Colistin Resistance among Multi-Drug Resistant Gram-Negative Bacteria in Iran: A Systematic Review and Meta-Analysis
Novelty in Biomedicine,
Vol. 13 No. 2 (2025),
19 April 2025
,
Page 105-118
https://doi.org/10.22037/nbm.v13i2.46666
Abstract
Background: Colistin, a last-resort antibiotic, faces a growing threat from antibiotic resistance. This study aims to comprehensively assess colistin resistance in clinical isolates of Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae in Iran.
Materials and Methods: Relevant studies on the prevalence of colistin resistance among multidrug-resistant Gram-negative bacteria in Iran, published up to December 15, 2023, were identified through searches of databases such as PubMed/Medline, EMBASE, and Scopus. The overall frequency of colistin resistance for each bacterial species was determined using CMA version 3.
Results: The comprehensive analysis of clinical isolates revealed varying frequencies of colistin resistance among the studied Gram-negative bacteria. E. coli displayed a resistance rate of 3.6%, while P. aeruginosa exhibited a rate of 6.5%. A. baumannii demonstrated a resistance rate of 4.7%, and K. pneumoniae displayed the highest resistance rate at 7.2%. Importantly, the analysis found no significant evidence of publication bias, enhancing the reliability of these resistance rate estimates.
Conclusion: Colistin resistance among these clinically significant Gram-negative bacteria in Iran is rising, limiting treatment options and posing serious challenges to healthcare providers. These findings underscore the urgency of enhanced surveillance, the development of alternative treatments, and the implementation of strict infection control measures. Addressing colistin resistance is crucial to effectively managing infections caused by these pathogens in Iran and globally.
- Colistin resistance
- Klebsiella pneumonia
- Pseudomonas aeruginosa
- Acinetobacter baumannii
- Escherichia coli
- Iran
How to Cite
References
Kanj SS, Bassetti M, Kiratisin P, Rodrigues C, Villegas MV, Yu Y, et al. Clinical data from studies involving novel antibiotics to treat multidrug-resistant Gram-negative bacterial infections. Int J Antimicrob Agents. 2022;60(3):106633.
Giske CG, Monnet DL, Cars O, Carmeli Y. Clinical and economic impact of common multidrug-resistant gram-negative bacilli. Antimicrob Agents Chemother. 2008;52(3):813-21.
Organization WH. Guidelines for the prevention and control of carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa in health care facilities. Guidelines for the prevention and control of carbapenem-resistant enterobacteriaceae, acinetobacter baumannii and pseudomonas aeruginosa in health care facilities2017.
Giamarellou H. Multidrug-resistant Gram-negative bacteria: how to treat and for how long. International Journal of Antimicrobial Agents. 2010;36:S50-S4.
Bolla J-M, Alibert-Franco S, Handzlik J, Chevalier J, Mahamoud A, Boyer G, et al. Strategies for bypassing the membrane barrier in multidrug resistant Gram-negative bacteria. FEBS letters. 2011;585(11):1682-90.
Falagas ME, Kasiakou SK, Saravolatz LD. Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clinical infectious diseases. 2005;40(9):1333-41.
Li J, Nation RL, Turnidge JD, Milne RW, Coulthard K, Rayner CR, et al. Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. The Lancet infectious diseases. 2006;6(9):589-601.
Huang C, Chen I, Tang T. Colistin monotherapy versus colistin plus meropenem combination therapy for the treatment of multidrug-resistant Acinetobacter baumannii infection: a meta-analysis. Journal of clinical medicine. 2022;11(11):3239.
Sato Y, Ubagai T, Tansho-Nagakawa S, Yoshino Y, Ono Y. Effects of colistin and tigecycline on multidrug-resistant Acinetobacter baumannii biofilms: advantages and disadvantages of their combination. Scientific Reports. 2021;11(1):11700.
Wang Z, Koirala B, Hernandez Y, Zimmerman M, Park S, Perlin DS, et al. A naturally inspired antibiotic to target multidrug-resistant pathogens. Nature. 2022;601(7894):606-11.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. bmj. 2021;372.
Aloush V, Navon-Venezia S, Seigman-Igra Y, Cabili S, Carmeli Y. Multidrug-resistant Pseudomonas aeruginosa: risk factors and clinical impact. Antimicrobial agents and chemotherapy. 2006;50(1):43-8.
