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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.
Strep Throat Research:
2002-2006
Am Fam Physician. 2006 Sep 15;74(6):956-66.
Guidelines for the use of antibiotics in acute upper respiratory
tract infections.
Wong DM, Blumberg DA, Lowe LG.
Arrowhead Regional Medical Center Family Medicine Residency Program, Colton,
California 92324, USA.
To help physicians with the appropriate use of antibiotics in children and
adults with upper respiratory tract infection, a multidisciplinary team
evaluated existing guidelines and summarized key practice points. Acute otitis
media in children should be diagnosed only if there is abrupt onset, signs of
middle ear effusion, and symptoms of inflammation. A period of observation
without immediate use of antibiotics is an option for certain children. In
patients with sinus infection, acute bacterial rhinosinusitis should be
diagnosed and treated with antibiotics only if symptoms have not improved after
10 days or have worsened after five to seven days. In patients with sore throat,
a diagnosis of group A beta-hemolytic streptococcus pharyngitis generally
requires confirmation with rapid antigen testing, although other guidelines
allow for empiric therapy if a validated clinical rule suggests a high
likelihood of infection. Acute bronchitis in otherwise healthy adults should not
be treated with antibiotics; delayed prescriptions may help ease patient fears
and simultaneously reduce inappropriate use of antibiotics.
-----
Pediatr Infect Dis J. 2006 Sep;25(9):761-7.
Treatment of streptococcal pharyngitis with once-daily compared
with twice-daily amoxicillin: a noninferiority trial.
Clegg HW, Ryan AG, Dallas SD, Kaplan EL, Johnson DR, Norton HJ, Roddey OF,
Martin ES, Swetenburg RL, Koonce EW, Felkner MM, Giftos PM.
Eastover Pediatrics, Charlotte, NC 28204, USA. hwclegg@novanthealth.org
BACKGROUND: Two relatively small previous studies comparing once-daily
amoxicillin with conventional therapy for group A streptococcal (GAS)
pharyngitis reported similar rates of bacteriologic success for each treatment
group. The purpose of this study was to further evaluate once-daily amoxicillin
for GAS pharyngitis in a larger study. METHODS: In a single pediatric practice,
from October through May for 2 consecutive years (2001-2003), we recruited
children 3 to 18 years of age who had symptoms and signs suggestive of GAS
pharyngitis. Patients with a positive rapid test for GAS were stratified by
weight (<40 kg or >or=40 kg) and then randomly assigned to receive once-daily
(750 mg or 1000 mg) or twice-daily (2 doses of 375 mg or 500 mg) amoxicillin for
10 days. We determined bacteriologic failure rates for GAS in the pharynx from
subsequent swabs taken at 14 to 21 (visit 2) and 28 to 35 (visit 3) days after
treatment initiation. We conducted a randomized, controlled,
investigator-blinded, noninferiority trial to evaluate whether amoxicillin given
once daily would have a bacteriologic failure rate no worse than that of
amoxicillin given twice daily within a prespecified margin of 10%. GAS isolates
were characterized to distinguish bacteriologic failures from new acquisitions.
Adverse events were described and adherence was evaluated by review of returned
daily logs and dosage bottles. RESULTS: Of 2139 potential study patients during
the 2-year period, we enrolled 652 patients, 326 into each treatment group.
Children in the 2 groups were comparable with respect to all demographic and
clinical characteristics except that children <40 kg more often presented with
rash in each treatment group. At visit 2, failure rates were 20.1% (59 of 294)
for the once-daily group and 15.5% (46 of 296) for the twice-daily group
(difference, 4.53%; 90% confidence interval [CI], -0.6 to 9.7). At visit 3,
failure rates were 2.8% (6 of 216) for the once-daily group and 7.1% (16 of 225)
for the twice-daily group (difference, -4.33; 90% CI, -7.7 to -1.0).
Gastrointestinal and other adverse events occurred in the once-daily treatment
group with a frequency comparable to that in the twice-daily treatment group.
Presumed allergic reactions occurred in 0.9% (6 of 635). More than 95% (516 of
541) of patients complied with 10 days of therapy with no significant
differences between groups. CONCLUSIONS: We conclude that amoxicillin given once
daily is not inferior to amoxicillin given twice daily. Gastrointestinal and
other events did not occur significantly more often in the once-daily treatment
group. From the data in this large, investigator-blinded, controlled study,
once-daily amoxicillin appears to be a suitable regimen for treatment of GAS
pharyngitis.
-----
Clin Pediatr (Phila). 2006 Sep;45(7):641-8.
Comparative tolerability, safety and efficacy of tablet
formulations of twice-daily clarithromycin 250 mg versus once-daily
extended-release clarithromycin 500 mg in pediatric and adolescent patients.
Block SL.
201 South 5th Street, Bardstown, KY 40004, USA.
Clarithromycin is widely used to treat respiratory tract and superficial skin
infections in pediatric and adult populations. Using clinical endpoints and
7-day therapy, we compared the efficacy of clarithromycin 250 mg tablets given
twice daily versus clarithromycin 500 mg extendedrelease tablets given once
daily in ambulatory children and adolescents 6 to 16 years old. Of the 199
evaluable patients, 124 were infected with group A streptococcal pharyngitis, 39
with sinusitis, 21 with ambulatory pneumonia, and 15 with superficial skin
infections. The overall cure rate exceeded 90% for each treatment group.
Discontinuation rates and adverse events were 4.5% and 24.6%, respectively.
-----
Semin Pediatr Infect Dis. 2006 Jul;17(3):140-8.
Group A streptococcus.
Martin JM, Green M.
Department of Pediatrics, University of Pittsburgh School of Medicine, Division
of Infectious Diseases, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213,
USA. Judy.martin@chp.edu
Group A streptococci (GAS) are gram positive cocci that can be divided into more
than 100 M-serotypes or emm types based on their M proteins. Their virulence is
related directly to the M protein on the cell surface that inhibits phagocytosis.
Although it is more commonly thought of in the context of causing clinical
illness, Streptococcus pyogenes can colonize the pharynx and skin. Infections
due to GAS include pharyngitis, impetigo, ecthyma, erysipelas, and cellulitis.
These infections, as well as the manifestations of invasive disease including
streptococcal toxic shock syndrome and necrotizing fasciitis, will be reviewed
in this article. Also included will be the nonsuppurative complications of GAS
infections, acute rheumatic fever and post streptococcal glomerular nephritis.
GAS is an important cause of infections in children in both the ambulatory and
hospital settings. Current efforts aimed at the development of a vaccine are
warranted but remain in preliminary stages at this time.
-----
J Fam Pract. 2006 Jul;Suppl:S9-16.
Considerations in the use of antibiotics for streptococcal
pharyngitis.
Brunton S, Pichichero M.
Cabarrus Family Medicine Residency Concord, NC, USA.
Microbiologic testing is recommended to diagnose GABHS pharyngitis and is
required to maximize the selection of patients at highest risk of complications
from true infection. The primary goal of therapy is eradication of GABHS.
Penicillin has been the first-line treatment of choice for nonallergic patients;
yet, there may be reason to reexamine the role of penicillin since there are now
considerable data from clinical trials, pooled multicenter studies, and
meta-analyses demonstrating frequent bacteriologic and clinical failure. While
the contribution of pathogen resistance remains unclear, evolving evidence
suggests that these failures also may be related to bacterial coaggregation or
copathogenicity; GABHS reinfection; antibiotic nonadherence or subtherapeutic
drug levels; penicillin tolerance; or blunting of an effective immune response.
At the same time, some clinical evidence suggests that treatment failure with
some cephalosporins may occur less frequently than with penicillin. Although
cephalosporins are generally more expensive than oral penicillin, the benefits
of cephalosporins include activity against BLPB and evolving data that support
less frequent dosing than penicillin. Consequently, a reassessment of the role
of cephalosporins in the treatment of pharyngitis may be appropriate.
-----
Eur J Clin Microbiol Infect Dis. 2006 Jun;25(6):354-64.
Comparison of European and U.S. results for cephalosporin versus
penicillin treatment of group A streptococcal tonsillopharyngitis.
Pichichero M, Casey J.
University of Rochester Medical Center, Elmwood Pediatric Group, 601 Elmwood
Avenue, PO Box 672, Rochester, NY 14642, USA. michael_pichichero@urmc.rochester.edu
The outcome of cephalosporin versus penicillin treatment of group A
streptococcal tonsillopharyngitis may differ between Europe and the USA. In the
present study, Medline, Embase, reference lists, and abstract searches were used
to identify randomized, controlled trials of cephalosporin versus penicillin
treatment of group A streptococcal (GAS) tonsillopharyngitis. The outcomes of
interest were bacteriologic and clinical cure rates from investigations
conducted in Europe versus those conducted in the USA. Forty-seven trials
involving 11,426 patients were included in the meta-analyses. For the comparison
of 10 days of treatment with cephalosporins versus 10 days of treatment with
penicillin, there were ten European and 25 U.S. trials, all involving pediatric
subjects. The overall odds ratio (OR) favored cephalosporins more strongly in
bacteriologic cure rate in Europe (OR=4.27, p<0.00001) than in the USA (OR=2.70,
p<0.00001). Studies of 4-5 days of cephalosporin treatment versus 10 days of
penicillin treatment were also analyzed. For nine European trials, the OR
significantly favored cephalosporins (OR=1.30, p=0.03) in bacteriologic cure
rates, but not as strongly as in the USA, (OR=2.41, p<0.00001). When results for
4-5 days of cephalosporin treatment were divided into pediatric versus adult
populations, the differences in bacteriologic eradication rates obtained with
cephalosporins were more pronounced in children. The likelihood of bacteriologic
and clinical failure of GAS tonsillopharyngitis treatment in both European and
U.S. patients is significantly less if a 10-day course of oral cephalosporin is
prescribed, and is at least similar, if not significantly less, with a 4- to
5-day course of oral cephalosporin compared with a 10-day course of oral
penicillin.
-----
BMC Med Inform Decis Mak. 2006 Mar 13;6:14.
Optimal management of adults with pharyngitis--a multi-criteria
decision analysis.
Singh S, Dolan JG, Centor RM.
Department of Medicine, Wake Forest University, Winston Salem, NC, USA. sosingh@wfubmc.edu
BACKGROUND: Current practice guidelines offer different management
recommendations for adults presenting with a sore throat. The key issue is the
extent to which the clinical likelihood of a Group A streptococcal infection
should affect patient management decisions. To help resolve this issue, we
conducted a multi-criteria decision analysis using the Analytic Hierarchy
Process. METHODS: We defined optimal patient management using four criteria: 1)
reduce symptom duration; 2) prevent infectious complications, local and
systemic; 3) minimize antibiotic side effects, minor and anaphylaxis; and 4)
achieve prudent use of antibiotics, avoiding both over-use and under-use. In our
baseline analysis we assumed that all criteria and sub-criteria were equally
important except minimizing anaphylactic side effects, which was judged very
strongly more important than minimizing minor side effects. Management
strategies included: a) No test, No treatment; b) Perform a rapid strep test and
treat if positive; c) Perform a throat culture and treat if positive; d) Perform
a rapid strep test and treat if positive; if negative obtain a throat culture
and treat if positive; and e) treat without further tests. We defined four
scenarios based on the likelihood of group A streptococcal infection using the
Centor score, a well-validated clinical index. Published data were used to
estimate the likelihoods of clinical outcomes and the test operating
characteristics of the rapid strep test and throat culture for identifying group
A streptococcal infections. RESULTS: Using the baseline assumptions, no testing
and no treatment is preferred for patients with Centor scores of 1; two
strategies--culture and treat if positive and rapid strep with culture of
negative results--are equally preferable for patients with Centor scores of 2;
and rapid strep with culture of negative results is the best management strategy
for patients with Centor scores 3 or 4. These results are sensitive to the
priorities assigned to the decision criteria, especially avoiding over-use
versus under-use of antibiotics, and the population prevalence of Group A
streptococcal pharyngitis. CONCLUSION: The optimal clinical management of adults
with sore throat depends on both the clinical probability of a group A
streptococcal infection and clinical judgments that incorporate individual
patient and practice circumstances.
-----
JAMA. 2005 Nov 9;294(18):2315-22.
Antibiotic treatment of children with sore throat.
Linder JA, Bates DW, Lee GM, Finkelstein JA.
Division of General Medicine, Brigham and Women's Hospital and Harvard Medical
School, Boston, MA 02120, USA. jlinder@partners.org
CONTEXT: Of children with sore throat, 15% to 36% have pharyngitis caused by
group A beta-hemolytic streptococci (GABHS). Performance of a GABHS test prior
to antibiotic prescribing is recommended for children with sore throat.
Penicillin, amoxicillin, erythromycin, and first-generation cephalosporins are
the recommended antibiotics for treatment of sore throat due to GABHS.
OBJECTIVES: To measure rates of antibiotic prescribing and GABHS testing and to
evaluate the association between testing and antibiotic treatment for children
with sore throat. DESIGN, SETTING, AND PARTICIPANTS: Analysis of visits by
children aged 3 to 17 years with sore throat to office-based physicians,
hospital outpatient departments, and emergency departments in the National
Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care
Survey, 1995 to 2003 (N = 4158) and of a subset of visits with GABHS testing
data (n = 2797). MAIN OUTCOME MEASURES: National rates of antibiotic
prescribing, prescribing of antibiotics recommended and not recommended for
GABHS, and GABHS testing. RESULTS: Physicians prescribed antibiotics in 53% (95%
confidence interval [CI], 49%-56%) of an estimated 7.3 million annual visits for
sore throat and nonrecommended antibiotics to 27% (95% CI, 24%-31%) of children
who received an antibiotic. Antibiotic prescribing decreased from 66% of visits
in 1995 to 54% of visits in 2003 (P = .01 for trend). This decrease was
attributable to a decrease in the prescribing of recommended antibiotics (49% to
38%; P = .002). Physicians performed a GABHS test in 53% (95% CI, 48%-57%) of
visits and in 51% (95% CI, 45%-57%) of visits at which an antibiotic was
prescribed. GABHS testing was not associated with a lower antibiotic prescribing
rate overall (48% tested vs 51% not tested; P = .40), but testing was associated
with a lower antibiotic prescribing rate for children with diagnosis codes for
pharyngitis, tonsillitis, and streptococcal sore throat (57% tested vs 73% not
tested; P<.001). CONCLUSIONS: Physicians prescribed antibiotics to 53% of
children with sore throat, in excess of the maximum expected prevalence of GABHS.
Although there was a decrease in the proportion of children receiving
antibiotics between 1995 and 2003, this was due to decreased prescribing of
agents recommended for GABHS. Although GABHS testing was associated with a lower
rate of antibiotic prescribing for children with diagnosis codes of pharyngitis,
tonsillitis, and streptococcal sore throat, GABHS testing was underused.
-----
Pediatr Infect Dis J. 2005 Oct;24(10):909-17.
Metaanalysis of short course antibiotic treatment for group a
streptococcal tonsillopharyngitis.
Casey JR, Pichichero ME.
Department of Pediatrics, Elmwood Pediatric Group, University of Rochester
Medical Center, NY, USA. jrcasey@rochester.rr.com
OBJECTIVE: To compare bacterial and clinical cure rates in patients with group A
streptococcal (GAS) tonsillopharyngitis treated with oral beta-lactam or
macrolide antibiotics for 4-5 days versus 10-day comparators. METHODS: Medline,
Embase, reference lists and abstract searches were used to identify available
publications. Trials were included if there was bacteriologic confirmation of
GAS tonsillopharyngitis, random assignment to antibiotic therapy for a beta-lactam
or macrolide antibiotic of a shortened course versus a 10-day comparator and
assessment of bacteriologic outcome using a throat culture. RESULTS: Twenty-two
trials involving 7470 patients were included in 4 separate analyses. Trials were
grouped by a short course of cephalosporins (n = 14), macrolides (other than
azithromycin) (n = 6) and penicillin (n = 2). Cephalosporin trials were further
grouped by the comparator, penicillin or the same cephalosporin. Short course
cephalosporin treatment was superior for bacterial cure rate compared with 10
days of penicillin [odds ratio (OR), 1.47; 95% confidence interval (CI),
1.06-2.03]. For trials with short course macrolide therapy, OR = 0.79 (95% CI
0.59-1.06) neither the macrolides nor the 10-day comparators. Short course
penicillin therapy was inferior in achieving bacterial cure versus 10 days of
penicillin, OR = 0.29 (95% CI 0.13-0.63). Clinical cure rates mirrored
bacteriologic cure rates. CONCLUSION: Superior cure rates can be achieved with
shortened courses of cephalosporin therapy, but 5 days is inferior to 10 days of
penicillin treatment.
-----
Clin Infect Dis. 2005 Oct 15;41(8):1114-22. Epub 2005 Sep 12.
