Gentamicin- and methicillin-resistant, clinical isolates of Staphylococcus aureus: comparative in vitro and in vivo efficacy of alternative antimicrobial drugs

Abstract

Six representative clinical isolates of gentamicin- and methicillin-resistant (GRMR) Staphylococcus aureus, constituting phage groups II and III, were susceptible only to amikacin, cefamandole, clindamycin, fosfomycin, fusidic acid, netilmicin, nitrofurantoin, trimethoprim-sulfamethoxazole, and vancomycin (Bauer-Kirby test). With few exceptions, the minimal bactericidal concentrations of the beta-lactam and aminoglycoside antibiotics tested, fusidic acid, and irregularly those of vancomycin, but not those of fosfomycin and rifampin, exceeded minimal inhibitory concentrations values by at least 8-fold. In vitro, combinations of rifampin with cefamandole, cefazolin, cefotaxime, erythromycin, fosfomycin, fusidic acid, netilmicin, and vancomycin yielded indifferent effects. The GRMR S. aureus strains were refractory against 50, 65, and 80 vol% of fresh defibrinated blood; following reduction of viable counts at 2 h (greater than or equal to 90%), rebound growth invariably occurred within 4 h after exposure. Combined human blood (55 vol%)-antibiotic assays revealed rifampin as the most effective drug, followed by vancomycin, fusidic acid, and cefamandole, in that order. Blood plus cefotaxime, cefazolin, or netilmicin yielded indifferent effects; fosfomycin failed in vitro. In terms of speed of recovery and survival data (chi 2 test), cyclophosphamide-pretreated, i.e., leukopenic NMRI mice responded best to chemotherapy with rifampin, followed by vancomycin, cefamandole, netilmicin, and fosfomycin, in that order; cefazolin yielded variable results.