rate in clinically evaluable patients at the follow-up visit was 90% each for the clarithromycin ER group (318/353) and the comparator group (318/355). The patient bacteriological cure rate and the overall target pathogen eradication rate in clinically and bacteriologically evaluable patients were each 92% for the clarithromycin ER group (155/168 and 189/205, respectively) and 93% for the comparator group (147/158 and 183/197, respectively) at the follow-up visit. The study drugs were generally well tolerated, with < 2% of patients discontinuing their treatment prematurely due to a drug-related adverse event. The incidence of drug-related adverse events was 18% (73/411) in the clarithromycin ER group and 24% (97/407) in the comparator group. Clarithromycin ER-treated patients reported statistically significantly fewer episodes of abdominal pain than did patients treated with a comparator agent (0.2% vs. 1.7%, respectively; p = 0.037). This combined analysis is limited by differing blinding methods, comparator agents, and their duration of administration. Furthermore, many patients were excluded from the clinically and bacteriologically evaluable group due to lack of a pretreatment target pathogen. CONCLUSION: A once daily, 5-day clarithromycin ER regimen appears to be a suitable choice for treating patients with ABECB.

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Curr Med Res Opin. 2007 Feb;23(2):323-31.
Treatment of acute bronchitis with a liquid herbal drug preparation from Pelargonium sidoides (EPs 7630): a randomised, double-blind, placebo-controlled, multicentre study.
Matthys H, Heger M.
Department of Pneumology, University Hospital Freiburg, Freiburg, Germany. hmatthys@t-online.de

OBJECTIVE: The objective of this study was to examine the efficacy and safety of a herbal drug preparation from the roots of Pelargonium sidoides (EPs 7630) in the treatment of acute bronchitis in adults outside the very restricted indication for an antibiotic therapy. Research design and methods: This was a randomised, double-blind, placebo-controlled, multicentre study with 217 patients aged between 18 and 66 years with acute bronchitis. One hundred and eight patients were given 30 drops of EPs 7630-solution three times daily and 109 patients 30 drops of placebo three times daily for a period of 7 days. MAIN OUTCOME MEASURES: Individual change in bronchitis symptom score (BSS) over 7 days, individual symptoms, patient satisfaction and adverse events. RESULTS: After 7 days of treatment, the BSS decreased by 7.6 +/- 2.2 points in the EPs 7630 group and by 5.3 +/- 3.2 points in the placebo group. The 95% confidence interval for the difference between the effects was calculated as 1.6-3.1, showing highly significant superiority for the EPs 7630 treatment (p < 0.0001). There were also marked improvements in the individual symptoms, which are the components of BSS - cough, chest pain on coughing, sputum, rales/rhonchi and dyspnoea - in the treatment group, relative to placebo. Patient satisfaction was very good. Only minor and transitory adverse events were recorded. No serious adverse events occurred during the trial. CONCLUSION: EPs 7630-solution is a well tolerated and effective treatment for acute bronchitis in adults outside the very restricted indication for an antibiotic therapy.

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Expert Rev Anti Infect Ther. 2007 Feb;5(1):29-43.
Cefdinir: an oral cephalosporin for the treatment of respiratory tract infections and skin and skin structure infections.
Sader HS, Jones RN.
JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, Iowa 52317, USA. helio-sader@jmilabs.com

Cefdinir is an oral third-generation cephalosporin (also known as an advanced-spectrum or generation cephem) with good in vitro activity against the pathogens responsible for community-acquired respiratory tract infections and uncomplicated skin and skin structure infections. The drug distributes very well in respiratory tract tissues and fluids, as well as skin blisters and ear fluids; its pharmacokinetic profile allows once- or twice-daily administration. Oral cefdinir 300 mg twice daily or 600 mg once daily in adults and adolescents, or 14 mg/kg/day in one or two daily doses in pediatric patients, administered for 5 or 10 days, has shown good clinical and bacteriological efficacy, at least equivalent to that of other oral agents in randomized controlled trials conducted in patients with community-acquired pneumonia, acute bacterial exacerbation of chronic bronchitis, sinusitis, acute otitis media, pharyngitis and uncomplicated skin and skin structure infections. Cefdinir is well tolerated and the oral suspension has shown superior taste or palatability over other comparator oral antimicrobial agents. Thus, cefdinir continues to represent an important cephalosporin option for the treatment of adult, adolescent and pediatric patients with mild or moderate respiratory tract or cutaneous infections, especially in areas with elevated rates of beta-lactamase production in Haemophilus influenzae and where resistance to other commonly used agents has emerged (e.g., macrolides, penicillins, tetracyclines, fluoroquinolones and trimethoprim-sulfamethoxazole).