Safety and immunogenicity of 26-valent group a streptococcus
vaccine in healthy adult volunteers.
McNeil SA, Halperin SA, Langley JM, Smith B, Warren A, Sharratt GP, Baxendale
DM, Reddish MA, Hu MC, Stroop SD, Linden J, Fries LF, Vink PE, Dale JB.
Clinical Trials Research Center, IWK Health Centre, Dalhousie University,
Halifax, Nova Scotia, Canada. shelly.mcneil@cdha.nshealth.ca
BACKGROUND: Group A streptococcus (GAS) causes illness ranging from
uncomplicated pharyngitis to life-threatening necrotizing fasciitis, toxic
shock, and rheumatic fever. Attempts to develop an M protein-based vaccine have
been hindered by the fact that some M proteins elicit both protective antibodies
and antibodies that cross-react with human tissues. New molecular techniques
have allowed the previous obstacles to be largely overcome. METHODS: The vaccine
is comprised of 4 recombinant proteins adsorbed to aluminum hydroxide that
contain N-terminal peptides from streptococcal protective antigen and M proteins
of 26 common pharyngitis, invasive, and/or rheumatogenic serotypes. Thirty
healthy adult subjects received intramuscular 26-valent GAS vaccine (400 microg)
at 0, 1, and 4 months, with clinical and laboratory follow-up for safety and
immunogenicity using assays for tissue cross-reactive antibodies, type-specific
M antibodies to 27 vaccine antigens, and functional (opsonization) activity of M
protein antibodies. RESULTS: The incidence of local reactogenicity was similar
to that for other aluminum hydroxide-adsorbed vaccines in adults. No subject
developed evidence of rheumatogenicity or nephritogenicity, and no induction of
human tissue-reactive antibodies was detected. Overall, 26 of 27 antigenic
peptides evoked a >4-fold increase in the geometric mean antibody titer over
baseline. The mean log2 fold-increase in serum antibody titer (+/- standard
error of the mean) for all 27 antigens was 3.67 +/- 0.21. A significant mean
log2 reduction in streptococcal bacterial counts in serum samples obtained after
immunization was seen in opsonization assays for all M serotypes. CONCLUSIONS:
On the basis of epidemiological data demonstrating that the majority of cases of
pharyngitis, necrotizing fasciitis, and other invasive streptococcal infections
are caused by a limited number of serotypes, this 26-valent vaccine could have
significant impact on the overall burden of streptococcal disease.
-----
JAMA. 2005 Nov 9;294(18):2315-22.
Antibiotic treatment of children with sore throat.
Linder JA, Bates DW, Lee GM, Finkelstein JA.
Division of General Medicine, Brigham and Women's Hospital and Harvard Medical
School, Boston, MA 02120, USA. jlinder@partners.org
CONTEXT: Of children with sore throat, 15% to 36% have pharyngitis caused by
group A beta-hemolytic streptococci (GABHS). Performance of a GABHS test prior
to antibiotic prescribing is recommended for children with sore throat.
Penicillin, amoxicillin, erythromycin, and first-generation cephalosporins are
the recommended antibiotics for treatment of sore throat due to GABHS.
OBJECTIVES: To measure rates of antibiotic prescribing and GABHS testing and to
evaluate the association between testing and antibiotic treatment for children
with sore throat. DESIGN, SETTING, AND PARTICIPANTS: Analysis of visits by
children aged 3 to 17 years with sore throat to office-based physicians,
hospital outpatient departments, and emergency departments in the National
Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care
Survey, 1995 to 2003 (N = 4158) and of a subset of visits with GABHS testing
data (n = 2797). MAIN OUTCOME MEASURES: National rates of antibiotic
prescribing, prescribing of antibiotics recommended and not recommended for
GABHS, and GABHS testing. RESULTS: Physicians prescribed antibiotics in 53% (95%
confidence interval [CI], 49%-56%) of an estimated 7.3 million annual visits for
sore throat and nonrecommended antibiotics to 27% (95% CI, 24%-31%) of children
who received an antibiotic. Antibiotic prescribing decreased from 66% of visits
in 1995 to 54% of visits in 2003 (P = .01 for trend). This decrease was
attributable to a decrease in the prescribing of recommended antibiotics (49% to
38%; P = .002). Physicians performed a GABHS test in 53% (95% CI, 48%-57%) of
visits and in 51% (95% CI, 45%-57%) of visits at which an antibiotic was
prescribed. GABHS testing was not associated with a lower antibiotic prescribing
rate overall (48% tested vs 51% not tested; P = .40), but testing was associated
with a lower antibiotic prescribing rate for children with diagnosis codes for
pharyngitis, tonsillitis, and streptococcal sore throat (57% tested vs 73% not
tested; P<.001). CONCLUSIONS: Physicians prescribed antibiotics to 53% of
children with sore throat, in excess of the maximum expected prevalence of GABHS.
Although there was a decrease in the proportion of children receiving
antibiotics between 1995 and 2003, this was due to decreased prescribing of
agents recommended for GABHS. Although GABHS testing was associated with a lower
rate of antibiotic prescribing for children with diagnosis codes of pharyngitis,
tonsillitis, and streptococcal sore throat, GABHS testing was underused.
-----
Pediatr Infect Dis J. 2005 Oct;24(10):909-17.
Metaanalysis of short course antibiotic treatment for group a
streptococcal tonsillopharyngitis.
Casey JR, Pichichero ME.
Department of Pediatrics, Elmwood Pediatric Group, University of Rochester
Medical Center, NY, USA. jrcasey@rochester.rr.com
OBJECTIVE: To compare bacterial and clinical cure rates in patients with group A
streptococcal (GAS) tonsillopharyngitis treated with oral beta-lactam or
macrolide antibiotics for 4-5 days versus 10-day comparators. METHODS: Medline,
Embase, reference lists and abstract searches were used to identify available
publications. Trials were included if there was bacteriologic confirmation of
GAS tonsillopharyngitis, random assignment to antibiotic therapy for a beta-lactam
or macrolide antibiotic of a shortened course versus a 10-day comparator and
assessment of bacteriologic outcome using a throat culture. RESULTS: Twenty-two
trials involving 7470 patients were included in 4 separate analyses. Trials were
grouped by a short course of cephalosporins (n = 14), macrolides (other than
azithromycin) (n = 6) and penicillin (n = 2). Cephalosporin trials were further
grouped by the comparator, penicillin or the same cephalosporin. Short course
cephalosporin treatment was superior for bacterial cure rate compared with 10
days of penicillin [odds ratio (OR), 1.47; 95% confidence interval (CI),
1.06-2.03]. For trials with short course macrolide therapy, OR = 0.79 (95% CI
0.59-1.06) neither the macrolides nor the 10-day comparators. Short course
penicillin therapy was inferior in achieving bacterial cure versus 10 days of
penicillin, OR = 0.29 (95% CI 0.13-0.63). Clinical cure rates mirrored
bacteriologic cure rates. CONCLUSION: Superior cure rates can be achieved with
shortened courses of cephalosporin therapy, but 5 days is inferior to 10 days of
penicillin treatment.
-----
Clin Infect Dis. 2005 Oct 15;41(8):1114-22. Epub 2005 Sep 12.
Safety and immunogenicity of 26-valent group a streptococcus
vaccine in healthy adult volunteers.
McNeil SA, Halperin SA, Langley JM, Smith B, Warren A, Sharratt GP, Baxendale
DM, Reddish MA, Hu MC, Stroop SD, Linden J, Fries LF, Vink PE, Dale JB.
Clinical Trials Research Center, IWK Health Centre, Dalhousie University,
Halifax, Nova Scotia, Canada. shelly.mcneil@cdha.nshealth.ca
BACKGROUND: Group A streptococcus (GAS) causes illness ranging from
uncomplicated pharyngitis to life-threatening necrotizing fasciitis, toxic
shock, and rheumatic fever. Attempts to develop an M protein-based vaccine have
been hindered by the fact that some M proteins elicit both protective antibodies
and antibodies that cross-react with human tissues. New molecular techniques
have allowed the previous obstacles to be largely overcome. METHODS: The vaccine
is comprised of 4 recombinant proteins adsorbed to aluminum hydroxide that
contain N-terminal peptides from streptococcal protective antigen and M proteins
of 26 common pharyngitis, invasive, and/or rheumatogenic serotypes. Thirty
healthy adult subjects received intramuscular 26-valent GAS vaccine (400 microg)
at 0, 1, and 4 months, with clinical and laboratory follow-up for safety and
immunogenicity using assays for tissue cross-reactive antibodies, type-specific
M antibodies to 27 vaccine antigens, and functional (opsonization) activity of M
protein antibodies. RESULTS: The incidence of local reactogenicity was similar
to that for other aluminum hydroxide-adsorbed vaccines in adults. No subject
developed evidence of rheumatogenicity or nephritogenicity, and no induction of
human tissue-reactive antibodies was detected. Overall, 26 of 27 antigenic
peptides evoked a >4-fold increase in the geometric mean antibody titer over
baseline. The mean log2 fold-increase in serum antibody titer (+/- standard
error of the mean) for all 27 antigens was 3.67 +/- 0.21. A significant mean
log2 reduction in streptococcal bacterial counts in serum samples obtained after
immunization was seen in opsonization assays for all M serotypes. CONCLUSIONS:
On the basis of epidemiological data demonstrating that the majority of cases of
pharyngitis, necrotizing fasciitis, and other invasive streptococcal infections
are caused by a limited number of serotypes, this 26-valent vaccine could have
significant impact on the overall burden of streptococcal disease.
-----
Lancet Infect Dis. 2005 Aug;5(8):494-500.
Invasive group A streptococcal disease: should close contacts
routinely receive antibiotic prophylaxis?
Smith A, Lamagni TL, Oliver I, Efstratiou A, George RC, Stuart JM.
Health Protection Agency, Centre for Infections, London, UK. alan.smith@hpa.org.uk
Group A streptococci (Streptococcus pyogenes) causes a wide range of illnesses
from non-invasive disease--eg, pharyngitis--to more severe invasive infections--eg,
necrotising fasciitis and toxic shock-like syndrome. There remains uncertainty
about the risk of secondary cases of invasive disease occurring among close
contacts of an index case and how best to manage that risk. We do not consider
that currently available evidence justifies the routine administration of
chemoprophylaxis to close contacts. We suggest that the appropriate response
should be to routinely inform all household contacts of a patient with invasive
group A streptococcal disease about the clinical manifestations of invasive
disease and to seek immediate medical attention if they develop such symptoms.
-----
Clin Infect Dis. 2005 Jun 15;40(12):1748-55. Epub 2005 May 13.
Higher dosages of azithromycin are more effective in treatment of
group A streptococcal tonsillopharyngitis.
Casey JR, Pichichero ME.
Department of Pediatrics, Elmwood Pediatric Group, University of Rochester
Medical Center, New York, USA. jrcasey@rochester.rr.com
BACKGROUND: Azithromycin has become a frequent choice for the treatment of group
A streptococcal (GAS) tonsillopharyngitis. In this study, our objective was to
determine the optimal dose of azithromycin for treatment of GAS
tonsillopharyngitis in children and adults by analyzing trials that used
different dose regimens. METHODS: We performed a meta-analysis of randomized,
controlled trials that involved bacteriological confirmation of GAS
tonsillopharyngitis, random assignment to receive either azithromycin or a
10-day comparator antibiotic, and assessment of bacteriological eradication by
throat culture after therapy. The primary outcomes of interest were
bacteriological and clinical cure rates. RESULTS: Nineteen trials involving 4626
patients were included in the analysis. One trial used 10-day course of 2
different comparator antibiotics, and 2 trials compared 2 dose regimens of
azithromycin with a 10-day course of comparator antibiotic; all other trials
compared 1 dose regimen of azithromycin with a single 10-day course of
comparator antibiotic. In children, azithromycin administered at 60 mg/kg per
course was superior to the 10-day courses of comparators (P < .00001), with
bacterial failure occurring 5 times more often in patients receiving the 10-day
courses of antibiotics. Azithromycin administered at 30 mg/kg per course was
inferior to the 10-day courses of comparators (P = .02), with bacterial failure
occurring 3 times more frequently in patients receiving azithromycin. Three-day
regimens were inferior to 5-day regimens (P = .002). In adults, no studies
compared dosages by weight. Three-day regimens of 500 mg/day showed a trend
favoring azithromycin over the 10-day courses of comparators (P = .14); 5-day
regimens were inferior to 3-day regimens (P = .006). Clinical cure rates were
significantly different for the different azithromycin regimens, with
differences that resembled those for bacterial cure rate. CONCLUSION: This
analysis suggests that azithromycin administered at a dosage of 60 mg/kg in
children or administered for 3 days at a dosage of 500 mg/day in adults is more
effective than other treatment regimens in producing eradication and clinical
cure of GAS tonsillopharyngitis.
-----
Pediatr Clin North Am. 2005 Jun;52(3):729-47, vi.
Diagnosis and treatment of pharyngitis in children.
Gerber MA.
Department of Pediatrics, University of Cincinnati College of Medicine,
Cincinnati, OH 45229, USA. michael.gerber@cchmc.org
Acute pharyngitis is one of the most common illnesses for which children visit
primary care physicians. Most cases of acute pharyngitis in children are caused
by viruses and are benign and self-limited. Group A beta-hemolytic streptococcus
is the most important of the bacterial causes of acute pharyngitis. Strategies
for diagnosis and treatment of acute pharyngitis are directed at distinguishing
children with viral pharyngitis, who would not benefit from antimicrobial
therapy, from children with group A beta-hemolytic streptococcal pharyngitis,
for whom antimicrobial therapy would be beneficial. Making this distinction is
crucial in attempting to minimize the unnecessary use of antimicrobial agents in
children.
-----
J Otolaryngol. 2005 Jun;34 Suppl 1:S45-9.
Tonsillopharyngitis: clinical highlights.
Tewfik TL, Al Garni M.
Department of Otolaryngology, McGill University, Montreal, QC.
Tonsillopharyngitis is an extremely common infection seen in adults and
children. Although the symptoms and signs of this disease are usually sufficient
to make a diagnosis, it is often difficult to make a distinction between
bacterial and viral etiology on clinical grounds alone. The complications of
tonsillopharyngitis may be classified into suppurative and nonsuppurative
complications. The nonsuppurative complications include scarlet fever, acute
rheumatic fever, and post-streptococcal glomerulonephritis. Suppurative
complications include peritonsillar, parapharyngeal, and retropharyngeal
cellulites and/or abscess. Features suggestive of viral bacterial (GABHS)
etiologies, the medical and surgical guidelines for managing tonsillopharyngitis,
and its complications are highlighted in this article.
-----
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.
-----
Wien Klin Wochenschr. 2005 Apr;117(7-8):256-68.
Anthroposophic vs. conventional therapy of acute respiratory and
ear infections: a prospective outcomes study.
Hamre HJ, Fischer M, Heger M, Riley D, Haidvogl M, Baars E, Bristol E, Evans M,
Schwarz R, Kiene H.
Institute for Applied Epistemology and Medical Methodology, Freiburg, Germany.
harald.hamre@ifaemm.de
CONTEXT: Acute respiratory and ear symptoms are frequently treated with
antibiotics. Anthroposophic treatment of these symptoms relies primarily on
anthroposophic medications. OBJECTIVE: To compare anthroposophic treatment to
conventional treatment of acute respiratory and ear symptoms regarding clinical
outcome, medication use and safety, and patient satisfaction. DESIGN:
Prospective, non-randomised comparison of outcomes in patients self-selected to
anthroposophic or conventional therapy under real-world conditions. SETTING: 29
primary care practices in Austria, Germany, Netherlands, UK, and USA.
