PREVALENCE, RISK FACTORS, AND CLINICAL OUTCOMES ASSOCIATED WITH CARBAPENEM-RESISTANT GRAM-NEGATIVE BACILLI INFECTIONS IN A TERTIARY CARE HOSPITAL: A PROSPECTIVE CROSS-SECTIONAL STUDY
Main Article Content
Keywords
Carbapenem resistance, Gram-negative bacilli, Antimicrobial stewardship, Healthcare-associated infections, Multidrug resistance
Abstract
Introduction: Carbapenem resistance among Gram-negative bacilli represents a critical global health challenge. This study aimed to determine the prevalence of carbapenem resistance, identify associated risk factors, and evaluate clinical outcomes in a tertiary care setting in India.
Methods: A prospective cross-sectional study was conducted over six months in Department of Microbiology at Vyas Medical College & Hospital, Jodhpur, a tertiary care teaching hospital. Consecutive non-duplicate Gram-negative bacilli isolated from clinical specimens underwent antimicrobial susceptibility testing according to CLSI guidelines. Demographic and clinical data were collected using standardized forms. Chi-square tests and logistic regression were performed to identify risk factors, with p<0.05 considered statistically significant.
Results: Among 330 Gram-negative isolates, 48.5% exhibited carbapenem resistance, with the highest rates in Acinetobacter baumannii (85.7%), followed by Pseudomonas aeruginosa (60.7%), Klebsiella pneumoniae (58.6%), and Escherichia coli (27.1%). Resistance rates varied across clinical settings: intensive care units (66.9%), surgical wards (41.2%), medical wards (39.1%), and outpatient departments (28.3%). Multivariate analysis identified prior carbapenem use (adjusted OR: 3.95, 95% CI: 2.41-6.48), ICU stay >7 days (adjusted OR: 3.22, 95% CI: 1.96-5.29), and mechanical ventilation (adjusted OR: 2.86, 95% CI: 1.74-4.71) as independent risk factors. Patients with carbapenem-resistant infections experienced higher mortality (26.9% vs. 11.2%, p<0.001), longer hospital stays (18.7 vs. 11.3 days, p<0.001), and lower clinical cure rates (57.5% vs. 80.0%, p<0.001) compared to those with susceptible infections.
Conclusion: The high prevalence of carbapenem resistance, particularly in ICUs, underscores the urgent need for antimicrobial stewardship, enhanced infection control practices, and routine surveillance. The significant association with poorer clinical outcomes highlights the importance of early detection and appropriate management strategies to mitigate the impact of these challenging infections.
References
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5. Gandra, S., Mojica, N., Klein, E. Y., Ashok, A., Nerurkar, V., Kumari, M., Ramesh, U., Dey, S., Vadwai, V., Das, B. R., & Laxminarayan, R. (2019). Trends in antibiotic resistance among major bacterial pathogens isolated from blood cultures tested at a large private laboratory network in India, 2008-2014. International Journal of Infectious Diseases, 88, 41-49. https://doi.org/10.1016/j.ijid.2019.08.007
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8. Manohar, P., Shanthini, T., Ayyanar, R., Bozdogan, B., Wilson, A., Tamhankar, A. J., Nachimuthu, R., & Lopes, B. S. (2017). The distribution of carbapenem- and colistin-resistance in Gram-negative bacteria from the Tamil Nadu region in India. Journal of Medical Microbiology, 66(7), 874-883. https://doi.org/10.1099/jmm.0.000510
9. Nordmann, P., Naas, T., & Poirel, L. (2011). Global spread of carbapenemase-producing Enterobacteriaceae. Emerging Infectious Diseases, 17(10), 1791-1798. https://doi.org/10.3201/eid1710.110655
10. Tacconelli, E., Carrara, E., Savoldi, A., Harbarth, S., Mendelson, M., Monnet, D. L., Pulcini, C., Kahlmeter, G., Kluytmans, J., Carmeli, Y., Ouellette, M., Outterson, K., Patel, J., Cavaleri, M., Cox, E. M., Houchens, C. R., Grayson, M. L., Hansen, P., Singh, N., ... WHO Pathogens Priority List Working Group. (2018). Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. The Lancet Infectious Diseases, 18(3), 318-327. https://doi.org/10.1016/S1473-3099(17)30753-3
