Investigation of fosfomycin resistance in Klebsiella pneumoniae isolates obtained from clinically significant samples and evaluation of the antibacterial synergistic activity of fosfomycin in combination with amikacin, meropenem, and colistin

Aim: Klebsiella pneumoniae, a Gram-negative bacterium at the forefront of the rapidly escalating global antibiotic resistance problem, poses a significant threat particularly in intensive care units and hospital-acquired infections, where its high mortality rates and multi-drug or pan-resistant profile severely limit treatment options. This thesis aims to evaluate the potential synergistic effects of fosfomycin combined with amikacin, meropenem, and colistin in carbapenem-resistant Klebsiella pneumoniae isolates. The data obtained are expected to contribute to the development of novel and effective therapeutic strategies against resistant pathogens, thereby offering contemporary and clinically applicable solutions for managing multi-drug resistant bacterial infections. Materials and Methods: A total of 150 carbapenem-resistant Klebsiella pneumoniae strains, isolated from blood culture samples sent to the Laboratory of the Departments of Infectious Diseases and Clinical Microbiology and Medical Microbiology at Istanbul University-Cerrahpaşa, Cerrahpaşa Medical Faculty, and meeting the study criteria, were included in the study. To evaluate the potential synergistic effects of meropenem, amikacin and colistin in combination with fosfomycin, the agar dilution-based checkerboard synergy test was performed. Results: In studies investigating combination therapies on the strains, a synergistic effect was observed in 48.8% of the fosfomycin-amikacin combinations, 84.2% of the fosfomycin-meropenem combinations, and 15.6% of the fosfomycin-colistin combinations. Among all combinations, antagonistic interaction was observed only in the fosfomycin-colistin combination (17.0%). Conclusion: In conclusion, the combination of fosfomycin disodium with amikacin, meropenem and colistin is considered a potentially effective therapeutic option for the treatment of invasive infections caused by carbapenem-resistant Klebsiella pneumoniae. In this context, conducting in vivo efficacy and safety studies on the combinations of fosfomycin-meropenem, fosfomycin-colistin, and fosfomycin-amikacin is of great importance in translating the in vitro synergistic effects into clinical practice and in combating the increasing resistance profile. Key words: Fosfomycin disodium, Klebsiella pneumoniae, Synergy tests, Agar dilution