Outstanding presence of New Delhi metallo-beta-lactamase in carbapenem-resistant Enterobacterales and exceptionally potent in vitro activity of cefiderocol and aztreonam-avibactam emphasises their immediate access in India

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BACKGROUND: Therapeutic options for critical infections by carbapenem-resistant Enterobacterales (CRE) are largely limited to polymyxins in India. They have significant toxicity, unpredictable kinetics and prohibitive cost. The objective of the current study was to find the mechanisms of resistance in CRE and to evaluate the in vitro efficacy of potential treatment options. METHODS: In a prospective study performed during October 2023-March 2024, all Enterobacterales clinical isolates of our laboratory were screened for carbapenem resistance. All CRE isolates were phenotypically and genotypically tested for mechanisms of resistance and underwent extended antimicrobial susceptibility testing. RESULTS: During the study period, 12.90% (100/775) of Enterobacterales were CRE, among which 99% (99/100) were multidrug resistant. Phenotypic metallo-beta-lactamase screening was positive in 87/100 (87%) of isolates. Aztreonam-avibactam was found to effectively inhibit 96% of isolates, while cefiderocol effectively inhibited 87%. Two isolates resistant to aztreonam-avibactam were susceptible to cefiderocol, both of which harboured blaNDM. The blaNDM gene was detected in 87% of the isolates, one of which also co-harboured blaKPC. CONCLUSIONS: Our study showed an exceptionally high prevalence of the blaNDM gene among CRE clinical isolates. Either aztreonam-avibactam or cefiderocol was found to be effective against 98% of CRE isolates highlighting the immediate need of making these two drugs accessible to patients in India.

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