To compare different modes of action of penicillin in preventing recurrences of rheumatic fever, one group of young rheumatic patients received oral penicillin repetitively in high, "therapeutic" dosage for the first ten days of each month, but no "prophylactic" dosage thereafter. The other group received monthly injections of benzathine penicillin, which acts both "therapeutically" to eradicate streptococci during the immediate period after injection, and "prophylactically" for the remainder of the month. The attack rates for streptococcal infections and rheumatic recurrences with the intermittent "therapeutic" oral regimen were significantly higher than the same rates with the injections or with previously tested oral regimens in which low, "prophylactic" doses were given daily throughout the month. The results suggest that both the intermittent "therapeutic" and the continuous "prophylactic" actions of penicillin are needed for the most effective form of antirheumatic prophylaxis.
Feinstein AR, Spaguolo M, Jonas S, Tursky E, Stern EK, Levitt M. Prophylaxis of Recurrent Rheumatic FeverIneffectiveness of Intermittent "Therapeutic" Oral Penicillin. JAMA. 1965;191(6):451–454. doi:10.1001/jama.1965.03080060025004