Lee H-Y, Chen C-L, Wang S-B, Su L-H, Chen S-H, Liu S-Y, et al. Imipenem heteroresistance induced by imipenem in multidrug-resistant Acinetobacter baumannii: mechanism and clinical implications. International journal of antimicrobial agents. 2011;37(4):302-8.
Firoozeh F, Bakhshi F, Dadashi M, Badmasti F, Zibaei M, Omidinia N. Detection of multidrug-resistant Acinetobacter baumannii from burn patients and healthcare workers in Iran. Acta Microbiol Immunol Hung. 2023;70(1):22-8.
Afsharipour M, Mahmoudi S, Raji H, Pourakbari B, Mamishi S. Three-year evaluation of the nosocomial infections in pediatrics: bacterial and fungal profile and antimicrobial resistance pattern. Ann Clin Microbiol Antimicrob. 2022;21(1):6.
Farajnia S, Lotfi F, Dehnad A, Shojaie M, Raisi R, Rahbarnia L, et al. The molecular characterization of colistin-resistant isolates of Acinetobacter baumannii from patients at intensive care units. Iran J Microbiol. 2022;14(3):319-27.
Heidari R, Farajzadeh Sheikh A, Hashemzadeh M, Farshadzadeh Z, Salmanzadeh S, Saki M. Antibiotic resistance, biofilm production ability and genetic diversity of carbapenem-resistant Pseudomonas aeruginosa strains isolated from nosocomial infections in southwestern Iran. Mol Biol Rep. 2022;49(5):3811-22.
Khoshbayan A, Shariati A, Razavi S, Baseri Z, Ghodousi A, Darban-Sarokhalil D. Mutation in mgrB is the major colistin resistance mechanism in Klebsiella pneumoniae clinical isolates in Tehran, Iran. Acta Microbiol Immunol Hung. 2022.
Niazadeh M, Nikkhahi F, Robatjazi S, Javadi A, Farzam SA, Babaei S, et al. 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):31-7.
Ordoni R, Amini Y, Ranayi MA, Avestan Z, Mohagheghi-Fard AH, Zandhaghighi M, et al. Prevalence of the per, tem, veb, shv genes in Acinetobacter baumannii Isolated from Educational Hospital of Zahedan, Iran. Iranian Journal of Medical Microbiology. 2022;16(6):566-72.
Saki M, Amin M, Savari M, Hashemzadeh M, Seyedian SS. Beta-lactamase determinants and molecular typing of carbapenem-resistant classic and hypervirulent Klebsiella pneumoniae clinical isolates from southwest of Iran. Front Microbiol. 2022;13:1029686.
Shahri FN, Izanloo A, Goharrizi M, Jamali A, Bagheri H, Hjimohammadi A, et al. Antimicrobial resistance, virulence factors, and genotypes of Pseudomonas aeruginosa clinical isolates from Gorgan, northern Iran. Int Microbiol. 2022;25(4):709-21.
Alizadeh H, Khodavandi A, Alizadeh F, Bahador N. Molecular Characteristics of Carbapenem-Resistant Klebsiella pneumoniae Isolates Producing blaVIM, blaNDM, and blaIMP in Clinical Centers in Isfahan, Iran. Jundishapur J Microbiol. 2021;14(2):e114473.
Babaei S, Pourabdollah M, Aslanimehr M, Nikkhahi F, Mahmoodian S, Hasani Y, et al. Frequency of Multi-Drug Resistance and Molecular Characteristics of Resistance to Colistin in Acinetobacter baumannii Collected from Patients in Intensive Care Units with Ventilator-Associated Pneumonia. Tanaffos. 2021;20(4):345-52.
Bolourchi N, Shahcheraghi F, Giske CG, Nematzadeh S, Noori Goodarzi N, Solgi H, et al. Comparative genome analysis of colistin-resistant OXA-48-producing Klebsiella pneumoniae clinical strains isolated from two Iranian hospitals. Annals of Clinical Microbiology and Antimicrobials. 2021;20:1-11.
Farhadi M, Ahanjan M, Goli HR, Haghshenas MR, Gholami M. High frequency of multidrug-resistant (MDR) Klebsiella pneumoniae harboring several β-lactamase and integron genes collected from several hospitals in the north of Iran. Ann Clin Microbiol Antimicrob. 2021;20(1):70.
