EFFECT OF GENTAMICIN DOSING INTERVAL ON THERAPY OF VIRIDANS STREPTOCOCCAL EXPERIMENTAL ENDOCARDITIS WITH GENTAMICIN PLUS PENICILLIN

This study compares the effects of a total daily dose of gentamicin gi ven once a day (q.d.) or three times a day (t.i.d.) in the therapy of experimental endocarditis in rabbits caused by penicillin-susceptible, penicillin-tolerant, or penicillin-resistant viridans streptococci. F our isolates were used in vivo: one penicillin susceptible (MIC less t han or equal to 0.03 mu g/ml), one penicillin tolerant (MBC/MIC, less than or equal to 0.03/>32 mu g/ml, and two penicillin resistant (MICs = 0.5 and 2 mu g/ml). Animals were infected with one of the four isola tes and assigned to one of the following treatment regimens: no treatm ent, procaine penicillin at 1.2 million IU intramuscularly (i.m.) t.i. d., procaine penicillin plus gentamicin at 1 mg/kg of body weight i.m. t.i.d., procaine penicillin plus gentamicin at 3 mg/kg i.m. q.d., or procaine penicillin plus gentamicin at 1 mg/kg i.m. q.d. (only animals infected with the penicillin-susceptible isolate). Serum drug concent rations measured 30 min after administration of 1.2 million IU of peni cillin and 1 or 3 mg of gentamicin per kg were 22.6, 3.8, and 8.5 mu g /ml, respectively, The reduced total daily dose of gentamicin was inef fective among animals infected with penicillin-susceptible viridans st reptococci; treatment with 1 mg of gentamicin per kg per day plus peni cillin was less effective (P < 0.05) than was treatment with 3 mg of g entamicin per kg per day plus penicillin. The 1-mg/kg/day gentamicin t reatment regimen was not further studied. The gentamicin dosing interv al did not significantly affect (q.d. versus t.i.d., P > 0.05) the rel ative efficacy of penicillin plus gentamicin for treatment of experime ntal endocarditis among animals infected with each of the four isolate s tested.