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Arch Bronconeumol. 2007 Jan;43(1):22-8.
[Clinical efficacy of moxifloxacin in the treatment of exacerbations of chronic bronchitis: a systematic review and meta-analysis]
[Article in Spanish]
Miravitlles M, Molina J, Brosa M.
Servei de Pneumologia, Institut Clinic del Torax (IDIBAPS), Hospital Clinic, Barcelona, Espana. marcm@clinic.ub.es

OBJECTIVE: As the research undertaken to date on the efficacy of the new antibiotics in the treatment of exacerbations of chronic bronchitis has taken the form of trials designed to demonstrate equivalence, we have no data on the advantages associated with the use of these new drugs with greater bactericidal activity. Our objective was to compare the clinical efficacy of moxifloxacin to that of the antibiotic regimens routinely used to treat such exacerbations by a systematic review of the literature and a meta-analysis. METHODS: A manual and electronic search was performed to identify all clinical trials carried out between January 1997 and July 2005 to compare moxifloxacin and the antibiotics that are currently the first line treatment for exacerbations of chronic bronchitis. Once it had been established that the designs of the trials included were acceptable, a meta-analysis of clinical outcomes was performed. RESULTS: Of the 45 studies identified, 9 met the inclusion criteria. Of these, 5 were double-blind randomized trials and 4 were randomized open trials. The 9 trials comprised a total of 3905 patients. The aggregate standardized mean difference in clinical success rate was 1.5% (95% confidence interval, -0.4 to 3.4%). Bacterial eradication rates ranged from 68.4% to 96% for the standard regimens, and from 87.7% to 96% for moxifloxacin. No intergroup differences in the percentages of patients lost to follow-up were observed in any of the studies. CONCLUSIONS: Although the trials reviewed were designed to demonstrate equivalence, meta-analysis revealed that the clinical success rate achieved with moxifloxacin tended to be higher than that obtained in the groups that received standard antibiotic treatment.

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Int J Antimicrob Agents. 2007 Jan;29(1):56-61.
Efficacy and safety of 3-day azithromycin versus 5-day moxifloxacin for the treatment of acute bacterial exacerbations of chronic bronchitis.
Zervos M, Martinez FJ, Amsden GW, Rothermel CD, Treadway G.
Henry Ford Hospital, Detroit, MI, USA.

Antibiotic therapy is of clinical benefit in certain patients with acute exacerbations of chronic bronchitis (AECB). In this randomised, investigator-blinded, multicentre trial, azithromycin (500mg once a day (qd) for 3 days) was compared with moxifloxacin (400mg qd for 5 days) for the treatment of outpatients with AECB (forced expiratory volume in 1s (FEV(1)) >35%). Of 342 patients randomised to either treatment, 169 received azithromycin and 173 received moxifloxacin. The mean age in the azithromycin and moxifloxacin groups was 56.4 years and 55.5 years, respectively. In the intent-to-treat analysis, clinical success rates for azithromycin and moxifloxacin were comparable at Days 10-12 (90% versus 90%, respectively) and Days 22-26 (81% versus 82%, respectively). Among patients who were culture-positive at baseline for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis or Haemophilus parainfluenzae, clinical efficacy for azithromycin versus moxifloxacin at Days 10-12 was 93% versus 84%, respectively, and at Days 22-26 it was 89% versus 73%, respectively. The incidence of at least one treatment-related adverse event (AE) in the azithromycin and moxifloxacin groups was 18.3% and 19.1%, respectively. The most common AEs were diarrhoea, nausea, abdominal pain and vaginitis. Most treatment-related AEs were of mild or moderate severity, with no serious treatment-related AEs. One subject in the moxifloxacin group discontinued treatment owing to a treatment-related AE (precordial pain and dry throat). Compliance with both regimens was >90%. Three-day azithromycin and 5-day moxifloxacin demonstrate comparable efficacy and safety for the treatment of AECB in outpatients.

