Detection and prevalence of the blaNDM-1 gene in carbapenem-resistant Klebsiella pneumoniae bloodstream isolates from a tertiary care institute
-
Susheem Ramakrishnan
,
Gulnaz Bashir
,
Nargis Kaur Bali
,
Sabah Rashid
,
Dona Mathew
,
Qounser Nisar
,
Mohd Iqbal Mir
Abstract
Background and Objectives: Carbapenem resistance mediated by blaNDM-1 in Klebsiella pneumoniae has emerged as a major challenge, particularly in intensive care settings with high antibiotic pressure. This compromises therapeutic options and contributes to poor clinical outcomes. The present study aimed to determine the prevalence of blaNDM-1 among isolates of K. pneumoniae from a tertiary care hospital, evaluate the performance of phenotypic tests against PCR-based detection, assess antimicrobial susceptibility profiles, and analyze clinical outcomes.
Materials and Methods: In this study, over 18 months, 130 non-duplicate K. pneumoniae isolates were identified, and antimicrobial susceptibility testing was performed by VITEK-2 Compact and broth microdilution for colistin. Imipenem-resistant isolates were subjected to the Combined disc diffusion test (CDDT) and Double disc synergy test (DDST) for metallo-beta-lactamase (MBL), and conventional PCR targeting blaNDM-1. Demographic data and outcomes were recorded.
Results: Of the 130 isolates, 111 were imipenem-resistant, of which CDDT detected MBLs in 94.6%, and DDST detected MBLs in 76.6%. PCR confirmed blaNDM-1 in 77.5% and was more commonly associated with cases of sepsis. blaNDM-1 -positive isolates were resistant to β-lactams, fluoroquinolones and aminoglycosides. No isolate was found to be colistin-resistant. 26.7% of the patients with blaNDM-1 -positive bacteremia died.
Conclusion: This study highlights the high prevalence of blaNDM-1 in K. pneumoniae isolates. Among the phenotypic tests, CDDT outperformed DDST and showed the best agreement with PCR, supporting its use as a screening method for MBL, but confirmatory PCR remains essential. The restricted treatment options underscore the need for stringent infection control and robust antimicrobial stewardship to curb transmission and preserve last-line agents.
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18. Gautam S, Bhattarai NR, Rai K, Poudyal A, Khanal B. Detection of blaNDM-1 Encoding Imepenemase among the Imipenem-Resistant Gram-Negative Bacilli Isolated from Various Clinical Samples at a Tertiary Care Hospital of Eastern Nepal: A Descriptive Cross-Sectional Study. Int J Microbiol 2020; 2020: 8861204.
19. Zhu J, Sun L, Ding B, Yang Y, Xu X, Liu W, et al. Outbreak of NDM-1-producing Klebsiella pneumoniae ST76 and ST37 isolates in neonates. Eur J Clin Microbiol Infect Dis 2016; 35: 611-618.
20. Mohan B, Hallur V, Singh G, Sandhu HK, Appannanavar SB, Taneja N. Occurrence of blaNDM-1 and absence of blaKPC genes encoding carbapenem resistance in uropathogens from a tertiary care centre from north India. Indian J Med Res 2015; 142: 336-343.
21. Devi LS, Broor S, Rautela RS, Grover SS, Chakravarti A, & Chattopadhya D. Increasing Prevalence of Escherichia coli and Klebsiella pneumoniae Producing CTX-M-Type Extended-Spectrum Beta-Lactamase, Carbapenemase, and NDM-1 in Patients from a Rural Community with Community Acquired Infections: A 3-Year Study. Int J Appl Basic Med Res 2020 10: 156-163.
22. Khajuria A, Praharaj AK, Kumar M, Grover N, Aggarwal A. Multidrug resistant NDM-1 metallo-beta-lactamase producing Klebsiella pneumoniae sepsis outbreak in a neonatal intensive care unit in a tertiary care center at central India. Indian J Pathol Microbiol 2014; 57: 65-68.
23. Falcone M, Giordano C, Leonildi A, Galfo V, Lepore A, Suardi LR, et al. Clinical Features and Outcomes of Infections Caused by Metallo-β-Lactamase-Producing Enterobacterales: A 3-Year Prospective Study from an Endemic Area. Clin Infect Dis 2024; 78: 1111-1119.
24. Nordmann P, Poirel L, Walsh TR, Livermore DM. The emerging NDM carbapenemases. Trends Microbiol 2011; 19: 588-595.
25. Poirel L, Dortet L, Bernabeu S, Nordmann P. Genetic features of blaNDM-positive Enterobacteriaceae. Antimicrob Agents Chemother 2011; 55: 5403-5407.
26. Franklin C, Liolios L, Peleg AY. Phenotypic detection of carbapenem-susceptible metallo-β-lactamase-producing Gram-negative bacilli in the clinical laboratory. J Clin Microbiol 2006; 44: 3139–3144.
27. Nordmann P, Poirel L, Dortet L. Rapid detection of carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis 2012; 18: 1503-1507.
