New Delhi metallo-β-lactamases among extensively drug-resistant clinical isolates from Lahore, Pakistan

<b>Aim:</b> The study determines rates of carbapenem resistance (CR) and frequency of <i>bla</i>_NDM in multidrug-resistance (MDR) or extensive drug resistance (XDR), and evaluates the potential of phenotypic tests for detecting NDM production. <b>Materials &amp; methods:</b> Singleplex PCR was used to detect <i>bla</i>_NDM. Phenotypic tests, including combination disc test (CDST) and modified Hodge test (MHT), were evaluated for NDM production. <b>Results:</b> Among 338 CR isolates, 47.63% were MDR, whereas 52.36% were XDR with 53.25% carrying <i>bla</i>_NDM. MHT was found to be discriminative for detecting NDM production, whereas no significant association was observed for CDST. <b>Conclusion:</b> The high incidence of CR and MDR and XDR isolates possessing <i>bla</i>_NDM presents an impending threat in therapeutics. Limitations of phenotypic tests suggest better testing, including molecular detection of the enzyme. The study addresses the emergence of New Delhi Metallo-β-lactamases (NDM) as a cause of carbapenem resistance with its scope limited to Pakistan. 47.63% MDR and 52.36% XDR isolates among 338 carbapenem resistance isolates where 53.25% possessing <i>bla</i>_NDM gene reflects the high prevalence of <i>bla</i>_NDM in the region. Phenotypic tests, including modified hodge test (MHT) and combination disc test (CDST), were evaluated for NDM detection accuracy where MHT demonstrated significant discriminative accuracy (p = 0.03) in detecting NDM production, while CDST did not show a significant association (p = 0.12). Sequencing analysis revealed the dominance of NDM-1 and NDM-5 variants, underscoring their prevalence in the region. The presence of <i>NDM-1</i> and <i>NDM-5</i> variants among in-patients and out-patients highlights the dissemination of <i>bla</i>_NDM and poses challenges in therapeutic interventions. Limitations of phenotypic tests emphasize the need for improved testing strategies, including molecular detection, to accurately identify carbapenemase-producing isolates.