Journal of Current Biomedical Reports jcbior.com Volume 3, Number 3, 2022 eISSN: 2717-1906 1 Brief report Prevalence and antibiotic susceptibility pattern of quinolones and cephalosporins resistant uropathogenic Escherichia coli in the north Iran Saman Shalibeik1, Hossein Ghafori2, Kourush Delpasand3,*, Nafiseh Zamani3, Zaman Darvish3, Hassan Pourmoshtagh4,* 1Department of Microbiology, Faculty of Biological Sciences, Falavarjan Branch, Islamic Azad University, Isfahan, Iran 2Department of Microbiology, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran 3Poursina Clinical Research Development Unit, Poursina Hospital, Guilan University of Medical Science, Rasht, Iran 4Department of Pediatrics, Loghman-Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Abstract Escherichia coli is a Gram-negative bacillus of the Enterobacterales order that is considered an opportunistic pathogen. One of the places they can enter is the urinary tract, which is called the Uropathogenic E. coli (UPEC) strains and the infections that result from it are called urinary tract infection (UTI). The aims of this study was to obtain new information about the antibiotic susceptibility pattern of quinolones and cephalosporins resistant E. coli. In this retrospective cross-sectional study, all cases of urinary tract infections caused by E. coli isolates referred to Razi Hospital in Rasht, the North of Iran over a period of three years were evaluated. Antimicrobial susceptibility patterns were evaluated using disk diffusion method. The total number of E. coli bacteria isolated from urine samples of patients with UTIs from 2016 to 2018 was 1224 cases. Totally, 382 out of 612 tested E. coli isolates were ciprofloxacin resistant (62.4%). While, 251 out of 446 tested E. coli isolates were cephalosporins (56.3%). Among the tested isolated, 206 cases were resistant to both antibiotics (cephalosporin and ciprofloxacin), of which 71 (34.5%) were recovered from male and 135 (65.5%) from female samples. The highest antibiotic susceptibility to E. coli was related to amikacin (74.8%) and followed by nitrofurantoin (67.5%). The results showed an alarming rate of cephalosporin and ciprofloxacin resistance among E. coli causing UTI in our region. These findings suggest optimizing local stewardship programs and infection control policy. Keywords: Escherichia coli, Urinary tract infection, Quinolone, Cephalosporin, Antibiotic resistance 1. Introduction Currently, one of the most important problems of public health in the world are nosocomial infections. Nosocomial infections are caused by organisms that *Corresponding author: Hasan Pourmoshtagh, MD Department of Pediatric, Mosavi Hospital, Zanjan University of Medical Sciences, Zanjan, Iran Tel/Fax: +98 912 6402128 Email: hpourmoshtagh@gmail.com http://orcid.org/0000-0001-8478-8226 Kourush Delpasand, MD kd388@yahoo.com http://orcid.org/0000-0001-6842-3374 Received: April, 02, 2022 Accepted: August, 06, 2022 are resistant to or eventually become resistant to antibiotics [1, 2]. Nosocomial infections generally refer to infections that occur 48 to 72 hours after admission, or three days after discharge, or 30 days after surgery © The Author(s) 2022 https://jcbior.com/ https://jcbior.com/ Shalibeik et al. 2 [3]. The World Health Organization (WHO) has conducted an epidemiological study of nosocomial infections in 14 countries and reported an overall prevalence of 8.7%. According to this report, the prevalence of nosocomial infections in Iran is 4.5%, and the most common infections are related to urinary tract, and respiratory tract infections [4]. Nosocomial infections increase the use of antibiotics and thus increase the resistance of bacteria to several drugs [5]. Escherichia coli is the most common of the nosocomial infections. Urinary tract infections (UTIs) is one of the most common bacterial infections in humans. Although several different microorganisms, such as fungi, viruses, and bacteria, cause UTIs, but the uropathogenic E. coli (UPEC) strains are responsible for 80% of these infections. They may be symptomatic or asymptomatic and in most cases will not cause death [6-8]. Antibiotic treatment is the most common way to treat infectious diseases, but overuse over the years can cause organisms to become resistant to any known antibiotic. Antibiotic resistance is one of