Susceptibility of Carbapenem-Resistant Acinetobacter baumannii and Carbapenem-Resistant Klebsiella pneumoniae Against Cefiderocol with Reference to Their Genetic Profile in India.

Cefiderocol (FDC) shows promise against carbapenem resistance, with differing carbapenemase epidemiology across Southeast and East Asia, including India. This study evaluated the susceptibility of carbapenem-resistant Klebsiella pneumoniae (CRKP) and carbapenem-resistant Acinetobacter baumannii (CRAB) against FDC and assessed carbapenemase genetic influences on susceptibility. A total of 100 clinical isolates of CRAB and 100 clinical isolates of CRKP were studied. The minimum inhibitory concentration for FDC, ceftazidime-avibactam (CZA), aztreonam, polymyxins in CRKP, and polymyxins and minocycline in CRAB was determined by the broth microdilution method. Carbapenemases were detected using the ethylenediaminetetraacetic acid-modified carbapenem inactivation method in CRKP and the modified Hodge test for CRAB. The confirmation of carbapenemases (blaSME, blaNMC, blaGES, blaKPC, blaIMP, blaVIM, and blaNDM for all; blaOXA-48 in CRKP; and blaOXA-23 like blaOXA-24/40 and blaOXA-58 in CRAB) was performed by multiplex PCR. FDC resistance in CRKP and CRAB was 1% and 6%, respectively. CRKP isolates showed significant resistance to polymyxin B (31%), colistin (21%), aztreonam (34%), and CZA (41%; p < 0.05) as compared to FDC, while CRAB isolates exhibited higher FDC resistance (p < 0.05). Moreover, 96% of CRKP and 100% of CRAB were carbapenemase producers. For CRKP, blaOXA-48 + blaNDM combination and for CRAB, blaNDM was significantly associated with FDC resistance. The study revealed the presence of blaNDM as one of the causes for reduced susceptibility to FDC in these isolates.