Antibiotic Concentrations in Serum, Serum Bactericidal Activity, and Results of Therapy of Streptococcal Endocarditis in Rabbits

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Abstract
The correlation between antibiotic concentrations in serum, serum bactericidal activity, and results of therapy was studied in rabbits with streptococcal endocarditis. Five days of procaine penicillin G reduced bacterial titers to <10 per g in 12 of 14 vegetations in rabbits receiving 75,000 U intramuscularly every 6 h and 10 of 20 in rabbits given 37,500 U. Ten days of 18,750 U every 6 h did not reduce the titers. To test for cure, rabbits were treated with 75,000 U every 6 h for 10 or 20 days and then received no therapy for 7 days. At the end of the 7-day period without therapy, vegetations were sterile in five of five and eight of eight animals, respectively. Rabbits received 37,500 U every 6 h for 5, 10, or 20 days and then no therapy for 7 days, after which vegetations were sterile in one of seven, four of nine, and seven of eight animals, respectively. The median maximal serum bactericidal dilutions at 1 h were 1/16 when 75,000 U of procaine penicillin G was administered, 1/8 to 1/16 with 37,500 U, and 1/4 to 1/8 with 18,750 U. Serum bactericidal activity could not be detected in 50% of the rabbits 6 h after administration of 37,500 U. Cure was related to a median maximal serum bactericidal dilution of at least 1/8 to 1/16 1 h after penicillin administration. A median maximal serum bactericidal dilution of 1/4 to 1/8 resulted in unsuccessful therapy.