Karimi K, Zarei O, Sedighi P, Taheri M, Doosti-Irani A, Shokoohizadeh L. Investigation of Antibiotic Resistance and Biofilm Formation in Clinical Isolates of Klebsiella pneumoniae. Int J Microbiol. 2021;2021:5573388.
Khoshbayan A, Shariati A, Shahmoradi S, Baseri Z, Mozafari H, Darban-Sarokhalil D. Prevalence and molecular mechanisms of colistin resistance in Acinetobacter baumannii clinical isolates in Tehran, Iran. Acta Microbiol Immunol Hung. 2021.
Mazloomirad F, Hasanzadeh S, Sharifi A, Nikbakht G, Roustaei N, Khoramrooz SS. Identification and detection of pathogenic bacteria from patients with hospital-acquired pneumonia in southwestern Iran; evaluation of biofilm production and molecular typing of bacterial isolates. BMC Pulm Med. 2021;21(1):408.
Meshkat Z, Salimizand H, Amini Y, Mansury D, Zomorodi AR, Avestan Z, et al. Detection of efflux pump genes in multiresistant Acinetobacter baumannii ST2 in Iran. Acta Microbiol Immunol Hung. 2021;68(2):113-20.
Meybodi MME, Foroushani AR, Zolfaghari M, Abdollahi A, Alipour A, Mohammadnejad E, et al. Antimicrobial resistance pattern in healthcare-associated infections: investigation of in-hospital risk factors. Iran J Microbiol. 2021;13(2):178-82.
Mostafavi SN, Rostami S, Nokhodian Z, Ataei B, Cheraghi A, Ataabadi P, et al. Antibacterial resistance patterns of Acinetobacter baumannii complex: The results of Isfahan antimicrobial resistance surveillance-1 program. Asian Pacific Journal of Tropical Medicine. 2021;14(7):316-22.
Namaei MH, Yousefi M, Askari P, Roshanravan B, Hashemi A, Rezaei Y. High prevalence of multidrug-resistant non-fermentative Gram-negative bacilli harboring bla (IMP-1) and bla (VIM-1) metallo-beta-lactamase genes in Birjand, south-east Iran. Iran J Microbiol. 2021;13(4):470-9.
Nikibakhsh M, Firoozeh F, Badmasti F, Kabir K, Zibaei M. Molecular study of metallo-β-lactamases and integrons in Acinetobacter baumannii isolates from burn patients. BMC Infectious Diseases. 2021;21:1-6.
Rad ZR, Rad ZR, Goudarzi H, Goudarzi M, Alizade H, Mazraeh FN, et al. Detection of NDM-1 producing Klebsiella pneumoniae ST15 and ST147 in Iran during 2019–2020. Acta Microbiologica et Immunologica Hungarica. 2021;68(3):177-82.
Salehi B, Ghalavand Z, Yadegar A, Eslami G. Characteristics and diversity of mutations in regulatory genes of resistance-nodulation-cell division efflux pumps in association with drug-resistant clinical isolates of Acinetobacter baumannii. Antimicrobial Resistance & Infection Control. 2021;10:1-12.
Seyyedi M, Shapouri R, Zeighami H, Shokoohizadeh L. Genetic diversity of colistin resistance Nosocomial Acinetobacter baumannii strains from Iran. Journal of Research in Medical Sciences: The Official Journal of Isfahan University of Medical Sciences. 2021;26.
Sharahi JY, Hashemi A, Ardebili A, Davoudabadi S. Molecular characteristics of antibiotic-resistant Escherichia coli and Klebsiella pneumoniae strains isolated from hospitalized patients in Tehran, Iran. Annals of clinical microbiology and antimicrobials. 2021;20(1):1-14.
Yousefi Nojookambari N, Sadredinamin M, Dehbanipour R, Ghalavand Z, Eslami G, Vaezjalali M, et al. Prevalence of β-lactamase-encoding genes and molecular typing of Acinetobacter baumannii isolates carrying carbapenemase OXA-24 in children. Annals of Clinical Microbiology and Antimicrobials. 2021;20(1):1-8.
