In Vitro Synergistic Activity of Fosfomycin-Colistin Combination Against Carbapenem-Resistant Pseudomonas Aeruginosa from Ventilator-Associated Pneumonia Patients

Objective: Infections caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) are a global health problem due to its multidrug resistance, often leading to treatment failure. This study aimed to assess the synergistic activity of fosfomycin plus colistin combination against clinical CRPA isolates from ventilator-associated pneumonia (VAP) patients.Material and Methods: This cross-sectional study retrospectively collected clinical data on 40 VAP patients with CRPA infections in 2023. CRPA clinical isolates were obtained between 2022 and 2023 from the sputum of VAP patients as part of the carbapenem-resistant isolate collection. The susceptibility to carbapenems, fosfomycin, and colistin was evaluated on CRPA isolates using the broth microdilution method. The synergistic activity of fosfomycin and colistin combination against CRPA isolates was assessed using the checkerboard assay. The time-kill study was then conducted on CRPA isolates that exhibited treatment synergism with the combination.Results: The most common comorbidities were chronic pulmonary disease and diabetes mellitus, which were found in 73% and 70% of VAP patients with CRPA infection. Previous carbapenem exposure was observed in 93% of the patients. Since VAP diagnosis, these patients were on a ventilator for a median of 13 days with an interquartile range of 10-22 days. Approximately 92% and 95% of the CRPA isolates exhibited high and low carbapenem and colistin resistance, respectively. In contrast, only 3 (7%) isolates were extremely resistant to fosfomycin, classifying as the non-wild type (bacterial isolates with reduced susceptibility or resistance). Synergism between fosfomycin and colistin was only observed in 2 (5%) isolates. Time-kill kinetics of these 2 isolates revealed a ≥2-log reduction in 1/4 minimum inhibitory concentration of fosfomycin and colistin.Conclusion: In vitro findings indicate that the synergistic activity of fosfomycin combined with colistin against CRPA isolates was rare. While this combination showed potential activity in these few isolates, further studies are needed to determine its clinical relevance and effectiveness in treating severe CRPA infections.