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Thorax. 2007 Jan;62(1):80-84. Epub 2006 Nov 14.
Outcomes in children treated for persistent bacterial bronchitis.
Donnelly D, Critchlow A, Everard ML.
Paediatric Respiratory Unit, Sheffield Children's Hospital, Western Bank, Sheffield S10 2TH, UK. m.l.everard@sheffield.ac.uk.

BACKGROUND: Persistent bacterial bronchitis (PBB) seems to be under-recognised and often misdiagnosed as asthma. In the absence of published data relating to the management and outcomes in this patient group, a review of the outcomes of patients with PBB attending a paediatric respiratory clinic was undertaken. METHODS: A retrospective chart review was undertaken of 81 patients in whom a diagnosis of PBB had been made. Diagnosis was based on the standard criterion of a persistent, wet cough for >1 month that resolves with appropriate antibiotic treatment. RESULTS: The most common reason for referral was a persistent cough or difficult asthma. In most of the patients, symptoms started before the age of 2 years, and had been present for >1 year in 59% of patients. At referral, 59% of patients were receiving asthma treatment and 11% antibiotics. Haemophilus influenzae and Streptococcus pneumoniae were the most commonly isolated organisms. Over half of the patients were completely symptom free after two courses of antibiotics. Only 13% of patients required >/=6 courses of antibiotics. CONCLUSION: PBB is often misdiagnosed as asthma, although the two conditions may coexist. In addition to eliminating a persistent cough, treatment may also prevent progression to bronchiectasis. Further research relating to both diagnosis and treatment is urgently required.

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Phytomedicine. 2006 Dec 19; [Epub ahead of print]
EPs((R)) 7630-solution - an effective therapeutic option in acute and exacerbating bronchitis.
Matthys H, Heger M.
Medical Dir. emeritus, Department of Pneumology, University Hospital Freiburg, Freiburg, Germany.

Acute bronchitis is one of the most common diagnoses in ambulatory care medicine. Although the benefit of antibiotics for acute bronchitis, which is mostly virally induced, is disputed, they are often prescribed. A therapeutic option for respiratory tract infections that do not fall within the strict indication range for antibiotic administration is the liquid herbal drug preparation from the roots of Pelargonium sidoides, EPs((R)) 7630 (Umckaloabo((R))), which has been tested against placebo in double-blind clinical trials. EPs((R)) 7630 has both antibacterial and immuno-modulating properties. The efficacy and tolerability of EPs((R)) 7630 was investigated in a prospective, open, multicentric outcomes study with 205 patients suffering from acute bronchitis or acute exacerbation of chronic bronchitis. The main outcome measure was the change in the total score of five symptoms typical for bronchitis (cough, expectoration, wheezing/whistling on expiration, chest pain during coughing, and dyspnoea), which were each rated using a 5-point scale (from 0=not present to 4=extremely pronounced). Further symptoms (hoarseness, headache, aching limbs and fatigue) were assessed using a four-point scale (from 0=not present to 3=very pronounced). The total score of the typical bronchitis symptoms amounted to 6.1+/-2.8 points on average at the start of treatment and decreased by 3.3+/-3.8 points to 2.8+/-2.6 points by the final examination on day 7. About 60.5% of the patients assessed their health condition at the end of the study as much improved or free from symptoms. The onset of action appeared after two days on average. Adverse events occurred in a total of 16 patients. There were no serious adverse events. Altogether, 78% of the patients were satisfied or very satisfied with the treatment.

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Phytomedicine. 2006 Dec 19; [Epub ahead of print]
Treatment effect and safety of EPs((R)) 7630-solution in acute bronchitis in childhood: Report of a multicentre observational study.
Haidvogl M, Heger M.
Ludwig Boltzmann-Institute for Homoeopathy, Graz, Austria.

