In vitro activity of cefiderocol against comparators (ceftazidime-avibactam, ceftazidime-avibactam/ aztreonam combination, and colistin) against clinical isolates of meropenem-resistant Klebsiella pneumoniae from India

Cefiderocol (FDC), a novel siderophore drug, is active against Gram-negative bacteria producing carbapenemases, including metallo-beta-lactamases. The objective of this study is 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. From the 2,052 clinical specimens submitted for culture testing, 245 K. pneumoniae isolates were recovered within a 6-month period in 2021. One hundred three non-duplicate, non-outbreak, MER-R (minimum inhibitory concentration, MIC >4 µg/mL) strains were included in the study. Identification and susceptibility were performed using VITEK-2 (bioMérieux). Meropenem-susceptible isolates (n = 10) served as controls. For FDC, broth microdilution (BMD) was performed after in-house standardization. Disk diffusion (Liofilchem, Italy) and broth microdilution (ComASP, STC, Liofilchem, Italy) were used for susceptibility testing of CZA and CST, respectively. Synergy testing for CZA and AT was performed using disk approximation method. CLSI breakpoints were used for the interpretation of the results. For FDC, MIC(50) and MIC(90) were 2 and 8 µg/mL, respectively. A total of 80% of isolates were susceptible to FDC, 26.2% of isolates were susceptible to CZA, synergy testing with CZA/AT was positive for 74 (72%) of the isolates, and 89.3% were intermediate to CST. Nine (8.7%) were susceptible only to FDC. 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 to assess the clinical efficacy of this novel drug in this region with a high prevalence of carbapenem resistance among Gram-negative organisms. IMPORTANCE: Management of infections with multi-drug resistant Klebsiella pneumoniae is a major challenge in hospital settings, with few treatment options. In this study, the authors aim to assess the in vitro susceptibility of these clinical isolates to cefiderocol, a novel siderophore. Comparators are colistin, ceftazidime-avibactam, and ceftazidime-avibactam/aztreonam synergy, which are currently available options for treatment in this region. Baseline-resistance rates against cefiderocol are higher than those in the previously published studies, with MIC50 and MIC90 at 2 and 8 µg/mL, respectively.