Detection of carbapenemase production in Enterobacterales by mCIM and eCIM: a tertiary care hospital study
-
Touseefa Shafi
,
Anjum Ara Mir
,
Shagufta Roohi
,
Bashir Fomda
,
Sanam Rasool Wani
,
Tufail Ahmed
,
Samiah Yousuf
Abstract
Background and Objectives: Carbapenem-resistant Enterobacterales (CRE) pose a major healthcare challenge due to high resistance rates and limited treatment options. This study characterized carbapenemase production among CRE isolates using phenotypic methods—Modified Carbapenem Inactivation Method (mCIM) and EDTA-Carbapenem Inactivation Method (eCIM)—as genotypic methods have limitations like restricted gene targets and mutations.
Materials and Methods: This six-month study was conducted at Sher-i-Kashmir Institute of Medical Sciences (SKIMS). Samples including swabs, respiratory specimens, pus, body fluids, and blood were cultured on Blood Agar and MacConkey Agar (HiMedia, India). Enterobacterales were identified using conventional methods and screened for carbapenem resistance. CRE isolates underwent mCIM and eCIM testing per CLSI guidelines.
Results: Among 471 Enterobacterales isolates tested, 160 (33.9%) were carbapenem-resistant. Of these, 97 (60.6%) were mCIM positive, indicating carbapenemase production. eCIM further identified 83 (85.5%) as metallo-beta-lactamase (MBL) producers and 14 (14.4%) as serine carbapenemase producers. CRE prevalence was higher in ICU settings and among males. Isolates showed high cephalosporin resistance, with multi-drug resistance (MDR) common in both MBL and serine carbapenemase producers.
Conclusion: The prevalence of CRE was found to be 33.9%. The findings underscore the critical need for continuous surveillance and stringent infection control measures to manage the spread of CRE in healthcare settings.
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23. Vamsi SK, Moorthy RS, Hemiliamma MN, Chandra Reddy RB, Chanderakant DJ, Sirikonda S. Phenotypic and genotypic detection of carbapenemase production among Gram-negative bacteria isolated from hospital-acquired infections. Saudi Med J 2022; 43: 236-243.
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25. Parveen RM, Harish BN, Parija SC. Emerging carbapenem resistance among nosocomial isolates of Klebsiella pneumoniae in South India. Int J Pharma Bio Sci 2010; 1: 1-11.
26. Pawar SK, Mohite ST, Shinde RV, Patil SR, Karande GS. Carbapenem-resistant Enterobacteriaceae: prevalence and bacteriological profile in a tertiary teaching hospital from rural western India. Indian J Microbiol Res 2018; 5: 342-347.
27. Nair PK, Vaz MS. Prevalence of carbapenem-resistant Enterobacteriaceae from a tertiary care hospital in Mumbai, India. J Microbiol Infect Dis 2013; 3: 207-210.
28. Robert J, Pantel A, Mérens A, Lavigne JP, Nicolas-Chanoine MH; ONERBA’s Carbapenem Resistance Study Group. Incidence rates of carbapenemase-producing Enterobacteriaceae clinical isolates in France: a prospective nationwide study in 2011-12. J Antimicrob Chemother 2014; 69: 2706-2712.
29. Nagaraj S, Chandran SP, Shamanna P, Macaden R. Carbapenem resistance among Escherichia coli and Klebsiella pneumoniae in a tertiary care hospital in South India. Indian J Med Microbiol 2012; 30: 93-95.
30. Sood S. Identification and differentiation of carbapenemases in Klebsiella pneumoniae: a phenotypic test evaluation study from Jaipur, India. J Clin Diagn Res 2014; 8: DC01-DC03.
31. Lorenzoni VV, Silva DDC, Rampelotto RF, Brats PC, Villa B, Hörner R. Evaluation of carbapenem-resistant Enterobacteriaceae in a tertiary-level reference hospital in Rio Grande do Sul, Brazil. Rev Soc Bras Med Trop 2017; 50: 685-688.
32. Fattouh M, El-din AN, Omar MA. Detection of Klebsiella pneumoniae carbapenemase (KPC) producing Gram-negative superbugs: an emerging cause of multidrug-resistant infections in general surgery department of Sohag University Hospital, Egypt. Int J Curr Microbiol App Sci 2015; 4: 1-15.
33. Chakraborty D, Basu S, Das S. A study on infections caused by metallo beta-lactamase producing Gram-negative bacteria in intensive care unit patients. Am J Infect Dis 2010; 6: 34-39.
