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-Hemolytic Streptococcal Tonsillopharyngitis in Children
Symptomatic Relapse of Group A
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Clinical Pediatrics
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Symptomatic Relapse of Group A
β-Hemolytic Streptococcal
Tonsillopharyngitis in Children
Janet R. Casey, MD, and Michael E. Pichichero, MD The frequency of symptomatic relapses following var- symptomatic relapse more often with penicillin than ious antibiotic treatments for group A β-hemolytic with cephalosporins (P = .02). Clinicians should be aware streptococcal tonsillopharyngitis was evaluated in that the rate of symptomatic failures after antibiotic 1080 pediatric patients. Within 5 days of completing therapy for group A β-hemolytic streptococcal tonsil- therapy, the rank-order frequency of treatment failures lopharyngitis differs by drug and is not an uncommon was (1) penicillin, (2) amoxicillin, (3) first-generation cephalosporins, (4) β-lactamase stable cephalo-sporins and amoxicillin-clavulanate (P = .005). Retreat- Keywords: streptococcal tonsillopharyngitis; treatment;
ment of symptomatic failures resulted in another In a recent meta-analysis, we found that clinical and bacterial failures after treatment for group A β-hemolytic streptococcal (GABHS) tonsil- Setting and Patients
lopharyngitis with penicillin occur 2 and 3 times Included in this retrospective study were children more frequently, respectively, than with oral aged 2 to 18 years who presented to the Elmwood cephalosporin.1 Our group has also recently reported Pediatric Group in Rochester, New York from a failure rate of 24% with amoxicillin at a daily September 1, 2004 to June 30, 2005, with acute dosage range of 10 to more than 70 mg/kg compared onset of symptoms and signs of GABHS tonsil- with failure rate of 36% with oral penicillin at a daily lopharyngitis (sore throat, fever, headache, abdomi- dosage range of 10 to more than 70 mg/kg2 and a nal pain, vomiting, pharyngeal erythema, tonsillar exudates, and/or tender lymphadenopathy), and who These data were collected as part of clinical had a positive result on a rapid antigen detection trials and raise the question of whether such relatively test or throat culture. Patients were excluded from high rates of failure occur in everyday pediatric prac- study if their symptom complex included rhinorrhea tice and how frequently these patients return for or cough, if antibiotic treatment had been used within care because of symptoms recurrence. We therefore the past 7 days, if there was a diagnosis of GABHS undertook the current study to examine the fre- tonsillopharyngitis within the past 30 days, or if quency of return office visits within 5 and 20 days there was an allergy to penicillins or cephalosporins.
after completion of therapy for GABHS tonsillo-pharyngitis with penicillin, amoxicillin, first-generationcephalosporins, or β-lactamase antibiotics that are Treatment
more stable, such as second-generation or third-generation cephalosporins or amoxicillin-clavulanate.
Children were treated with oral penicillin VK, amox-icillin, cephalexin, cefadroxil, amoxicillin-clavulanate,cefprozil, cefuroxime, cefdinir, or cefpodoxime twice From the University of Rochester School of Medicine, ElmwoodPediatric Group, Rochester, New York.
daily for 10 days according to the discretion of theprescribing physician. Antibiotic dosage was appro- Address correspondence to: Janet R. Casey, MD, 125 LattimoreRd, Rochester, NY 14620; e-mail [email protected]
priate for weight according to the manufacturers’ Clinical Pediatrics / Vol. 46, No. 4, May 2007 directions. If a patient returned with symptoms consis- failure from group 1 to group 4 favored the β-lactamase tent with GABHS tonsillopharyngitis, a second rapid antigen detection test or throat culture was done. If Among the 182 patients with clinical and bacte- the test confirmed GABHS tonsillopharyngitis, then a rial failure within 20 days of completion of primary second antibiotic treatment course was prescribed.
treatment, penicillin was prescribed for 4 (2%),amoxicillin for 2 (1%), cephalexin or cefadroxil for142 (78%), and a β-lactamase stable antibiotic for Outcomes
34 (19%). The clinical and bacterial failures within Outcomes of interest were the frequency of unsched- 5 days of completion of the second course of antibi- uled return office visits after primary and secondary otic treatment were 2 (50%), 0 (0%), 10 (7%), and treatment of GABHS tonsillopharyngitis because of 2 (6%); and within 5 and 20 days were 2 (50%), 1 (50%), symptoms and signs of GABHS illness.