PARTICIPANTS AND THERAPY: 1016 consecutive outpatients aged > or = 1 month,
consulting an anthroposophic (n = 715 A-patients) or conventional physician (n =
301 C-patients) with a chief complaint of acute (< or = 7 days) sore throat, ear
pain, sinus pain, runny nose or cough. Patients were treated according to the
physician's discretion. PRIMARY OUTCOME: Patients' self-report of treatment
outcome (complete recovery/major improvement/slight to moderate improvement/no
change/deterioration) at Day 14. RESULTS: Most common chief complaints were
cough (39.9% of A-patients vs. 33.9% of C-patients, p = 0.0772), sore throat
(26.3% vs. 23.3%, p=0.3436), and ear pain (20.0% vs. 18.9%, p=0.7302). Baseline
chief complaint severity was severe or very severe in 60.5% of A-patients and
53.3% of C-patients (p=0.0444), mean severity (0-4) of complaint-related
symptoms was 1.3 +/- 0.7 vs. 1.2 +/- 0.6 (p=0.5197). During the 28-day follow-up
antibiotics were prescribed to 5.5% of A-patients and 33.6% of C-patients
(p<0.0001), anthroposophic medicines were prescribed to all A-patients and no
C-patient. OUTCOMES: Improvement within 24 hours occurred in 30.9% (221/715) of
A-patients and 16.6% (50/301) of C-patients (p<0.0001), improvement within 3
days in 73.1% and 57.1% (p<0.0001). At Day 7 complete recovery or major
improvement was reported by 77.1% of A-patients and 66.1% of C-patients
(p=0.0004), at Day 14 by 89.7% and 84.4% (p=0.0198). Complete recovery rates at
Day 7 were 30.5% and 23.3% (p<0.0001); at Day 14 they were 64.2% and 49.5%
(p<0.0001). 69.9% of A-patients and 60.5% of C-patients were very satisfied with
their physician (p=0.0043); 95.7% and 83.4% would choose the same therapy again
for their chief complaint (p<0.0001). After adjustment for country, gender, age,
chief complaint, duration of complaint, previous episode of complaint within
last year, and baseline symptom severity, odds ratios favoured the A-group for
all these outcomes. Adverse drug reactions were reported in 2.7% of A-patients
and 6.0% of C-patients (p=0.0157). CONCLUSION: Compared to conventional
treatment, anthroposophic treatment of primary care patients with acute
respiratory and ear symptoms had more favourable outcomes, lower antibiotic
prescription rates, less adverse drug reactions, and higher patient
satisfaction.
-----
Treat Respir Med. 2005;4(2):149-52.
Spotlight on cefditoren pivoxil in bacterial infections.
Wellington K, Curran MP.
Adis International Inc., Yardley, Pennsylvania, USA.
Cefditoren pivoxil (Spectracef((R)), Meiact((R))) is a third-generation oral
cephalosporin with a broad spectrum of activity against pathogens, including
both Gram-positive and -negative bacteria, and is stable to hydrolysis by many
common beta-lactamases. Cefditoren pivoxil is approved for use in the treatment
of acute exacerbations of chronic bronchitis (AECB), mild-to-moderate
community-acquired pneumonia (CAP), acute maxillary sinusitis, acute pharyngitis/tonsillitis,
and uncomplicated skin and skin structure infections (indications may differ
between countries).In clinical trials in adults and adolescents, cefditoren
pivoxil demonstrated good clinical and bacteriological efficacy in AECB, CAP,
acute maxillary sinusitis, acute pharyngitis/tonsillitis, and uncomplicated skin
and skin structure infections, and was generally well tolerated. Thus,
cefditoren pivoxil is a good option for the treatment of adult and adolescent
patients with specific respiratory tract or skin infections, particularly if
there is concern about Streptococcus pneumoniae with decreased susceptibility to
penicillin, or beta-lactamase-mediated resistance among the common
community-acquired pathogens.
-----
Arch Pediatr Adolesc Med. 2005 Mar;159(3):278-82.
Effectiveness of oral dexamethasone in the treatment of moderate
to severe pharyngitis in children.
Olympia RP, Khine H, Avner JR.
Section of Emergency Medicine, Department of Pediatrics, Children's Hospital at
Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA.
robert_p_olympia@yahoo.com
OBJECTIVE: To determine the effectiveness of a single dose of oral dexamethasone
in reducing the pain associated with moderate to severe pharyngitis in pediatric
patients. DESIGN: Prospective, randomized, double-blind, placebo-controlled
clinical trial. SETTING: Large, urban pediatric emergency department between
March 2002 and November 2003. PATIENTS: Children aged 5 to 18 years with
moderate to severe pharyngitis (odynophagia or dysphagia, moderate to severe
pharyngeal erythema or swelling, and a McGrath Facial Affective Scale score of
0.75 or higher [scale 0.0-1.0]). INTERVENTIONS: Study patients were randomly
assigned to receive 1 dose of either oral dexamethasone suspension (0.6 mg/kg
with a maximum of 10 mg) or placebo of the same volume. All participants were
tested for group A beta-hemolytic streptococcal pharyngitis and treated
accordingly. Daily telephone follow-up was conducted until complete resolution
of sore throat. MAIN OUTCOME MEASURES: Primary outcome variables included hours
to initial relief of sore throat and time to the complete resolution of pain.
Secondary outcome variables included changes in the McGrath Facial Affective
Scale score at 24 and 48 hours, persistence of associated symptoms, use of
anti-inflammatory or antipyretic medication, and subsequent use of medical
resources for dehydration or pain. RESULTS: A convenience sample of 150 patients
was randomized to receive either dexamethasone (n = 75) or placebo (n = 75).
Twenty-five patients were lost to follow-up, leaving 125 patients available for
data analysis; 57 received dexamethasone and 68 received placebo. Patients who
received dexamethasone reported earlier onset of pain relief (9.2 vs 18.2 hours;
P<.001), fewer hours to complete resolution of sore throat (30.3 vs 43.8 hours;
P = .04), and larger changes in the McGrath Facial Affective Scale score in the
first 24 hours (-0.58 vs -0.43; P = .002). Children who tested negative for
group A beta-hemolytic streptococci had greater pain relief with dexamethasone
compared with placebo (onset of pain relief, 8.7 vs 24 hours; P = .001), less
time to complete resolution of sore throat (37.9 vs 70.8 hours; P = .006), and
greater changes in the McGrath Facial Affective Scale score in the first 24
hours (-0.50 vs -0.21; P<.001). CONCLUSION: Children with moderate to severe
pharyngitis had earlier onset of pain relief and shorter duration of sore throat
when given oral dexamethasone.
-----
Adv Ther. 2004 Sep-Oct;21(5):277-87.
Group A beta-hemolytic streptococcal pharyngitis in children.
Leung AK, Kellner JD.
Department of Pediatrics, University of Calgary, Alberta Children's Hospital
Calgary, Alberta, Canada.
Group A beta-hemolytic streptococcus (GABHS) is the most common bacterial cause
of acute pharyngitis in children. Because clinical findings can be nonspecific,
even experienced physicians cannot reliably diagnose GABHS pharyngitis solely on
the basis of clinical presentation. Suspected cases should be confirmed by a
throat culture or a rapid antigen detection test before antibiotic therapy is
initiated. Microbiologic testing is generally not necessary in patients with
pharyngitis whose clinical and epidemiologic findings are not suggestive of
GABHS. Clinical score systems have been developed to help physicians decide
which patients should undergo diagnostic testing and to reduce the unnecessary
use of antibiotics. Antibiotic therapy should be initiated as soon as the
diagnosis is confirmed. Penicillin V remains the drug of choice. Alternative
therapy, e.g., with cephalosporin or macrolide, is often sought because of
penicillin allergy, noncompliance, and treatment failure.
-----
Prescrire Int. 2004 Dec;13(74):227-32.
Antibiotics for acute group A streptococcal pharyngitis.
[No authors listed]
(1) Since the 1940s, a large number of comparative randomised placebo-controlled
trials have evaluated antibiotic therapy for pharyngitis, initially parenteral
benzathine benzylpenicillin, then oral phenoxymethylpenicillin (penicillin V).
Our literature search identified a Cochrane meta-analysis of all these trials,
with the exception of one published in 2003. (2) When group A betahemolytic
streptococci (group A streptococci) are present in the throat, antibiotic
therapy accelerates symptom relief (particularly fever and pain) by a day or
two. This has been shown with 7-day treatments but not with 3-day treatments.
There is no convincing evidence that antibiotics relieve symptoms in children.
(3) According to the Cochrane meta-analysis, signs of progression to
locoregional suppuration were noted in 1% of patients receiving placebo,
compared to 0.09% of patients receiving antibiotics in the most recent trials
(statistically significant difference). (4) Comparative trials done in the 1950s
showed that benzathine benzylpenicillin helped prevent acute rheumatic fever,
reducing the risk by about 75%. Since 1985 nearly 1000 patients with pharyngitis
have been given a placebo in clinical trials, and none have developed acute
rheumatic fever. (5) There is no firm evidence that antibiotics reduce the risk
of acute glomerulonephritis. (6) The adverse effects associated with most
antibiotics are mild. This is especially true for penicillin. However, there is
a risk of rare but serious adverse effects: anaphylaxis is estimated to occur in
5 per 10 000 patients treated with injectable penicillin, while the risk
associated with oral penicillin used to treat pharyngitis has not been
quantified. Moreover, antibiotics affect the bacterial ecology, encouraging
resistance among some bacterial species other than group A streptococci. (7) A
strategy based on the use of a clinical diagnostic score, followed by a rapid
test if the score is intermediate, seems to be the best way of restricting
antibiotics to patients with pharyngitis due to group A streptococci. (8) In
patients with group A streptococcal pharyngitis, a strategy of starting
antibiotics only after 48 hours of symptoms delays symptom control but seems to
reduce the risk of relapse. According to a clinical trial in patients with
pharyngitis from all causes, advising patients to postpone antibiotic therapy
reduces antibiotic use by about 85%, without increasing the risk of serious
clinical complications. (9) In practice, immediate antibiotic therapy is
justified for patients with severe symptoms or signs of progression to
locoregional suppuration, and when the local incidence of acute rheumatic fever
is high. In other situations, whether or not group A streptococci are involved,
antibiotic therapy should be started only if symptoms do not begin to improve
after 48 hours of symptomatic treatments.
-----
Drugs. 2004;64(22):2597-618.
Cefditoren pivoxil: a review of its use in the treatment of
bacterial infections.
Wellington K, Curran MP.
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
Cefditoren pivoxil (Spectracef, Meiact) is a third-generation oral cephalosporin
with a broad spectrum of activity against pathogens, including both
Gram-positive and -negative bacteria, and is stable to hydrolysis by many common
beta-lactamases. Cefditoren pivoxil is approved for use in the treatment of
acute exacerbations of chronic bronchitis (AECB), mild-to-moderate
community-acquired pneumonia (CAP), acute maxillary sinusitis, acute pharyngitis/tonsillitis
and uncomplicated skin and skin structure infections (indications may differ
between countries).In clinical trials in adults and adolescents, cefditoren
pivoxil demonstrated good clinical and bacteriological efficacy in AECB, CAP,
acute maxillary sinusitis, acute pharyngitis/tonsillitis and uncomplicated skin
and skin structure infections and was generally well tolerated. Thus, cefditoren
pivoxil is a good option for the treatment of adult and adolescent patients with
specific respiratory tract or skin infections, particularly if there is concern
about Streptococcus pneumoniae with decreased susceptibility to penicillin, or
beta-lactamase-mediated resistance among the common community-acquired
pathogens.
-----
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.
-----
Pediatr Infect Dis J. 2004 Sep;23(9):857-65.
Two dosages of clarithromycin for five days, amoxicillin/clavulanate
for five days or penicillin V for ten days in acute group A streptococcal
tonsillopharyngitis.
Syrogiannopoulos GA, Bozdogan B, Grivea IN, Ednie LM, Kritikou DI, Katopodis GD,
Beratis NG, Applebaum PC; Hellenic Antibiotic-Resistant Respiratory Pathogens
Study Group.
Division of Infectious Disease, Department of Pediatrics, University of Patras,
Greece. syrogian@otenet.gr
BACKGROUND: Short course antimicrobial therapy is suggested for group A
streptococcal tonsillopharyngitis. METHODS: The bacteriologic and clinical
efficacies of clarithromycin [30 or 15 mg/kg/day twice daily (b.i.d.)] or
amoxicillin/clavulanate (43.8/6.2 mg/kg/day b.i.d.) for 5 days or penicillin V
(30 mg/kg/day 3 times a day) for 10 days were compared. In a randomized, open
label, parallel group, multicenter study, 626 children (2-16 years old) with
tonsillopharyngitis were enrolled; 537 were evaluable for efficacy. Follow-up
evaluations were performed at 4-8 and 21-28 days after therapy. RESULTS: At
enrollment, 26% of the Streptococcus pyogenes isolates were
clarithromycin-nonsusceptible. All regimens had an apparently similar clinical
efficacy. The long term S. pyogenes eradication rates were 102 of 123 (83%) with
amoxicillin/clavulanate and 88 of 114 (77%) with penicillin V. In the 30- and
15-mg/kg/day clarithromycin groups, eradication occurred in 71 of 86 (83%) and
59 of 80 (74%) of the clarithromycin-susceptible isolates (P = 0.33), and in 4
of 28 (14%) and 5 of 26 (19%) of the clarithromycin-resistant isolates,
respectively (clarithromycin-susceptible versus -resistant, P < 0.0001). Both
clarithromycin dosages were well-tolerated. CONCLUSIONS: In group A
streptococcal tonsillopharyngitis, 5 days of clarithromycin or amoxicillin/clavulanate
treatment had clinical efficacy comparable with that of 10 days of penicillin V
treatment; however, amoxicillin/clavulanate and penicillin V were
bacteriologically more effective than clarithromycin because of its failure to
eradicate the clarithromycin-resistant S. pyogenes isolates. The 5-day
clarithromycin regimens are not recommended for treatment of streptococcal
tonsillopharyngitis in areas where in vitro resistance of group A streptococci
to clarithromycin is common.
-----
Clin Microbiol Infect. 2004 Jul;10(7):615-23.
Evaluation of 5-day therapy with telithromycin, a novel ketolide
antibacterial, for the treatment of tonsillopharyngitis.
Norrby SR, Quinn J, Rangaraju M, Leroy B.
Swedish Institute for Infectious Disease Control, Solna, Sweden. Ragnar.Norrby@smi.ki.se
A pooled analysis of two double-blind, multicentre, Phase III studies compared
oral telithromycin 800 mg once-daily for 5 days with penicillin V 500 mg
three-times-daily or clarithromycin 250 mg twice-daily for 10 days in the
treatment of Streptococcus pyogenes (group A beta-haemolytic streptococcus;
GABHS) tonsillopharyngitis. Patients aged > or = 13 years with acute GABHS
tonsillopharyngitis were randomised to receive telithromycin (n = 430),
penicillin (n = 197) or clarithromycin (n = 231). Clinical isolates of S.
pyogenes (n = 590) obtained from throat swab samples on study entry were tested
for their in-vitro susceptibility to telithromycin, clarithromycin and
azithromycin. Telithromycin demonstrated in-vitro activity against the clinical
isolates of S. pyogenes (MIC50/90 0.03/0.06 mg/L) higher than clarithromycin or
azithromycin (MIC50/90 0.06/0.06 mg/L and 0.12/0.25 mg/L, respectively),
including erythromycin-resistant strains. At the post-therapy/test of cure (TOC)
visit (days 16-23), satisfactory bacteriological outcome was demonstrated for
88.3% (234/265) and 88.6% (225/254) of telithromycin- and comparator-treated
patients, respectively (per-protocol population). Overall, GABHS eradication
rates were 88.7% (235/265) for telithromycin and 89.0% (226/254) for
comparators. The clinical cure rates at the post-therapy/TOC visit were 93.6%
(248/265) and 90.9% (220/242) for telithromycin and pooled comparators,
respectively. Telithromycin was generally well-tolerated. Most adverse events
considered to be possibly related to study medication were gastrointestinal and
of mild intensity. Discontinuations as a result of adverse events were few in
both treatment groups. In conclusion, telithromycin 800 mg once-daily for 5 days
was as effective as penicillin V or clarithromycin for 10 days in the treatment
of GABHS tonsillopharyngitis.
-----
S Afr Med J. 2004 Jun;94(6 Pt 2):475-83.
Guideline for the management of upper respiratory tract
infections.
Brink AJ, Cotton MF, Feldman C, Geffen L, Hendson W, Hockman MH, Maartens G,
Madhi SA, Mutua-Mpungu M, Swingler GH; Working Group of the Infectious Diseases
Society of South Africa.
Du Buisson, Bruinette and Partners, Ampath, Johannesburg.
INTRODUCTION: Inappropriate use of antibiotics for upper respiratory tract
infections (URTIs), many of which are viral, adds to the burden of antibiotic
resistance. Antibiotic resistance is increasing in Streptococcus pneumoniae,
responsible for most cases of acute otitis media (AOM) and acute bacterial
sinusitis (ABS). METHOD: The Infectious Diseases Society of Southern Africa held
a multidisciplinary meeting to draw up a national guideline for the management
of URTIs. Background information reviewed included randomised controlled trials,
existing URTI guidelines and local antibiotic susceptibility patterns. The
initial document was drafted at the meeting. Subsequent drafts were circulated
to members of the working group for modification. The guideline is a consensus
document based upon the opinions of the working group. OUTPUT: Penicillin
remains the drug of choice for tonsillopharyngitis. Single-dose parenteral
administration of benzathine penicillin is effective, but many favour oral
administration twice daily for 10 days. Amoxycillin remains the drug of choice
for both AOM and ABS. A dose of 90 mg/ kg/day is recommended in general, which
should be effective for pneumococci with high-level penicillin resistance (this
is particularly likely in children < or = 2 years of age, in day-care attendees,
in cases with prior AOM within the past 6 months, and in children who have
received antibiotics within the last 3 months). Alternative antibiotic choices
are given in the guideline with recommendations for their specific indications.
