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

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.