A comparison was made between two dosage plans for the intramuscular administration of benzathine penicillin G as prophylaxis against rheumatic fever, nephritis, and streptococcic infections in the armed forces. One group of 1,567 men received 600,000 units every four weeks; the other group, of 1,708 men, received 900,000 units every six weeks. No reactions of the anaphylactoid type occurred, but during the six months of the study 16 men were hospitalized for urticaria, angioneurotic edema, or joint symptoms; 1 1 were hospitalized after the first injection, 4 after the second, and 1 after the third. Most (11) of these severer reactions occurred after the injection of 900,000 units, but the probability of reaction to subsequent doses decreased in both groups, and prolong the interval between injections did not affect the probability of a reaction. Because few streptococcic infections were seen, this study did not test the effectiveness of the prophylaxis, but it did demonstrate the safety and feasibility of administering benzathine penicillin G in this way.
Sherwood RW, Gronbeck C, Denny FW. REACTIONS FROM MULTIPLE INJECTIONS OF BENZATHINE PENICILLIN G. JAMA. 1957;165(6):667–671. doi:10.1001/jama.1957.02980240025007
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