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12. Cai, B., Echols, R., Magee, G., Arjona Ferreira, J. C., Morgan, G., Ariyasu, M., Sawada, T., & Nagata, T. D. (2017). Prevalence of carbapenem-resistant Gram-negative infections in the United States predominated by Acinetobacter baumannii and Pseudomonas aeruginosa. Open Forum Infectious Diseases, 4(3), ofx176. https://doi.org/10.1093/ofid/ofx176
13. Centers for Disease Control and Prevention (CDC). (2020). Antibiotic Resistance & Patient Safety Portal. https://arpsp.cdc.gov/
14. Chatterjee, S., Datta, S., Roy, S., Ramanan, L., Saha, A., Viswanathan, R., Som, T., & Basu, S. (2017). Carbapenem resistance in Acinetobacter baumannii and other Acinetobacter spp. causing neonatal sepsis: Focus on NDM-1 and its linkage to ISAba125. Frontiers in Microbiology, 8, 1126. https://doi.org/10.3389/fmicb.2017.01126
15. Dhawan, B., Bonnet, R., Shukla, N. K., Mathur, P., Das, B. K., & Kapil, A. (2017). Infection with an extended-spectrum β-lactamase-producing strain of Serratia marcescens following tongue reconstruction. Journal of Clinical Microbiology, 41(5), 2233-2234. https://doi.org/10.1128/JCM.41.5.2233-2234.2003
16. European Centre for Disease Prevention and Control (ECDC). (2021). Surveillance of antimicrobial resistance in Europe 2020. ECDC. https://doi.org/10.2900/543587
17. Goel, V., Hogade, S. A., & Karadesai, S. G. (2019). Prevalence of extended-spectrum beta-lactamases, AmpC beta-lactamase, and metallo-beta-lactamase producing Pseudomonas aeruginosa and Acinetobacter baumannii in an intensive care unit in a tertiary care hospital. Journal of Scientific Society, 40(1), 28-32. https://doi.org/10.4103/jss.JSS_33_12
18. Jaiswal, S. R., Gupta, S., Kumar, R. S., Sherawat, A., Rajoreya, A., Dash, S. K., Bhagwati, G., & Chakrabarti, S. (2018). Gut colonization with carbapenem-resistant Enterobacteriaceae adversely impacts the outcome in patients with hematological malignancies: Results of a prospective surveillance study. Mediterranean Journal of Hematology and Infectious Diseases, 10(1), e2018025. https://doi.org/10.4084/MJHID.2018.025
19. Kaur, A., Singh, S., Gill, A. K., Kaur, N., & Mahajan, A. (2017). Isolation and characterization of carbapenem-resistant Acinetobacter baumannii from various clinical specimens in a tertiary care hospital. Journal of Global Antimicrobial Resistance, 10, 277-282. https://doi.org/10.1016/j.jgar.2017.05.022
20. Khurana, S., Mathur, P., Kapil, A., Valisan, R., & Behera, B. (2018). Molecular epidemiology of beta-lactamase producing nosocomial Gram-negative pathogens from North and South Indian hospitals. Journal of Medical Microbiology, 66(7), 999-1004. https://doi.org/10.1099/jmm.0.000507
21. Kumar, M., Dutta, R., Saxena, S., & Singhal, S. (2020). Risk factor analysis in clinical isolates of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae from a tertiary care center in India. Journal of Global Antimicrobial Resistance, 20, 66-72. https://doi.org/10.1016/j.jgar.2019.11.007
22. Malchione, M. D., Torres, L. M., Hartley, D. M., Koch, M., & Goodman, J. L. (2019). Carbapenem and colistin resistance in Enterobacteriaceae in Southeast Asia: Review and mapping of emerging and overlapping challenges. International Journal of Antimicrobial Agents, 54(4), 381-399. https://doi.org/10.1016/j.ijantimicag.2019.07.019
23. Martins-Sorenson, N., Snesrud, E., Xavier, D. E., Cacci, L. C., Iavarone, A. T., McGann, P., Riley, L. W., & Moreira, B. M. (2020). A novel plasmid-encoded mcr-4.3 gene in a colistin-resistant Acinetobacter baumannii clinical strain. Journal of Antimicrobial Chemotherapy, 75(1), 60-64. https://doi.org/10.1093/jac/dkz413
24. Mohd Sazlly Lim, S., Wong, P. L., Sulaiman, H., Atiya, N., Shunmugam, R. H., & Liew, S. M. (2019). Clinical prediction models for carbapenem-resistant Enterobacteriaceae colonization or infection: a systematic review. Journal of Hospital Infection, 104(2), 130-140. https://doi.org/10.1016/j.jhin.2019.10.022
25. Morrissey, I., Hackel, M., Badal, R., Bouchillon, S., Hawser, S., & Biedenbach, D. (2016). A review of ten years of the Study for Monitoring Antimicrobial Resistance Trends (SMART) from 2002 to 2011. Pharmaceuticals, 6(11), 1335-1346. https://doi.org/10.3390/ph6111335
