Antibiotic Combinations Preventing Bacterial Resistance: Studies on an in vitro Model with Staphylococcus aureus Exposed to Linezolid–Daptomycin

Abstract

To predict the anti-mutant effects of antibiotic combinations against Staphylococcus aureus, the mutant prevention concentrations (MPCs) of linezolid and daptomycin were determined at a linezolid-to-daptomycin concentration ratio that corresponds to the ratio of the 24-hour areas under the concentration-time curve (AUC24s) that were used in pharmacokinetic simulations in an in vitro dynamic model. The enrichment of linezolid-resistant mutants of two S.aureus strains was observed under linezolid exposure. The growth of daptomycin-resistant mutants exposed to daptomycin was less pronounced. Combination therapy prevented or restricted the development of S.aureus resistance to linezolid or daptomycin, respectively. These findings support the applicability of MPC determination to predict the anti-mutant effects of combination therapy with linezolid and daptomycin.