Prevalence of integron classes in Gram-negative clinical isolated bacteria in Iran: a systematic review and meta-analysis

Document Type: Review Article


1 Student Research Committee, Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 English Language Teaching Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran


Objective(s): Integrons, as a potential element in the distribution and maintenance of drug resistance, have thoroughly been established. It is known that the high prevalence of integrons in multidrug-resistant (MDR) clinical isolates has become a serious public health concern. The objective of the present study was to determine the frequency of different classes of integrons in clinical isolates in Iran.
Materials and Methods: Electronic global databases were systematically searched. The raw data for integrons among bacterial isolates were collected and their prevalence was analyzed using Comprehensive Meta-Analysis V2.0 (Biostat, Englewood, NJ, USA) software.
Results: In a comprehensive literature review, 29 eligible studies were determined with their meta-analyses indicating the prevalence of integron class 1 to be 41% (95% CI 36.3-46.1) and integron class 2 as 17.7% (95% CI 13-23.3) in Gram-negative bacteria. The highest prevalence of integron class 1 was reported in Acinetobacter spp (58%) while the highest prevalence of integron class 2 was reported in Shigella isolates (83.7%). The frequencies of class 1 integron in MDR (79%) and non-MDR isolates (41%) were higher than those for class 2 integron in MDR (13.4%) and non-MDR isolates (17.7%).
Conclusion: The current systematic review demonstrated the significant presence of integrons among clinical isolates. Our analysis showed that measures such as estimates of the prevalence of this transposable element and diligence in continued surveillance might be necessary to prevent its spread.


