Resistance pattern of Escherichia coli to levofloxacin in Iran: a narrative review

  • Gholamhossein Hassanshahi Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Ali Darehkordi Department of Chemistry and Biophysics, School of Sciences, Vali-e-Asr University of Rafsanjan, Rafsanjan, Iran
  • Mahmood Sheikh Fathollahi Department of Social Medicine, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Soudeh Khanamani Falahati-Pour Pistachio Safety Research Centre, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Ebrahim Rezazadeh Zarandi Department of Microbiology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Shokrollah Assar Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran AND Department of Microbiology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
Escherichia coli; Fluoroquinolones; Levofloxacin; Iran; Antibiotic resistance


Fluoroquinolones (FQs) are widely used in the treatment of infections caused by Escherichia coli. FQs are broad spectrum antibiotics with high tissue penetration, and ease of use. Therefore, given the concerns existing about drug resistance, we aim to review the latest findings about resistance patterns to levofloxacin (LVX) along with other FQs in E. coli infections in different parts of Iran. Evidence shows that quinolones have been used in Iran for nearly 50 years, and that 0-65% of E. coli isolates show resistance to FQs. In the western parts of Iran, the highest rate of resistance to LVX (66.7%) has been reported among patients having urinary tract infections with E. coli isolates. Few studies and information exist on the antimicrobial resistance of E. coli to LVX in different geographical locations of Iran. However, the findings of various studies on this subject show that E. coli resistance to LVX is more in the western part of Iran than in central and southern regions, but it is similar among inpatients and outpatients. Therefore, it is reasonable advisable to limit the overuse, inappropriate prescription, and self-medication of LVX to prevent the induction of FQ-resistant strains. Accordingly, in order to obtain a clearer image of resistance to FQs, especially LVX in E. coli in Iran, more extensive investigations in different geographical locations and periods of time are required. In addition, antimicrobial stewardship would be helpful in this regard.


1. Prasad K, Lekshmi G, Ostrikov K, Lussini V, Blinco J, Mohandas M, et al. Synergic bactericidal effects of reduced graphene oxide and silver nanoparticles against Gram-positive and Gram-negative bacteria. Sci Rep 2017;7: 1-11.
2. Burnham C-AD, Leeds J, Nordmann P, O'Grady J, Patel J. Diagnosing antimicrobial resistance. Nat Rev Microbiol 2017; 15: 697-703.
3. Paharik AE, Schrebier HL, Spaulding CN, Dodson KW, Hultgren SJ. Narrowing the spectrum: the new frontier of precision antimicrobials. Genome Med 2017; 9: 110.
4. Eurosurveillance editorial team. European union summary report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food 2012 published. Euro Surveill 2014; 19: 20748.
5. Allocati N, Masulli M, Alexeyev MF, Di Ilio C. Escherichia coli in Europe: an overview. Int J Environ Res Public Health 2013; 10: 6235-6254.
6. Leimbach A, Hacker J, Dobrindt U. E. coli as an all-rounder: the thin line between commensalism and pathogenicity. Curr Top Microbiol Immunol 2013; 358: 3-32.
7. Blount ZD. The unexhausted potential of E. coli. eLife 2015; 4: e05826.
8. Baeshen MN, Al-Hejin AM, Bora RS, Ahmed M, Ramadanass H, Saini KS, et al. Production of biopharmaceuticals in E. coli: current scenario and future perspectives. J Microbiol Biotechnol 2015; 25: 953-962.
9. Miri ST, Dashti A, Mostaan S, Kazemi F, Bouzari S. Identification of different Escherichia coli pathotypes in north and north-west provinces of Iran. Iran J Microbiol 2017; 9: 33-37.
10. Pham TD, Ziora ZM, Blaskovich MA. Quinolone antibiotics. Medchemcomm 2019; 10: 1719-1739.
11. Darehkordi A, Javanmiri M, Ghazi S, Assar S. Synthesis of N-aryl-2, 2, 2-trifluoroacetimidoyl piperazinylquinolone derivatives and their antibacterial evaluations. J Fluor Chem 2011; 132: 263-268.
