Original Article

Antimicrobial susceptibility pattern of carbapenemase-producing Gram-negative nosocomial bacteria at Al Zahra hospital, Isfahan, Iran


Background and Objectives: Bacterial antibiotic resistance is one of the most important threats for public health around the world. Carbapenemase-producing Gram-negative bacteria have resistance to most antibiotics including carbapenems complicating the treatment of infections. The aim of this study was to determine the antimicrobial susceptibility pattern of carbapenemase-producing nosocomial Gram-negative pathogens at a referral teaching hospital to reveal the best options for treatment of related infections.
Materials and Methods: Gram-negative bacteria, isolated from hospitalized patients with nosocomial infections, underwent meropenem susceptibility test by disk diffusion method. Meropenem-resistant strains were evaluated for the presence of carbapenemase using Modified Hodge test (MHT). Finally, the antibiotic susceptibility test was performed to determine the sensitivity of each carbapenemase-positive strain against various antimicrobial agents according to the guidelines of Clinical and Laboratory Standards Institute (CLSI).
Results: Over the study period, 155 carbapenemase-positive isolates were detected. Pneumonia was the most frequent related nosocomial infection (67.1%) followed by UTI (23.2%). Acinetobacter baumannii (53.5%) and Klebsiella pneumoniae (40%) were the most frequently isolated pathogens. The pathogens had high rate of resistance to all antibiotics. Colistin had the most in vitro effect against all pathogens. Also, K. pneumoniae had a co-trimoxazole sensitivity rate equal to colistin (30.6%).
Conclusion: Carbapenemase-positive Gram-negative bacteria causing nosocomial infections are common in our hospital and have high rate of resistance to most antibiotics. Improvement in the pattern of antibiotic use and infection control measures are necessary to overcome this resistance.

