Distribution of MBL and serine-β-lactamase-producing pathogens in ventilator-associated pneumonia: insights into MDR and XDR strains
,
Abstract
Background and Objectives: Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Gram-negative bacteria is a serious ICU challenge. This study determined the prevalence, antimicrobial susceptibility profiles, and phenotypic carbapenemase resistance mechanisms of Gram-negative isolates from VAP patients in two tertiary hospitals in Karachi, Pakistan.
Materials and Methods: We included 104 consecutive cases of VAP (July 2021–January 2023). A total of 67 carbapenem-resistant Gram-negative isolates were identified and tested. Antibiotic susceptibility was assessed by disk diffusion and broth micro dilution, according to CLSI and EUCAST guidelines. Modified and enhanced carbapenem inactivation methods (mCIM/eCIM) were used to distinguish metallo-β-lactamase (MBL) and serine carbapenemase production.
Results: The mean age was 44.6 ± 18.3 years; 52.2% were male. Early-onset VAP accounted for 37.3% and late-onset for 62.7%. The most frequent pathogens were Acinetobacter baumannii (49.3%, 33/67) and Klebsiella pneumoniae (20.9%, 14/67). Notably, 67% of isolates produced MBLs, and 33% produced serine carbapenemases (phenotypically). The prevalence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan drug-resistant (PDR) phenotypes was 42.6%, 31.3%, and 19.4%, respectively.
Conclusion: VAP in our ICUs was dominated by A. baumannii and K. pneumoniae with high levels of MBL-mediated resistance. These findings highlight the urgent need for surveillance, stewardship, and new therapeutic options.
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7. Jhalora V, Bist R. A Comprehensive review of molecular mechanisms leading to the emergence of multidrug resistance in bacteria. Indian J Microbiol 2025; 65: 844-865.
8. Soltani B, Ahmadrajabi R, Kalantar-Neyestanaki D. Critical resistance to carbapenem and aminoglycosides in Pseudomonas aeruginosa: spread of bla(NDM)/16S methylase armA harboring isolates with intrinsic resistance mechanisms in Kerman, Iran. BMC Infect Dis 2024; 24: 1188.
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10. Zajmi A, Teo J, Yeo CC. Epidemiology and characteristics of Elizabethkingia spp. infections in southeast Asia. Microorganisms 2022; 10: 882.
11. Gondal AJ, Choudhry N, Bukhari H, Rizvi Z, Jahan S, Yasmin N. Estimation, evaluation and characterization of carbapenem resistance burden from a tertiary care hospital, Pakistan. Antibiotics (Basel) 2023; 12: 525.
12. Apanga PA, Ahmed J, Tanner W, Starcevich K, VanDerslice JA, Rehman U, et al. Carbapenem-resistant Enterobacteriaceae in sink drains of 40 healthcare facilities in Sindh, Pakistan: A cross-sectional study. PLoS One 2022; 17(2): e0263297.
13. Mirha HT, Ali SH, Aamar H, Sadiq M, Tharwani ZH, Habib Z, et al. The impact of antibiotic resistance on the rampant spread of infectious diseases in Pakistan: Insights from a narrative review. Health Sci Rep 2024; 7(4): e2050.
14. Metersky ML, Kalil AC. Management of Ventilator-Associated Pneumonia: Guidelines. Infect Dis Clin North Am 2024; 38: 87-101.
15. Khalil KA, Alsultan M, Daher NA. Microbial profile and antimicrobial resistance patterns in ventilator-associated pneumonia (VAP): A cross-sectional study from Syria. J Postgrad Med 2025; 71: 7-14.
16. Walana W, Vicar EK, Kuugbee ED, Sakida F, Yabasin IB, Faakuu E, et al. Antimicrobial resistance of clinical bacterial isolates according to the WHO's AWaRe and the ECDC-MDR classifications: the pattern in Ghana's Bono East Region. Front Antibiot 2023; 2: 1291046.
17. Naing L, Nordin RB, Abdul Rahman H, Naing YT. Sample size calculation for prevalence studies using scalex and scalaR calculators. BMC Med Res Methodol 2022; 22: 209.