12. Stone MRL, Masi M, Phetsang W, Pagès JM, Cooper MA, Blaskovich MAT. Fluoroquinolone-derived fluorescent probes for studies of bacterial penetration and efflux. Medchemcomm 2019; 10: 901-906.
13. Rehman A, Patrick WM, Lamont IL. Mechanisms of ciprofloxacin resistance in Pseudomonas aeruginosa: new approaches to an old problem. J Med Microbiol 2018; 68: 1-10.
14. Bernard J, Armand-Lefèvre L, Luce E, El Mniai A, Chau F, Casalino E, et al. Impact of a short exposure to levofloxacin on faecal densities and relative abundance of total and quinolone-resistant Enterobacteriaceae. Clin Microbiol Infect 2016; 22: 646.e1-646.e4.
15. Gill GK, Chhabra M, Chawla SP. Levofloxacin-induced desquamation: A possible and rare case report. Curr Drug Saf 2020; 15: 61-64.
16. Pan Z, Liu R, Zhang P, Zhou H, Fu Y, Zhou J. Combination of tigecycline and levofloxacin for successful treatment of nosocomial pneumonia caused by New Delhi Metallo-β-Lactamase-1-producing Raoultella planticola. Microb Drug Resist 2017; 23: 127-131.
17. Hsu PI, Tsai FW, Kao SS, Hsu WH, Cheng JS, Peng NJ, et al. Ten-day quadruple therapy comprising proton pump inhibitor, bismuth, tetracycline, and levofloxacin is more effective than standard levofloxacin triple therapy in the second-line treatment of Helicobacter pylori infection: A randomized controlled trial. Am J Gastroenterol 2017; 112: 1374-1381.
18. Humphries RM, Hindler JA, Shaffer K, Campeau SA. Evaluation of ciprofloxacin and levofloxacin disk diffusion and Etest using the 2019 Enterobacteriaceae CLSI breakpoints. J Clin Microbiol 2019; 57: e01797-18.
19. Ismail SJ, Mahmoud SS. First detection of New Delhi metallo-β-lactamases variants (NDM-1, NDM-2) among Pseudomonas aeruginosa isolated from Iraqi hospitals. Iran J Microbiol 2018; 10: 98-103.
20. Asif M. Role of quinolones and quinoxaline derivatives in the advancement of treatment of tuberculosis. Int J Sci World 2015; 3: 18-36.
21. Garoff L, Yadav K, Hughes D. Increased expression of Qnr is sufficient to confer clinical resistance to ciprofloxacin in Escherichia coli. J Antimicrob Chemother 2018; 73: 348-352.
22. Kusachi S, Oe K, Okuda Y, Sasaki J, Maetani I, Watanabe M, et al. Clinical study on levofloxacin injection for surgical infection. Japan J Chemother 2017; 65: 445-455.
23. Noel GJ. A review of levofloxacin for the treatment of bacterial infections. Clin Med Ther 2009; 1: 433-458.
24. Wu H-H, Liu H-Y, Lin Y-C, Hsueh P-R, Lee Y-J. Correlation between levofloxacin consumption and the incidence of nosocomial infections due to fluoroquinolone-resistant Escherichia coli. J Microbiol Immunol Infect 2016; 49: 424-429.
25. Bax BD, Chan PF, Eggleston DS, Fosberry A, Gentry DR, Gorrec F, et al. Type IIA topoisomerase inhibition by a new class of antibacterial agents. Nature 2010; 466: 935-940.
26. Iredell J, Brown J, Tagg K. Antibiotic resistance in Enterobacteriaceae: mechanisms and clinical implications. BMJ 2016; 352:h6420.
27. Aldred KJ, Kerns RJ, Osheroff N. Mechanism of quinolone action and resistance. Biochemistry 2014; 53: 1565-1574.
28. Cormier R, Burda WN, Harrington L, Edlinger J, Kodigepalli KM, Thomas J, et al. Studies on the antimicrobial properties of N-acylated ciprofloxacins. Bioorg Med Chem Lett 2012; 22: 6513-6520.
