IN VITRO EVALUATION OF THE COMBİNATION OF CEFTOLOZANE/TAZOBACTAM AND COLISTIN IN INTENSIVE CARE UNIT–ASSOCIATED MULTIDRUG-RESISTANT ACINETOBACTER BAUMANNII INFECTIONS

Objective: Multidrug-resistant Acinetobacter baumannii (MDR-AB), a major cause of nosocomial infections, poses a global threat, particularly in immunosuppressed patients. Increasing resistance rates necessitate alternative therapeutic strategies for MDR-AB infections. In this study, we investigated the in vitro interactions of colistin (C) and the novel β-lactam/β-lactamase inhibitor combination ceftolozane/tazobactam (C/T) against MDR-AB isolates using the E-test and checkerboard methods. Methods: Thirty MDR-AB isolates obtained between January and June 2017 from intensive care unit (ICU) patients were included. Isolate identification was performed using the BD Phoenix 100 and VITEK MS systems. Routine antimicrobial susceptibility testing was conducted with the BD Phoenix 100 system, and results were interpreted according to EUCAST guidelines. In vitro interactions of the C/T–C combination were evaluated using the fractional inhibitory concentration (FIC) index. The agreement between the E-test and checkerboard methods was analyzed using simple agreement rates and Cohen’s kappa coefficient. Results: Resistance rates among MDR-AB isolates were as follows: imipenem, meropenem, ciprofloxacin, and gentamicin 100%; amikacin 86.7%; trimethoprim/sulfamethoxazole 46.7%; and colistin 10%. According to FIC index results, no synergistic interaction was observed with the E-test, whereas the checkerboard method demonstrated synergy in two isolates (6.7%). Antagonistic interactions were detected in 20% of isolates by the E-test but were absent with the checkerboard method. The overall agreement between the two methods was 50%, with a Cohen’s kappa coefficient of 0.13, indicating poor agreement. Conclusion: The intrinsic susceptibility of MDR-AB isolates to C/T alone was low; however, the minimum inhibitory concentrations (MICs) of C/T decreased in the presence of colistin. The detection of synergistic activity and the absence of antagonism with the checkerboard method suggest the potential of combining C/T with reduced doses of colistin to minimize toxicity. However, further validation in in vivo experimental models is needed to substantiate the clinical significance of the observed synergistic effect.