16 (18%), and 7 (26%) for penicillin, amoxicillin,cephalexin or cefadroxil, and β-lactamase stable anti-biotic, respectively; the frequency of failure was sig- Statistics
nificantly different within 5 days after a second Frequency of unscheduled return office visits because of symptomatic GABHS tonsillopharyngitisfor the primary and secondary antibiotic treatmentregimens was compared using a Fisher exact test Discussion
and a Cochrane Armitage trend test. Significancewas assumed at P < .05.
This study of early symptomatic bacterial failure inGABHS tonsillopharyngitis was done to quantifywhat pediatricians might be seeing in clinical prac- tice. Early symptomatic bacterial failure, within5 days of antibiotic completion, occurred more fre- The analysis included 1080 patients (612 males, 468 quently with penicillin and amoxicillin, less fre- females) with a mean age of 7.6 years. Each patient quently with first-generation cephalosporins, and was assigned to one of 4 groups according to antibiotic least frequently with β-lactamase stable antibiotics.
treatment: group 1, penicillin VK; group 2, amoxi- Failures within 5 days of completion of treatment cillin; group 3, cephalexin and cefadroxil; group 4, would most likely be recognized by clinicians in prac- β-lactamase stable antibiotics (amoxicillin-clavulanate, tice. These are almost certainly bona fide bacterial fail- cefprozil, cefuroxime, cefdinir, or cefpodoxime). The ures uncontaminated by new intercurrent infections, symptoms present at diagnosis were fever, 68%; sore but the failure rate for amoxicillin, the most frequently throat, 100%; headache, 33%; abdominal pain, 24%; prescribed antibiotic for GABHS tonsillopharyngitis, vomiting, 14%; pharyngeal erythema and exudates, was 7% within the 5-day posttreatment time frame; a 7% failure rate may not be readily appreciated by cli- Age, gender proportion, and percentage of patients nicians. Overall, symptomatic failure occurred in 16% with various GABHS symptoms and signs did not of the patients, which likely would be recognized as an differ between the 4 antibiotic groups. Dosage range issue in everyday clinical practice. Failures between 6 was 15 to 65 mg/kg for penicillin, 20 to 60 mg/kg for and 20 days posttreatment may involve some new amoxicillin, 20 to 50 mg/kg for first-generation infection. Group A β-hemolytic streptococcal serotyp- cephalosporins, and 10 to 40 mg/kg for the β-lactamase ing is not performed in clinical practice nor was it stable antibiotics. Figure 1 shows the number of done in our study. However, previous work from our patients treated in each group and the symptomatic group and others suggests that 70% to 80% of bacter- bacterial failure rate within 5 and 20 days after com- ial failures within 20 days after completing therapy pletion of antibiotic treatment. Symptomatic failures are of the same serotype and due to ineffective antibi- within 5 days of completion of therapy occurred more frequently after penicillin and amoxicillin Penicillin and amoxicillin bacterial failure rates treatment than after amoxicillin-clavulanate or a for GABHS tonsillopharyngitis have risen over the past cephalosporin treatment (P = .03). Similar results 3 decades despite the absence of penicillin resistance for symptomatic failures occurred within 6 to 20 days to these drugs.4,5 One explanation may be the increased of completion of treatment (P = .03). The trend for production of β-lactamase in normal oral flora and the Symptomatic Relapse of Group A β-Hemolytic Streptococcal Tonsillopharyngitis / Casey, Pichichero Symptomatic Relapses Following Treatment of GABHS Tonsillopharyngitis
% Symptomatic Relapses Within 20 days of Antibiotic Completion % Symptomatic Relapses Within 5 days of Antibiotic Completion Figure 1.