These antibiotics include amoxycillin-clavulanate, some cephalosporins, the
macrolide/azalide and ketolide groups of agents and the respiratory
fluoroquinolones. CONCLUSION: The guideline should assist rational antibiotic
prescribing for URTIs. However, it should be updated when new information
becomes available from randomised controlled trials and surveillance studies of
local antibiotic susceptibility patterns.
-----
Clin Infect Dis. 2004 Jun 1;38(11):1526-34. Epub 2004 May 11.
Meta-analysis of cephalosporins versus penicillin for treatment
of group A streptococcal tonsillopharyngitis in adults.
Casey JR, Pichichero ME.
University of Rochester, Elmwood Pediatric Group, Rochester, New York 14620,
USA. jrcasey@rochester.rr.com
We conducted a meta-analysis of 9 randomized controlled trials (involving 2113
patients) comparing cephalosporins with penicillin for treatment of group A beta
-hemolytic streptococcal (GABHS) tonsillopharyngitis in adults. The summary odds
ratio (OR) for bacteriologic cure rate significantly favored cephalosporins,
compared with penicillin (OR,1.83; 95% confidence interval [CI], 1.37-2.44); the
bacteriologic failure rate was nearly 2 times higher for penicillin therapy than
it was for cephalosporin therapy (P=.00004). The summary OR for clinical cure
rate was 2.29 (95% CI, 1.61-3.28), significantly favoring cephalosporins
(P<.00001). Sensitivity analyses for bacterial cure significantly favored
cephalosporins over penicillin in trials that were double-blinded and of high
quality, trials that had a well-defined clinical status, trials that performed
GABHS serotyping, trials that eliminated carriers from analysis, and trials that
had a test-of-cure culture performed 3-14 days after treatment. This
meta-analysis indicates that the likelihood of bacteriologic and clinical
failure in the treatment of GABHS tonsillopharyngitis is 2 times higher for oral
penicillin than for oral cephalosporins.
-----
Pediatrics. 2004 Aug;114(2):342-7.
Developing community-specific recommendations for first-line
treatment of acute otitis media: is high-dose amoxicillin necessary?
Garbutt J, St Geme JW 3rd, May A, Storch GA, Shackelford PG.
Division of General Medical Sciences, Washington University School of Medicine,
St Louis, Missouri, USA. jgarbutt@im.wustl.edu
OBJECTIVES: National recommendations are to use high-dose amoxicillin (80-90
mg/kg per day) to treat uncomplicated acute otitis media (AOM) in children who
are at high risk for infection with nonsusceptible Streptococcus pneumoniae (NSSP).
However, high-dose treatment may not be necessary if the local prevalence of
NSSP is low. The objective of this study was to estimate the local prevalence of
NSSP in children with acute upper respiratory illnesses and to develop
community-specific recommendations for first-line empiric treatment of AOM.
METHODS: We conducted a cross-sectional prevalence study in the offices of 7
community pediatricians in St Louis, Missouri. S pneumoniae was isolated from
nasopharyngeal swabs collected from children who were younger than 7 years and
had AOM, nonspecific upper respiratory infection, cough, acute sinusitis, or
pharyngitis. Children were excluded from the study when they had received an
antibiotic in the previous 4-week period. Parents and providers completed a
brief questionnaire to assess risk factors for carriage of NSSP. On the basis of
National Clinical Chemistry Laboratory Standards, isolates with a penicillin
minimum inhibitory concentration > or =0.12 microg/mL were considered to be
nonsusceptible to penicillin (NSSP), and isolates with a penicillin minimum
inhibitory concentration >2 microg/mL were categorized as nonsusceptible to
standard-dose amoxicillin (35-45 mg/kg per day; NSSP-A). RESULTS: S pneumoniae
was isolated from the nasopharynx of 85 (40%) of 212 study patients (95%
confidence interval [CI]: 33%-47%); 41 (48%) of 85 isolates were NSSP (95% CI:
37%-59%), and 6 (7%) were NSSP-A (95% CI: 1.5%-13%). Among the 212 study
patients, the prevalence of NSSP was 19% (95% CI: 14%-25%), and the prevalence
of NSSP-A was 3% (95% CI: 0.6%-5%). Carriage of NSSP was increased in child care
attendees compared with nonattendees (29% vs 14%; odds ratio: 2.6; 95% CI:
1.3-5.2). CONCLUSIONS: In our community, although the prevalence of NSSP among
isolates of S pneumoniae identified from the nasopharynx of symptomatic children
is high (48%), the probability of NSSP-A infection among symptomatic children is
<5%. Our data support a recommendation to treat most children who have
uncomplicated AOM with standard-dose amoxicillin. Children who attend child care
or have recently received an antibiotic may require treatment with high-dose
amoxicillin. Other communities may benefit from a similar assessment of the
prevalence of NSSP and NSSP-A.
------
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.
-----
Curr Infect Dis Rep. 2004 Jun;6(3):191-199.
The Use of Ketolides in Treatment of Upper Respiratory Tract
Infections.
Zhanel GG, Wierzbowski AK, Hisanaga P, Hoban DJ.
Department of Medical Microbiology, Faculty of Medicine, University of Manitoba,
MS673-Microbiology, Health Sciences Centre, 820 Sherbrook Street, Winnipeg,
Manitoba R3A 1R9, Canada. ggzhanel@pcs.mb.ca
Recent surveillance studies suggest that the incidence of resistance to
macrolide antibiotics in common community-acquired respiratory tract pathogens,
particularly Streptococcus pneumoniae and Streptococcus pyogenes, is increasing
and limiting the usefulness of these drugs. The ketolides, of which
telithromycin is the first to be available for clinical use (but not yet in the
United States), represent a new class of antibacterials developed specifically
to combat respiratory tract pathogens that have acquired resistance to
macrolides. The ketolides possess innovative structural modifications, a 3-keto
group and a large N-substituted C11, C12-carbamate side chain. This novel
structure allows ketolides, which are inhibitors of protein synthesis, to exert
a more effective interaction with domain II of the 23S rRNA, enhancing binding
to bacterial ribosomes and allowing binding to
macrolide-lincosamide-streptogramin B-resistant ribosomes. This novel chemical
structure also promotes greater stability of telithromycin in acid conditions,
providing the potential for greater stability in gastric fluid and at
cellular/tissue levels. Early clinical trials support the bacteriologic and
clinical efficacy of telithromycin in the treatment of upper respiratory tract
infections (RTIs) such as streptococcal pharyngitis and acute sinusitis,
including infections caused by macrolide-resistant S. pneumoniae and S. pyogenes.
Common adverse side effects associated with telithromycin are predominantly
gastrointestinal, usually of mild to moderate severity, and rarely involve
withdrawal of the drug. Telithromycin represents an attractive option for the
empiric treatment of upper RTIs, especially as resistance to macrolides is
likely to continue to increase.
-----
J Antimicrob Chemother. 2004 Jun;53(6):918-27. Epub 2004 Apr 29.
Clinical efficacy of ketolides in the treatment of respiratory
tract infections.
Reinert RR.
Institute of Medical Microbiology, National Reference Centre for Streptococci,
Pauwelsstrasse 30, 52074 Aachen, Germany. reinert@rwth-aachen.de
Ketolides are a new class of semi-synthetic agents derived from erythromycin A
designed to overcome erythromycin A resistance in Streptococcus pneumoniae.
Telithromycin (HMR 3647) is the first member of this new class to be approved
for clinical use. Cethromycin (ABT-773) has been developed up to Phase III, but
its further development seems questionable at the moment. Other ketolides are
only in the first stages of preclinical development and may not be available
within the foreseeable future. Ketolide compounds inhibit bacterial protein
synthesis by interacting with the peptidyl transferase site of the 50S ribosomal
subunit, and interact closely with domains II at A752 and V at A2058 and A2059
of the 23S rRNA. These compounds also inhibit the formation of the 50S subunit
of the ribosome. Ketolides show good activity against the Gram-positive bacteria
responsible for respiratory tract infections including penicillin G- and
erythromycin A-resistant S. pneumoniae. The 15 clinical trials with
telithromycin published to date include four randomized, double-blind
comparative trials and three open-label studies in community-acquired pneumonia,
three randomized double-blind trials in acute exacerbation of chronic
bronchitis, two randomized double-blind trials in pharyngitis, and two
double-blind comparative trials and one open-label trial in acute maxillary
sinusitis. Clinical response rates were favourable in all clinical trials, with
eradication rates in patients with pneumococcal bacteraemia and penicillin G-
and erythromycin A-resistant pneumococcal infections at least as high as those
of comparators. As resistance to macrolides continues to emerge, the
availability of other ketolides besides telithromycin and a development
programme for the application of ketolides in children would appear to be
warranted to obtain a new class of antibiotics that may one day replace
macrolides.
-----
Chemotherapy. 2004 Apr;50(1):51-4.
Streptococcal-A tonsillopharyngitis: a 5-day course of cefuroxime
axetil versus a 10-day course of penicillin V. results depending on the
children's age.
Scholz H.
Institute for Infectious Diseases, Microbiology and Hygienics, Municipal
Hospital of Berlin-Buch, Berlin, Germany. horstscholz1@compuserve.de
BACKGROUND: The recommended duration of antibiotic treatment of
tonsillopharyngitis caused by group A beta-hemolytic streptococci (GABHS) with
penicillin V (PenV) is mostly 10 days. However, compliance with 10-day courses
is bad. Shorter therapeutic courses are necessary, especially in young children.
METHODS: In a prospective, randomized, multi-center study, children aged 1-17
years with acute tonsillopharyngitis and a positive culture for GABHS were
treated with cefuroxime axetil (CAE) 20 mg/kg/day (max. 500 mg) b.i.d. for 5
days or with PenV 50,000 IU/kg (30 mg/kg) t.i.d. for 10 days. Patients were
evaluated for clinical efficacy 2-4 and 7-9 days after the end of therapy.
Throat swabs were taken 2-4 days after the end of therapy and at the first
follow-up visit. Follow-up visits were carried out 7-8 weeks, 6 months and 12
months after study inclusion. RESULTS: 1,952 patients (CAE for 5 days, 496
patients/PenV for 10 days, 1,456 patients) could be included in the
intent-to-treat analysis. Two to 4 days after completion of the treatment
course, the bacteriological eradication in group A (1-5 years) and group B (6-17
years) was 90.52 and 89.53% (CAE) vs. 84.13 and 84.20% (PenV), respectively; p =
0.0172; 0.0382; clinical success was 98.30% (CAE) versus 93.25% (PenV), p =
0.0017. Recurrent infections were significantly higher in younger children
(group A) under both treatment regimens. Poststreptococcal sequelae (glomerulonephritis)
were observed in only 1 case, in the PenV group. CONCLUSIONS: CAE b.i.d. for 5
days was at least as effective as PenV t.i.d. for 10 days. Incountries with a
low incidence of rheumatic fever, CAE for 5 days can be recommended for the
therapy of tonsillopharyngitis due to GABHS - also in young children. Copyright
2004 S. Karger AG, Basel
-----
Pediatrics. 2004 Apr;113(4):866-82.
Meta-analysis of cephalosporin versus penicillin treatment of
group A streptococcal tonsillopharyngitis in children.
Casey JR, Pichichero ME.
Department of Pediatrics, Elmwood Pediatric Group, University of Rochester,
Rochester, New York 14620, USA. jrcasey@rochester.rr.com
OBJECTIVE: To conduct a meta-analysis of randomized, controlled trials of
cephalosporin versus penicillin treatment of group A beta-hemolytic
streptococcal (GABHS) tonsillopharyngitis in children. METHODOLOGY: Medline,
Embase, reference lists, and abstract searches were conducted to identify
randomized, controlled trials of cephalosporin versus penicillin treatment of
GABHS tonsillopharyngitis in children. Trials were included if they met the
following criteria: patients <18 years old, bacteriologic confirmation of GABHS
tonsillopharyngitis, random assignment to antibiotic therapy of an orally
administered cephalosporin or penicillin for 10 days of treatment, and
assessment of bacteriologic outcome using a throat culture after therapy.
Primary outcomes of interest were bacteriologic and clinical cure rates.
Sensitivity analyses were performed to assess the impact of careful clinical
illness descriptions, compliance monitoring, GABHS serotyping, exclusion of
GABHS carriers, and timing of the test-of-cure visit. RESULTS: Thirty-five
trials involving 7125 patients were included in the meta-analysis. The overall
summary odds ratio (OR) for the bacteriologic cure rate significantly favored
cephalosporins compared with penicillin (OR: 3.02; 95% confidence interval [CI]:
2.49-3.67, with the individual cephalosporins [cephalexin, cefadroxil,
cefuroxime, cefpodoxime, cefprozil, cefixime, ceftibuten, and cefdinir] showing
superior bacteriologic cure rates). The overall summary OR for clinical cure
rate was 2.33 (95% CI: 1.84-2.97), significantly favoring the same individual
cephalosporins. There was a trend for diminishing bacterial cure with penicillin
over time, comparing the trials published in the 1970s, 1980s, and 1990s.
Sensitivity analyses for bacterial cure significantly favored cephalosporin
treatment over penicillin treatment when trials were grouped as double-blind
(OR: 2.31; 95% CI: 1.39-3.85), high-quality (OR: 2.50; 95% CI: 1.85-3.36) trials
with well-defined clinical status (OR: 2.12; 95% CI: 1.54-2.90), with detailed
compliance monitoring (OR: 2.85; 95% CI: 2.33-3.47), with GABHS serotyping (OR:
3.10; 95% CI: 2.42-3.98), with carriers eliminated (OR: 2.51; 95% CI:
1.55-4.08), and with test of cure 3 to 14 days posttreatment (OR: 3.53; 95% CI:
2.75-4.54). Analysis of comparative bacteriologic cure rates for the 3
generations of cephalosporins did not show a difference. CONCLUSIONS: This
meta-analysis indicates that the likelihood of bacteriologic and clinical
failure of GABHS tonsillopharyngitis is significantly less if an oral
cephalosporin is prescribed, compared with oral penicillin.
-----
Clin Pediatr (Phila). 2004 Mar;43(2):135-51.
Optimizing antibacterial therapy for community-acquired
respiratory tract infections in children in an era of bacterial resistance.
Low DE, Pichichero ME, Schaad UB.
Mount Sinai Hospital, Toronto, Canada.
The spread of antibacterial resistance in bacteria that commonly cause childhood
community-acquired respiratory tract infections (RTIs), such as acute otitis
media, community-acquired pneumonia, and acute pharyngitis, is a major
healthcare problem. One of the foremost concerns is the rapid increase in
penicillin, macrolide, and multidrug resistance in Streptococcus pneumoniae.
There is also a rising prevalence of macrolide resistance in Streptococcus
pyogenes in pockets of the United States, and beta-lactamase production in
Haemophilus influenzae is widespread. Although data are limited, some evidence
suggests that resistance to antibacterials can impair bacteriologic and clinical
outcomes in childhood RTIs. Optimizing antibacterial use is important both in
the care of individual patients and within strategies to address the wider
problem of antibacterial resistance. This involves encouraging judicious
antibacterial use (i.e., reducing overuse for viral infection and prophylaxis),
and preventing misuse through the wrong choice, dosage, and duration of therapy.
Given that initial therapy is usually empiric, antibacterials used to treat
community-acquired RTIs in children should ideally have the following
properties: an optimal targeted spectrum of activity; high clinical and
bacteriologic efficacy against respiratory pathogens, including resistant
strains; simple, short-course therapy; and good tolerability and palatability.
New antibacterials will continue to have a role in the treatment of RTIs in
children, especially where resistance compromises existing therapies.
-----
Am Fam Physician. 2004 Mar 15;69(6):1465-70.
Pharyngitis.
Vincent MT, Celestin N, Hussain AN.
Department of Family Practice, State University of New York-Downstate
Medical Center, Brooklyn, New York 11203-2098, USA. mvincent@downstate.edu
Sore throat is one of the most common reasons for visits to
family physicians. While most patients with sore throat have an
infectious cause (pharyngitis), fewer than 20 percent have a clear
indication for antibiotic therapy (i.e., group A beta-hemolytic
streptococcal infection). Useful, well-validated clinical decision
rules are available to help family physicians care for patients
who present with pharyngitis. Because of recent improvements in
rapid streptococcal antigen tests, throat culture can be reserved
for patients whose symptoms do not improve over time or who do
not respond to antibiotics.
-----
Pediatr Infect Dis J. 2004 Feb;23(2 Suppl):S129-34.
Defining the optimum treatment regimen for azithromycin
in acute tonsillopharyngitis.
Cohen R.
Centre Hospitalier Intercommunal de Creteil, Creteil, France.
