Pharmacodynamics of Moxifloxacin, Meropenem, Caspofungin, and Their Combinations against In Vitro Polymicrobial Interkingdom Biofilms.

Biofilms colonize medical devices and are often recalcitrant to antibiotics. Interkingdom biofilms, where at least a bacterium and a fungus are present, increase the likelihood of therapeutic failures. In this work, a three-species in vitro biofilm model including Staphylococcus aureus, Escherichia coli, and Candida albicans was used to study the activity of the antibiotics moxifloxacin and meropenem, the antifungal caspofungin, and combinations of them against interkingdom biofilms. The culturable cells and total biomass were evaluated to determine the pharmacodynamic parameters of the drug response for the incubation with the drugs alone. The synergic or antagonistic effects (increased/decreased effects) of the combination of drugs were analyzed with the highest-single-agent method. Biofilms were imaged in confocal microscopy after live/dead staining. The drugs had limited activity when used alone against single-, dual-, and three-species biofilms. When used in combination, additive effects against single- and dual-species biofilms and increased effects (synergy) against biomass of three-species biofilms were observed. In addition, the two antibiotics showed different patterns, moxifloxacin being more active when targeting S. aureus and meropenem when targeting E. coli. All these observations were confirmed by confocal microscopy images. Our findings highlight the interest in combining caspofungin with antibiotics against interkingdom biofilms.