Effective treatment of multidrug-resistant enterococcal experimental endocarditis with combinations of cell wall-active agents.

The efficacy of treatment with a combination of ampicillin, imipenem, and vancomycin was compared with that of two-drug combinations or monotherapy in a model of experimental endocarditis using a strain of Enterococcus faecium with high-level resistance to vancomycin and moderate intrinsic resistance to ampicillin and imipenem. In vitro time-kill synergy studies demonstrated bactericidal synergistic activity only for the triple combination. In vivo, monotherapy with vancomycin was not effective.

Effective treatment of cephalosporin-rifampin combinations against cryptic methicillin-resistant beta-lactamase-producing coagulase-negative staphylococcal experimental endocarditis.

The efficacy of cefazolin or cefpirome alone or combined with rifampin was compared with that of vancomycin alone or combined with rifampin in an experimental model of methicillin-resistant, beta-lactamase-producing, coagulase-negative staphylococcal endocarditis. Phenotypically, the mecA gene-positive strain used in vivo did not exhibit methicillin resistance by the agar dilution or disk susceptibility method but was resistant in vitro (oxacillin MIC, 64 micrograms/ml) by the microtiter dilution method with 2% NaCl supplementation. Macrodilution broth susceptibilities of standard inocula failed to demonstrate cross-resistance of staphylococci to cefazolin (MIC, 8 micrograms/ml) or cefpirome (MIC, 4 micrograms/ml).