Robert.Cohen@wanadoo.fr
Pharyngitis is one of the most common infectious diseases affecting
children. Group A streptococci are the leading bacterial cause
of pharyngitis in children and adults. Because inappropriate antibiotic
treatment for pharyngitis is becoming a major issue, only true
group A beta-hemolytic streptococcus (GABHS) infections, proven
by rapid antigen test or culture, should be treated with antibiotics.
GABHS pharyngitis is often a mild and self-limiting infection
in the absence of antimicrobial therapy. However, antimicrobial
treatment must be administered to eradicate the pathogen from
the throat, limit the spread of the infection and prevent possible
progression to rheumatic fever, suppurative disease or toxin-mediated
complications. Penicillin V for 10 days is the standard therapy
and is effective in the management of GABHS pharyngitis. However,
there are drawbacks to penicillin V therapy, including the length
of the dosing regimen, which are leading to decreasing penicillin
prescription rates in many countries. In addition bacteriologic
treatment failures have been documented in up to 35% of GABHS
patients treated with penicillin V, particularly in children <6
years old. A number of mechanisms may be responsible for these
failures, but poor compliance with the standard 10-day penicillin
treatment is likely to be a major factor. There is growing evidence
to suggest that children with GABHS pharyngitis can be effectively
treated with non-penicillin V antibiotics, which have the advantage
of simpler and shorter dosing regimens compared with penicillin
V. Among the antibiotics that have been tested clinically, azithromycin
is the most widely studied. A total dose of 60 mg/kg azithromycin,
given either as 12 mg/kg once daily for 5 days or 20 mg/kg once
daily for 3 days, provides the best rate of GABHS eradication.
Thus a total dose of 60 mg/kg azithromycin given during 3 or 5
days constitutes an alternative treatment to standard penicillin
therapy in cases of penicillin hypersensitivity, when patient
nonadherence to a 10-day penicillin regimen is suspected or for
patients who fail therapy with a beta-lactam.
-----
J Int Med Res. 2004 Jan-Feb;32(1):1-13.
Acute streptococcal tonsillopharyngitis: a review
of clinical efficacy and bacteriological eradication.
Schaad UB.
University Children's Hospital, Basel, Switzerland. urs-b.schaad@unibas.ch
This review evaluates studies published between January 1997
and August 2003 comparing clinical outcome and bacteriological
eradication rates for patients with acute streptococcal tonsillopharyngitis
treated with penicillin or other antimicrobial agents. Studies
were identified using MEDLINE, and clinical outcome and bacteriological
eradication at end of treatment and 2 weeks after end of treatment
were ascertained. Any longer-term follow-up was also noted, along
with treatment-related adverse events and compliance. Clinical
efficacy rates between penicillin and comparator antibiotics were
generally high and similar. Bacterial eradication rates were more
variable and, 2 weeks after treatment, ranged from 64% to 93%
for penicillin and 31% to 98% for comparators. Simpler dosing
schedules and shorter therapy durations produced higher compliance
rates. This review highlights the similarities and differences
between treatment with penicillin and a wide range of comparator
antibiotics. Therapy for acute group A streptococcal pharyngitis
should combine excellent clinical efficacy, high bacteriological
eradication rates, good tolerance and a simple, convenient dosing
regimen.
-----
Clin Microbiol Infect. 2004 Jan;10(1):27-36.
Clinical and bacteriological efficacy of the ketolide
telithromycin against isolates of key respiratory pathogens: a
pooled analysis of phase III studies.
Low DE, Brown S, Felmingham D.
Mount Sinai Hospital, Department of Microbiology, University of
Toronto, 600 University Avenue, Room 1487, Toronto, Ontario, Canada
M5G 1X5. dlow@mtsinai.on.ca
A pooled analysis of data from 13 phase III studies of telithromycin
in the treatment of community-acquired pneumonia, acute exacerbations
of chronic bronchitis, acute sinusitis or group A beta-haemolytic
streptococcal pharyngitis and tonsillitis was undertaken. Causative
key respiratory tract pathogens (Streptococcus pneumoniae, Haemophilus
influenzae, Moraxella catarrhalis, Staphylococcus aureus and Streptococcus
pyogenes) were isolated at entry to the studies from cultures
of relevant respiratory samples and tested for their susceptibility
to telithromycin, penicillin and macrolides (erythromycin A).
The combined clinical and bacteriological efficacy of telithromycin
at the post-therapy, test-of-cure visit (days 17-24) was assessed
in patients from whom a microbiologically evaluable pathogen was
isolated at entry. More than 98% of key respiratory pathogens
isolated, including penicillin G- and macrolide (erythromycin
A)-resistant strains of S. pneumoniae, demonstrated full or intermediate
susceptibility to telithromycin in vitro at the breakpoints of
< or = 1.0 mg/L (susceptible) and 2.0 mg/L (intermediate) used
for the purpose of evaluating the susceptibility of isolates recovered
during the clinical trials. Treatment with telithromycin 800 mg
once-daily for 5, 7 or 7-10 days resulted in high rates of clinical
cure (88.5%) and a satisfactory bacteriological outcome (88.9%),
similar to the figures seen with comparator antibacterial agents.
Clinical cure and eradication rates were good for all key respiratory
pathogens, including penicillin G- and macrolide (erythromycin
A)-resistant S. pneumoniae. The results suggest that telithromycin
will provide effective empirical therapy for community-acquired
upper and lower respiratory tract infections.
-----
J Am Geriatr Soc. 2004 Jan;52(1):39-45.
Antibiotic Treatment of Acute Respiratory Tract
Infections in the Elderly: Effect of a Multidimensional Educational
Intervention.
Gonzales R, Sauaia A, Corbett KK, Maselli JH, Erbacher
K, Leeman-Castillo BA, Darr CA, Houck PM.
Division of General Internal Medicine, Department of Medicine,
University of California at San Francisco, San Francisco, California
Division of Health Care Policy and Research, University of Colorado
Health Sciences Center, Denver Colorado Colorado Foundation for
Medical Care, Aurora, Colorado Department of Anthropology Health
and Behavioral Sciences Program, University of Colorado, Denver,
Colorado Centers for Medicare and Medicaid Services, Baltimore,
Maryland.
OBJECTIVES: : To measure and improve antibiotic use for acute
respiratory tract infections (ARIs) in the elderly. DESIGN: :
Prospective, nonrandomized controlled trial. SETTING: : Ambulatory
office practices in Denver metropolitan area (n=4 intervention
practices; n=51 control practices). PARTICIPANTS: : Consecutive
patients enrolled in a Medicare managed care program who were
diagnosed with ARIs during baseline (winter 2000/2001) and intervention
(winter 2001/2002) periods. A total of 4,270 patient visits were
analyzed (including 341 patient visits in intervention practices).
INTERVENTION: : Appropriate antibiotic use and antibiotic resistance
educational materials were mailed to intervention practice households.
Waiting and examination room posters were provided to intervention
office practices. MEASUREMENTS: : Antibiotic prescription rates,
based on administrative office visit and pharmacy data, for total
and condition-specific ARIs. RESULTS: : There was wide variation
in antibiotic prescription rates for ARIs across unique practices,
ranging from 21% to 88% (median=54%). Antibiotic prescription
rates varied little by patient age, sex, and underlying chronic
lung disease. Prescription rates varied by diagnosis: sinusitis
(69%), bronchitis (59%), pharyngitis (50%), and nonspecific upper
respiratory tract infection (26%). The educational intervention
was not associated with greater reduction in antibiotic prescription
rates for total or condition-specific ARIs beyond a modest secular
trend (P=.79). CONCLUSION: : Wide variation in antibiotic prescription
rates suggests that quality improvement efforts are needed to
optimize antibiotic use in the elderly. In the setting of an ongoing
physician intervention, a patient education intervention had little
effect. Factors other than patient expectations and demands may
play a stronger role in antibiotic treatment decisions in elderly
populations.
-----
BMJ. 2003 Dec 6;327(7427):1324.
Penicillin for acute sore throat in children:
randomised, double blind trial.
Zwart S, Rovers MM, de Melker RA, Hoes AW.
Julius Center for Health Sciences and Primary Care, University
Medical Center Utrecht, Stratenum 6.131, PO Box 85060, 3508 AB
Utrecht, Netherlands. S.Zwart@med.uu.nl
OBJECTIVE: To assess the effectiveness of penicillin for three
days and treatment for seven days compared with placebo in resolving
symptoms in children with sore throat. DESIGN: Randomised, double
blind, placebo controlled trial. SETTING: 43 family practices
in the Netherlands. PARTICIPANTS: 156 children aged 4-15 who had
a sore throat for less than seven days and at least two of the
four Centor criteria (history of fever, absence of cough, swollen
tender anterior cervical lymph nodes, and tonsillar exudate).
Interventions Patients were randomly assigned to penicillin for
seven days, penicillin for three days followed by placebo for
four days, or placebo for seven days. MAIN OUTCOME MEASURES: Duration
of symptoms, mean consumption of analgesics, number of days of
absence from school, occurrence of streptococcal sequelae, eradication
of the initial pathogen, and recurrences of sore throat after
six months. RESULTS: Penicillin treatment was not more beneficial
than placebo in resolving symptoms of sore throat, neither in
the total group nor in the 96 children with group A streptococci.
In the groups randomised to seven days of penicillin, three days
of penicillin, or placebo, one, two, and eight children, respectively,
experienced a streptococcal sequela. CONCLUSION: Penicillin treatment
had no beneficial effect in children with sore throat on the average
duration of symptoms. Penicillin may, however, reduce streptococcal
sequelae.
-----
Paediatr Drugs. 2003;5 Suppl 1:13-23.
Acute streptococcal pharyngitis in pediatric medicine:
current issues in diagnosis and management.
Shulman ST.
Division of Infectious Disease, Northwestern University Medical
School, Children's Memorial Hospital, Chicago, Illinois, USA.
sshulman@nwu.edu
Group A beta-hemolytic streptococcus (GABHS) is the most common
bacterial cause of acute pharyngitis. Although children infected
with GABHS will recover clinically without antibiotics, treatment
is recommended in order to prevent acute rheumatic fever and probably
suppurative complications, hasten resolution of clinical signs
and symptoms, and prevent transmission to close contacts. Streptococcal
pharyngitis usually cannot be reliably distinguished from other
etiologies on the basis of epidemiologic or physical findings,
and therefore a throat culture or a rapid antigen detection test
is generally necessary to confirm the diagnosis. All isolates
of GABHS are sensitive to penicillins and cephalosporins, whereas
resistance to macrolides has been identified in some geographic
regions. The recommended first-line therapy for streptococcal
pharyngitis is a 10-day course of penicillin V, usually given
2 or 3 times per day. A number of alternatives to penicillin V
are available, including other penicillins, macrolides, and cephalosporins.
As a class, the cephalosporins are noteworthy because they may
provide somewhat higher bacteriologic eradication rates than penicillin
V. Many cephalosporins can be administered twice daily, but they
also must be given for 10 days. Two third-generation cephalosporins,
cefdinir and cefpodoxime proxetil, are approved for use in a more
convenient 5-day dosing schedule, thus possibly increasing the
likelihood of adherence to the full course of therapy. Palatability
is also an important consideration when prescribing antibiotics
to children. In a series of studies, children preferred the pleasant
strawberry-cream taste of cefdinir to that of amoxicillin/clavulanate,
cefprozil, and azithromycin. Cefdinir may offer an alternative
to penicillin V for children with streptococcal pharyngitis, particularly
when compliance is a clinical concern.
-----
Clin Pediatr (Phila). 2003 Oct;42(8):663-71.
Short-course antimicrobial therapy of streptococcal
pharyngitis.
Block SL.
Kentucky Pediatric Research, Bardstown, Kentucky, USA.
While penicillin administered orally or intramuscularly is
the least expensive course of pharyngitis treatment, there are
many limitations to its use. These include the need for extended
treatment (i.e., 10 days) and poor palatability of its liquid
formulation and an alarming increase in the rates of failure with
standard doses of either IM or oral penicillin. Increasing rates
of beta-lactamase-producing normal flora and eradication of protective
alpha-streptococci may also play a role in penicillin treatment
failure. Thus practitioners may consider switching to amoxicillin
in higher doses (up to 40 to 60 mg/kg/day divided twice daily,
maximum dose 1 gram twice daily) as first-line therapy (Figure
1), similar to what we have done for acute otitis media. Five-day
short-course treatment with cefdinir or cefpodoxime may be suitable
alternatives, especially in patients with penicillin hypersensitivity
(not anaphylaxis). Concerns with higher costs of these second-line
agents and potential for resistance must be balanced with concerns
for patient adherence with penicillin treatment and the recent
increasing rate of penicillin failures. In light of recent reports
regarding the high rate of failure with azithromycin and increasing
macrolide resistance, clinicians should prescribe standard doses
of this drug for 5 days with caution.
-----
Altern Ther Health Med. 2003 Sep-Oct;9(5):68-79.
Efficacy of extract of Pelargonium sidoides in
children with acute non-group A beta-hemolytic streptococcus tonsillopharyngitis:
a randomized, double-blind, placebo-controlled trial.
Bereznoy VV, Riley DS, Wassmer G, Heger M.
Pediatric Department II, Academy for Continuing Medical Education,
Kiev, Ukraine.
BACKGROUND: Clinical trial data suggest that antibiotics are
not indicated for the treatment of acute non-group A beta hemolytic
strep (non-GABHS) tonsillopharyngitis. Nevertheless patients are
symptomatic and effective alternatives for its treatment are needed
that have been evaluated in clinical trials. OBJECTIVE: To confirm
that treatment with an extract of Pelargonium sidoides (EPs 7630)
is superior to placebo for the treatment of non-GABHS tonsillopharyngitis
in children. DESIGN: Randomized, double-blind, placebo-controlled
trial. SETTING: Six study sites in 4 pediatric and ENT primary
care outpatient clinics. PATIENTS: One hundred forty-three children
aged 6-10 years with non-GABHS tonsillopharyngitis present <
or = 48 h, a negative rapid strep screen, a Tonsillopharyngitis
Severity Score (TSS) > or = 8 points, and informed consent.
INTERVENTION: EPs 7630 or placebo (20 drops tid) for 6 days. MEASUREMENT:
The primary outcome criterion was the decrease of the TSS from
baseline (day 0) to day 4. RESULTS: The decrease of the TSS from
baseline (day 0) to day 4 was 7.1 +/- 2.1 points under EPs 7630
(n = 73), and 2.5 +/- 3.6 points under placebo (n = 70). The covariate
adjusted decrease was 7.0 +/- 2.4 points under EPs 7630, and 2.9
+/- 2.4 points under placebo. The 95% RCI for the difference between
the groups was [2.7; 4.9] demonstrating a significant difference
in efficacy of EPs 7630 compared to placebo (P < 0.0001). Adverse
events (AEs) occurred in 15/143 patients (EPs 7630: 4/73 patient,
placebo: 44/70) and were not related to the investigational medication.
CONCLUSIONS: EPs 7630 was superior compared to placebo for the
treatment of acute non-GABHS tonsillopharyngitis in children.
Treatment with EPs 7630 reduced the severity of symptoms and shortened
the duration of illness by at least 2 days.
-----
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.
------
Int J Clin Pract. 2003 Jul-Aug;57(6):519-29.
Telithromycin: the first ketolide antibacterial
for the treatment of community-acquired
respiratory tract infections.
Lorenz J.
Medical Department, Ludenscheid General Hospital, Germany.
Telithromycin is the first ketolide antibacterial to be approved
for clinical use. The ketolides represent a novel class of antibacterial
agents structurally related to the macrolides, which has been
developed specifically to offer an optimal spectrum for the treatment
of upper and lower respiratory tract infections (RTIs) caused
by common and atypical pathogens, including strains that are resistant
to currently used antibiotics. The innovative structural changes
that distinguish telithromycin from macrolides contribute to its
unique microbiological profile. Its well-balanced spectrum of
antibacterial activity is highly appropriate for the empirical
treatment of upper and lower community-acquired RTIs, offering
activity against common, including resistant, and atypical/intracellular
pathogens. Furthermore, telithromycin demonstrates a low propensity
to select for or induce resistance to macrolide-lincosamide-streptogramin
antibacterials. A once-daily dose of telithromycin 800 mg rapidly
achieves high concentrations in both plasma and respiratory tissues
and fluids and is maintained at effective levels throughout the
24-hour dosing period. In clinical trials, telithromycin has demonstrated
high clinical and bacteriological efficacy in the treatment of
community-acquired pneumonia, acute exacerbations of chronic bronchitis,
acute sinusitis and group A beta-haemolytic streptococcal tonsillitis/pharyngitis.
High efficacy was maintained in those patient groups considered
to be at high risk of complications and those with infections
caused by penicillin and/or macrolide (erythromycin) resistant
Streptococcus pneumoniae. Together with its favourable tolerability
profile and short course of once-daily therapy, these properties
indicate that telithromycin will be a valuable new antibacterial
for the empirical treatment of community-acquired RTIs.