29. Collin F, Karkare S, Maxwell A. Exploiting bacterial DNA gyrase as a drug target: current state and perspectives. Appl Microbiol Biotechnol 2011; 92: 479-497.
30. Ahmed A, Daneshtalab M. Nonclassical biological activities of quinolone derivatives. J Pharm Pharm Sci 2011; 15: 52-72.
31. Wu H-H, Liu H-Y, Lin Y-C, Hsueh P-R, Lee Y-J. Correlation between levofloxacin consumption and the incidence of nosocomial infections due to fluoroquinolone-resistant Escherichia coli. J Microbiol Immunol Infect 2016; 49: 424-429.
32. Zhanel GG, Hartel E, Adam H, Zelenitsky S, Zhanel MA, Golden A, et al. Solithromycin: a novel fluoroketolide for the treatment of community-acquired bacterial pneumonia. Drugs 2016; 76: 1737-1757.
33. Dalhoff A. Global fluoroquinolone resistance epidemiology and implictions for clinical use. Interdiscip Perspect Infect Dis 2012; 2012: 1-37.
34. Lee S-J, Lee DS, Choe HS, Shim BS, Kim CS, Kim ME, et al. Antimicrobial resistance in community-acquired urinary tract infections: results from the Korean antimicrobial resistance monitoring system. J Infect Chemother 2011; 17: 440-446.
35. Akram M, Shahid M, Khan AU. Etiology and antibiotic resistance patterns of community-acquired urinary tract infections in JNMC Hospital Aligarh, India. Ann Clin Microbiol Antimicrob 2007; 6: 1-7.
36. Yassine I, Rafei R, Osman M, Mallat H, Dabboussi F, Hamze M. Plasmid-mediated quinolone resistance: Mechanisms, detection, and epidemiology in the Arab countries. Infect Genet Evol 2019; 76:104020.
37. Yokota S-i, Sato T, Okubo T, Ohkoshi Y, Okabayashi T, Kuwahara O, et al. Prevalence of fluoroquinolone-resistant Escherichia coli O25: H4-ST131 (CTX-M-15-nonproducing) strains isolated in Japan. Chemotherapy 2012; 58: 52-59.
38. Jang WH, Yoo DH, Park SW. Prevalence of and risk factors for levofloxacin-resistant E. coli isolated from outpatients with urinary tract infection. Korean J Urol 2011; 52: 554-559.
39. Hsueh P-R, Hoban DJ, Carmeli Y, Chen S-Y, Desikan S, Alejandria M, et al. Consensus review of the epidemiology and appropriate antimicrobial therapy of complicated urinary tract infections in Asia-Pacific region. J Infect 2011; 63: 114-123.
40. Bengtsson-Palme J, Kristiansson E, Larsson DJ. Environmental factors influencing the development and spread of antibiotic resistance. FEMS Microbiol Rev 2018; 42: 68-80.
41. Ventola CL. The antibiotic resistance crisis: part 1: causes and threats. Pharm Ther 2015; 40: 277-283.
42. Gharagozloo R, Ghavamian P. Bacteriological survey of urinary tract infection. Acta Med Iran 1968; 3-4: 105-119.
43. Haeili MGA, Nomanpour B, Omrani M, Feizabadi MM. Drug resistance patterns of bacteria isolated from patients with nosocomial pneumonia at Tehran hospitals during 2009-2011. J Infect Dev Countr 2013; 7: 312-317.
44. Akya A, Chegenelorestani R, Elahi A, Hamzavi Y. Frequency of plasmid-mediated quinolone resistance genes in extended-spectum β-lactamase-producing Escherichia coli. J Mazandaran Univ Med Sci 2017; 27: 41-51.
