In-vitro activity of Cefiderocol against clinical isolates of meropenem-resistant Klebsiella pneumoniae from India

Abstract

Background: Cefiderocol (FDC), a novel siderophore drug, is active against gram negative bacteria producing carbapenemases, including metallo-beta-lactamases. Objective: To compare the in-vitro activity of FDC with ceftazidime-avibactam (CZA), CZA/ aztreonam (AT) combination and colistin (CST), in clinical isolates of meropenem-resistant (MER-R) Klebsiella pneumoniae. Methods: From 2052 clinical specimens submitted for culture testing, 245 K. pneumoniae isolates were recovered within a six month period in 2021. 103 non-duplicate, non-outbreak, MER-R (MIC >4 μg/ml) strains were included in the study. Identification and susceptibility was performed using VITEK-2 (bioMérieux). 10 meropenem-susceptible isolates served as controls. For FDC, BMD was performed after in-house standardization. Disc diffusion (Liofilchem, Italy) and broth microdilution (BMD; ComASP, STC, Liofilchem, Italy) were used for susceptibility testing of CZA and CST respectively. Synergy testing for CZA and aztreonam (AT) was performed using disk approximation method. CLSI breakpoints were used for interpretation of results. Results: For FDC, MIC50 and MIC90 was 2 μg/ml and 8 μg/ml, respectively. 80% isolates were susceptible to FDC. 26.2% isolates were susceptible to CZA, synergy testing with CZA/ AT was positive for 74 (72%) of the isolates. 89.3% had intermediate susceptibility to CST. Nine (8.7%) were susceptible only to FDC. Conclusion: FDC is active in-vitro against MER-R K. pneumoniae > CZA/AT> CZA > CST, as observed in this study, applying CLSI criteria. Clinico-microbiological studies should be performed for assessing clinical efficacy of this novel drug in this region with high prevalence of carbapenem resistance among gram-negative organisms.