-----
J Altern Complement Med. 2003 Apr;9(2):285-98.
Safety and efficacy of a traditional herbal medicine
(Throat Coat) in symptomatic temporary relief of pain in patients
with acute pharyngitis: a multicenter, prospective, randomized,
double-blinded, placebo-controlled study.
Brinckmann J, Sigwart H, van Houten Taylor L.
Research and Development, Traditional Medicinals Inc., Sebastopol,
CA, USA. brink@sonic.net
OBJECTIVE: To investigate the safety and efficacy of Throat
Coat) (Traditional Medicinals,) Sebastopol, CA), a traditional
demulcent herbal tea, in comparison with a placebo tea in the
symptomatic treatment of acute pharyngitis. DESIGN: Multicenter,
prospective, randomized, double-blinded, placebo-controlled, two-armed,
parallel-group clinical trial. SETTINGS: Three primary care clinics
in Duluth, MN, Madison, WI, and Middleton, WI. SUBJECTS: Patients
of both genders (>or=18 years of age) with clinical diagnoses
of acute pharyngitis. INTERVENTIONS: Patients (n = 60) were randomly
assigned to receive 5-8 oz of Throat Coat (n = 30) or a placebo
(n = 30), four to six times daily. The study period was 2 to 7
days with a window for the follow-up visit of 2-10 days accounting
for the variable duration of sore throat symptoms. OUTCOME MEASURES:
Primary efficacy parameter: sum of pain intensity differences
(SPID) for pain in throat on swallowing, calculated as the area
under the curve (AUC) of pain intensity difference scores (assessed
at 1 minute, 5 minutes, 10 minutes, 15 minutes, 20 minutes, and
30 minutes after treatment). Secondary efficacy parameter: total
pain relief (TOTPAR), calculated as the AUC from time 0 (baseline)
to 30 minutes of pain relief (assessed at 1 minute, 5 minutes,
10 minutes, 15 minutes, 20 minutes, and 30 minutes). RESULTS:
Compared to placebo, intensity of throat pain when swallowing
was significantly reduced by Throat Coat in intention to treat
and valid for efficacy analysis (VEA). Significant differences
in change from baseline pain were observed at 5 min (p = 0.007),
10 min (p = 0.005), 15 minutes (p = 0.01), 20 minutes (p = 0.05),
and 30 minutes (p = 0.04) after completion of the first dose (VEA
analysis). There was a statistically significant improvement of
SPID in the Throat Coat-treated group: Least square means +/-
standard error of the means (SEM) of SPID were -16.5 +/- 13.9
in the placebo group and -43.8 +/- 11.9 in the Throat Coat-treated
group (p = 0.012). TOTPAR was also significantly higher in the
Throat Coat-treated group: Least square means +/- SEM of TOTPAR
were 32.4 +/- 12.8 in the placebo group and 53.6 +/- 10.9 in the
Throat Coat-treated group (p = 0.031). This study shows that Throat
Coat is significantly superior to placebo and provided a rapid,
temporary relief of sore throat pain in patients with pharyngitis.
-----
Clin Pediatr (Phila). 2003 Apr;42(3):219-25.
Efficacy of penicillin vs. amoxicillin in children
with group A beta hemolytic streptococcal tonsillopharyngitis.
Curtin-Wirt C, Casey JR, Murray PC, Cleary CT, Hoeger WJ,
Marsocci SM, Murphy ML, Francis AB, Pichichero ME.
Elmwood Pediatric Group, University of Rochester Medical Center,
601 Elmwood Avenue, Rochester, NY 14642, USA.
The purpose of this study was to compare the bacteriologic
and clinical efficacy of oral penicillin versus amoxicillin as
first-line therapy for group A beta-hemolytic streptococcal (GABHS)
tonsillopharyngitis. The prospective observational study was conducted
over 18 months (January 2000-June 2001). Children enrolled had
acute onset of symptoms and signs and a laboratory-documented
GABHS tonsillopharyngitis illness. Follow-up examination and laboratory
testing occurred 10 +/- 4 days following completion of treatment.
In total, 389 patients were enrolled (intent-to-treat group):
195 received penicillin V and 194 received amoxicillin. Fifty-six
of the penicillin-treated and 57 amoxicillin-treated patients
refused to take the drug, or were noncompliant, or did not return
for the follow-up visit, leaving 276 patients in the per-protocol
group: 139 penicillin-treated and 137 amoxicillin-treated. Bacteriologic
cure for amoxicillin-treated children occurred in 76% versus 64%
in the penicillin-treated children (p = 0.04). The clinical cure
rate for amoxicillin-treated children was 84% compared to 73%
in the penicillin-treated children (p = 0.03). Since treatment
allocation was not randomized, logistic regression analysis was
used to adjust for treatment group differences. The odds ratio
(OR) estimate for cure for patients in the amoxicillin versus
penicillin V treatment group remained significant (OR = 1.84,
95% confidence interval 1.02-3.29); the same was true for dinical
cure (OR = 1.99, 95% CI = 1.02-3.87). Amoxicillin may be superior
to penicillin for bacteriologic and clinical cure of GABHS tonsillopharyngitis.
-----
Ann Emerg Med. 2003 May;41(5):601-8.
Oral dexamethasone for the treatment of pain in
children with acute pharyngitis: a randomized, double-blind, placebo-controlled
trial.
Bulloch B, Kabani A, Tenenbein M.
Department of Pediatrics, Children's Hospital, University of Manitoba,
Winnipeg, Canada. bbulloch@phoenixchildrens.com
STUDY OBJECTIVE: We compare oral dexamethasone with placebo
for the relief of pain in children with acute pharyngitis. METHODS:
We performed a prospective, randomized, double-blind, placebo-controlled
trial of children aged 5 to 16 years who presented to the emergency
department with acute pharyngitis. Children rated their pain on
a standardized color analog scale and had a rapid streptococcal
antigen detection test performed to determine group assignment.
Children were randomized to dexamethasone (0.6 mg/kg, maximum
dose 10 mg) or placebo. Blinded research assistants called all
families daily to determine pain scores until the point of complete
pain relief. The primary outcome measures were the time to clinically
significant pain relief and the time to complete pain relief.
RESULTS: A total of 184 children were enrolled in the study. There
were 85 children in the antigen-positive group, of whom 45 were
randomized to dexamethasone and 40 to placebo. In children with
group A beta-hemolytic streptococcal pharyngitis, the median time
to clinically significant pain relief was 6 hours in the dexamethasone
group versus 11.5 hours in the placebo group (P =.02; effect size
of 5.5 hours with 95% confidence interval [CI] of 1.0 and 10.0
hours), and the time to complete pain relief was similar (36 hours
for placebo versus 40 hours for dexamethasone, P =.86; effect
size of 4.0 hours with 95% CI of -9.3 and 17.3 hours) in the placebo
group. There were 99 children enrolled in the antigen-negative
group, of whom 47 received dexamethasone and 52 received placebo.
In this group, the median time to clinically significant pain
relief was 13 hours in the dexamethasone group versus 9 hours
in the placebo group (P =.32; effect size of 4 hours with 95%
CI of -2 and 10 hours), and the time to complete pain relief was
similar (48 hours for placebo versus 50 hours for dexamethasone,
P =.61; effect size of 2 hours with 95% CI of -11.8 and 15.8 hours).
CONCLUSION: For all children with acute pharyngitis, oral dexamethasone
does not decrease the time to onset of clinically significant
pain relief or time to complete pain relief. However, in the subset
of children with positive antigen detection test results, there
is a statistically significant improvement in time to onset of
pain relief, but it is of marginal clinical importance.
-----
J Fam Pract. 2003 Aug;52(8):592-3.
Steroids ineffective for pain in children with
pharyngitis.
Via RM.
Department of Family and Community Medicine, Scott and White Memorial
Hospital, Texas A and M University Health Science Center College
of Medicine, Temple, TX, USA. mvia@swmail.sw.org
In children with acute pharyngitis, oral dexamethasone does
not provide clinically significant reductions in time to initial
or complete pain relief. Reserve its use for children with group
A beta-hemolytic streptococcus pharyngitis who have moderate to
severe pain, realizing that the benefit is of questionable significance.
-----
Med J Aust. 2002 Nov 4;177(9):512-5.
Treatment of sore throat in light of the Cochrane
verdict: is the jury still out?
Danchin MH, Curtis N, Nolan TM, Carapetis JR.
Clinical Research Fellow, University Department of General Paediatrics/Murdoch
Children's Research Institute, Royal Children's Hospital, Flemington
Road, Parkville, VIC 3052, Australia. danchinm@cryptic.rch.unimelb.edu.au
There are few good-quality studies of the effectiveness of
antibiotic treatment of proven group A streptococcal (GAS) pharyngitis
in children; available data suggest that antibiotics may reduce
symptom duration. While there is limited justification for antibiotic
treatment of GAS pharyngitis to prevent acute rheumatic fever
in non-Indigenous Australians, there is no justification for routine
antibiotic treatment of all patients with sore throat. Two strategies
are open to clinicians: not to treat GAS pharyngitis with antibiotics,
in which case no investigations should be done; or to treat cases
of sore throat with clinical features that suggest GAS, in which
case diagnosis should be confirmed with a throat swab, and penicillin
started while awaiting the result. Penicillin should be discontinued
if the swab is negative, or continued for 10 days if it is positive
for GAS. Surveillance of GAS infections and acute rheumatic fever
is needed in Australia, as are further studies of effectiveness
(including cost-effectiveness) of antibiotic treatment of proven
GAS pharyngitis.
-----
Paediatr Drugs. 2002;4(11):747-54.
Antibacterial therapy for acute group a streptococcal
pharyngotonsillitis: short-course versus traditional 10-day oral
regimens.
Brook I.
Department of Pediatrics, Georgetown University School of Medicine,
Washington, DC, USA. ib6@georgetown.edu
The objective of this review is to examine the use of short-course
antibacterial therapy of group A beta-hemolytic streptococcal
(GABHS) pharyngotonsillitis, compared with traditional 10-day
therapy. In preparing this paper we reviewed the medical literature
of studies comparing 10 days of penicillin with shorter courses
of antibacterial therapy. Short-course therapy of 6 days of amoxicillin,
4 to 5 days of cephalosporins, and 5 days of azithromycin was
found to be as, or more effective than traditional 10-day penicillin
therapy. The benefits of short-course therapy include superior
compliance and adherence, lower incidence of adverse effects,
less effect on the bacterial flora, improved patient and parent
satisfaction, and lower drug costs. In conclusion, short courses
of amoxicillin, cephalosporins, and macrolides provide superior
or equal efficacy to a 10-day course of penicillin therapy in
the treatment of GABHS pharyngotonsillitis.
-----
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.
-----
Pediatr Infect Dis J. 2002 Apr;21(4):304-8.
Azithromycin versus penicillin V for treatment
of acute group A streptococcal pharyngitis.
Schaad UB, Kellerhals P, Altwegg M; Swiss Pharyngitis Study
Group.
University Children's Hospital of Basel, Zurich, Switzerland.
urs-b.schaad@unibas.ch
OBJECTIVE: To compare a 3-day azithromycin vs. a 10-day penicillin
V regimen for treatment of acute group A streptococcal (GAS) pharyngitis
in children and to determine whether viral infection and/or pharyngeal
GAS carriage in patients and adult contacts affect clinical and
bacteriologic efficacy. METHODS: This multicenter, randomized,
comparative, open label study compared 3-day, once daily 10 mg/kg
azithromycin oral suspension with a 10-day regimen of 100,000
IU/kg/day penicillin V oral suspension in three divided doses
in children with acute GAS pharyngitis. Clinical and bacteriologic
efficacy and tolerability of the antibiotics were evaluated. Recurrence
of symptoms and infection was monitored for 6 months. RESULTS:
In total, 292 children (age range, 2 to 12 years) received at
least one dose of study medication. Clinical success (cure/improvement)
with either antibiotic was similar at the end of therapy (Day
14; azithromycin, 95%; penicillin V, 97%) and at Day 28 (azithromycin,
94%; penicillin V, 95%). Bacteriologic eradication was significantly
less with azithromycin than with penicillin V at Day 14 (azithromycin,
38%; penicillin V, 81%; P < 0.001) and at Day 28 (azithromycin,
31%; penicillin V, 68%; P < 0.001). There was no associated
increase in GAS-related sequelae. The lower incidence of bacteriologic
eradication with azithromycin was not the result of possible concomitant
viral infections in the patients, GAS carriage in one parent/guardian
or any reduced susceptibility in pretreatment GAS isolates. Both
antibiotics were equally well-tolerated. CONCLUSIONS: Treatment
with 3-day, once daily 10 mg/kg azithromycin for GAS pharyngitis
is associated with similar high levels of clinical efficacy, but
lower levels of bacteriologic eradication, than with 10-day 100,000
IU/kg/day penicillin V.
-----
Pediatr Infect Dis J. 2002 Apr;21(4):297-303.
Comparison of two dosages of azithromycin for
three days versus penicillin V for ten days in acute group A streptococcal
tonsillopharyngitis.
Cohen R, Reinert P, De La Rocque F, Levy C, Boucherat M,
Robert M, Navel M, Brahimi N, Deforche D, Palestro B, Bingen E.
Association Clinique et Therapeutique Infantile du Val de Marne,
Paris, France. cohen@wanadoo.fr
BACKGROUND: Three-day, 10 mg/kg/day azithromycin (AZM) studies
in pediatric acute group A streptococcal tonsillopharyngitis have
shown contradictory bacteriologic results. This study investigates
the efficacy and tolerability of two dosages of 3-day azithromycin
(20 mg/kg/day and 10 mg/kg/day) compared with 10-day penicillin
V. METHODS: This was a prospective, comparative, randomized, multicenter
trial. Children were scheduled to return for visits at 14 days
(main end point) and 1 month after the onset of treatment for
clinical and bacteriologic assessment. Molecular tools were used
to compare pre- and posttreatment group A beta-hemolytic Streptococcus
(GABHS) isolates. RESULTS: Between November, 1997, and July, 1998,
501 patients (169 AZM 10 mg, 165 AZM 20 mg, 167 penicillin V)
between 2 and 12 years old were enrolled; 500 were assessable
for safety, 469 for intent to treat analysis and 420 for efficacy
in the per protocol analysis. Before treatment 25 (7.9%) of 315
GABHS stains isolated from patients receiving AZM were resistant
to this compound. On Day 14 pretreatment GABHS were eradicated
from 78 (57.8%) of the 135 children receiving the AZM 10 mg regimen,
131 (94.2%) of the 139 receiving AZM 20 mg and 123 (84.2%) of
the 146 taking penicillin. One month after the outset of treatment,
bacteriologic relapses were observed in 40.5% (n = 30) of the
children receiving AZM 10 mg, 14.8% (n = 18) of children taking
AZM 20 mg and 13.2% (n = 15) of those treated with penicillin
V. AZM 20 mg/kg/day was statistically superior to AZM 10 mg/kg/day
microbiologically on Day 14 (P = 0.0001) and Day 30 (P = 0.0001)
and clinically on Day 14 (P = 0.0035). AZM 20 mg/kg/day was statistically
equivalent both microbiologically and clinically to standard therapy
with penicillin V at all endpoints. The incidence of treatment-related
adverse events was similar in the two azithromycin groups [AZM
10 mg, 31 of 169 (18.3%); AZM 20 mg, 37 of 164 (23%)] but significantly
higher than those observed in the penicillin V group [5 of 166
(3%); P < 0.0001]. Most treatment-related adverse events were
gastrointestinal and of mild-to-moderate severity. Fourteen patients
withdrew from the trial because of adverse events (1 in the penicillin
V group, 7 in the AZM 10 mg group and 6 in the AZM 20 mg group).
CONCLUSION: This is the first study to demonstrate a daily dose-dependent
difference in microbiologic efficacy of a regimen; 3-day AZM 20
mg/kg/day is a more effective regimen than 3-day AZM 10 mg/kg/day
for pediatric GABHS tonsillopharyngitis.
-----
Arzneimittelforschung. 2002;52(3):194-9.
Local anaesthetic properties of ambroxol hydrochloride
lozenges in view of sore throat.
Clinical proof of concept.
Schutz A, Gund HJ, Pschorn U, Aicher B, Peil H, Muller
A, de Mey C, Gillissen A.
Ear, Nose and Throat Institute, Stuttgart, Germany.
Acute oro-pharyngeal catarrh is characterised by mild to severe
sore throat, such as pain on swallowing, feeling of scratchiness,
burning and urge to cough. The present study was conducted to
explore whether the test compound is going to show clinical relevance
and is a suitable medication for the relief of these symptoms.