28. Rahman M, Shukla SK, Prasad KN, Ovejero CM, Pati BK, Tripathi A, et al. Prevalence and molecular characterisation of New Delhi metallo-β-lactamases NDM-1, NDM-5, NDM-6 and NDM-7 in multidrug-resistant Enterobacteriaceae from India. Int J Antimicrob Agents 2014; 44: 30-37.
29. Li J, Wu W, Wu M, Zhou Z, Wang J, Qiu M, et al. Clinical and molecular characteristics of patients with Bloodstream infections caused by KPC and NDM co-producing carbapenem-resistant Klebsiella pneumoniae. Infect Drug Resist 2024; 17: 1685-1697.
30. Huang X, Cheng X, Sun P, Tang C, Ni F, Liu G. Characteristics of NDM-1-producing Klebsiella pneumoniae ST234 and ST1412 isolates spread in a neonatal unit. BMC Microbiol 2018; 18: 186.
31. Pathak A, Tejan N, Dubey A, Chauhan R, Fatima N, Jyoti, et al. Outbreak of colistin resistant, carbapenemase (blaNDM, blaOXA-232) producing Klebsiella pneumoniae causing bloodstream infection among neonates at a tertiary care hospital in India. Front Cell Infect Microbiol 2023; 13: 1051020.
32. Liu P, Li X, Luo M, Xu X, Su K, Chen S, et al. Risk factors for carbapenem-resistant Klebsiella pneumoniae infection: A meta-analysis. Microb Drug Resist 2018; 24: 190-198.
2. Saharman YR, Karuniawati A, Sedono R, Aditianingsih D, Goessens WHF, Corné HW, et al. Clinical impact of endemic NDM-producing Klebsiella pneumoniae in intensive care units of the national referral hospital in Jakarta, Indonesia. Antimicrob Resist Infect Control 2020; 9: 61.
3. Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K, et al. Characterization of a new metallo-β-lactamase gene, blaNDM-1, and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 2009; 53: 5046-5054.
4. Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F, Balakrishnan R, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis 2010; 10: 597-602.
5. Khan AU, Maryam L, Zarrilli R. Structure, Genetics and Worldwide Spread of New Delhi Metallo-β-lactamase (NDM): a threat to public health. BMC Microbiol 2017; 17: 101.
6. Protiti B, Aseem R, Prabha D. NDM-beta-lactamase-1: Where do we stand? Indian J Med Res 2022; 155: 243-252.
7. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. 32nd ed. CLSI supplement M100. Wayne (PA): Clinical and Laboratory Standards Institute. 2022.
8. Yong D, Lee K, Yum JH, Shin HB, Rossolini GM, Chong Y. Imipenem-EDTA disk method for differentiation of metallo-beta-lactamase-producing clinical isolates of Pseudomonas spp. and Acinetobacter spp. J Clin Microbiol 2002; 40: 3798-3801.
9. Lee K, Lim YS, Yong D, Yum JH, Chong Y. Evaluation of the Hodge test and the imipenem-EDTA double-disk synergy test for differentiating metallo-beta-lactamase-producing isolates of Pseudomonas spp. and Acinetobacter spp. J Clin Microbiol 2003; 41:4623-4629.
10. Center for Disease Control and Prevention. Multiplex Real-Time PCR Detection of Klebsiella pneumoniae Carbapenemase (KPC) and New Delhi metallo-β-lactamase (NDM-1) [Internet]. 2011. Available at https://www.cdc.gov/gram-negative-bacteria/media/pdfs/KPC-NDM-Protocol-2011-P.pdf [Accessed Jan 30, 2026]
11. Solanki R, Vanjari L, Subramaniam S, Aparna B, Nagapriyanka E, Lakshmi V. Comparative evaluation of multiplex PCR and routine laboratory phenotypic methods for detection of carbapenemases among Gram negative Bacilli. J Clin Diagn Res 2004; 8(12): DC23-26.
12. Nicitra E, Terrana M, Bongiorno D, Dodaro S, Greco F, Greco S, et al. Circulation of a Unique Klebsiella pneumoniae Clone, ST147 NDM-1/OXA-48, in Two Diverse Hospitals in Calabria (Italy). Antibiotics (Basel) 2025; 14: 128.
13. Fomda BA, Khan A, Zahoor D. NDM-1 (New Delhi metal beta lactamase-1) producing Gram negative bacilli:emergence and clinical implications. Indian J Med Res 2014; 140:672-678.
14. Kaur A, Gandra S, Gupta P, Mehta Y, Laxminarayan R, Sengupta S. Clinical outcome of dual colistin- and carbapenem-resistant K. pneumoniae bloodstream infections: A single-center retrospective study of 75 cases in India. Am J Infect Control 2017; 45: 1289-1291.
15. Das S. The crisis of carbapenemase-mediated carbapenem resistance across the human animal environmental interface in India. Infect Dis Now 2023; 53: 104628.
16. Bali NK, Fomda BA, Bashir H, Zahoor D, Lone S, Koul PA. Emergence of carbapenem resistant Acinetobacter in a temperate in a temperate North Indian state. Br J Biomed Sci 2013; 70: 156-160.
