AMPICILLIN-SULBACTAM IS EFFECTIVE IN PREVENTION AND THERAPY OF EXPERIMENTAL ENDOCARDITIS CAUSED BY BETA-LACTAMASE-PRODUCING COAGULASE-NEGATIVE STAPHYLOCOCCI

Optimal strategies for the prophylaxis and therapy of endocarditis cau sed by oxacillin resistant, coagulase negative staphylococci in patien ts with native or prosthetic valvular heart disease are not well defin ed, We compared the in vivo efficacies of ampicillin-sulbactam-based r egimens with those of vancomycin-based regimens in preventing and trea ting: experimental staphylococcal endocarditis caused by a homogeneous ly oxacillin-resistant, beta-lactamase-producing coagulase negative st aphylococcal isolate (Staphylococcus haemolyticus SE220). Ampicillin-s ulbactam (100 and 20 mg/kg of body weight, respectively, given intramu scularly in a two-dose regimen) was equivalent to vancomycin (30 mg/kg given intravenously in a two-dose regimen) in its prophylactic effica cy against the coagulase-negative staphylococcal strain (93 and 80%, r espectively). The combination of ampicillin-sulbactam plus either rifa mpin or vancomycin did not enhance the prophylactic efficacy compared with that of ampicillin-sulbactam or vancomycin alone, In the therapy of established aortic valve endocarditis in rabbits caused by this sam e coagulase-negative staphylococcal strain, animals received 7-day amp icillin-sulbactam-based or vancomycin-based regimens with or without r ifampin. All treatment regimens were effective at lowering intravegeta tion coagulase-negative staphylococcal densities and rendering vegetat ions culture negative compared with the coagulase-negative staphylococ cal densities and vegetations of untreated controls, with ampicillin-s ulbactam in combination with rifampin or vancomycin being the most act ive regimen, However, only the regimen of ampicillin-sulbactam in comb ination with vancomycin effectively prevented relapse of endocarditis posttherapy after a 5-day antibiotic-free period, For animals receivin g rifampin-containing regimens, relapses of endocarditis were associat ed with the in vivo development of rifampin resistance among coagulase -negative staphylococcal isolates in the vegetation, Ampicillin-sulbac tam was highly effective in the prevention of experimental endocarditi s caused by a P-lactamase-producing, oxacillin-resistant coagulase-neg ative staphylococcal strain, Ampicillin-sulbactam was also efficacious for the therapy of coagulase-negative staphylococcal endocarditis, es pecially when it was combined with vancomycin to prevent posttherapeut ic relapses.