Review of In Vitro Efficacy of Ceftazidime-Avibactam, Meropenem-Vaborbactam and Imipenem-Relebactam in Carbapenemase Producing Klebsiella pneumoniae Isolates

Abstract

Introduction: To investigate the in vitro efficacy of three new antimicrobial agents [ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam (V/R) and imipenem/cilastatin-relebactam] in isolates of carbapenemase-producing Klebsiella pneumoniae (CPKP). Materials and Methods: Thirty CPKP strains were included in our study. The strains were identified at the species level using Vitek MS, and antimicrobial susceptibility tests were performed using the Vitek 2 automated system. Carbapenemase production in all strains was confirmed by the combination disc test. The blaKPC, blaNDM-1, blaOXA-48 and blaVIM genes were identified using the Gene-Xpert (R) System Carba R (R) kit (Cepheid, Sunnyvale, USA). Imipenem/relebactam (I/R), V/R, CAZ-AVI susceptibilities were investigated by using gradient strip test. Antimicrobial susceptibility results were interpreted according to the recommendations the EUCAST. Minimal inhibitory concentration (MIC) cut-off values were as follows: For IR, MIC >2 susceptible, MIC =2 resistant; for M/V, MIC >8 resistant, MIC <8 susceptible; and for CAZ-AVI, MIC >8 resistant, MIC <8 susceptible. Results: All of the strains included in the study were resistant to all antibiotics except colistin. BlaOXA-48 was detected in 76.6% of the isolates; NDM-1 in 16.6%; NDM-1 and OXA-48 in 3.3%, and KPC in 3.3%. Twenty (66.6%) strains were susceptible to I/R, 18 (60%) were susceptible to M/V, and 21 (70%) were susceptible to CAZ/AVI. While 90% of the I/R susceptible isolates carried OXA-48, the other two isolates had KPC and NDM-1. Of the I/R resistant isolates 50% carried OXA-48, 40% NDM-1, and 1 NDM-1 and OXA-48. Of the M/V susceptible isolates, 88.8% carried OXA-48, other isolates NDM-1 and KPC. Of the resistant isolates, 58.3% carried OXA-48, 33.3% NDM-1, and 8.1% NDM-1/OXA-48. Of the isolates susceptible to CAZ/AVI 95.2% carried OXA-48 and 4.7% NDM-1. Of the I/R resistant isolates with a MIC >8, two carried the blaOXA-48 gene and two carried the NDM-1 gene. NDM-1 gene was present in four of the M/V resistant isolates with MIC >8. It was determined that 56.6% of the strains were susceptible to all antimicrobial agents and 23.3% were found to be resistant to all agents. While 4 (57.1%) of these strains carried NDM gene, Conclusion: The most common gene detected in CPKP strains inour center was found to be OXA-48 gene. These results were similar to the data for Turkey. This situation should be considered during the clinical use of I/R and M/V, which are known to have low susceptibility in OXA-48 carrying strains in our country. Our study showed that CAZ/AVI susceptibility was higher in KPC strains.