Afshar M, Fathizadeh S, Boustanshenas M, Soleymanzadeh Moghadam S, Roham M. Evaluation of molecular epidemiology and antibiotic susceptibility of Acinetobacter baumanii, in burned patients of Motahari hospital. Journal of Critical Reviews. 2020;7(1):91-5.
Ezadi F, Jamali A, Heidari A, Javid N, Ardebili A. Heteroresistance to colistin in oxacillinase-producing carbapenem-resistant Acinetobacter baumannii clinical isolates from Gorgan, Northern Iran. Journal of Global Antimicrobial Resistance. 2020;21:380-5.
Ghahraman MRK, Hosseini-Nave H, Azizi O, Shakibaie MR, Mollaie HR, Shakibaie S. Molecular characterization of lpxACD and pmrA/B two-component regulatory system in the colistin resistance Acinetobacter baumannii clinical isolates. Gene reports. 2020;21:100952.
Khanjani S, Sedigh Ebrahim-Saraie H, Shenagari M, Ashraf A, Mojtahedi A, Atrkar Roushan Z. In vitro activity of colistin against multidrug-resistant Acinetobacter baumannii isolates harboring blaOXA-23-like and blaOXA-24-like genes: A multicenter based study. Acta Microbiol Immunol Hung. 2020;67(3):182-6.
Moosavian M, Emam N, Pletzer D, Savari M. Rough-type and loss of the LPS due to lpx genes deletions are associated with colistin resistance in multidrug-resistant clinical Escherichia coli isolates not harbouring mcr genes. PLoS One. 2020;15(5):e0233518.
Sobouti B, Mirshekar M, Fallah S, Tabaei A, Fallah Mehrabadi J, Darbandi A. Pan drug-resistant Acinetobacter baumannii causing nosocomial infections among burnt children. Med J Islam Repub Iran. 2020;34:24.
Solgi H, Nematzadeh S, Giske CG, Badmasti F, Westerlund F, Lin YL, et al. Molecular Epidemiology of OXA-48 and NDM-1 Producing Enterobacterales Species at a University Hospital in Tehran, Iran, Between 2015 and 2016. Front Microbiol. 2020;11:936.
Tahmasebi H, Dehbashi S, Arabestani MR. Prevalence and Molecular Typing of Colistin-Resistant Pseudomonas aeruginosa (CRPA) Among β-Lactamase-Producing Isolates: A Study Based on High-Resolution Melting Curve Analysis Method. Infect Drug Resist. 2020;13:2943-55.
Tahmasebi H, Dehbashi S, Arabestani MR. Co-harboring of mcr-1 and β-lactamase genes in Pseudomonas aeruginosa by high-resolution melting curve analysis (HRMA): Molecular typing of superbug strains in bloodstream infections (BSI). Infect Genet Evol. 2020;85:104518.
Farajzadeh Sheikh A, Shahin M, Shokoohizadeh L, Halaji M, Shahcheraghi F, Ghanbari F. Molecular epidemiology of colistin-resistant Pseudomonas aeruginosa producing NDM-1 from hospitalized patients in Iran. Iran J Basic Med Sci. 2019;22(1):38-42.
Ghasemnejad A, Doudi M, Amirmozafari N. The role of the bla (KPC) gene in antimicrobial resistance of Klebsiella pneumoniae. Iran J Microbiol. 2019;11(4):288-93.
Haeili M, Kafshdouz M, Pishnian Z, Feizabadi MM, Martinez-Martinez L. Comparison of susceptibility testing methods for determining the activity of colistin against Gram-negative bacilli of clinical origin. J Med Microbiol. 2019;68(1):60-6.
Malekzadegan Y, Abdi A, Heidari H, Moradi M, Rastegar E, Sedigh Ebrahim-Saraie H. In vitro activities of colistin, imipenem and ceftazidime against drug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii isolates in the south of Iran. BMC Res Notes. 2019;12(1):301.
Monfared AM, Rezaei A, Poursina F, Faghri J. Detection of genes involved in biofilm formation in MDR and XDR Acinetobacter baumannii isolated from human clinical specimens in Isfahan, Iran. Archives of Clinical Infectious Diseases. 2019;14(2):6.
Moosavian M, Emam N. The first report of emerging mobilized colistin-resistance (mcr) genes and ERIC-PCR typing in Escherichia coli and Klebsiella pneumoniae clinical isolates in southwest Iran. Infect Drug Resist. 2019;12:1001-10.