1. Khan HA, Baig FK, Mehboob R. Nosocomial infections: Epidemiology, prevention, control and surveillance. Asian Pac J Trop Biomed 2017; 7: 478-482.
2. Rajabi M, Abdar ME, Rafiei H, Aflatoonia MR, Abdar ZE. Nosocomial infections and epidemiology of antibiotic resistance in teaching hospitals in south east of Iran. Glob J Health Sci 2016; 8: 190-197.
3. Klevens RM, Edwards JR, Richards CL, Horan TC, Gaynes RP, Pollock DA, et al. Estimating health care-associated infections and deaths in U.S. hospitals, 2002. Public Health Rep 2007; 122: 160-166.
4. Haque M, Sartelli M, McKimm J, Abu Bakar M. Health care-associated infections – an overview. Infect Drug Resist 2018; 11: 2321-2333.
5. Heydarpour F, Rahmani Y, Heydarpour B, Asadmobini A. Nosocomial infections and antibiotic resistance pattern in open-heart surgery patients at Imam Ali Hospital in Kermanshah, Iran. GMS Hyg Infect Control 2017; 12:Doc07.
6. Van Duin D, Doi Y. The global epidemiology of carbapenemase-producing Enterobacteriaceae. Virulence 2017; 8: 460-469.
7. Nordmann P, Dortet L, Poirel L. Carbapenem resistance in Enterobacteriaceae: here is the storm! Trends Mol Med 2012; 18: 263-272.
8. Castanheira M, Gales AC, Mendes RE, Jones R, Sader HS. Antimicrobial susceptibility of Streptococcus pneumoniae in Latin America: results from five years of the SENTRY Antimicrobial Surveillance Program. Clin Microbiol Infect 2004; 10: 645-651.
9. Kazmierczak KM, Biedenbach DJ, Hackel M, Rabine S, de Jonge BL, Bouchillon SK, et al. Global dissemination of blaKPC into bacterial species beyond Klebsiella pneumoniae and in vitro susceptibility to ceftazidime-avibactam and aztreonam-avibactam. Antimicrob Agents Chemother 2016; 60: 4490-4500.
10. Lee C-R, Lee JH, Park KS, Kim YB, Jeong BC, Lee SH. Global dissemination of carbapenemase-producing Klebsiella pneumoniae: epidemiology, genetic context, treatment options, and detection methods. Front Microbiol 2016; 7:895.
11. Spyropoulou A, Papadimitriou-Olivgeris M, Bartzavali C, Vamvakopoulou S, Marangos M, Spiliopoulou I, et al. A ten-year surveillance study of carbapenemase-producing Klebsiella pneumoniae in a tertiary care Greek university hospital: predominance of KPC-over VIM-or NDM-producing isolates. J Med Microbiol 2016; 65: 240-246.
12. Albiger B, Glasner C, Struelens MJ, Grundmann H, Monnet DL, European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) working group. Carbapenemase-producing Enterobacteriaceae in Europe: assessment by national experts from 38 countries, May 2015. Euro Surveill 2015; 20:30062.
13. Clinical and Laboratory Standards Institute (CLSI) performance standards for antimicrobial susceptibility testing. M100-S28, 2018, Wayne, PA.
14. Amjad A, Mirza IA, Abbasi S, Farwa U, Malik N, Zia F. Modified Hodge test: A simple and effective test for detection of carbapenemase production. Iran J Microbiol 2011; 3: 189-193.
15. Galani I, Kontopidou F, Souli M, Rekatsina PD, Koratzanis E, Deliolanis J, et al. Colistin susceptibility testing by Etest and disk diffusion methods. Int J Antimicrob Agents 2008; 31: 434-439.
16. Zhang Y, Wang Q, Yin Y, Chen H, Jin L, Gu B, et al. Epidemiology of carbapenem-resistant Enterobacteriaceae infections: report from the China CRE Network. Antimicrob Agents Chemother 2018; 62(2):e01882-17.
17. Okoche D, Asiimwe BB, Katabazi FA, Kato L, Najjuka CF. Prevalence and characterization of carbapenem-resistant Enterobacteriaceae isolated from Mulago National Referral Hospital, Uganda. PLoS One 2015; 10(8):e0135745.
18. Singh-Moodley A, Perovic O. Antimicrobial susceptibility testing in predicting the presence of carbapenemase genes in Enterobacteriaceae in South Africa. BMC Infect Dis 2016; 16: 536.
19. Alexander BT, Marschall J, Tibbetts RJ, Neuner EA, Dunne Jr WM, Ritchie DJ. Treatment and clinical outcomes of urinary tract infections caused by KPC-producing Enterobacteriaceae in a retrospective cohort. Clin Ther 2012; 34: 1314-1323.
20. Gheitani L, Fazeli H. Prevalence of bla VIM, bla IMP, and bla KPC genes among carbapenem-resistant Klebsiella pneumoniae (CRKP) isolated from Kurdistan and Isfahan hospitals, Iran. Res Mol Med (RMM) 2018; 6: 12-20.
21. Gaynes R, Edwards JR, National Nosocomial Infections Surveillance System. Overview of nosocomial infections caused by Gram-negative bacilli. Clin Infect Dis 2005; 41: 848-854.
22. Tatman-Otkun M, Gürcan S, Ozer B, Shokrylanbaran N. Annual trends in antibiotic resistance of nosocomial Acinetobacter baumannii strains and the effect of synergistic antibiotic combinations. New Microbiol 2004; 27: 21-28.
23. Munoz-Price LS, Weinstein RA. Acinetobacter infection. N Engl J Med 2008; 358: 1271-1281.
24. Wolff MA, Young CL, Ramphal R. Antibiotic therapy for enterobacter meningitis: a retrospective review of 13 episodes and review of the literature. Clin Infect Dis 1993; 16: 772-777.
25. Kurtaran B, Kuscu F, Ulu A, Inal AS, Komur S, Kibar F, et al. The causes of postoperative meningitis: the comparison of Gram-negative and gram-positive pathogens. Turk Neurosurg 2018; 28: 589-596.
26. Lesho E, Yoon EJ, McGann P, Snesrud E, Kwak Y, Milillo M, et al. Emergence of colistin-resistance in extremely drug-resistant Acinetobacter baumannii containing a novel pmrCAB operon during colistin therapy of wound infections. J Infect Dis 2013; 208: 1142-1151.
27. Lopez-Rojas R, McConnell MJ, Jimenez-Mejias ME, DominguezHerrera J, Fernandez-Cuenca F, Pachon J. Colistin resistance in a clinical Acinetobacter baumannii strain appearing after colistin treatment: effect on virulence and bacterial fitness. Antimicrob Agents Chemother 2013; 57: 4587-4589.
28. Pelletier MR, Casella LG, Jones JW, Adams MD, Zurawski DV, Hazlett KR, et al. Unique structural modifications are present in the lipopolysaccharide from colistin-resistant strains of Acinetobacter baumannii. Antimicrob Agents Chemother 2013; 57: 4831-4840.
29. Azimi L, Talebi M, Pourshafie M-R, Owlia P, Lari AR. Characterization of carbapenemases in extensively drug resistance Acinetobacter baumannii in a burn care center in Iran. Int J Mol Cell Med 2015; 4: 46-53.
30. Paranandi A, Maloney M, Grogan E, Macierowski B, Noel D, Razeq J, et al. 548. Carbapenem-resistant Acinetobacter baumannii antibiotic susceptibility testing and antibiogram formation, connecticut 2017–2019. Open Forum Infect Dis 2019; 6(Suppl 2): S261.
31. Nepka M, Perivolioti E, Kraniotaki E, Politi L, Tsakris A, Pournaras S. In vitro bactericidal activity of trimethoprim-sulfamethoxazole alone and in combination with colistin against carbapenem-resistant Acinetobacter baumannii clinical isolates. Antimicrob Agents Chemother 2016; 60: 6903-6906.
32. Falagas ME, Vardakas KZ, Roussos NS. Trimethoprim/sulfamethoxazole for Acinetobacter spp: a review of current microbiological and clinical evidence. Int J Antimicrob Agents 2015; 46: 231-241.
33. Campos AC, Albiero J, Ecker AB, Kuroda CM, Meirelles LE, Polato A, et al. Outbreak of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: A systematic review. Am J Infect Control 2016; 44: 1374-1380.
34. Battikh H, Harchay C, Dekhili A, Khazar K, Kechrid F, Zribi M, et al. Clonal spread of colistin-resistant Klebsiella pneumoniae coproducing KPC and VIM carbapenemases in neonates at a Tunisian university hospital. Microb Drug Resist 2017; 23: 468-472.
35. Woodford N, Zhang J, Warner M, Kaufmann ME, Matos J, Macdonald A, et al. Arrival of Klebsiella pneumoniae producing KPC carbapenemase in the United Kingdom. J Antimicrob Chemother 2008; 62: 1261-1264.
36. Doi Y. Treatment options for carbapenem-resistant Gram-negative bacterial infections. Clin Infect Dis 2019; 69(Suppl 7):S565-S575.
IssueVol 13 No 1 (2021) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijm.v13i1.5492
Nosocomial infections; Carbapenemase; Antibiotic; Susceptibility

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Bahrami S, Shafiee F, Hakamifard A, Fazeli H, Soltani R. Antimicrobial susceptibility pattern of carbapenemase-producing Gram-negative nosocomial bacteria at Al Zahra hospital, Isfahan, Iran. Iran J Microbiol. 13(1):50-57.