Investigation of <i>in-vitro</i> Efficacy of Antibiotic Combinations and Presence of Carbapenemases in Multidrug-Resistant <i>Klebsiella pneumoniae</i> Isolates

Abstract

Background: Multidrug resistance (MDR) is increasingly being detected in Klebsiella pneumoniae strains. The combined use of antibiotics is one of the important choices in the treatment of these infections. Objectives: This study aimed to evaluate the in-vitro activity of the binary combinations of colistin (COL), meropenem (MEM), and ceftazidime/avibactam (CZA) against multidrug-resistant K. pneumoniae clinical isolates and to identify carbapenemase genes. Methods: Between January 2022 and November 2023, randomly selected MDR K. pneumoniae isolates (n = 90) isolated from patient samples were included in the study. All isolates were investigated for carbapenem resistance genes using the PCR method. Additionally, the carbapenem inactivation method (CIM) was used as a phenotypic method to investigate carbapenemase production. Antimicrobial interactions (synergy test) were determined using the checkerboard method. Results: The most common carbapenem resistance gene was OXA-48 (72 isolates). The KPC gene was detected in 10 isolates, and the NDM gene in 5 isolates. A synergy test was performed on isolates randomly selected from among those resistant to at least one of the antibiotics COL, CZA, and MEM. Synergistic effect was detected in 50% of the COL-CZA combination, 75% of the MEM-CZA combination, and 45% of the MEM-COL combination. Conclusions: OXA-48 was the most frequently detected carbapenemase gene in MDR K. pneumoniae isolates in our region, and KPC and NDM carbapenemase genes were also detected. The high synergy-partial synergy ratios identified in antibiotics may represent a promising treatment option for infections caused by MDR K. pneumoniae, but this requires confirmation in studies with larger sample sizes.