34. Sadeghi MR, Ghotaslou R, Akhi MT, Asgharzadeh M, Hasani A. Molecular characterization of extended-spectrum β-lactamase, plasmid-mediated AmpC cephalosporinase and carbapenemase genes among Enterobacteriaceae isolates in five medical centres of East and West Azerbaijan, Iran. J Med Microbiol 2016; 65: 1322-1331.
2. Armin S, Fallah F, Karimi A, Karbasiyan F, Alebouyeh M, Rafiei Tabatabaei S, et al. Antibiotic susceptibility patterns for carbapenem-resistant Enterobacteriaceae. Int J Microbiol 2023; 2023: 8920977.
3. ECDC (2023). European Centre for Disease Prevention and Control, Antimicrobial resistance surveillance in Europe 2023-2021. Available from: https://www.ecdc.europa.eu/en/publications-data/antimicrobial-resistance-surveillance-europe-2023-2021-data
4. Verma G, Nayak SR, Jena S, Panda SS, Pattnaik D, Praharaj AK, et al. Prevalence of carbapenem-resistant Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa in a tertiary care hospital in eastern India: a pilot study. J Pure Appl Microbiol 2023; 17: 10.22207/JPAM.17.4.21.
5. Mohammed MU, Manisha DR, Nagamani K. Clinical, phenotypic and genotypic profile of carbapenem resistant gram negative infections in intensive care units. Indian J Microbiol Res 2021; 8: 28-34.
6. Queenan AM, Bush K. Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev 2007; 20: 440-458.
7. Marchaim D, Gottesman T, Schwartz O, Korem M, Maor Y, Rahav G, et al. National multicenter study of predictors and outcomes of bacteremia upon hospital admission caused by Enterobacteriaceae producing extended-spectrum beta-lactamases. Antimicrob Agents Chemother 2010; 54: 5099-5104.
8. Bush K, Bradford PA. β-Lactams and β-lactamase inhibitors: an overview. Cold Spring Harb Perspect Med 2016; 6: a025247.
9. Noval M, Banoub M, Claeys KC, Heil E. The battle is on: new beta-lactams for the treatment of multidrug-resistant Gram-negative organisms. Curr Infect Dis Rep 2020; 22: 1.
10. Kardaś-Słoma L, Fournier S, Dupont JC, Rochaix L, Birgand G, Zahar JR, et al. Cost-effectiveness of strategies to control the spread of carbapenemase-producing Enterobacterales in hospitals: a modelling study. Antimicrob Resist Infect Control 2022; 11: 117.
11. CLSI (2022). CLSI Publishes CLSI M100-Performance Standards for Antimicrobial Susceptibility Testing, 32nd Edition.
12. Haji SH, Aka STH, Ali FA. Prevalence and characterisation of carbapenemase encoding genes in multidrug-resistant Gram-negative bacilli. PLoS One 2021; 16(11): e0259005.
13. Aslan AT, Paterson DL. Epidemiology and clinical significance of carbapenemases in Australia: a narrative review. Intern Med J 2024; 54: 535-544.
14. Xiao W, Wang X, Qu Y, Sun M, Chang Y, Li W, et al. Identification of two novel carbapenemase-encoding hybrid plasmids harboring blaNDM-5 and blaKPC-2 in a clinical ST11-KL47 Klebsiella pneumoniae. Infect Drug Resist 2023; 16: 4073-4081.
15. Hara Y, Iguchi M, Tetsuka N, Morioka H, Hirabayashi A, Suzuki M, et al.
16. Sfeir MM, Hayden JA, Fauntleroy KA, Mazur C, Johnson JK, Simner PJ, et al. EDTA-modified carbapenem inactivation method: a phenotypic method for detecting metallo-beta-lactamase-producing Enterobacteriaceae. J Clin Microbiol 2019; 57(5): e01757-18.
17. Koul N, Kakati B, Agarwal S. Use of the combined modified carbapenem inactivation method and EDTA-modified carbapenem inactivation method for detection of carbapenemase-producing Enterobacteriaceae causing ventilator-associated respiratory infections. J Pure Appl Microbiol 2022; 16: 1239-1244.
18. Verma G, Singh N, Smriti S, Panda SS, Pattnaik D, Tripathy S, et al. Modified carbapenem inactivation method and ethylenediaminetetraacetic acid (EDTA)-carbapenem inactivation method for detection of carbapenemase-producing Enterobacterales and Pseudomonas aeruginosa. Cureus 2024; 16(6): e63340.
19. 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.
