Enhancing colistin efficacy with combination therapies for multidrug-resistant P. aeruginosa and A. baumannii isolates

Résumé fourni par la source

Aim Increasing resistance among ESKAPEEc pathogens, particularly Acinetobacter baumannii and Pseudomonas aeruginosa, has necessitated the use of last-resort antibiotics such as colistin. This study aimed to evaluate the effectiveness and reveal a dynamic picture of colistin-based combination therapies.Materials & methods This study evaluated the in vitro efficacy of colistin in combination with doxycycline, doripenem, and rifampicin against multidrug-resistant clinical isolates of P. aeruginosa (n = 23) and A. baumannii (n = 26). Susceptibility testing performed by microbroth dilution method, and synergistic interactions were assessed via checkerboard and time–kill curve (TKC) assays.Results All isolates were resistant to colistin, according to their MICs. In checkerboard assays, according to synergism rates, colistin-doripenem and colistin-doxycycline combinations were particularly effective. The degrees of synergy for doripenem, doxycycline, and rifampicin were 30%, 90%, and 20%, respectively, against P. aeruginosa, and 30%, 60%, and 30%, respectively, against A. baumannii. In TKC analysis, synergistic interactions are generally observed with colistin at 1/4×MIC or 1×MIC, and indifference effects at 4×MIC, similar to colistin monotherapy. TKCs also confirmed the bactericidal activities of combinations that achieved ≥3-log10 reductions in initial bacterial counts.Conclusions Colistin-based combination therapies, especially colistin-doripenem, may be promising approaches for combating multidrug-resistant pathogens while potentially reducing nephrotoxicity risk.

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