18. Codjoe FS, Donkor ES. Carbapenem resistance: A review. Med Sci (Basel) 2017; 6: 1.
19. Melinte V, Radu MA, Văcăroiu MC, Mîrzan L, Holban TS, Ileanu BV, et al. Epidemiology of carbapenem-Resistant Klebsiella Pneumoniae Co-Producing MBL and OXA-48-Like in a romanian tertiary hospital: A call to action. Antibiotics (Basel) 2025; 14: 783.
20. Saharman YR, Karuniawati A, Severin JA, Verbrugh HA. Infections and antimicrobial resistance in intensive care units in lower-middle income countries: a scoping review. Antimicrob Resist Infect Control 2021; 10: 22.
21. Kurihara MNL, Sales RO, Silva KED, Maciel WG, Simionatto S. Multidrug-resistant Acinetobacter baumannii outbreaks: a global problem in healthcare settings. Rev Soc Bras Med Trop 2020; 53: e20200248.
22. Sharma S, Das A, Banerjee T, Barman H, Yadav G, Kumar A. Adaptations of carbapenem resistant Acinetobacter baumannii (CRAB) in the hospital environment causing sustained outbreak. J Med Microbiol 2021; 70: 10.1099/jmm.0.001345.
23. Abushanab D, Nasr ZG, Al-Badriyeh D. Efficacy and Safety of colistin versus Tigecycline for Multi-Drug-Resistant and extensively Drug-Resistant Gram-Negative Pathogens-A Meta-Analysis. Antibiotics (Basel) 2022; 11: 1630.
24. Rosenthal VD, Memish ZA, Bearman G. Preventing ventilator-associated pneumonia: A position paper of the international society for infectious diseases, 2024 update. Int J Infect Dis 2025; 151: 107305.
25. Teerawattanapong N, Panich P, Kulpokin D, Na Ranong S, Kongpakwattana K, Saksinanon A, et al.A Systematic review of the burden of multidrug-resistant healthcare-associated infections among intensive care unit patients in southeast Asia: The rise of Multidrug-Resistant Acinetobacter baumannii. Infect Control Hosp Epidemiol 2018; 39: 525-533.
26. Galani I, Papoutsaki V, Karaiskos I, Moustakas N, Galani L, Maraki S, et al. In vitro activities of omadacycline, eravacycline, cefiderocol, apramycin, and comparator antibiotics against Acinetobacter baumannii causing bloodstream infections in Greece, 2020-2021: a multicenter study. Eur J Clin Microbiol Infect Dis 2023; 42: 843-852.
27. Ejaz H, Ahmad M, Younas S, Junaid K, Abosalif KOA, Abdalla AE, et al. Molecular Epidemiology of Extensively-Drug Resistant Acinetobacter baumannii Sequence Type 2 Co-Harboring bla (NDM) and bla (OXA) From Clinical Origin. Infect Drug Resist 2021; 14: 1931-1939.
28. Gondal AJ, Saleem S, Jahan S, Choudhry N, Yasmin N. Novel Carbapenem-Resistant klebsiella pneumoniae ST147 Coharboring bla (NDM-1), bla (OXA-48) and Extended-Spectrum β-Lactamases from Pakistan. Infect Drug Resist 2020; 13: 2105-2115.
29. Sangiorgio G, Calvo M, Stefani S. Aztreonam and avibactam combination therapy for metallo-β-lactamase-producing gram-negative bacteria: A Narrative review. Clin Microbiol Infect 2025; 31: 971-978.
30. Guchhait P, Choudhuri N, Chaudhuri BN, Datta T, Dawn AK, Das P, et al.Improved diagnostic stewardship in carbapenem-resistant Enterobacterales gene detection helps in early initiation of targeted therapy. J Med Microbiol 2025; 74: 002029.
31. Uechi K, Nishiyama N, Arakaki W, Nakano A, Uechi A, Nakamura T, et al.An evaluation of the modified carbapenem inactivation method (mCIM) in conjunction with EDTA or sodium mercaptoacetate, for detecting metallo β-lactamase production for Aeromonas species harboring bla(CphA). J Infect Chemother 2025; 31: 102678.
2. Li W, Cai J, Ding L, Chen Y, Wang X, Xu H. Incidence and risk factors of ventilator-associated pneumonia in the intensive care unit: a systematic review and meta-analysis. J Thorac Dis 2024; 16: 5518-5528.
