Penicillin Failures?!

Abstract

To the Editor.—How can a “treatment of choice” have a failure rate of 35% to 42% and remain a preferred agent? Members of the American Academy of Pediatrics (AAP), it is time for a change. The paper by Kaplan’s group1 on penicillin treatment results for group A streptococcal (GAS) tonsillopharyngitis puts an exclamation point to my position for the past decade.2 In 1991 our group made the observation that penicillin, whether administered by injection or the oral route, produced inferior microbiologic results when compared with past eradication rates and compared with oral cephalosporins2; we accumulated more data pointing to the need for change3 and controversy followed.4,5 More recently our group was able to show that the drop in penicillin efficacy occurred around 1980,6 as hypothesized earlier by Kaplan.7 We also found that the major variables associated with penicillin treatment failure include the number of days ill before initiation of treatment and the patient’s age, with adolescents and adults experiencing reasonable cure rates.8 Despite the evidence, penicillin remained the recommended antibiotic of choice for treating these infections according to guidelines published by respected national and international advisory bodies. Why have these committees over the past 10 years not accepted the mounting body of data challenging the universal recommendation of penicillin as the treatment of choice for all patients with GAS tonsillopharyngitis?Perhaps the data were slow to be accepted because we don’t know why the microbiologic efficacy of penicillin in eradication of GAS from children with acute tonsillopharyngitis has occurred. In their excellent article, Kaplan and Johnson1 discuss the possibilities that they considered: Kaplan and Johnson declined to present the clinical outcomes in their patient population. They noted that “many participants” who are categorized by the examining physician as clinical failures were noted to have pharyngeal erythema alone at the time of the convalescent visit. Although the authors are clearly correct in their argument that virtually all patients with GAS tonsillopharyngitis improve with or without antibiotic therapy in a matter of 3 to 5 days from onset of symptoms, this does not eliminate the need for considering clinical results. In a recent study, our group found that fewer and milder symptoms were the rule in GAS relapses involving the same serotypes and these patients had bona fide infection as documented with GAS serology.10Truthfully, the resistance and trepidation to suggest change has been attributable to the recognized fact that many physicians in the United States and certainly worldwide do not use laboratory diagnosis as the gold standard for GAS throat infections. Overdiagnosis is rampant, probably occurring in >90% of teenagers and adults with sore throat illness and >70% of children. With such a high overdiagnosis rate, continued advocacy of penicillin seemed prudent because unnecessary treatment in the majority of patients clearly occurs. This rationale from a public health policy viewpoint has definite merit. All authorities recommend that a confirmatory laboratory test, either GAS rapid antigen detection or throat culture, be performed and be positive for an antibiotic prescription to be administered for patients with tonsillopharyngitis. Although I view the absence of such a confirmatory test as substandard care, most physicians in the United States and especially worldwide treat nearly all sore throats empirically with antibiotics. This is a major challenge without a clear answer.Kaplan and Johnson describe a 42% documented failure rate of injectable benzathine G based on all follow-up visits, and a 35% to 37% rate focusing on the third and fourth follow-up visits after oral or injectable drug. Both are quite high. The time has come, it is not premature, for the AAP members and committees to initiate change. In my view, cephalosporins should become the treatment of choice for documented GAS tonsillopharyngitis in children below age 12 years.2,3,8 They clearly have superior efficacy compared with penicillin, have been the most widely studied, and produce the most consistent high level of microbiologic and clinical cure.11 Easing into the acceptability of cephalosporin therapy, several recommending groups have pointed to first-generation cephalosporins as preferred among the class. However, it should be pointed out that very few comparative clinical trials exist among the cephalosporins to reach a conclusion whether one generation is equivalent to the next. Such studies are needed.