Oral penicillin has been standard therapy for group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis for almost 50 years. Antibiotic treatment is presumed to prevent acute rheumatic fever. However, the data to support this practice were derived from studies performed in the 1950s on adults in the U.S. military. The method of treatment was long-acting injectable penicillin, and no studies were ever repeated with an oral formulation. It has been shown that oral penicillin, if given for less than 10 days for streptococcal tonsillopharyngitis, has a high clinical failure rate. Studies performed over the past few years using nonpenicillin antibiotic therapies given for less than 10 days found that they are indeed curative. Adam and colleagues performed a large randomized study to evaluate the clinical and bacterial response of nonpenicillin therapy for GABHS infections and also to assess the incidence of acute rheumatic fever.

Patients enrolled in the study were between one and 18 years of age and presented to one of 137 pediatric practices with a clinical diagnosis of tonsillopharyngitis. The diagnosis was confirmed by a rapid antigen test for GABHS. Excluded were patients whose diagnosis was not confirmed by culture of GABHS and those who had received antibiotics within the past 48 hours. At the initial visit, eligible patients were randomized to receive oral penicillin V given in three divided doses for 10 days or one of six other antibiotics for five days. The alternative therapies included amoxicillin/clavulanate potassium, ceftibuten, cefuroxime, loracarbef, clarithromycin or erythromycin estolate. Treatment started on the day of the clinic visit. Follow-up visits were scheduled at two to four days after completion of treatment to assess clinical and bacteriologic response, at seven to nine days to reassess clinical response and at seven to eight weeks to identify asymptomatic carriers of GABHS. Clinical responses were graded as cure, improvement or failure. Bacteriologic response was determined by repeat throat swabs at the first follow-up visit and again at the seven-week to eight-week visit. The patients were also evaluated for signs and symptoms of acute rheumatic fever and glomerulonephritis at every visit and also at six and 12 months after enrollment in the study.

The study enrolled 4,782 patients, of whom 3,214 were randomized to a five-day course of antibiotic and 1,568 to 10 days of treatment with penicillin. The clinical response rate (defined as improvement and cure) was 94.5 percent in the five-day antibiotic group and 93.4 percent in the penicillin group at the first follow-up visit. The resolution of clinical symptoms was significantly faster in the five-day antibiotic group, and there were more recurrences in the 10-day group. Regarding eradication of GABHS, the rate was 84.4 percent in the penicillin group and 83.3 percent in the five-day antibiotic group. These numbers remained essentially the same at the seven-week to eight-week follow-up visit. The rate of asymptomatic carriers was 15 percent in the five-day group and 13.2 percent in the 10-day group. Only three patients met Jones criteria for rheumatic fever (all from the five-day group), and one patient from each group was diagnosed with glomerulonephritis.

The authors conclude from this study that a five-day course of an oral antibiotic is just as effective as a 10-day course of oral penicillin V for GABHS tonsillopharyngitis. Complications of GABHS, including acute rheumatic fever and glomerulonephritis, were uncommon and when these sequelae were further analyzed, were found to have occurred outside of the time frame of the study.

editor's note: This large and rather convincing study should be reassuring to physicians who have been treating GABHS with non-pencillin therapies. It may force the Infectious Diseases Society of America to reevaluate its Clinical Practice Guideline from 1998. However, whether the significant additional cost of a macrolide or cephalosporin antibiotic compared with penicillin is worth a quicker clinical cure is a matter of debate.—j.t.k.