IN-VITRO ACTIVITY OF CEFIDEROCOL AGAINST CARBAPENEM-RESISTANT GRAM-NEGATIVE BACILLI: FIRST STUDY FROM INDIA

Abstract

Intro: Cefiderocol is a siderophore cephalosporin and recently FDA-approved drug possessing potent activity against carbapenem-resistant gram-negative bacilli (CR-GNB) (Enterobacterales, and Nil-fermenter) due to its modified structure, iron-chelation mechanism, stability to hydrolysis by nearly all β-lactamases (including Metallo beta-lactamases and AmpC), overcoming capacity against efflux pump overexpression and porin channels mutations. This is the first study from India evaluating in-vitro susceptibility of Cefiderocol against CRGNBs. Methods: A prospective observational study was conducted at a tertiary care hospital in India during 2021-2022. CR-GNB isolates from patients with bloodstream infection, urinary tract infection, and pneumonia were tested for Cefiderocol in-vitro susceptibility using broth microdilution technique (BMD) as per CLSI 2022 guideline. Two Acinetobacter baumanii (AB) isolates observed resistant to Cefiderocol (MIC>32mg/ml) were further analysed by whole genome sequencing (WGS). Findings: Forty CR-GNB isolates were tested for BMD [5: Escherichia coli (EC), 7: Pseudomonas aeruginosa (PA), 13: Klebsiella pneumoniae (KP) and 15: Acinetobacter baumanii (AB)]. The susceptibility of EC, PA, KP and AB against Cefiderocol was observed as 60%, 43%, 100%, and 13.3% respectively. Approximately, 20% of EC isolates and 28.5% of PA isolates showed intermediate susceptibility using BMD. All the AB isolates from respiratory specimens were observed resistant to Cefiderocol (MIC > 32mg/ml). On WGS analysis, the two resistant AB isolates were found to harbour blaPER-7 in combination with blaOXA-23/blaNDM- 1 along with other carbapenemase genes blaOXA-66 & blaOXA-68. Conclusion: In our study, Cefiderocol was found to have potent in-vitro activity against K. pneumoniae, in comparison to other CR-GNB. Higher resistance was seen in A. baumanii isolates, which might be attributed to the synergistic effect of PER-7 type of beta-lactamases in presence of blaOXA-23 and blaNDM-1 gene.