Symptomatic bacterial failure rates of group A β-hemolytic streptococcal tonsillopharyngitis treated with different antibiotics.
prevalence of β-lactamase producing Staphylococcal research has established that penicillin-treated and aureus, Haemophilus influenzae, Moraxella catarrhalis, amoxicillin-treated patients have 37% and 24% bacte- and mouth anaerobes in the tonsillopharynx.6 These rial failure rates, respectively.1-2 About 70% to 80% of β-lactamase-producing copathogens may inactivate patients in clinical trials have a concurrent clinical penicillin and amoxicillin within the nasopharyngeal failure (relapse of symptoms with a positive culture).
milieu, thereby resulting in bacterial eradication On this basis, we would have predicted 25% and 17% failure.7 Coaggregation of GABHS with β-lactamase- clinical failures with penicillin and amoxicillin, producing Moraxella catarrhalis could also partly respectively. We found 25% and 18%. As previously shown by Kaplan and Johnson10 we observed a 50% In an earlier report, we showed that bona fide symptomatic bacterial failure rate for recurrent recurrent GABHS tonsillopharyngitis produces fewer GABHS tonsillopharyngitis in patients treated with and milder symptoms.9 In this study, we examined only those patients who had symptoms severe enough This study has limitations. Treatment allocation to return for an unscheduled visit. It is likely that was not double blind nor randomized. The choice of there were children with fewer and milder symptoms antibiotic for primary and relapse treatment was who did not present for an illness visit. Recent at the discretion of the practitioner and therefore Clinical Pediatrics / Vol. 46, No. 4, May 2007 subject to selection bias. However, use of penicillin daily for streptococcal tonsillopharyngitis. Clin Peds.
and amoxicillin at our practice is usually in the patient without recent or recurrent diagnosis of 4. Kaplan E, Johnson D. Unexplained reduced microbio- GABHS, thereby favoring a more positive outcome.
logical efficacy of intramuscular benzathine penicillin g Compliance was not monitored, and we did not do and of oral penicillin V in eradication of group AStreptococci from children with acute pharyngitis.
Pediatrics. 2001;108:1180-1186.
5. Stillerman M. Comparison of oral cephalosporins with Conclusion
penicillin therapy for group A streptococcal pharyngitis.
Pediatr Infect Dis J. 1986;5:649-654.
6. Brook I. Emergence and persistence of beta-lactamase- This study alerts pediatricians and family physicians producing bacteria in the oropharynx following peni- that the prevalence of symptomatic failures seen cillin treatment. Arch Otolaryngol Head Neck Surg.
with antibiotic treatment of GABHS tonsillopharyn- gitis is occurring with measurable frequency in pri- 7. Pichichero M. Group A streptococcal tonsillopharyngi- tis: cost-effective diagnosis and treatment. Ann EmergMed. 1995;25:390-403.
8. Lafontaine E, Wall D, Vanlerberg SL, Donabedian H, References
Sledjeski DD. Moraxella catarrhalis coaggregates withStreptococcus pyogenes and modulates interactions of 1. Casey J, Pichichero M. Meta-analysis of cephalosporin S. pyogenes with human epithelial cells. Infect Immun.
versus penicillin treatment of group A streptococcal ton- sillopharyngitis in children. Pediatrics. 2004;113:866-882.
9. Lee L, Ayoub E, Pichichero M. Fewer symptoms occur in 2. Curtin-Wirt C, Casey J, Murray P, et al. Efficacy of same-serotype recurrent streptococcal tonsillopharyngitis.
penicillin vs. amoxicillin in children with group A beta Arch Otolaryngol Head Neck Surg. 2000;126:1359-1362.
hemolytic streptococcal tonsillopharyngitis. Clin Peds.
10. Kaplan E, Johnson D. Eradication of group A strepto- cocci from the upper respiratory tract by amoxicillin 3. Curtin-Wirt C, Casey J, Murray P, et al. Efficacy of with clavulanate after oral penicillin V treatment failure.
cephalexin two vs. three times daily vs cefadroxil once

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