Original Article

Evaluation of mechanisms of colistin resistance in Klebsiella pneumoniae strains isolated from patients with urinary tract infection in ICU


Background and Objectives: One of the major causes of urinary tract infections is Klebsiella pneumoniae. Currently, few studies investigated the mechanisms of resistance to colistin in Iran. The current study aimed to determine the prevalence of plasmid and chromosome-mediated resistance to colistin in K. pneumoniae isolates.
Materials and Methods: 177 urine samples were collected from patients with urinary tract infections hospitalized in the intensive care unit (ICU) of hospitals in the city of Qazvin. K. pneumoniae isolates were identified by standard biochemical methods, resistance to colistin among K. pneumoniae isolates were tested by disk diffusion and microbroth dilution methods. The chromosomal mutation and presence of the mcr genes in colistin-resistant K. pneumoniae were evaluated by PCR.
Results: Out of 177 samples, 65 K. pneumoniae were obtained from patients in the ICU. Six colistin-resistant isolates were isolated with MIC values ≥4 μg/mL, none of them was positive for mcr1-5. In 4 isolates, missense mutation in mgrB gene resulted in amino acid substitutions and in one isolate of mgrB gene was found intact mgrB gene.
Conclusion: The results suggest that mgrB mutation was the main mutation among colistin-resistant isolates and plasmid-borne colistin resistance was not expanded among strains.