45. Leylabadlo HEEH, Pourlak T, Aghazadeh M, Kafil HS, Samadi H. Extended-spectrum beta-lactamase producing Gram negative bacteria in Iran. Afr J Infect Dis 2017; 11: 39-53.
46. Firoozeh F, Zibaei M, Soleimani-Asl Y. Detection of plasmid-mediated qnr genes among the quinolone-resistant Escherichia coli isolates in Iran. J Infect Dev Ctries 2014; 8: 818-822.
47. Rezazadeh M, Baghchesaraei H, Peymani A. Plasmid-mediated quinolone-resistance (qnr) genes in clinical isolates of Escherichia coli collected from several hospitals of Qazvin and Zanjan provinces, Iran. Osong Public Health Res Perspect 2016; 7: 307-312.
48. Rashki A, Rahdar M, Ghalehnoo ZR. Characterization of uropathogenic Escherichia coli: Distribution of adhesin-encoding genes and O-serotypes among ciprofloxacin susceptible and resistant isolates. Jundishapur J Microbiol 2019; 12(9):e89179.
49. Iranpour D, Hassanpour M, Ansari H, Tajbakhsh S, Khamisipour G, Najafi A. Phylogenetic groups of Escherichia coli strains from patients with urinary tract infection in Iran based on the new Clermont phylotyping method. Biomed Res Int 2015; 2015: 846219.
50. Malekzadegan Y, Rastegar E, Moradi M, Heidari H, Sedigh Ebrahim-Saraie H. Prevalence of quinolone-resistant uropathogenic Escherichia coli in a tertiary care hospital in south Iran. Infect Drug Resist 2019; 12: 1683-1689.
51. Abbasi P, Kargar M, Doosti A, Mardaneh J, Ghorbani-Dalini S, Dehyadegari MA. Molecular detection of diffusely adherent Escherichia coli strains associated with diarrhea in Shiraz, Iran. Arch Pediatr Infect Dis 2017; 5 (2); e37629.
52. Ghorbani-Dalini S, Kargar M, Doosti A, Abbasi P, Sarshar M. Molecular epidemiology of ESBL genes and multi-drug resistance in diarrheagenic Escherichia coli strains isolated from adults in Iran. Iran J Pharm Res 2015; 14: 1257-1262.
53. Kazemian H, Heidari H, Ghanavati R, Mohebi R, Ghafourian S, Shavalipour A, et al. Characterization of antimicrobial resistance pattern and molecular analysis among extended spectrum β-Lactamase-producing Escherichia coli. Pharm Sci 2016; 22: 279-284.
54. Pajand O, Ghassemi K, Kamali F, Taghavipoor S, Hojabri Z. Investigation of phylogenetic diversity among Eschereshia coli isolates recovered from hospitalized patients. Koomesh 2017; 19: 207-212.
55. Azimi T, Maham S, Fallah F, Azimi L, Gholinejad Z. Evaluating the antimicrobial resistance patterns among major bacterial pathogens isolated from clinical specimens taken from patients in Mofid Children's Hospital, Tehran, Iran: 2013-2018. Infect Drug Resist 2019; 12: 2089-2102.
56. Mirzaii M, Jamshidi S, Zamanzadeh M, Marashifard M, Hosseini SAAM, Haeili M, et al. Determination of gyrA and parC mutations and prevalence of plasmid-mediated quinolone resistance genes in Escherichia coli and Klebsiella pneumoniae isolated from patients with urinary tract infection in Iran. J Glob Antimicrob Resist 2018;13:197-200.
57. Manyi-Loh C, Mamphweli S, Meyer E, Okoh A. Antibiotic use in agriculture and its consequential resistance in environmental sources: potential public health implications. Molecules 2018; 23: 795.
How to Cite
Hassanshahi G, Darehkordi A, Sheikh Fathollahi M, Khanamani Falahati-Pour S, Rezazadeh Zarandi E, Assar S. Resistance pattern of Escherichia coli to levofloxacin in Iran: a narrative review. Iran J Microbiol. 12(3):177-184.
Review Article(s)