Main Subjects

1. Ferri M, Ranucci E, Romagnoli P, Giaccone V. Antimicrobial resistance: a global emerging threat to public health systems. Crit Rev Food Sci Nutr 2017; 57:2857-2876.
2.  Prestinaci F, Pezzotti P, Pantosti A. Antimicrobial resistance: a global multifaceted phenomenon. Pathog Glob Health 2015; 109:309-318.
3. Cambray G, Guerout AM, Mazel D. Integrons. Annu Rev Genet 2010; 44:141-166.
4.Boucher Y, Labbate M, Koenig JE, Stokes HW. Integrons: mobilizable platforms that promote genetic diversity in bacteria. Trends Microbiol 2007; 15:301-309.
5.  Hall RM. Integrons and gene cassettes: hotspots of diversity in bacterial genomes. Ann N Y Acad Sci 2012; 1267:71-78.
6.  Gillings MR. Integrons: past, present, and future. Microbiol Mol Biol Rev 2014; 78:257-277.
7.  Messier N, Roy PH. Integron integrases possess a unique additional domain necessary for activity. J Bacteriol 2001; 183:6699-6706.
8.  Jove T, Da Re S, Denis F, Mazel D, Ploy MC. Inverse correlation between promoter strength and excision activity in class 1 integrons. PLoS Genet 2010; 6:e1000793.
9. Davies J, Davies D. Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev 2010; 74:417-433.
10. Partridge SR. Analysis of antibiotic resistance regions in Gram-negative bacteria. FEMS Microbiol Rev 2011; 35:820-855.
11. Hochhut B, Lotfi Y, Mazel D, Faruque SM, Woodgate R, Waldor MK. Molecular analysis of antibiotic resistance gene clusters in vibrio cholerae O139 and O1 SXT constins. Antimicrob Agents Chemother 2001; 45:2991-3000.
12.  Sorum H, Roberts MC, Crosa JH. Identification and cloning of a tetracycline resistance gene from the fish pathogen Vibrio salmonicida. Antimicrob Agents Chemother 1992; 36:611-615.
13.  Partridge SR, Tsafnat G, Coiera E, Iredell JR. Gene cassettes and cassette arrays in mobile resistance integrons. FEMS Microbiol Rev 2009; 33:757-784.
14.  Wright GD. Antibiotic resistome: A framework linking the clinic and the environment: John Wiley & Sons, Inc., Hoboken, New Jersey; 2012.
15. Mazel D. Integrons: agents of bacterial evolution. Nat Rev Microbiol 2006; 4:608-620.
16. Mobaraki S, Aghazadeh M, Barhaghi MH, Memar MY, Goli HR, Gholizadeh P, Kafil HS. Prevalence of integrons 1, 2, 3 associated with antibiotic resistance in Pseudomonas aeruginosa isolates from Northwest of Iran. BioMedicine. 2018;8:12-17.
17. Zeighami H, Haghi F, Masumian N, Hemmati F, Samei A, Naderi G. Distribution of Integrons and Gene Cassettes Among Uropathogenic and Diarrheagenic Escherichia coli Isolates in Iran. Microb Drug Resist 2015; 21:435-440.
18. Moazami Goudarzi S, Eftekhar F. Multidrug resistance and integron carriage in clinical isolates of Pseudomonas aeruginosa in Tehran, Iran. Turk J Med Sci 2015; 45:789-793.
19. Peymani A, Farajnia S, Nahaei MR, Sohrabi N, Abbasi L, Ansarin K, et al. Prevalence of class 1 integron among multidrug-resistant Acinetobacter baumannii in Tabriz, northwest of Iran. Pol J Microbiol 2012; 61:57-60.
20. Van Tulder M, Furlan A, Bombardier C, Bouter L, Group EBotCCBR. Updated method guidelines for systematic reviews in the Cochrane Collaboration Back Review Group. Spine 2003; 28:1290-1299.
21. Houri H, Pormohammad A, Riahi SM, Nasiri MJ, Fallah F, Dabiri H, et al. Acute bacterial meningitis in Iran: Systematic review and meta-analysis. PloS one 2017; 12:e0169617.
22.  Pormohammad A, Riahi S-M, Nasiri MJ, Fallah F, Aghazadeh M, Doustdar F, et al. Diagnostic test accuracy of adenosine deaminase for tuberculous meningitis: A systematic review and meta-analysis. J Infect 2017; 74:545-554.
23. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 2009; 151:W-65-W-94.
24. Munn Z, Moola S, Lisy K, Riitano D. The Joanna Briggs Institute Reviewers’ Manual 2014. The systematic review of prevalence and incidence data. Adelaide, SA: The Joanna Briggs Institute 2014.
25.  Ranjbar R, Aleo A, Giammanco GM, Dionisi AM, Sadeghifard N, Mammina C. Genetic relatedness among isolates of Shigella sonnei carrying class 2 integrons in Tehran, Iran, 2002–2003. BMC Infect Dis 2007; 7:1.
26. Japoni S, Japoni A, Farshad S, Ali AA, JAMALIdOUST M. Association between existence of integrons and multi-drug resistance in Acinetobacter isolated from patients in southern Iran. Pol J Microbiol 2011; 60:163-168.
27. Adabi M, Bakhshi B, Goudarzi H, Zahraei SM, Pourshafie MR. Distribution of class I integron and sulfamethoxazole trimethoprim constin in Vibrio cholerae isolated from patients in Iran. Microb Drug Resist 2009; 15:179-184.
28.  Taherikalani M, Maleki A, Sadeghifard N, Mohammadzadeh D, Soroush S, Asadollahi P, et al. Dissemination of class 1, 2 and 3 integrons among different multidrug resistant isolates of Acinetobacter baumannii in Tehran hospitals, Iran. Iran Pol J Microbiol 2011; 60:169-174.
29. Peymani A, Farajnia S, Mohammad R, Nasrollah Sohrabi L, Abbasi Ka, Azhari F. Prevalence of class 1 integron among multidrug-resistant Acinetobacter baumannii in Tabriz, northwest of Iran. Pol J Microbiol 2012;61(1):57-60.
30. Naghoni A, Ranjbar R, Tabaraie B, Farshad S, Owlia P, Safiri Z, et al. High prevalence of integron-mediated resistance in clinical isolates of Salmonella enterica. Jpn J InfectDis 2010; 63:417-421.
