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Most authorities continue to recommend penicillin as the treatment of choice for group A streptococcal pharyngitis. If penicillin is used, 10 days of treatment are necessary to achieve a clinical and bacteriologic cure. The usually recommended penicillin V dose is 250 mg (400 000 IU) three times daily. Twice daily dosing is acceptable to some authorities if compliance is good. However, oral penicillin fails to eradicate group A streptococci from the pharynx in up to 17% of cases; in some studies 30% failure rates have been reported. Several European and United States studies indicate that a variety of oral cephalosporins, when used for 10 days, are significantly superior to penicillin V in eradicating group A streptococci from the pharynx. For example cefpodoxime proxetil given twice daily for 10 days is comparable to penicillin V given three times daily for 10 days in achieving a clinical cure and appears to be significantly superior to penicillin in eradicating group A streptococci from the pharynx. Preliminary studies from Europe and the United States strongly suggest that 5-day therapy with cefpodoxime (or other selected oral cephalosporins) is at least as effective, clinically and microbiologically, as 10-day therapy with penicillin V. Further clinical trials are warranted to confirm the adequacy of 5-day treatment and to assess the efficacy of cefpodoxime and other agents in preventing rheumatic fever.