An open post-marketing surveillance study was conducted to examine the treatment effect and safety of EPs((R)) 7630-solution in the treatment of acute bronchitis in children. This study included a total of 742 children (aged between 0 and 12 years) with acute bronchitis (83.4%) or acute exacerbations of chronic bronchitis (14.3%), who were treated with different doses of the herbal drug for up to 14 days. Five bronchitis specific symptoms (BSS) were summed up to give an overall measure of disease severity. Non-specific disease symptoms (loss of appetite, diarrhoea, headache, vomiting, and fever) were also recorded, together with adverse events and overall ratings of efficacy and tolerability. The overall BSS score decreased during treatment from 6.0+/-3.0 points at baseline to 2.7+/-2.5 points after 7 days and to 1.4+/-2.1 points after 14 days. Remission or improvement in at least 80% of patients was recorded for all the individual component symptoms. The proportion of patients suffering from non-specific symptoms also substantially improved during treatment. For example, loss of appetite was present in 65.8% of patients at study begin, but only in 27.6% at the time point of last observation visit. In 88.3% of cases, the responsible physician rated the treatment as successful. Adverse events were minor and transitory. In conclusion, EPs((R)) 7630-solution was shown to be a safe and an effective treatment option for acute bronchitis or acute exacerbations of chronic bronchitis in children.

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Phytomedicine. 2006 Dec 19; [Epub ahead of print]
Pelargonium sidoides preparation (EPs((R)) 7630) in the treatment of acute bronchitis in adults and children.
Matthys H, Kamin W, Funk P, Heger M.
Department of Pneumology, University Hospital, Freiburg, Germany.

Acute bronchitis, although mostly caused by viral infections, is commonly treated with antibiotics. As antibiotics should only be prescribed upon strict indication, treatment options like a liquid herbal drug preparation from the roots of Pelargonium sidoides (EPs((R)) 7630) gain more and more interest. To evaluate the efficacy and safety of treatment with EPs((R)) 7630 in patients with acute bronchitis, a multi-centre, prospective, open observational study was conducted in 440 study sites located in Germany. A total of 2099 patients aged 0-93 years with productive cough for less than six days without indication for treatment with antibiotics were given EPs((R)) 7630-solution in an age-dependent dosage for 14 days. The primary outcome criterion was the mean change of the Bronchitis Severity Score (BSS: cough, sputum, rales/rhonchi, chest pain at cough, dyspnoea) from baseline to patient's individual last observation. During treatment, the mean BSS of all patients decreased from 7.1+/-2.9 points at baseline to 1.0+/-1.9 points at patients' individual last visit. Subgroup analysis for children showed a decrease of mean BSS from 6.3+/-2.8 points to 0.9+/-1.8 points and analysis of children younger than three years showed a decrease of mean BSS from 5.2+/-2.5 points to 1.2+/-2.1 points. Adverse events occurred in 26/2099 (1.2%) patients. Serious adverse events were not reported. In conclusion, EPs((R)) 7630 is an effective and well tolerated treatment of acute bronchitis in adults, children and infants outside the strict indication for antibiotic treatment.

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Treat Respir Med. 2006;5(6):437-465.
A Review of New Fluoroquinolones : Focus on their Use in Respiratory Tract Infections.
Zhanel GG, Fontaine S, Adam H, Schurek K, Mayer M, Noreddin AM, Gin AS, Rubinstein E, Hoban DJ.
Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, CanadaDepartment of Clinical Microbiology, Health Sciences Centre, Winnipeg, Manitoba, CanadaDepartment of Medicine, Health Sciences Centre, Winnipeg, Manitoba, Canada.