Rajaee Behbahani M, Keshavarzi A, Pirbonyeh N, Javanmardi F, Khoob F, Emami A. Plasmid-related β-lactamase genes in Pseudomonas aeruginosa isolates: a molecular study in burn patients. J Med Microbiol. 2019;68(12):1740-6.
Ranjbar R, Farahani A. Study of genetic diversity, biofilm formation, and detection of Carbapenemase, MBL, ESBL, and tetracycline resistance genes in multidrug-resistant Acinetobacter baumannii isolated from burn wound infections in Iran. Antimicrob Resist Infect Control. 2019;8:172.
Tafreshi N, Babaeekhou L, Ghane M. Antibiotic resistance pattern of Acinetobacter baumannii from burns patients: increase in prevalence of bla (OXA-24-like) and bla (OXA-58-like) genes. Iran J Microbiol. 2019;11(6):502-9.
Tehrani S, Saffarfar V, Hashemi A, Abolghasemi S. A Survey of Genotype and Resistance Patterns of Ventilator-Associated Pneumonia Organisms in ICU Patients. Tanaffos. 2019;18(3):215-22.
Hedayat Yaghoobi M, Karami P, Khaledi A, Rafie E, Sabahi M, Habibipour B, et al. Comparison of antimicrobial resistance pattern in hospital versus community-acquired infections in pediatric patients. Journal of Advances in Medical and Biomedical Research. 2019;27(123):1-8.
Yazdansetad S, Najari E, Ghaemi EA, Javid N, Hashemi A, Ardebili A. Carbapenem-resistant Acinetobacter baumannii isolates carrying bla(OXA) genes with upstream ISAba1: First report of a novel OXA subclass from Iran. J Glob Antimicrob Resist. 2019;18:95-9.
Saadatian Farivar A, Nowroozi J, Eslami G, Sabokbar A. RAPD PCR Profile, Antibiotic Resistance, Prevalence of armA Gene, and Detection of KPC Enzyme in Klebsiella pneumoniae Isolates. Can J Infect Dis Med Microbiol. 2018;2018:6183162.
Shariati A, Azimi T, Ardebili A, Chirani A, Bahramian A, Pormohammad A, et al. Insertional inactivation of oprD in carbapenem-resistant Pseudomonas aeruginosa strains isolated from burn patients in Tehran, Iran. New microbes and new infections. 2018;21:75-80.
Bagheri-Nesami M, Rezai MS, Ahangarkani F, Rafiei A, Nikkhah A, Eslami G, et al. Multidrug and co-resistance patterns of non-fermenting Gram-negative bacilli involved in ventilator-associated pneumonia carrying class 1 integron in the North of Iran. Germs. 2017;7(3):123.
Shokri D, Rabbani Khorasgani M, Fatemi SM, Soleimani-Delfan A. Resistotyping, phenotyping and genotyping of New Delhi metallo-β-lactamase (NDM) among Gram-negative bacilli from Iranian patients. J Med Microbiol. 2017;66(4):402-11.
Zafari M, Feizabadi MM, Jafari S, Abdollahi A, Sabokbar A. High prevalence of OXA-type carbapenemases among Acinetobacter baumannii strains in a teaching hospital of Tehran. Acta Microbiol Immunol Hung. 2017;64(4):385-94.
Alaei N, Aziemzadeh M, Bahador A. Antimicrobial resistance profiles and genetic elements involved in carbapenem resistance in Acinetobacter baumannii isolates from a referral hospital in Southern Iran. J Glob Antimicrob Resist. 2016;5:75-9.
Goudarzi H, Azad M, Seyedjavadi SS, Azimi H, Chirani AS, Omrani VF, et al. Characterization of integrons and associated gene cassettes in Acinetobacter baumannii strains isolated from intensive care unit in Tehran, Iran. Journal of Acute Disease. 2016;5(5):386-92.
Pourakbari B, Yaslianifard S, Yaslianifard S, Mahmoudi S, Keshavarz-Valian S, Mamishi S. Evaluation of efflux pumps gene expression in resistant Pseudomonas aeruginosa isolates in an Iranian referral hospital. Iran J Microbiol. 2016;8(4):249-56.
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