Evaluation of In Vitro Efficacy of Ceftazidime-Avibactam, Meropenem, and Colistin Single and Binary Combinations Against Carbapenem Resistant Klebsiella pneumoniae Strains Isolated from Various Clinical Specimens

It has been reported that many antibiotics used today, including the carbapenem group, fail to treat Klebsiella pneumoniae infections effectively. Despite many studies in recent years, the definitive treatment for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections is still uncertain. In this study, it was aimed to investigate in vitro activities of colistin (COL) and meropenem (MEM), which are frequently used in the treatment of CRKP infections, and ceftazidime-avibactam (CZA), which is recently used in our country, alone or in combination against different CRKP isolates having different carbapenem resistance mechanisms andto analyze whether the presence of colistin resistance, which is an important problem in CRKP strains, influences the drug interaction results. This study was carried out in 42 K.pneumoniae isolates, which were isolated from various clinical samples as an infectious agent in Silleyman Demirel University Faculty of Medicine, Department of Medical Microbiology, Bacteriology Laboratory and whose carbapenem resistance was confirmed by carbapenemase inactivation test. The carbapenemase genes of the isolates were determined by the polymerase chain reaction (PCR) method. Antimicrobial susceptibilities of CRKP strains to CZA, MEM, and COL were determined by the broth microdilution method and in vitro synergy activities of dual combinations of these drugs were evaluated by checkerboard and time-kill methods. Statistical evaluation of categorical data was performed using Fisher's exact test, and p-value of less than 0.05 was considered statistically significant in terms of difference between the groups. Of the 42 CRKP isolates 34 (81%) were only OXA-48 positive, 5 (11.9%) were OXA-48+NDM and 3 (7.1%) were OXA-48+KPC positive. In the checkerboard test, synergy was detected against 97.6% of the isolates both with CZA+MEM and CZA+COL combinations, whereas this rate was 50% with MEM+COL. In the time-kill test, synergy was detected with CZA+MEM and CZA+COL combinations in the OXA-48 positive isolate and OXA-48+KPC positive isolate, while synergy was detected with CZA+COL and MEM+COL combinations in the OXA-48+NDM positive isolate. There was no significant relationship between whether the isolates were resistant to colistin or not and the checkerboard test results of antibiotic combi nations (p(CZA+MEM)= 0.33, PCZA+COL= 0.11, p(MEM+COL) = 0.61). Results of our study revealed that the most common carbapenemase type in CRKP isolates was OXA-48 in our hospital, and the combinations of CZA with MEM and COL had high potential for synergism against these isolates.