In Vitro Evaluation of Synergy in Carbapenem-resistant Klebsiella pneumoniae Strains with Antibiotic Combinations of Meropenem, Fosfomycin, Colistin, and Tigecycline

Abstract

Introduction: Carbapenem-resistant (CR) Klebsiella pneumoniae is one of the most common CR Enterobacteriaceae species and is resistant to many antibiotics. Generally, combined use of antibiotics is preferred during infections of these microorganisms. This study aimed to demonstrate the in vitro synergy between meropenem (MEM), fosfomycin (FOS), colistin (CS), and tigecycline (TGC) in CR-K. pneumoniae (Kp) strains. Materials and Methods: A total of 52 CR-Kp strains were included. MicroScan WalkAway (Beckman Culture) plus system were used to identify strains. Antibiotic susceptibilities of the isolates were detected in the MicroScan WalkAway device (Beckman Culture) using MicroScan Gram-negative panel type 44 (Beckman Culture), and the minimal inhibitory concentrations (MIC) of antibiotics and extended-spectrum beta-lactamases (ESBL) formation were detected. Synergy studies were performed by the microdilution checkerboard method. A fractional inhibitory concentration index was used to interpret the results. Results: Of 52 strains, 11 had only carbapenem (MEM) resistance. Twenty-three of strains were also resistant to FOS, 27 to CS, and eight to TGC. When antibiotic combinations were compared, MEM + FOS, MEM + CS, and CS + TGC showed the best synergy in our strains. By contrast, the lowest synergy was observed with MEM + TGC, and the difference was significant (p50% synergistic effect in these strains. Conclusion: This study showed that high FOS and CS resistance was also present in our CR-Kp strains. However, even in case of resistance to one or more of the antibiotics mentioned in this study, the results showed that, in combination with these antibiotics, especially MEM + FOS, MEM + CS, and CS + TGC, a significant amount of in vitro synergy can be achieved.

Keywords

• k. pneumoniae
• fosfomycin
• colistin
• tigecycline
• synergy