title: 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.affiliation: Division of Infectious Diseases, Harbor-University of California, Los Angeles, Medical Center, Torrance 90509, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Ramos
authors.forename: M
authors.initials: M
authors.lastname: Ing
authors.forename: E
authors.initials: E
authors.lastname: Kim
authors.forename: M D
authors.initials: MD
authors.lastname: Witt
authors.forename: A S
authors.initials: AS
authors.lastname: Bayer
mesh_terms: D000667:Ampicillin / Q000627:therapeutic use; D000818:Animals; D003030:Coagulase / Q000378:metabolism; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology / Q000517:prevention & control; D005260:Female; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000517:prevention & control; D013210:Staphylococcus / Q000187:drug effects / Q000201:enzymology* / Q000472:pathogenicity; D013407:Sulbactam / Q000627:therapeutic use; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D003030:Coagulase; C035444:sultamicillin; D000667:Ampicillin; D001618:beta-Lactamases; D013407:Sulbactam