3. Li Q, Zhou X, Yang R, Shen X, Li G, Zhang C, et al. Carbapenem-resistant Gram-negative bacteria (CR-GNB) in ICUs: resistance genes, therapeutics, and prevention - a comprehensive review. Front Public Health 2024; 12: 1376513.
4. Lagadinou M, Amerali M, Michailides C, Chondroleou A, Skintzi K, Spiliopoulou A, et al. Antibiotic resistance trends in Carbapenem-Resistant Gram-Negative pathogens and Eight-Year surveillance of XDR bloodstream infections in a western greece Tertiary Hospital. Pathogens 2024; 13: 1136.
5. Kerimoglu E, Catak T, Kilinc A. Evaluation of Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae in an Intensive care unit: A Retrospective study. Antibiotics (Basel) 2025; 14: 700.
6. Hammoudi Halat D, Ayoub Moubareck C. Hospital-acquired and ventilator-associated pneumonia caused by multidrug-resistant Gram-negative pathogens: Understanding epidemiology, resistance patterns, and implications with COVID-19. F1000Res 2024; 12: 92.
7. Jhalora V, Bist R. A Comprehensive review of molecular mechanisms leading to the emergence of multidrug resistance in bacteria. Indian J Microbiol 2025; 65: 844-865.
8. Soltani B, Ahmadrajabi R, Kalantar-Neyestanaki D. Critical resistance to carbapenem and aminoglycosides in Pseudomonas aeruginosa: spread of bla(NDM)/16S methylase armA harboring isolates with intrinsic resistance mechanisms in Kerman, Iran. BMC Infect Dis 2024; 24: 1188.
9. Kadivarian S, Rostamian M, Dashtbin S, Kooti S, Zangeneh Z, Abiri R, et al. High burden of MDR, XDR, PDR, and MBL producing Gram negative bacteria causing infections in Kermanshah health centers during 2019-2020. Iran J Microbiol 2023; 15: 359-372.
10. Zajmi A, Teo J, Yeo CC. Epidemiology and characteristics of Elizabethkingia spp. infections in southeast Asia. Microorganisms 2022; 10: 882.
11. Gondal AJ, Choudhry N, Bukhari H, Rizvi Z, Jahan S, Yasmin N. Estimation, evaluation and characterization of carbapenem resistance burden from a tertiary care hospital, Pakistan. Antibiotics (Basel) 2023; 12: 525.
12. Apanga PA, Ahmed J, Tanner W, Starcevich K, VanDerslice JA, Rehman U, et al. Carbapenem-resistant Enterobacteriaceae in sink drains of 40 healthcare facilities in Sindh, Pakistan: A cross-sectional study. PLoS One 2022; 17(2): e0263297.
13. Mirha HT, Ali SH, Aamar H, Sadiq M, Tharwani ZH, Habib Z, et al. The impact of antibiotic resistance on the rampant spread of infectious diseases in Pakistan: Insights from a narrative review. Health Sci Rep 2024; 7(4): e2050.
14. Metersky ML, Kalil AC. Management of Ventilator-Associated Pneumonia: Guidelines. Infect Dis Clin North Am 2024; 38: 87-101.
15. Khalil KA, Alsultan M, Daher NA. Microbial profile and antimicrobial resistance patterns in ventilator-associated pneumonia (VAP): A cross-sectional study from Syria. J Postgrad Med 2025; 71: 7-14.
16. Walana W, Vicar EK, Kuugbee ED, Sakida F, Yabasin IB, Faakuu E, et al. Antimicrobial resistance of clinical bacterial isolates according to the WHO's AWaRe and the ECDC-MDR classifications: the pattern in Ghana's Bono East Region. Front Antibiot 2023; 2: 1291046.
17. Naing L, Nordin RB, Abdul Rahman H, Naing YT. Sample size calculation for prevalence studies using scalex and scalaR calculators. BMC Med Res Methodol 2022; 22: 209.
18. Codjoe FS, Donkor ES. Carbapenem resistance: A review. Med Sci (Basel) 2017; 6: 1.
19. Melinte V, Radu MA, Văcăroiu MC, Mîrzan L, Holban TS, Ileanu BV, et al. Epidemiology of carbapenem-Resistant Klebsiella Pneumoniae Co-Producing MBL and OXA-48-Like in a romanian tertiary hospital: A call to action. Antibiotics (Basel) 2025; 14: 783.