OBJECTIVE: Description and comparison of the efficacy and tolerability
of lozenges containing 20 mg ambroxol hydrochloride (trans-4-[(2-amino-3,5-dibrombenzyl)amino]cyclohexano
hydrochloride, CAS 18683-91-5) in relieving acute sore throat,
in comparison to placebo. DESIGN: Multi-centre, prospective, placebo-controlled,
randomised, double-blind trial involving two days of treatment
with up to 6 lozenges containing 20 mg ambroxol hydrochloride
per day. SUBJECTS: Two-hundred-eighteen (218) patients were enrolled
(97 males, 121 females, average age: 39.4 +/- 15 years, range:
17-81 years); 215 were treated: 107 with 20 mg ambroxol and 108
with placebo; 26 discontinued prematurely (13 in each treatment
group). 208 patients constituted the intent-to-treat (ITT) dataset
(105 and 103 for treatment with ambroxol and placebo, respectively);
196 patients constituted the perprotocol (PP) dataset (97 and
99, respectively); all treated patients were part of the dataset
for safety analysis. TREATMENTS: Double-blind treatment with up
to 6 lozenges per day containing 20 mg ambroxol hydrochloride
or placebo (a lozenge with a distinct minty flavour). MAIN OUTCOME
MEASURES: The time-weighted average pain relief over the first
3 h after the first lozenge as a ratio of the baseline pain intensity
of sore throat (SPIDnorm) and the patients' evaluation of efficacy
and tolerability at the end of each day of treatment. RESULTS:
Both treatments led to a reduction of pain intensity; the mean
(+/- SD) SPIDnorm after the 1st lozenge were 0.39 +/- 0.27 and
0.28 +/- 0.25 for 20 mg ambroxol hydrochloride and placebo, respectively;
the treatment effect of ambroxol was statistically significantly
superior compared to placebo (p: 0.0029; 95% confidence interval
estimate of the mean treatment difference for ambroxol minus placebo:
0.04 to 0.18). At the end of each subsequent ambulatory treatment
day with up to 6 lozenges per day, a statistically significantly
higher proportion of patients scored a higher level of efficacy
for the active treatments with ambroxol hydrochloride compared
to placebo. The investigational treatments were equally well tolerated.
CONCLUSIONS: Sucking lozenges containing 20 mg ambroxol hydrochloride
has a beneficial pain relieving effect in patients with acute
sore throat, superior to that which otherwise can be achieved
by sucking a placebo lozenge. This finding confirms that the preclinical
local anaesthetic properties of ambroxol hydrochloride may have
beneficial clinical implications.
-----
East Afr Med J 2002 Nov;79(11):588-92
Antibacterial effect of Zingiber officinale and
Garcinia kola on respiratory tract pathogens.
Akoachere JF, Ndip RN, Chenwi EB, Ndip LM, Njock TE, Anong DN.
Department of Life Sciences, Faculty of Science, University of
Buea, PO Box 63, Cameroon.
OBJECTIVE: To investigate the antibacterial activity of Zingiber
officinale (ginger) Garcinia kola (bitter kola) on four respiratory
tract pathogens. DESIGN: A prospective study based on laboratory
investigations. SETTING: Department of Life Sciences, University
of Buea. Throat swabs were collected from 333 individuals with
running nostrils, cough and/or catarrh in three localities of
Buea namely Bokwango, Molyko and Bolifamba. Staphylococcus aureus,
Streptococcus pyogenes, Streptococcus pneumoniae and Haemophilus
influenzae were isolated from the specimens using standard microbiological
procedures. The antibacterial activity of ethanolic extracts of
ginger and bitter kola, were investigated on these pathogens using
the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal
Concentration (MBC) assays. RESULTS: The extracts exhibited antibacterial
activity against the pathogens. The MIC of extracts ranged from
0.0003 microg/ml to 0.7 microg/ml for ginger and 0.00008 microg/ml,
to 1.8 microg/mL for bitter kola, while MBC ranged from 0.1.35
microg/ml to 2.04 microg/ml for ginger and 0.135 microg/ml to
4.2 microg/ml for bitter kola. CONCLUSION: Results indicated that
extracts of ginger root and bitter kola may contain compounds
with therapeutic activity.
-----
Pediatr Allergy Immunol 2003 Feb;14(1):50-4
Relationship between group A beta-hemolytic streptococcal
tonsillopharyngitis and asthma.
Del Carmen Trojavchich M, Crisci CD, Shafa M, Rybicki BA.
Department of Pediatrics, San Antonio de Areco General Hospital,
Buenos Aires, Argentina. mctroja@areconet.com.ar
Increasing morbidity due to asthma in children and antimicrobial
resistance among human pathogens are both major public-health
concerns. Frequent use of antibiotics during childhood might be
a factor underlying the rising severity and prevalence of asthma
and other allergic disorders. The objective of the study was to
determine if pediatric patients with asthma or allergic rhinitis
have an altered rate of group A beta hemolytic streptococcal (GABHS)
tonsillopharyngeal infection which might support any change in
guidelines for antibiotic prescription. A prospective analysis
of all patients presenting a clinical feature of GABHS pharyngitis
with a sore throat in two pediatric clinics located in Detroit,
MI, USA and San Antonio de Areco, Buenos Aires, Argentina. Eligible
patients aged between 2 and 18 years were screened for the presence
of asthma and/or allergic rhinitis and administered a test (rapid
strep test) and throat culture to determine GABHS infection. At
the Redford Medical Center, Detroit, 500 patients met the eligibility
criteria, with 168 (33.6%) having a positive strep test. At the
San Antonio de Areco's Hospital, in a rural area 100 km away from
Buenos Aires, 188 patients met the eligibility criteria, with
41 (21.8%) having a positive strep test or GABHS throat cultures.
In both the Detroit [odds ratio (OR) = 1.36; 95% confidence interval
(CI) 0.72-2.57] and Buenos Aires clinics (OR = 0.50; 95% CI 0.23-1.07),
patients with asthma or allergic rhinitis were not at an increased
risk for true GABHS tonsillopharyngeal infections when compared
with the general pediatric population. These results suggest that
children with asthma do not differ from the normal population
in their risk of developing GABHS tonsillopharyngeal infection
and should not be liberally prescribed antibiotics.
-----
Scand J Infect Dis 2002;34(11):847-8
Primary group A streptococcal peritonitis in a
previously healthy child.
Gillespie RS, Hauger SB, Holt RM.
Division of Nephrology, Children's Hospital and Regional Medical
Center, Seattle, Washington 98105-0371, USA. rgille@chmc.org
Primary peritonitis in a child without underlying medical conditions
is rare outside the neonatal period. A girl with no past medical
history presented with acute abdominal pain. Laparotomy revealed
primary peritonitis due to group A Streptococcus (serotype emm89).
She was treated with antibiotics and immune globulin, and recovered
fully.
-----
Epidemiol Infect 2002 Dec;129(3):471-8
Invasive group A streptococcal infections in the
San Francisco Bay area, 1989-99.
Passaro DJ, Smitht DS, Hett EC, Reingold AL, Daily P, van Beneden
CA, Vugia DJ.
California Emerging Infections Program, Oakland, CA 94617, USA.
To describe the epidemiology of invasive group A streptococcal
(iGAS) infections in the San Francisco Bay Area, population-based
active surveillance for laboratory-confirmed iGAS was conducted
by the California Emerging Infections Program in three California
counties. From January 1989 to December 1999, 1415 cases of iGAS
were identified. Mean iGAS incidence was 4.06/100,000 person-years
and case fatality ratio was 13%, with no linear trends over time.
Incidence was lowest in adolescents, was higher in men than women
(4.4 vs. 3.2/100,000 person-years), and was higher in African-Americans
(6.7) than in non-Hispanic (4.1) or Hispanic (3.4) Whites, Asians
(2.2) or Native Americans (17/100,000 person-years). Injecting
drug use was the riskiest underlying condition and was associated
with the highest attributable risk. Cases were associated with
several underlying conditions, but 23% occurred in previously
healthy persons. From 1989-1999, iGAS infections in the San Francisco
Bay Area became neither more common nor more deadly.
-----
Indian J Med Res 2002 Jun;115:215-41
A half-century of streptococcal research: then
& now.
Krause RM.
National Institute of Allergy & Infectious Diseases, National
Institutes of Health, Bethesda, Maryland, USA.
Research on Group A streptococci (GAS) before 1950 paved the
way for successful clinical trials to prevent acute rheumatic
fever (ARF) by treating the prior streptococcal infection with
penicillin. Prevention of ARF has led to almost complete disappearance
of rheumatic heart disease in the industrialized world, but has
yet to be accomplished in developing countries, where most of
the world's populations reside. Twenty years of research beginning
in 1918 by Lancefield and others delineated the modern classification
of haemolytic streptococci and led to the recognition that only
Group A is responsible for the pharyngitis that causes ARF. M-protein,
identified as a major virulence factor, is a powerful inhibitor
of phagocytosis, and antibodies to it promote type-specific phagocytosis
and therefore type-specific immunity. Other virulent properties
of GAS include a bulky capsule, as well as extracellular toxins
such as streptolysins S and O and streptococcal proteinase. McCarty
and others pursued the cell biology of GAS and identified the
cellular localization of various antigenic components. The discovery
of purified M-protein as a helical coiled-coiled fibrillar protein
has sparked development of M-protein vaccine. US, UK, and Trinidad
scientists described differences between streptococcal infections
of the throat and skin and noted particularly that many of the
GAS M-types that cause impetigo are less likely to cause pharyngitis.
GAS impetigo may cause acute glomerulonephritis, but such infections
do not result in ARF. The changing manifestations of disease over
time and the evolution of microbes are common themes in medicine
today. These themes are relevant to GAS pharyngitis and ARF, especially
the decline in the incidence of severe ARF and the decrease in
severity of GAS pharyngitis. Research on GAS bacteriophages led
to the discovery of a relationship between lysogenic GAS and production
of erythrogenic toxin and has broadened approaches to the molecular
epidemiology of GAS virulence. The 21st century begins with determination
of the complete genome sequence of M-1, M-18, and M-3 strains
of GAS. These studies provide evidence for phage-encoded toxins,
high-virulence phenotypes, and clone emergence. This research
will reveal genetic processes at the molecular level that control
the emergence and decline of streptococcal diseases in different
places and times and the shifting patterns in clinical manifestations.
-----
Arch Intern Med 2003 Feb 24;163(4):467-72
Clinical and epidemiologic features of group a
streptococcal pneumonia in Ontario, Canada.
Muller MP, Low DE, Green KA, Simor AE, Loeb M, Gregson D, McGeer
A; Ontario Group A Streptococcal Study.
Department of Microbiology, Mount Sinai Hospital, 600 University
Ave, Toronto, Ontario, Canada M5G 1X5.
BACKGROUND: Since the 1960s, group A streptococcus (GAS) has
accounted for less than 1% of cases of community-acquired pneumonia.
During the past 2 decades there has been a resurgence of invasive
GAS infection, but no large study of GAS pneumonia has been performed.
METHODS: To determine the clinical and epidemiologic features
of GAS pneumonia, we conducted prospective, population-based surveillance
of all invasive GAS infection in residents of Ontario from January
1, 1992, through December 31, 1999. RESULTS: Of 2079 cases of
invasive GAS infection, 222 (11%) represented GAS pneumonia. The
incidence of GAS pneumonia ranged from 0.16 per 100 000 in 1992
to 0.35 per 100 000 in 1999. Most cases were community acquired
(81%). Forty-four percent of nursing home-acquired cases occurred
during outbreaks. The case fatality rate was 38% for GAS pneumonia,
compared with 12% for the entire cohort with invasive GAS infection
and 26% for patients with necrotizing fasciitis. The presence
of streptococcal toxic shock syndrome (odds ratio, 19; 95% confidence
interval, 8.4-42; P =.001) and increasing age (odds ratio per
decade, 1.45; 95% confidence interval, 1.2-1.7; P<.001) were
associated with fatal outcome. Time to death was rapid, with a
median of 2 days despite antimicrobial therapy and supportive
measures. CONCLUSIONS: Group A streptococcal pneumonia is a common
form of invasive GAS disease but remains an uncommon cause of
community-acquired pneumonia. Progression is rapid despite appropriate
therapy. The incidence is similar to, and the case fatality rate
higher than, that of necrotizing fasciitis.
-----
Pediatr Infect Dis J 2003 Feb;22(2):105-9
Community outbreak of perianal group A streptococcal
infection in Denmark.
Petersen JP, Kaltoft MS, Misfeldt JC, Schumacher H, Schonheyder
HC.
Department of Pediatrics, Aarhus University Hospital, Denmark.
jesperpadkaer@yahoo.com
BACKGROUND: Perianal group A streptococcal infection (PASI)
occurs primarily in children. There is limited information on
the incidence, transmission and treatment of PASI. We report a
cluster of cases connected to a Danish kindergarten and observations
of the incidence of PASI in the local population. SETTING: A Danish
rural community with 1765 children 15 years and younger registered
with two general practice clinics. METHODS: After being alerted
of a possible cluster of PASI cases, all isolates of group A beta-hemolytic
streptococci were collected and subjected to T typing and pulsed
field gel electrophoresis (PFGE) if grown from either a rectal
swab or an accompanying throat swab obtained in the offices of
local general practitioners during the ensuing 4-month period.
Clinical data were obtained from the files of the local general
practitioners. RESULTS: Twelve cases of PASI were caused by group
A beta-hemolytic streptococci T type 28 with an identical PFGE
profile: 6 of the cases were in children attending the same kindergarten,
4 were connected otherwise to the cluster and 2 cases seemed to
be unrelated. Five cases of PASI with different T types and PFGE
profiles were diagnosed during the same period giving an estimated
annual incidence of 2 to 7 per 1000 children. Penicillin V was
ineffective in 3 cases, and no recurrence was seen after change
of the treatment to oral clarithromycin. CONCLUSIONS: A clone
of T type 28 seemed to be the cause of the largest cluster of
PASI cases described thus far. Clarithromycin was effective as
second line treatment. An estimated annual baseline incidence
of 2 to 7 per 1000 in the local population indicates that PASI
may not be as rare as previously estimated.
-----
J Clin Microbiol 2003 Jan;41(1):242-9
Comparison of LightCycler PCR, rapid antigen immunoassay,
and culture for detection of group A streptococci from throat
swabs.
Uhl JR, Adamson SC, Vetter EA, Schleck CD, Harmsen WS, Iverson
LK, Santrach PJ, Henry NK, Cockerill FR.
Division of Clinical Microbiology, Mayo Clinic and Foundation,
Rochester, Minnesota 55905, USA.
We compared the performance characteristics of a real-time
PCR method, the LightCycler Strep-A assay (Roche Applied Science,
Indianapolis, Ind.), to those of a rapid antigen immunoassay,
the Directigen 1-2-3 Group A Strep Test kit (BD Diagnostic Systems,
Sparks, Md.), and a standard culture method for detection of group
A streptococci (GAS) from 384 throat swabs. The LightCycler PCR
produced more positive results (n = 58) than either culture (n
= 55) or the Directigen immunoassay (n = 31). The results of the
LightCycler PCR and the Directigen method were independently compared
to the results of the accepted "gold standard," bacterial
culture. The sensitivities, specificities, and positive and negative
predictive values for this comparison were as follows: for the
Directigen method, 55, 99, 97, and 93%, respectively; for the
LightCycler PCR, 93, 98, 88, and 99%, respectively. In no case
was a throat swab positive by both the LightCycler PCR and the
Directigen method but negative by culture. The medical histories
of patients whose throat swabs were negative by culture but positive
by either the LightCycler PCR (n = 7) or the Directigen method
(n = 1) were reviewed. All of these patients had signs or symptoms
compatible with GAS disease, and therefore, all of these discordant
positive results (along with positive results by either the Directigen
method or the LightCycler PCR that agreed with the culture results)
were counted as true positives for statistical analysis. For this
analysis, the LightCycler PCR detected more true-positive results
than the culture method (58 versus 55 swabs); however, this difference
was not statistically significant (P = 0.5465). In contrast, statistically
significantly more true-positive results occurred by culture than
by the Directigen method (55 versus 31 swabs; P < 0.0001) and
by the LightCycler PCR than by the Directigen method (58 versus
31 swabs; P < 0.0001). The LightCycler PCR is a suitable stand-alone
method for the detection of GAS from throat swabs. Additionally,
this method requires less than half the personnel time and the
procedure can be completed in considerably less time ( approximately
1 h) than our standard approach (up to 2 days) for detection of
GAS in throat swabs (i.e., testing by the Directigen method with
negative results verified by culture).
-----
Antimicrob Agents Chemother 2003 Feb;47(2):489-93
Macrolide-Resistant Streptococcus pneumoniae and
Streptococcus pyogenes in the Pediatric Population in Germany
during 2000-2001.
