Ampicillin-sulbactam is effective in prevention and therapy of experimental endocarditis caused by beta-lactamase-producing coagulase-negative staphylococci.

Abstract

Optimal strategies for the prophylaxis and therapy of endocarditis caused by oxacillin-resistant, coagulase-negative staphylococci in patients with native or prosthetic valvular heart disease are not well defined. We compared the in vivo efficacies of ampicillin-sulbactam-based regimens with those of vancomycin-based oxacillin-resistant, beta-lactamase-producing coagulase-negative staphylococcal isolate (Staphylococcus haemolyticus SE220). Ampicillin-sulbactam (100 and 20 mg/kg of body weight, respectively, given intramuscularly in a two-dose regimen) was equivalent to vancomycin (30 mg/kg given intravenously in a two-dose regimen) in its prophylactic efficacy against the coagulase-negative staphylococcal strain (93 and 80%, respectively). The combination of ampicillin-sulbactam plus either rifampin 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 same coagulase-negative staphylococcal strain, animals received 7-day ampicillin-sulbactam-based or vancomycin-based regimens with or without rifampin. All treatment regimens were effective at lowering intravegetation coagulase-negative staphylococcal densities and rendering vegetations culture negative compared with the coagulase-negative staphylococcal densities and vegetations of untreated controls, with ampicillin-sulbactam in combination with rifampin or vancomycin being the most active regimen. However, only the regimen of ampicillin-sulbactam in combination with vancomycin effectively prevented relapse of endocarditis posttherapy after a 5-day antibiotic-free period. For animals receiving rifampin-containing regimens, relapses of endocarditis were associated with the in vivo development of rifampin resistance among coagulase-negative staphylococcal isolates in the vegetation. Ampicillin-sulbactam was highly effective in the prevention of experimental endocarditis caused by a beta-lactamase-producing, oxacillin-resistant coagulase-negative staphylococcal strain. Ampicillin-sulbactam was also efficacious for the therapy of coagulase-negative staphylococcal endocarditis, especially when it was combined with vancomycin to prevent posttherapeutic relapses.

• Authors: M C Ramos, M Ing, E Kim, M D Witt, A S Bayer
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 40 Issue 1 Pg. 97-101 (Jan 1996) ISSN: 0066-4804 [Print] United States
• PMID: 8787887 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Coagulase
• sultamicillin
• Ampicillin
• beta-Lactamases
• Sulbactam

Topics

• Ampicillin (therapeutic use)
• Animals
• Coagulase (metabolism)
• Drug Therapy, Combination (therapeutic use)
• Endocarditis, Bacterial (drug therapy, microbiology, prevention & control)
• Female
• Microbial Sensitivity Tests
• Penicillin Resistance
• Rabbits
• Staphylococcal Infections (drug therapy, microbiology, prevention & control)
• Staphylococcus (drug effects, enzymology, pathogenicity)
• Sulbactam (therapeutic use)
• beta-Lactamases (biosynthesis)