In-vitro susceptibility of cefiderocol and other comparators in carbapenem-resistant Gram-negative bacilli: A study from India

Abstract

Introduction

Cefiderocol is a parenteral catechol-type siderophore cephalosporin, which has been approved for the treatment of Gram-negative bacterial infections. Its activity among the carbapenem-resistant Gram-negative bacilli (CR-GNBs) in India is largely unknown.

Methodology

We tested in-vitro susceptibility of cefiderocol in 84 CR-GNB [ carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Escherichia coli (CREC) and carbapenem-resistant Klebsiella pneumoniae (CRKP)] by broth microdilution (BMD) and disc diffusion (DD) using Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints and concordance of DD was compared with BMD. Cefiderocol susceptibility was evaluated based on the presence of bla_NDM and bla_OXA-48 genes.

Results

Following CLSI and EUCAST breakpoints, 76.2% [CRKP: 95.65% (22/23); CRPA: 80% (16/20); CREC: 65% (13/20); CRAB: 61.9% (13/21)] and 52.3% [ CRKP: 82.6% (19/23); CRPA: 50% (10/20); CREC: 20% (4/20)] of CR-GNBs were observed susceptible to cefiderocol, respectively. The susceptibility to cefiderocol was seen higher with lower MIC₅₀ and MIC₉₀ values for CRKP [1 μg/ml; 4 μg/ml ] and CRPA [2 μg/ml; 8 μg/ml ] in comparison to the other two groups of organisms. The categorical agreement between BMD and DD was found between 90% and 100% for all organisms. Cefiderocol susceptibility among the isolates harbouring bla_NDM, bla_OXA-48, and both bla_NDM and bla_OXA-48 genes was observed 75% (24/32); 100% (3/3); and 66.6% (4/6), respectively.

Conclusion

Cefiderocol demonstrated high in-vitro activity against CRKP and CRPA isolates from India with lower MIC₅₀ and MIC₉₀ irrespective of the presence of bla_NDM and bla_OXA-48 genes.