1. Robatjazi S, Nikkhahi F, Niazadeh M, Amin Marashi SM, Peymani A, Javadi A, et al. Phenotypic identification and genotypic characterization of plasmid-mediated AmpC β-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates in Iran. Curr Microbiol 2021;78:2317-2323.
2. Walsh TR. Emerging carbapenemases: a global perspective. Int J Antimicrob Agents 2010;36 Suppl 3:S8-S14.
3. Livermore DM, Woodford N. The β-lactamase threat in Enterobacteriaceae, Pseudomonas and Acinetobacter. Trends Microbiol 2006;14:413-420.
4. Grégoire N, Aranzana-Climent V, Magréault S, Marchand S, Couet W. Clinical pharmacokinetics and pharmacodynamics of colistin. Clin Pharmacokinet 2017;56:1441-1460.
5. Maynard M, Drusano GL, Vicchiarelli M, Liu W, Myrick J, Nole J, et al. Polymyxin B pharmacodynamics in the hollow-fiber infection model: what you see may not be what you get. Antimicrob Agents Chemother 2021;16;65(8):e0185320.
6. Vaara M. New polymyxin derivatives that display improved efficacy in animal infection models as compared to polymyxin B and colistin. Med Res Rev 2018;38:1661-1673.
7. Velkov T, Deris ZZ, Huang JX, Azad MA, Butler M, Sivanesan S, et al. Surface changes and polymyxin interactions with a resistant strain of Klebsiella pneumoniae. Innate Immun 2014;20:350-363.
8. Falagas ME, Kasiakou SK. Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clin Infect Dis 2005;40:1333-1341.
9. Cheng HY, Chen YF, Peng HL. Molecular characterization of the PhoPQ-PmrD-PmrAB mediated pathway regulating polymyxin B resistance in Klebsiella pneumoniae CG43. J Biomed Sci 2010;17:60.
10. Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 2016;16:161-168.
11. Giani T, Arena F, Vaggelli G, Conte V, Chiarelli A, De Angelis LH, et al. Large nosocomial outbreak of colistin-resistant, carbapenemase-producing Klebsiella pneumoniae traced to clonal expansion of an mgrB deletion mutant. ‎J Clin Microbiol 2015;53:3341-3344.
12. Olaitan AO, Morand S, Rolain JM. Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria. Front Microbiol 2014;5:643.
13. Cannatelli A, D'Andrea MM, Giani T, Di Pilato V, Arena F, Ambretti S, et al. In vivo emergence of colistin resistance in Klebsiella pneumoniae producing KPC-type carbapenemases mediated by insertional inactivation of the PhoQ/PhoP mgrB regulator. Antimicrob Agents Chemother 2013;57:5521-5526.
14. Gunn JS. The Salmonella PmrAB regulon: lipopolysaccharide modifications, antimicrobial peptide resistance and more. Trends Microbiol 2008;16:284-290.
15. Nikkhahi F, Robatjazi S, Niazadeh M, Javadi A, Shahbazi GH, Aris P, et al. First detection of mobilized colistin resistance mcr-1 gene in Escherichia coli isolated from livestock and sewage in Iran. New Microbes New Infect 2021;41:100862.
16. Rebelo AR, Bortolaia V, Kjeldgaard JS, Pedersen SK, Leekitcharoenphon P, Hansen IM, et al. Multiplex PCR for detection of plasmid-mediated colistin resistance determinants, mcr-1, mcr-2, mcr-3, mcr-4 and mcr-5 for surveillance purposes. Euro Surveill 2018;23:17-00672.
17. Woodford N, Ellington MJ, Coelho JM, Turton JF, Ward ME, Brown S, et al. Multiplex PCR for genes encoding prevalent OXA carbapenemases in Acinetobacter spp. Int J Antimicrob Agents 2006;27:351-353.
18. Bardet L, Rolain JM. Development of new tools to detect colistin-resistance among Enterobacteriaceae strains. Can J Infect Dis Med Microbiol 2018;2018:3095249.
19. Azimi A, Peymani A, Pour PK. Phenotypic and molecular detection of metallo-β-lactamase-producing Pseudomonas aeruginosa isolates from patients with burns in Tehran, Iran. Rev Soc Bras Med Trop 2018;51:610-615.
20. Dallal MMS, Nikkhahi F, Alimohammadi M, Douraghi M, Rajabi Z, Foroushani AR, et al. Phage therapy as an approach to control Salmonella enterica serotype enteritidis infection in mice. Rev Soc Bras Med Trop 2019;52:e20190290.
21. Pishnian Z, Haeili M, Feizi A. Prevalence and molecular determinants of colistin resistance among commensal Enterobacteriaceae isolated from poultry in northwest of Iran. Gut Pathog 2019;11:2.
22. Jafari Z, Harati AA, Haeili M, Kardan-Yamchi J, Jafari S, Jabalameli F, et al. Molecular epidemiology and drug resistance pattern of carbapenem-resistant Klebsiella pneumoniae isolates from Iran. Microb Drug Resist 2019;25:336-343.
23. Haeili M, Javani A, Moradi J, Jafari Z, Feizabadi MM, Babaei E. MgrB alterations mediate colistin resistance in Klebsiella pneumoniae isolates from Iran. Front Microbiol 2017;8:2470.
24. Azam M, Gaind R, Yadav G, Sharma A, Upmanyu K, Jain M, et al. Colistin resistance among multiple sequence types of Klebsiella pneumoniae is associated with diverse resistance mechanisms: a report from India. Front Microbiol 2021;12:609840.
25. Esposito EP, Cervoni M, Bernardo M, Crivaro V, Cuccurullo S, Imperi F, et al. Molecular epidemiology and virulence profiles of colistin-resistant Klebsiella pneumoniae blood isolates from the hospital agency “Ospedale dei Colli,” Naples, Italy. Front Microbiol 2018;9:1463.
26. Ghafur A, Shankar C, GnanaSoundari P, Venkatesan M, Mani D, Thirunarayanan M, et al. Detection of chromosomal and plasmid-mediated mechanisms of colistin resistance in Escherichia coli and Klebsiella pneumoniae from Indian food samples. J Glob Antimicrob Resist 2019;16:48-52.
27. Malli E, Florou Z, Tsilipounidaki K, Voulgaridi I, Stefos A, Xitsas S, et al. Evaluation of rapid polymyxin NP test to detect colistin-resistant Klebsiella pneumoniae isolated in a tertiary Greek hospital. J Microbiol Methods 2018;153:35-39.
28. Leung LM, Cooper VS, Rasko DA, Guo Q, Pacey MP, McElheny CL, et al. Structural modification of LPS in colistin-resistant, KPC-producing Klebsiella pneumoniae. J Antimicrob Chemother 2017;72:3035-3042.
29. Tang KL, Caffrey NP, Nóbrega DB, Cork SC, Ronksley PE, Barkema HW, et al. Restricting the use of antibiotics in food-producing animals and its associations with antibiotic resistance in food-producing animals and human beings: a systematic review and meta-analysis. Lancet Planet Health 2017;1(8):e316-e327.
30. Aris P, Robatjazi S, Nikkhahi F, Amin Marashi SM. Molecular mechanisms and prevalence of colistin resistance of Klebsiella pneumoniae in the Middle East region: A review over five last years. J Glob Antimicrob Resist 2020;22:625-630.
IssueVol 14 No 1 (2022) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijm.v14i1.8798
Klebsiella pneumoniae; Colistin; MgrB; Mcr gene; Intensive care units

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Niazadeh M, Nikkhahi F, Robatjazi S, Javadi A, Farzam SA, Babaei S, Zeynali P. Evaluation of mechanisms of colistin resistance in Klebsiella pneumoniae strains isolated from patients with urinary tract infection in ICU. Iran J Microbiol. 2022;14(1):31-37.