20. Wattal C, Goel N, Oberoi JK, Raveendran R, Datta S, Prasad KJ. Surveillance of multidrug-resistant organisms in a tertiary care hospital in Delhi, India. J Assoc Physicians India 2010; 58 Suppl: 32-36.
21. Hirsch EB, Tam VH. Detection and treatment options for Klebsiella pneumoniae carbapenemases (KPCs): an emerging cause of multidrug-resistant infection. J Antimicrob Chemother 2010; 65: 1119-1125.
22. Parate A, Karyakarte R, Ambhore N. Phenotypic detection of carbapenemase production and difference in antimicrobial susceptibility pattern in clinical isolates of Klebsiella pneumoniae at a medical college hospital in Vidarbha region. Indian J Microbiol Res 2017; 4: 253-258.
23. Vamsi SK, Moorthy RS, Hemiliamma MN, Chandra Reddy RB, Chanderakant DJ, Sirikonda S. Phenotypic and genotypic detection of carbapenemase production among Gram-negative bacteria isolated from hospital-acquired infections. Saudi Med J 2022; 43: 236-243.
24. Diwakar J, Verma RK, Singh DP, Singh A, Kumari S. Phenotypic detection of carbapenem resistance in Gram-negative bacilli from various clinical specimens of a tertiary care hospital in Western Uttar Pradesh. Int J Res Med Sci 2017; 5: 3511-3514.
25. Parveen RM, Harish BN, Parija SC. Emerging carbapenem resistance among nosocomial isolates of Klebsiella pneumoniae in South India. Int J Pharma Bio Sci 2010; 1: 1-11.
26. Pawar SK, Mohite ST, Shinde RV, Patil SR, Karande GS. Carbapenem-resistant Enterobacteriaceae: prevalence and bacteriological profile in a tertiary teaching hospital from rural western India. Indian J Microbiol Res 2018; 5: 342-347.
27. Nair PK, Vaz MS. Prevalence of carbapenem-resistant Enterobacteriaceae from a tertiary care hospital in Mumbai, India. J Microbiol Infect Dis 2013; 3: 207-210.
28. Robert J, Pantel A, Mérens A, Lavigne JP, Nicolas-Chanoine MH; ONERBA’s Carbapenem Resistance Study Group. Incidence rates of carbapenemase-producing Enterobacteriaceae clinical isolates in France: a prospective nationwide study in 2011-12. J Antimicrob Chemother 2014; 69: 2706-2712.
29. Nagaraj S, Chandran SP, Shamanna P, Macaden R. Carbapenem resistance among Escherichia coli and Klebsiella pneumoniae in a tertiary care hospital in South India. Indian J Med Microbiol 2012; 30: 93-95.
30. Sood S. Identification and differentiation of carbapenemases in Klebsiella pneumoniae: a phenotypic test evaluation study from Jaipur, India. J Clin Diagn Res 2014; 8: DC01-DC03.
31. Lorenzoni VV, Silva DDC, Rampelotto RF, Brats PC, Villa B, Hörner R. Evaluation of carbapenem-resistant Enterobacteriaceae in a tertiary-level reference hospital in Rio Grande do Sul, Brazil. Rev Soc Bras Med Trop 2017; 50: 685-688.
32. Fattouh M, El-din AN, Omar MA. Detection of Klebsiella pneumoniae carbapenemase (KPC) producing Gram-negative superbugs: an emerging cause of multidrug-resistant infections in general surgery department of Sohag University Hospital, Egypt. Int J Curr Microbiol App Sci 2015; 4: 1-15.
33. Chakraborty D, Basu S, Das S. A study on infections caused by metallo beta-lactamase producing Gram-negative bacteria in intensive care unit patients. Am J Infect Dis 2010; 6: 34-39.
34. Sadeghi MR, Ghotaslou R, Akhi MT, Asgharzadeh M, Hasani A. Molecular characterization of extended-spectrum β-lactamase, plasmid-mediated AmpC cephalosporinase and carbapenemase genes among Enterobacteriaceae isolates in five medical centres of East and West Azerbaijan, Iran. J Med Microbiol 2016; 65: 1322-1331.
| Files | ||
| Issue | Vol 17 No 4 (2025) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v17i4.19227 | |
| Keywords | ||
| Carbapenem antibiotics Carbapenemases Beta-lactamases Metallo-beta-lactamase Microbial sensitivity tests | ||
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How to Cite
1.
Shafi T, Mir AA, Roohi S, Fomda B, Wani S, Ahmed T, Yousuf S. Detection of carbapenemase production in Enterobacterales by mCIM and eCIM: a tertiary care hospital study. Iran J Microbiol. 2025;17(4):539-548.