17. Manoharan A, Chatterjee S, Mathai D; SARI Study Group. Detection and characterization of metallo beta lactamases producing Pseudomonas aeruginosa. Indian J Med Microbiol 2010; 28: 241-244.
18. Gautam S, Bhattarai NR, Rai K, Poudyal A, Khanal B. Detection of blaNDM-1 Encoding Imepenemase among the Imipenem-Resistant Gram-Negative Bacilli Isolated from Various Clinical Samples at a Tertiary Care Hospital of Eastern Nepal: A Descriptive Cross-Sectional Study. Int J Microbiol 2020; 2020: 8861204.
19. Zhu J, Sun L, Ding B, Yang Y, Xu X, Liu W, et al. Outbreak of NDM-1-producing Klebsiella pneumoniae ST76 and ST37 isolates in neonates. Eur J Clin Microbiol Infect Dis 2016; 35: 611-618.
20. Mohan B, Hallur V, Singh G, Sandhu HK, Appannanavar SB, Taneja N. Occurrence of blaNDM-1 and absence of blaKPC genes encoding carbapenem resistance in uropathogens from a tertiary care centre from north India. Indian J Med Res 2015; 142: 336-343.
21. Devi LS, Broor S, Rautela RS, Grover SS, Chakravarti A, & Chattopadhya D. Increasing Prevalence of Escherichia coli and Klebsiella pneumoniae Producing CTX-M-Type Extended-Spectrum Beta-Lactamase, Carbapenemase, and NDM-1 in Patients from a Rural Community with Community Acquired Infections: A 3-Year Study. Int J Appl Basic Med Res 2020 10: 156-163.
22. Khajuria A, Praharaj AK, Kumar M, Grover N, Aggarwal A. Multidrug resistant NDM-1 metallo-beta-lactamase producing Klebsiella pneumoniae sepsis outbreak in a neonatal intensive care unit in a tertiary care center at central India. Indian J Pathol Microbiol 2014; 57: 65-68.
23. Falcone M, Giordano C, Leonildi A, Galfo V, Lepore A, Suardi LR, et al. Clinical Features and Outcomes of Infections Caused by Metallo-β-Lactamase-Producing Enterobacterales: A 3-Year Prospective Study from an Endemic Area. Clin Infect Dis 2024; 78: 1111-1119.
24. Nordmann P, Poirel L, Walsh TR, Livermore DM. The emerging NDM carbapenemases. Trends Microbiol 2011; 19: 588-595.
25. Poirel L, Dortet L, Bernabeu S, Nordmann P. Genetic features of blaNDM-positive Enterobacteriaceae. Antimicrob Agents Chemother 2011; 55: 5403-5407.
26. Franklin C, Liolios L, Peleg AY. Phenotypic detection of carbapenem-susceptible metallo-β-lactamase-producing Gram-negative bacilli in the clinical laboratory. J Clin Microbiol 2006; 44: 3139–3144.
27. Nordmann P, Poirel L, Dortet L. Rapid detection of carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis 2012; 18: 1503-1507.
28. Rahman M, Shukla SK, Prasad KN, Ovejero CM, Pati BK, Tripathi A, et al. Prevalence and molecular characterisation of New Delhi metallo-β-lactamases NDM-1, NDM-5, NDM-6 and NDM-7 in multidrug-resistant Enterobacteriaceae from India. Int J Antimicrob Agents 2014; 44: 30-37.
29. Li J, Wu W, Wu M, Zhou Z, Wang J, Qiu M, et al. Clinical and molecular characteristics of patients with Bloodstream infections caused by KPC and NDM co-producing carbapenem-resistant Klebsiella pneumoniae. Infect Drug Resist 2024; 17: 1685-1697.
30. Huang X, Cheng X, Sun P, Tang C, Ni F, Liu G. Characteristics of NDM-1-producing Klebsiella pneumoniae ST234 and ST1412 isolates spread in a neonatal unit. BMC Microbiol 2018; 18: 186.
31. Pathak A, Tejan N, Dubey A, Chauhan R, Fatima N, Jyoti, et al. Outbreak of colistin resistant, carbapenemase (blaNDM, blaOXA-232) producing Klebsiella pneumoniae causing bloodstream infection among neonates at a tertiary care hospital in India. Front Cell Infect Microbiol 2023; 13: 1051020.
32. Liu P, Li X, Luo M, Xu X, Su K, Chen S, et al. Risk factors for carbapenem-resistant Klebsiella pneumoniae infection: A meta-analysis. Microb Drug Resist 2018; 24: 190-198.
| Files | ||
| Issue | Vol 18 No 1 (2026) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v18i1.20902 | |
| Keywords | ||
| Carbapenemase Beta-lactamase New Delhi metallo-beta-lactamase Klebsiella pneumoniae Polymerase chain reaction Bloodstream infections Sepsis | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Ramakrishnan S, Bashir G, Bali N, Rashid S, Mathew D, Nisar Q, Mir M. Detection and prevalence of the blaNDM-1 gene in carbapenem-resistant Klebsiella pneumoniae bloodstream isolates from a tertiary care institute. Iran J Microbiol. 2026;18(1):14-22.
