Efficacy of Vancomycin, Arbekacin, and Gentamicin Alone or in Combination Against Methicillin-Resistant Staphylococcus aureus in In Vitro Infective Endocarditis Model / 감염과화학요법

ABSTRACT

BACKGROUND: Glycopeptide has been used for the one-and-only treatment of choice in methicillin resistant Staphylococcus aureus (MRSA) infection, but its exclusive use for the MRSA infection has led to the increased risk of glycopeptide-resistance. To find an alternative (s), we employed an in vitro infective endocarditis model (IVIEM) to compare the efficacy of vancomycin (VCM), arbekacin (ABK), and gentamicin (GM) alone or in combination. METHODS: Using two strains of clinically isolated MRSA, one GM susceptible (GS171) and the other GM resistant (GR153), fibrin clots were prepared and suspended in IVIEM. Antibiotics were added as a bolus to simulate human pharmacokinetics of regimens, including q 6 h, q 12 h, q 24 h, or continuous infusion with VCM, q 12 h or q 24 h with ABK, and q 8 h or q 24 h with GM. In cases of combination, regimens were VCM q 12 h plus ABK q 24 h, and VCM q 12 h plus GM q 24 h. Fibrin clots were removed from each model at 0, 8, 24, 32, 48, and 72 h, and the bacterial densities (in CFU/g) were determined. RESULTS: At 8 hour, the colony counts of GS171 were lower than those of GR153 (P=0.02), and the lowest with the ABK q12h against GS171 (P=0.01). At 72 hour, monotherapy with ABK or VCM produced same degree of bacterial reductions in IVIEM, regardless of dosing frequency or GM-resistance. In the case of GM-resistance, combination of VCM and ABK did show additive effect until 24 hours, although VCM and GM showed no indifference during all the experiments. Development of resistance during experiment was not observed with any regimens. CONCLUSIONS: Our data suggest that ABK monotherapy could be used as an alternative to VCM even in the treatment of GM-resistant staphylococcal endocarditis. Further studies with clinical trials are warranted to evaluate the additive effect of VCM and ABK.