20. Saharman YR, Karuniawati A, Severin JA, Verbrugh HA. Infections and antimicrobial resistance in intensive care units in lower-middle income countries: a scoping review. Antimicrob Resist Infect Control 2021; 10: 22.
21. Kurihara MNL, Sales RO, Silva KED, Maciel WG, Simionatto S. Multidrug-resistant Acinetobacter baumannii outbreaks: a global problem in healthcare settings. Rev Soc Bras Med Trop 2020; 53: e20200248.
22. Sharma S, Das A, Banerjee T, Barman H, Yadav G, Kumar A. Adaptations of carbapenem resistant Acinetobacter baumannii (CRAB) in the hospital environment causing sustained outbreak. J Med Microbiol 2021; 70: 10.1099/jmm.0.001345.
23. Abushanab D, Nasr ZG, Al-Badriyeh D. Efficacy and Safety of colistin versus Tigecycline for Multi-Drug-Resistant and extensively Drug-Resistant Gram-Negative Pathogens-A Meta-Analysis. Antibiotics (Basel) 2022; 11: 1630.
24. Rosenthal VD, Memish ZA, Bearman G. Preventing ventilator-associated pneumonia: A position paper of the international society for infectious diseases, 2024 update. Int J Infect Dis 2025; 151: 107305.
25. Teerawattanapong N, Panich P, Kulpokin D, Na Ranong S, Kongpakwattana K, Saksinanon A, et al.A Systematic review of the burden of multidrug-resistant healthcare-associated infections among intensive care unit patients in southeast Asia: The rise of Multidrug-Resistant Acinetobacter baumannii. Infect Control Hosp Epidemiol 2018; 39: 525-533.
26. Galani I, Papoutsaki V, Karaiskos I, Moustakas N, Galani L, Maraki S, et al. In vitro activities of omadacycline, eravacycline, cefiderocol, apramycin, and comparator antibiotics against Acinetobacter baumannii causing bloodstream infections in Greece, 2020-2021: a multicenter study. Eur J Clin Microbiol Infect Dis 2023; 42: 843-852.
27. Ejaz H, Ahmad M, Younas S, Junaid K, Abosalif KOA, Abdalla AE, et al. Molecular Epidemiology of Extensively-Drug Resistant Acinetobacter baumannii Sequence Type 2 Co-Harboring bla (NDM) and bla (OXA) From Clinical Origin. Infect Drug Resist 2021; 14: 1931-1939.
28. Gondal AJ, Saleem S, Jahan S, Choudhry N, Yasmin N. Novel Carbapenem-Resistant klebsiella pneumoniae ST147 Coharboring bla (NDM-1), bla (OXA-48) and Extended-Spectrum β-Lactamases from Pakistan. Infect Drug Resist 2020; 13: 2105-2115.
29. Sangiorgio G, Calvo M, Stefani S. Aztreonam and avibactam combination therapy for metallo-β-lactamase-producing gram-negative bacteria: A Narrative review. Clin Microbiol Infect 2025; 31: 971-978.
30. Guchhait P, Choudhuri N, Chaudhuri BN, Datta T, Dawn AK, Das P, et al.Improved diagnostic stewardship in carbapenem-resistant Enterobacterales gene detection helps in early initiation of targeted therapy. J Med Microbiol 2025; 74: 002029.
31. Uechi K, Nishiyama N, Arakaki W, Nakano A, Uechi A, Nakamura T, et al.An evaluation of the modified carbapenem inactivation method (mCIM) in conjunction with EDTA or sodium mercaptoacetate, for detecting metallo β-lactamase production for Aeromonas species harboring bla(CphA). J Infect Chemother 2025; 31: 102678.
| Files | ||
| Issue | Vol 17 No 5 (2025) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v17i5.19885 | |
| Keywords | ||
| Ventilator-associated pneumonia Carbapenems Raoultella terrigena Elizabethkingia meningoseptica Drug resistance Bacterial | ||
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How to Cite
1.
Hussain Z, Naim A, Fatima A, Karim A, Uddin F, Shams S. Distribution of MBL and serine-β-lactamase-producing pathogens in ventilator-associated pneumonia: insights into MDR and XDR strains. Iran J Microbiol. 2025;17(5):761-772.
