Pediatric Press Newsletter

Publication date: 2004-04-16

Superiority of Cephalosporin Therapy versus Penicillin for the Treatment of Group A Streptococcal Tonsillopharyngitis

This report was reviewed for medical and scientific accuracy by James M. Oleske, MD, MPH, Francois-Xavier Bagnoud Professor of Pediatrics, Director, Division of Pulmonary, Allergy, Immunology & Infectious Diseases, Department of Pediatrics, University of Medicine & Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey

Introduction

According to the results of a meta-analysis published in the April 2004 issue of Pediatrics, antibiotic therapy with cephalosporins was associated with significantly higher bacteriologic and clinical cure rates when compared to penicillin therapy in the treatment of Group A β-hemolytic streptococcal pharyngitis in children.¹ These findings confirm previously published meta-analyses^2,3 and reviews^4-7 that found cephalosporin therapy to be superior to penicillin in the treatment of Group A β-hemolytic streptococcal pharyngitis. The results of this meta-analysis will generate extensive debate because they contradict well-established practice guidelines from the American Academy of Pediatrics,⁸ the American Heart Association,⁹ the World Health Organization,¹⁰ and the Infectious Diseases Society of America recommending penicillin as the agent of choice for Group A β-hemolytic streptococcal pharyngitis.¹¹

Group A β-hemolytic streptococcus is the most common cause of bacterial pharyngitis and is responsible for 15% to 30% and 5% to 15% of all cases in children and adults, respectively.^12,13 The primary goal of antibiotic therapy is eradication of the bacterial pathogen. Eradication is necessary to prevent nonsuppurative and suppurative sequelae,¹⁴ eliminate contagion,¹⁵ and produce a more rapid resolution of patient symptoms.¹⁶

Due to its proven efficacy, relative safety, narrow spectrum and low cost, oral penicillin administered for 10 days has remained the agent of choice.^8-11 However, since the early 1980s, clinical studies have shown an increasing incidence of Group A β-hemolytic streptococcus not cured by penicillin treatment.^17-19 In 2001, Kaplan and Johnson found that intramuscular benzathine penicillin failed to eradicate Group A β-hemolytic streptococcus in 37% to 42% of children; oral penicillin failed in 35% of children.²⁰

Cephalosporins have been used successfully for the treatment of Group A β-hemolytic streptococcus since the early 1970s. Two previous meta-analyses have concluded that cephalosporin treatment was superior to penicillin therapy for Group A β-hemolytic streptococcal tonsillopharyngitis.^2,3 Since the publication of the last meta-analysis, a number of well-designed, controlled, randomized, comparative clinical trials have been conducted and published. Using updated and rigorous meta-analysis methodology, investigators compared the relative efficacy of cephalosporin and penicillin in treating Group A β-hemolytic tonsillopharyngitis in children. This Pediatric Press Newsletter reviews the methodology and results of their meta-analysis.

Superiority of Cephalosporins versus Penicillin for Group A β-hemolytic Streptococcus

A total of 140 citations of randomized, controlled trials comparing a cephalosporin and penicillin in the treatment of Group A β-hemolytic streptococcus were identified from Medline (1966-2000) and Embase (1974-2000) searches. Using stringent inclusion/exclusion criteria, an independent review identified 40 clinical trials of which 35 published trials that enrolled 7,125 pediatric subjects were included in the meta-analysis. The Jadad scale [0 to 5 (best quality trial) based on random- ization, being double-blinded, and accounting for study withdrawals] was used to assess the quality of the clinical trials.²¹ The 5 remaining unpublished trials were selected for inclusion in a sensitivity analysis that assessed publication b