Chemotherapy of experimental streptococcal endocarditis. IV. Further observations on prophylaxis.

Abstract

A B S T R A C T The ability of antibiotics to prevent Streptococcus sangutis endocarditis was tested in rabbits. Only vancomycin or a combination of penicillin G plus streptomycin always prevented infection when administered as a single dose. A loading dose of 30 mg/kg of phenoxymethyl penicillin (penicillin V) followed by additional 7.5 mg/kg doses for 48 h proved to be the only successful prophylactic program that could be given orally to man. Cefazolin alone or with streptomycin in multiple doses was also an effective alternative to penicillin or penicillin derivatives. Erythromycin uniformly failed to protect animals from bacterial endocarditis but showed greater prophylactic efficacy when a low inoculum of streptococci was used.

Successful prophylaxis of experimental streptococcal endocarditis with single doses of sublethal concentrations of penicillin

“…Therefore, a bactericidal activity appears to be required for efficient prophylaxis only when infection is induced by inocula 10 or 100 times higher than the ID 90 . Durack & Petersdorf (1973) used an inoculum of 10 8 cfu and presented evidence that this inoculum was much higher than the ID 90 (Pelletier, Durack & Petersdorf, 1975). Hess, Dankert & Durack (1983) used an inoculum of 10 7 cfu, a size which is likely to be also above the ID 90 .…”

“…Studies in the rabbit model of endocarditis have suggested that high and repeated doses of bactericidal antibiotics, including penicillin, were necessary to achieve successful protection (Durack & Petersdorf, 1973;Pelletier, Durack & Petersdorf, 1975) Furthermore, antibiotics like clindamycin or tetracycline were ineffective, suggesting that bacterial killing was the main mechanism by which antibiotics protected against endocarditis. However the number of micro-organisms used to induce infection in these experiments was very high and probably greatly exceeded that found in man after dental manipulation.…”

Successful Single-Dose Amoxicillin Prophylaxis Against Experimental Streptococcal Endocarditis: Evidence for Two Mechanisms of Protection

“…This strain has been used in experiments on endocarditis in both rabbits [10] and rats [9,11]. (2) S. sanguis biotype II was provided by Dr. D. T. Durack (Duke University Medical Center, Durham, N.C.) who had used it in his investigations of prophylaxis against endocarditis in rabbits [5,12]. (3) Streptococcus mitior was isolated from a patient in Lausanne with endocarditis.…”

“…The results of both studies appear to contradict those of previous observations in rabbits by Durack and Petersdorf [5] and Pelletier et at. [12], in which single injections of several antibiotics failed to prevent infection. However, the latter experiments were performed with an inoculum of 10 8 cfu of S. sanguis, an inoculum which was probably many times higher than the ID90 for rabbits.…”

Single-Dose Rifampin Prophylaxis for Experimental Endocarditis Induced by High Bacterial Inocula of Viridans Streptococci

“…Four strains of viridans streptococci isolated from patients with endocarditis were used. Streptococcus intermedius and Streptococcus sanguis (originally provided by Dr. D. Durack, Duke University Medical School, Durham, NC) have previously been used in experiments in rabbits [10,11] and in rats [1-3, 6, 12]. In addition, two strains of Streptococcus mitis, S. mitis 1000 [6] and S. mitis 518, were selected.…”