31. Firoozeh F, Shahcheraghi F, Salehi TZ, Karimi V, Aslani M. Antimicrobial resistance profile and presence of class I integrongs among Salmonella enterica serovars isolated from human clinical specimens in Tehran, Iran. Iran J Microbiol 2011; 3:112-117.
32. Rezaee MA, Sheikhalizadeh V, Hasani A. Detection of integrons among multi-drug resistant (MDR) Escherichia coli strains isolated from clinical specimens in northern west of Iran. Braz J Microbiol  2011; 42:1308-1313.
33. Mirnejad R, Mostofi S, Masjedian F. Antibiotic resistance and carriage class 1 and 2 integrons in clinical isolates of Acinetobacter baumannii from Tehran, Iran. Asian Pac J Trop Biomed 2013; 3:140-145.
34. Rajaei B, Siadat SD, Razavi MR, Aghasadeghi MR, Rad NS, Badmasti F, et al. Expanding drug resistance through integron acquisition in Salmonella spp. isolates obtained in Iran. Afr J Microbiol Res 2011; 5:2249-2253.
35. Mobarak-Qamsari M, Ashayeri-Panah M, Eftekhar F, Feizabadi MM. Integron mediated multidrug resistance in extended spectrum beta-lactamase producing clinical isolates of Klebsiella pneumoniae. Braz J Microbiol 2013; 44:849-854.
36. Derakhshan S, Peerayeh SN, Fallah F, Bakhshi B, Rahbar M, Ashrafi A. Detection of class 1, 2, and 3 integrons among Klebsiella pneumoniae isolated from children in Tehran hospitals. Arch Pediatr Infect Dis 2014; 2:164-168.
37. Eftekhari N, Bakhshi B, Pourshafie MR, Zarbakhsh B, Rahbar M, Hajia M, et al. Genetic diversity of Shigella spp. and their integron content. Foodborne Pathog Dis 2013; 10:237-242.
38. Kargar M, Mohammadalipour Z, Doosti A, Lorzadeh S, Japoni-Nejad A. High prevalence of class 1 to 3 integrons among multidrug-resistant diarrheagenic Escherichia coli in Southwest of Iran. Osong Public Health Res Perspect  2014; 5:193-198.
39. Goudarzi G, Lashkarara M. Prevalence of aac (3)-IIa, aph (3)-Ia and ant (2)-Ia Genes among Uropathogenic Escherichia coli Isolates. Med Lab J 2014; 8:61-67.
40. Peerayeh SN, Karmostaji A. Molecular identification of resistance determinants, integrons and genetic relatedness of extensively drug resistant Acinetobacter baumannii isolated from hospitals in Tehran, Iran. Jundishapur J Microbiol 2015; 8: e27021.
41. Azam H. Prevalence of class 1 and 2 integrons among the multidrug resistant uropathogenic strains of Escherichia coli. Asian Biomed 2015; 9:49-51.
42. Memariani M, Peerayeh SN, Mostafavi SKS, Salehi TZ. Detection of Class 1 and 2 Integrons Among Enteropathogenic Escherichia coli Isolates. Arch Ped Infect Dis 2014; 2: e16372.
43.  Rizi KS, Najar-Peerayeh S, Bakhshi B, Rahbar M. Prevalence of ESBLs and Integrons in Clinical Isolates of Salmonella spp. From Four Hospitals of Tehran. Int J Enteric Pathog 2015; 3: e21820.
44. Azami S, Abdi Ali A, Asgarani E. Association Between Metallo-β-lactamases and Integrons with Multi-Drug Resistance in Pseudomonas aeruginosa Isolates. J Med Microbiol Infect Dis 2013; 1:46-51.
45.  Ashayeri-Panah M, Feizabadi MM, Eftekhar F. Correlation of Multi-drug Resistance, Integron and bla ESBL Gene Carriage With Genetic Fingerprints of Extended-Spectrum β-Lactamase Producing Klebsiella pneumoniae. Jundishapur J Microbiol 2014; 7: e8747.
46.  Shams F, Hasani A, Rezaee MA, Nahaie MR, Hasani A, Haghi MHSB, et al. Carriage of Class 1 and 2 Integrons in Quinolone, Extended-Spectrum-β-Lactamase-Producing and Multi Drug Resistant E. coli and K. pneumoniae: High Burden of Antibiotic Resistance. Adv Pharm Bull 2015; 5:335.
47. Rezaee MA, Langarizadeh N, Aghazadeh M. First report of class 1 and class 2 integrons in multidrug-resistant Klebsiella pneumoniae isolates from northwest Iran. Jpn J InfectDis  2012; 65:256-259.
48. Seyedjavadi S, Eslami G, Goudarzi M, Goudarzi H, Fallah F. Integrons and multidrug resistance among E. coli and Klebsiella pneumoniae isolated from children with urinary tract infections. Research in Medicine 2013; 7:243.
49. Japoni A, Gudarzi M, Farshad S, Basiri E, Ziyaeyan M, Alborzi A, et al. Assay for integrons and pattern of antibiotic resistance in clinical Escherichia coli strains by PCR-RFLP in Southern Iran. Jpn J Infect Dis 2008; 61:85.
50. Fallah F, Karimi A, Goudarzi M, Shiva F, Navidinia M, Hadipour Jahromi M, et al. Determination of  integron frequency by a polymerase chain reaction–restriction fragment length polymorphism method in multidrug-resistant Escherichia coli, which causes Urinary tract infections. Microb Drug Resist 2012; 18:546-549.
51. Cambray G, Guerout A-M, Mazel D. Integrons. Annual review of genetics 2010; 44:141-166.
52.  Gillings MR. Integrons: past, present, and future. Microbiol Mol Biol Rev 2014; 78:257-277.
53. Fluit A, Schmitz FJ. Resistance integrons and superā€integrons. Clin Microbiol Infect  2004; 10:272-288.
54. Goldstein C, Lee MD, Sanchez S, Hudson C, Phillips B, Register B, et al. Incidence of class 1 and 2 integrases in clinical and commensal bacteria from livestock, companion animals, and exotics. Antimicrob Agents Chemother 2001; 45:723-726.
55. Abdollahiasl A, Kebriaeezadeh A, Nikfar S, Farshchi A, Ghiasi G, Abdollahi M. Patterns of antibiotic consumption in Iran during 2000–2009. I Int J Antimicrob Agents 2011; 37:489-490.
56. Soleymani F, Valadkhani M, Dinarvand R. Challenges and achievements of promoting rational use of drugs in Iran. Iran J Public Health 2009. 38:166-168.