26. Nair, P. K., Vaz, M. S., & Vadakekolathu, J. (2018). Antibiotic resistance profiles of Gram-negative bacteria associated with bloodstream infections in a tertiary care hospital in Mangalore, South India. Asian Journal of Pharmaceutical and Clinical Research, 11(8), 48-52. https://doi.org/10.22159/ajpcr.2018.v11i8.26082
27. Patel, A., Patel, K., Patel, J., Shah, H., & Bhavsar, R. (2019). Time series analysis of antimicrobial resistance patterns in academic teaching hospital in Southern Gujarat, India. Journal of Applied Pharmaceutical Science, 9(5), 48-54. https://doi.org/10.7324/JAPS.2019.90507
28. Prakash, V., Lewis, J. S., Herrera, M. L., Wickes, B. L., & Jorgensen, J. H. (2022). A prospective multicenter study to determine the incidence of carbapenem resistance among Enterobacterales isolates causing community-acquired infections in the Indian subcontinent. Antimicrobial Agents and Chemotherapy, 66(4), e02221-21. https://doi.org/10.1128/AAC.02221-21
29. Sahu, M. K., Siddharth, B., Choudhury, A., Vishnubhatla, S., Singh, S. P., Menon, R., Kapoor, P. M., Talwar, S., Choudhary, S., & Airan, B. (2020). Incidence, microbiological profile and risk factors of ventilator-associated pneumonia in a cardiac surgical intensive care unit. Indian Journal of Medical Microbiology, 34(1), 61-68. https://doi.org/10.4103/ijmm.IJMM_16_29
30. Singh, A. K., Bhushan, R., Maurya, A. K., Mishra, P., Singh, S. K., & Verma, R. (2021). Clonal spread of carbapenem-resistant Klebsiella pneumoniae ST147 in surgical wards of a tertiary care hospital, India. Journal of Global Antimicrobial Resistance, 25, 253-259. https://doi.org/10.1016/j.jgar.2021.04.001
31. Tian, X., Sun, S., Jia, X., Zou, H., Li, S., & Zhang, L. (2019). Epidemiology of and risk factors for infection with extended-spectrum β-lactamase-producing carbapenem-resistant Enterobacteriaceae: Results of a double case-control study. Infection and Drug Resistance, 12, 1863-1872. https://doi.org/10.2147/IDR.S209536
32. Veeraraghavan, B., Jesudason, M. R., Prakasah, J. A. J., Anandan, S., Sahni, R. D., Pragasam, A. K., Bakthavatchalam, Y. D., Selvakumar, R., & Dhole, T. N. (2018). Antimicrobial susceptibility profiles of Gram-negative bacteria causing infections collected across India during 2014-15: Study for monitoring antimicrobial resistance trend report. Indian Journal of Medical Microbiology, 36(1), 32-36. https://doi.org/10.4103/ijmm.IJMM_17_415
33. Vijayakumar, S., Rajenderan, S., Laishram, S., Anandan, S., Balaji, V., & Biswas, I. (2018). Biofilm formation and motility depend on the nature of the Acinetobacter baumannii clinical isolates. Frontiers in Public Health, 6, 105. https://doi.org/10.3389/fpubh.2018.00105
34. Walia, K., Madhumathi, J., Veeraraghavan, B., Chakrabarti, A., Kapil, A., Ray, P., Singh, H., Sistla, S., & Thomas, K. (2022). Establishing antimicrobial resistance surveillance & research network in India: Journey so far. Indian Journal of Medical Research, 150(2), 164-181. https://doi.org/10.4103/ijmr.IJMR_226_19
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Dr. Anju Gupta, & Dr. Ankur Mitruka. (2025). PREVALENCE, RISK FACTORS, AND CLINICAL OUTCOMES ASSOCIATED WITH CARBAPENEM-RESISTANT GRAM-NEGATIVE BACILLI INFECTIONS IN A TERTIARY CARE HOSPITAL: A PROSPECTIVE CROSS-SECTIONAL STUDY. Journal of Population Therapeutics and Clinical Pharmacology, 32(5), 75-85. https://doi.org/10.53555/0agn1s22
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Author Biographies
Dr. Anju Gupta
Assistant Professor, Department of Microbiology, Vyas Medical College & Hospital, Jodhpur, Rajasthan, India.
Dr. Ankur Mitruka
OSD, Community Medicine, RTL Office NPSN, Lucknow, Uttar Pradesh, India
How to Cite
Dr. Anju Gupta, & Dr. Ankur Mitruka. (2025). PREVALENCE, RISK FACTORS, AND CLINICAL OUTCOMES ASSOCIATED WITH CARBAPENEM-RESISTANT GRAM-NEGATIVE BACILLI INFECTIONS IN A TERTIARY CARE HOSPITAL: A PROSPECTIVE CROSS-SECTIONAL STUDY. Journal of Population Therapeutics and Clinical Pharmacology, 32(5), 75-85. https://doi.org/10.53555/0agn1s22