The new respiratory fluoroquinolones (gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin, and on the horizon, garenoxacin) offer many improved qualities over older agents such as ciprofloxacin. These include retaining excellent activity against Gram-negative bacilli, with improved Gram-positive activity (including Streptococcus pneumoniae and Staphylococcus aureus). In addition, gatifloxacin, moxifloxacin and garenoxacin all demonstrate increased anaerobic activity (including activity against Bacteroides fragilis). The new fluoroquinolones possess greater bioavailability and longer serum half-lives compared with ciprofloxacin. The new fluoroquinolones allow for once-daily administration, which may improve patient adherence. The high bioavailability allows for rapid step down from intravenous administration to oral therapy, minimizing unnecessary hospitalization, which may decrease costs and improve quality of life of patients. Clinical trials involving the treatment of community-acquired respiratory infections (acute exacerbations of chronic bronchitis, acute sinusitis, and community-acquired pneumonia) demonstrate high bacterial eradication rates and clinical cure rates. In the treatment of community-acquired respiratory tract infections, the various new fluoroquinolones appear to be comparable to each other, but may be more effective than macrolide or cephalosporin-based regimens. However, additional data are required before it can be emphatically stated that the new fluoroquinolones as a class are responsible for better outcomes than comparators in community-acquired respiratory infections. Gemifloxacin (except for higher rates of hypersensitivity), levofloxacin, and moxifloxacin have relatively mild adverse effects that are more or less comparable to ciprofloxacin. In our opinion, gatifloxacin should not be used, due to glucose alterations which may be serious. Although all new fluoroquinolones react with metal ion-containing drugs (antacids), other drug interactions are relatively mild compared with ciprofloxacin. The new fluoroquinolones gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin have much to offer in terms of bacterial eradication, including activity against resistant respiratory pathogens such as penicillin-resistant, macrolide-resistant, and multidrug-resistant S. pneumoniae. However, ciprofloxacin-resistant organisms, including ciprofloxacin-resistant S. pneumoniae, are becoming more prevalent, thus prudent use must be exercised when prescribing these valuable agents.

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Cochrane Database Syst Rev. 2006 Oct 18;(4):CD001726.
Beta2-agonists for acute bronchitis.
Smucny J, Becker L, Glazier R.
SUNY Upstate Medical University, Department of Family Medicine, Suite 200, 475 Irving Ave, Syracuse, NY 13210, USA. smucnyj@upstate.edu

BACKGROUND: There are no clearly effective treatments for the cough of acute bronchitis, and beta2-agonists are often prescribed, perhaps because clinicians suspect many patients also have reversible airflow restriction contributing to the symptoms. OBJECTIVES: To determine whether beta2-agonists improve symptoms of acute bronchitis in patients who do not have underlying pulmonary disease. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2005), MEDLINE (January 1966 to November 2005) and EMBASE (1974 to November 2005). SELECTION CRITERIA: Trials in which patients (adults or children over two years of age) who were diagnosed with acute bronchitis or acute cough (without known pulmonary disease and without other cause) were randomized to beta2-agonist versus placebo, no treatment or alternative treatment. DATA COLLECTION AND ANALYSIS: Three authors independently selected outcomes and evaluated trial quality while blinded to study results, they then extracted data. Trials in children and in adults were analyzed separately. MAIN RESULTS: Two trials in children (n = 109) with acute cough and no evidence of airway obstruction did not find any benefits from beta2-agonists. Combined data did not show a significant difference in daily cough scores between patients given oral beta2-agonists and those in the control groups. Five trials in adults (n = 418) with acute cough or acute bronchitis had mixed results but overall summary statistics did not reveal any significant benefits from oral (three trials) nor inhaled (two trials) beta2-agonists. There were no significant differences in daily cough scores nor in the number of patients still coughing after seven days (control rate 73%; relative risks (RR) 0.77, 95% CI 0.54 to 1.09). Subgroups of patients with evidence of airflow limitation had lower symptom scores if given beta2-agonists, in one trial. Furthermore, the trials that did note quicker resolution of cough in patients given beta2-agonists were those that had a higher proportion of patients with wheezing at baseline. Patients given beta2-agonists were more likely to report tremor, shakiness or nervousness than patients in the control groups (for trials in children: control rate 0%; RR 6.76, 95% CI 0.86 to 53.12; number needed to harm (NNH) 9, 95% CI 5 to 100; for trials in adults: control rate 11%; RR 7.94, 95% CI 1.17 to 53.94; NNH 2.3, 95% CI 2 to 3). AUTHORS' CONCLUSIONS: There is no evidence to support the use of beta2-agonists in children with acute cough who do not have evidence of airflow obstruction. There is also little evidence that the routine use of beta2-agonists is helpful for adults with acute cough. These agents may reduce symptoms, including cough, in patients with evidence of airflow obstruction. However, this potential benefit is not well-supported by the available data and must be weighed against the adverse effects associated with beta2-agonists.
  
Previous Bronchitis Research: 2002-2006   
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