Reinert RR, Lutticken R, Bryskier A, Al-Lahham A.
National Reference Center for Streptococci, Institute for Medical
Microbiology, University Hospital, D-52057 Aachen, Germany. Aventis
Pharma, Hoechst Marion Roussel, Romainville, France.
In a nationwide study in Germany covering 13 clinical microbiology
laboratories, a total of 307 Streptococcus pyogenes (mainly pharyngitis)
and 333 Streptococcus pneumoniae (respiratory tract infections)
strains were collected from outpatients less than 16 years of
age. The MICs of penicillin G, amoxicillin, cefotaxime, erythromycin
A, clindamycin, levofloxacin, and telithromycin were determined
by the microdilution method. In S. pyogenes isolates, resistance
rates were as follows: penicillin, 0%; erythromycin A, 13.7%;
and levofloxacin, 0%. Telithromycin showed good activity against
S. pyogenes isolates (MIC(90) = 0.25 micro g/ml; MIC range, 0.016
to 16 micro g/ml). Three strains were found to be telithromycin-resistant
(MIC >/= 4 micro g/ml). Erythromycin-resistant strains were
characterized for the underlying resistance genotype, with 40.5%
having the efflux type mef(A), 38.1% having the erm(A), and 9.5%
having the erm(B) genotypes. emm typing of macrolide-resistant
S. pyogenes isolates showed emm types 4 (45.2%), 77 (26.2%), and
12 (11.9%) to be predominant. In S. pneumoniae, resistance rates
were as follows: penicillin intermediate, 7.5%; penicillin resistant,
0%; erythromycin A, 17.4%; and levofloxacin, 0%. Telithromycin
was highly active against pneumococcal isolates (MIC(90) </=
0.016 micro g/ml; range, 0.016 to 0.5 micro g/ml). The overall
resistance profile of streptococcal respiratory tract isolates
is still favorable, but macrolide resistance is of growing concern
in Germany.
-----
Mayo Clin Proc 2003 Mar;78(3):289-93
Validation and modification of streptococcal pharyngitis
clinical prediction rules.
McGinn TG, Deluca J, Ahlawat SK, Mobo BH Jr, Wisnivesky JP.
Department of General Internal Medicine, Mount Sinai School of
Medicine, 1470 Madison Ave, Box 1087, New York, NY 10029, USA.
thomas.mcginn@mountsinai.org
OBJECTIVE: To validate a simplified version of the Walsh clinical
prediction rules (CPRs) for the presence of streptococcal pharyngitis
in an inner-city, ethnically diverse population. PATIENTS AND
METHODS: This prospective study conducted in New York City, NY,
from January 1,1997, to May 31,1997, consisted of 171 consecutive
adult walk-in patients who presented with symptoms of upper respiratory
tract infection and/or sore throat. The patients were assessed
by using 5 clinical factors: cough, exposure to known streptococcal
contact, temperature, tonsillar-pharyngeal exudates, and cervical
lymphadenopathy. Throat cultures for group A beta-hemolytic streptococcus
were obtained from all patients. Clinicians assessing the patients
were unaware of throat culture results, and those processing the
throat cultures were blinded to the clinical predictors. RESULTS:
The prevalence of streptococcal pharyngitis was 24% (95% confidence
interval, 18%-30%). The simplified version of the Walsh CPR for
streptococcal pharyngitis predicted accurately the probability
of a positive culture in our diverse population (area under the
receiver operating characteristic curve, 0.71). The simplified
CPR also showed clinically useful likelihood ratios and posterior
probabilities. CONCLUSION: A simplified version of the Walsh CPR
is accurate for diagnosing streptococcal pharyngitis in an inner-city
population. This finding should provide clinicians more confidence
in applying the CPR in similar clinical settings.
-----
Scand J Infect Dis 2002;34(12):880-6
Upper respiratory tract infections in general
practice: diagnosis, antibiotic prescribing, duration of symptoms
and use of diagnostic tests.
Andre M, Odenholt I, Schwan A, Axelsson I, Eriksson M, Hoffman
M, Molstad S, Runehagen A, Lundborg CS, Wahlstrom R; Swedish Study
Group on Antibiotic Use.
Center for Clinical Research, Falun, Sweden.
A diagnosis/antibiotic prescribing study was performed in 5
counties in Sweden for 1 week in November 2000. As part of this
study, the characteristics and clinical management of patients
with upper respiratory tract infections (n = 2899) in primary
care were analyzed. Almost half of the patients were aged <
15 y and one-fifth of the patients consulted out of hours. Of
all patients seeking primary care for upper respiratory tract
infections, 56.0% were prescribed an antibiotic. Almost all patients
who were given the diagnoses streptococcal tonsillitis, acute
otitis media or acute sinusitis were prescribed antibiotics, compared
to 10% of patients with common cold or acute pharyngitis. The
most frequently prescribed antibiotic was penicillin V (79.2%)
and this was even more pronounced out of hours, when the diagnoses
otitis media and streptococcal tonsillitis were more frequently
used. In patients with common cold and acute pharyngitis, the
percentage who received antibiotics increased with increasing
length of symptoms and increasing CRP levels. In patients with
acute pharyngitis or streptococcal tonsillitis, antibiotics were
prescribed less frequently provided streptococcal tests were performed.
The management of patients with upper respiratory tract infections
in general practice seems to be in good agreement with current
Swedish guidelines. However, the study indicates some areas for
improvement. The diagnosis of acute sinusitis seems to have been
overestimated and used only to justify antibiotic treatment.
-----
J Antimicrob Chemother. 2002 Feb;49(2):337-44.
Five day clarithromycin modified release versus
10 day penicillin V for group A streptococcal pharyngitis: a multi-centre,
open-label, randomized study.
Portier H, Filipecki J, Weber P, Goldfarb G, Lethuaire
D, Chauvin JP.
Dijon University Hospital, Hopital du Bocage, Service des Maladies
Infectieuses, 2 boulevard de Lattre de Tassigny, 21034, Dijon,
France. henriporter@chu-dijon.fr
OBJECTIVE: A multicentre, comparative, randomized, open-label,
Phase III trial evaluated the efficacy and tolerability of clarithromycin
modified release (MR) versus penicillin V for pharyngitis due
to group A beta-haemolytic streptococci (GABHS). METHODS: Three
hundred and forty-nine patients (12-40 years) with acute pharyngotonsillitis
and a positive Streptococcus A antigen immunoassay test were randomized
to receive clarithromycin MR 500 mg od for 5 days or penicillin
590 mg tds for 10 days. Patients were clinically evaluated and
a throat swab for culture obtained before treatment, after treatment
(day 8 or 13 depending on the treatment arm) and at the follow-up
visit (day 30). The main criterion for efficacy was the bacteriological
cure rate after treatment. RESULTS: Three hundred and forty-nine
patients were considered for the intent-to-treat analysis. After
treatment, clinical cure rates were 88.1% in the clarithromycin
group and 92.4% in the penicillin group, and eradication rates
were 82.8% and 83.6%, respectively. There were no statistically
significant differences between the two treatments. Three hundred
and three (87%) patients had a positive culture before treatment,
among which 29 (9.7%) were found to be clarithromycin resistant.
Two hundred and thirty-nine patients were clinically and bacteriologically
evaluable for per protocol analysis. After treatment, clinical
cure rates were 95.2% in the clarithromycin group and 97.3% in
the penicillin group, and eradication rates were 94.4% and 92%,
respectively. No statistically significant difference was shown.
Adverse events occurred in 46 patients of the clarithromycin group
and 31 of the penicillin group (with no statistical difference).
Most of them were of mild or moderate severity. CONCLUSION: Clarithromycin
MR administered once daily for 5 days is as safe and effective
as penicillin V administered three times a day for 10 days in
the treatment of GABHS pharyngitis.
-----
Laryngoscope. 2002 Jan;112(1):87-93.
Efficacy of single-dose dexamethasone as adjuvant
therapy for acute pharyngitis.
Wei JL, Kasperbauer JL, Weaver AL, Boggust AJ.
Department of Otorhinolaryngology, Mayo Clinic, 200 First Street
Southwest, Rochester, MN 55905, U.S.A.
HYPOTHESIS: Pharyngeal inflammatory pain is reduced by a single
dose of dexamethasone. STUDY DESIGN: Prospective, randomized,
double-blinded, placebo-controlled study. METHODS: From August
1998 to July 2000, a total of 118 patients were enrolled. We compared
placebo (n = 37), a 10-mg single dose of intramuscular injection
of dexamethasone (n = 39), and a 10-mg single dose of oral dexamethasone
(n = 42). All patients were given oral antibiotics and had bacterial
throat cultures. RESULTS: Complete telephone follow-up 12 hours
after treatment was available in 111 patients, and 24-hour follow-up
data were available in 116. The change in pain visual analogue
scale scores (pretreatment score minus 12-h follow-up score) reported
by patients who were given either intramuscular (median score,
4; mean score +/- SD, 4.2 +/- 2.3) or oral dexamethasone (median
score, 3; mean score +/- SD, 3.8 +/- 2.3) was significantly greater
than that of the patients who were given placebo (median score,
2; mean score +/- SD, 2.1 +/- 2.0) (P <.001 and P =.002, respectively).
This difference in improvement was also evident when the percentage
of change was compared in the three treatment arms at 12-hour
and 24-hour follow-up. Patients who were given dexamethasone had
the onset of pain relief a median of 4 hours earlier than those
who were given oral and intramuscular placebo (P =.029). Statistically
significant differences among the three treatment arms were confirmed
when a bacterial pathogen was identified (n = 47) but not in a
subset that did not have a pathogen identified. CONCLUSIONS: Single-dose
dexamethasone appears to be a safe, effective, and inexpensive
adjunctive treatment for acute pharyngitis in patients 15 years
of age and older. Patients treated with intramuscular or oral
dexamethasone had significant relief of pain (relative to baseline)
compared with patients who were given placebo. Identification
of a bacterial pathogen had a significant impact on the response
to dexamethasone.
-----
Acad Emerg Med. 2002 Jan;9(1):9-14.
A randomized clinical trial of oral versus intramuscular
delivery of steroids in acute exudative pharyngitis.
Marvez-Valls EG, Stuckey A, Ernst AA.
Department of Medicine, Division of Emergency Medicine, Louisiana
State University, New Orleans, LA, USA.
Previous study has shown that the use of intramuscular (IM)
steroid leads to improved symptoms in patients with group A beta-hemolytic
streptococcus (GABHS). OBJECTIVE: To compare oral with IM steroids
as an adjunct to antibiotic therapy in the treatment of acute
exudative pharyngitis. The null hypothesis was that there would
be no difference in effectiveness of oral versus IM steroids.
METHODS: The study was a randomized, double-blind outpatient clinical
trial. After consent was obtained, each patient was asked to rate
his or her pain on a 10-cm numbered visual analog scale (VAS;
0-10). All of the patients received injectable benzathine penicillin
or, if allergic to penicillin, a ten-day course of polyenteric-coated
erythromycin. Each patient was randomized to receive either injectable
steroid plus oral placebo or injectable placebo plus oral steroid.
All medications were given in the emergency department. All patients
were contacted by telephone at 24 hours (first follow-up) and
48 hours (second follow-up) by one of the study investigators
and asked to rate their pain based on another VAS. If their pain
was not resolved by 48 hours, they were called again daily for
the third to seventh day after the initial visit. The time to
total resolution of the sore throat was documented. The main outcome
measures were time to complete relief of pain and VAS scores.
Pain medication was not controlled; however, use of pain medications
and amounts were recorded. RESULTS: A total of 78 patients were
initially enrolled in the study. Eight patients were excluded
from the statistical analysis because of inability to follow up.
A total of 70 were entered, with 35 randomized to IM steroid plus
oral placebo and 35 to IM placebo plus oral steroid. There was
no difference in pain scores for the oral versus IM group at first
follow-up (p = 0.13) and second follow-up (p = 0.82), and in number
of hours to relief of pain (p = 0.06). Using repeated-measures
analysis of variance, no difference in the effects of the two
medications over time was detected (p = 0.83). CONCLUSIONS: The
results of this clinical trial suggest that oral steroid and IM
steroid provide similar levels of pain relief in acute exudative
pharyngitis.
-----
Med Sci Monit. 2001 Sep-Oct;7(5):1016-22.
A comparative study of cefaclor vs. amoxicillin/clavulanate
in tonsillopharyngitis.
Haczynski J, Bardadin J, Gryczynska D, Gryczynski M, Golabek
W, Kawalski H, Kazmierczak H, Krecicki T, Kubik P, Namyslowski
G, Popiel L.
Medical Department, Eli Lilly Polska, Warsaw, Poland. haczynski_jozef@lilly.com
BACKGROUND: Acute pharyngotonsillitis (APT) is one of the most
common inflammatory processes of adults and children in an outpatient
setting. Increasing failure rates, hypersensitivity to penicillin,
the required multiple daily doses and common side effects lead
to poor patients compliance and thus inadequate treatment duration,
providing therefore ground for considering alternative antimicrobial
agents. MATERIAL AND METHODS: This multicenter, randomized, single
blind study was undertaken in order to compare efficacy and safety
of cefaclor (375 mg BID) and amoxicillin/clavulanate (625 mg BID)
in 10 days treatment regiment of ambulatory patients with APT.
A total of 200 patients (age range between 12-65 years) with symptoms
of APT and positive antigen strep test were enrolled into the
study. Clinical and bacteriological responses were assessed after
the end of treatment (14th-18th day) and at the follow-up visit
(38th-45th day). All GABHS strains, isolated from throat cultures,
were tested for in vitro sensitivity to the antibiotics used in
the study and no strain was found resistant to both antibiotics.
RESULTS: The results indicated that both antibiotics had high--almost
99% effectiveness at the post therapy visit. On the follow up
visit an increased tendency of relapses was observed in the amoxicillin/clavulanate
treated group, compared to cefaclor treated group (8.33% vs 3.29%).
Relative risk of relapse in patients treated with amoxicillin/clavulanate
was 2.6 greater compared to cefaclor. There were significantly
higher rates of gastrointestinal adverse events in group treated
with amoxicillin/clavulanate (29/97 patients; 29.89%) compared
to cefaclor (16/95 patients; 16.84%) - p< 0.03. Frequency of
other adverse events did not differ significantly between the
groups. CONCLUSIONS: Cefaclor and amoxicillin/clavulonate provide
a clinically and bacteriologically effective treatment for patients
with pharyngotonsillitis caused by GABHS, but cefaclor treatment
is significantly safer in regard to gastrointestinal side effects.
-----
Drugs. 2001;61(6):815-29; discussion 830-1.
Telithromycin.
Balfour JA, Figgitt DP.
Adis International Limited, Mairangi Bay, Auckland, New Zealand.
Telithromycin is the first member of a new family of the macrolide-lincosamide-streptogramin-B
(MLS(B)) class of antimicrobials, the ketolides. It has a good
spectrum of activity against respiratory pathogens, including
penicillin- and erythromycin-resistant pneumococci, as well as
intracellular and atypical bacteria. Furthermore, it has a low
potential to select for resistance or induce cross-resistance
among other MLS(B) antimicrobials. At the recommended dosage of
800 mg orally once daily, telithromycin reaches maximal plasma
concentrations of about 2 mg/L. It penetrates rapidly into bronchopulmonary,
tonsillar, sinus and middle ear tissues and/or fluids and achieves
high concentrations at sites of infection. It also concentrates
within polymorphonuclear neutrophils. In clinical trials in patients
with community-acquired pneumonia (CAP), acute exacerbations of
chronic bronchitis (AECB) or pharyngitis/tonsillitis caused by
group A beta-haemolytic streptococci, telithromycin 800 mg once
daily achieved clinical cure rates of 86 to 95%. In acute maxillary
sinusitis (AMS), cure rates were 73 to 91%. A 7- to 10-day regimen
of telithromycin was as effective as a 10-day course of amoxicillin
1000 mg 3 times daily, clarithromycin 500 mg twice daily or a
7- to 10-day course of trovafloxacin 200 mg once daily for treating
CAP. A 5-day regimen of telithromycin was as effective as a 10-day
regimen of cefuroxime axetil 500 mg twice daily or amoxicillin/clavulanic
acid 500/125 mg 3 times daily in AECB. A 5-day regimen of telithromycin
was as effective as a 10-day regimen of clarithromycin 250 mg
twice daily or phenoxymethylpenicillin 500 mg 3 times daily in
pharyngitis/tonsillitis, or a 10-day regimen of amoxicillin/clavulanic
acid 500/125 mg 3 times daily in patients with AMS. Telithromycin
was well tolerated across all patient populations. Adverse events
associated with telithromycin were generally mild to moderate
in intensity and seldom led to treatment discontinuation. The
most frequent adverse events were diarrhoea (13.3%) and nausea
(8.1%). Other adverse events included dizziness and vomiting.
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