the health problems and its increase in developing countries such as Iran is worrying [9, 10]. Beta-lactams are the most widely used antibiotics in the treatment of bacterial infections. The widespread use of these antibiotics in pathogenic bacteria leads to the production and dynamic and continuous mutation of beta-lactamases in these bacteria, which increases their range of activity against antibiotics [11]. Due to the effect of UPEC strain on a wide range of populations, it can be considered as a major target for antimicrobial therapy. Quinolones and fluoroquinolones are first-line antibiotics in the treatment of UTIs, however, treatment of infections became more complicated with the advent of quinolones resistant strains [12, 13]. Due to the importance of evidence based therapy, the present study aimed to evaluate prevalence and antibiotic susceptibility pattern of quinolones and cephalosporins resistant E. coli in the North of Iran. 2. Materials and Methods 2.1 Study area and subjects This is a retrospective cross-sectional study of all cases of UTIs caused by E. coli isolates that were admitted to Razi Hospital in Rasht between 2016 and 2018. Razi hospital is one of the largest hospital in Guilan province, the North of Iran consists of 281 approved hospital beds and 240 active beds. In this study, the sampling method was census and from the results of the hospital archives, information about age and sex was extracted from the patients' admissions in the hospital. The results of inpatients who had a positive culture of E. coli isolated from urine samples were studied. Patients with incomplete file information (information about the main variables) and samples with patients with mixed culture report (simultaneous growth of two or more bacteria) and culture results of urine samples containing Gram- positive bacteria were excluded from the study. 2.2 Antibiotic susceptibility testing Antimicrobial susceptibility patterns were evaluated using disk diffusion method based on CLSI guidelines [14]. The results of antibiogram tests, which include antibiotics of the quinolones (nalidixic acid and ciprofloxacin) and cephalosporins of the 1st to 4th generation, were extracted and the frequency of E. coli isolates resistant to this family was determined. The results of antibiotic susceptibility pattern of isolates causing UTIs to routine antibiotics used in the region were extracted from laboratory results and reported. 2.3 Statistical analysis The collected and recorded results were analyzed by SPSS software version 22 (IBM Corp., USA). The results are presented as descriptive statistics in terms of relative frequency. Values were expressed as the mean ± standard deviation (continuous variables) or percentages of the group (categorical variables). 3. Results The total number of E. coli isolated from urine samples of patients with UTIs from 2016 to 2018 were 1224 cases. The mean age of patients was 46 years and the age range of patients ranged from 16 to 97 years. Totally, 382 out of 612 tested E. coli isolates were ciprofloxacin resistant (62.4%). While, 251 out of 446 tested E. coli isolates were cephalosporins (56.3%). Among the tested isolated, 206 cases were resistant to both antibiotics (cephalosporin and ciprofloxacin), of which 71 (34.5%) were recovered from male and 135 (65.5%) from female samples. The antibiotic susceptibility pattern of E. coli isolates resistant to cephalosporin and ciprofloxacin were listed in Table 1. Shalibeik et al. 3 The highest antibiotic susceptibility to E. coli was related to the antibiotic amikacin (74.8%). The highest antibiotic susceptibility to E. coli was related to amikacin (74.8%) and followed by nitrofurantoin (67.5%). 4. Discussion The wide spread of antibiotic-resistant bacterial species is one of the most serious challenges for physicians and health centers, which will lead to high costs in this regard. Research shows that the prevalence of antibiotic resistant E. coli is increasing in Iran; however, the patterns are varied geographically [15]. In the present study, the rate of cephalosporin resistance in UTIs caused by E. coli was 56.3%. Similar resistance rates are reported in some Iranian studies which does not recommend the use of cephalosporins and penicillins in the treatment of UTIs caused by E. coli without the laboratory report [16, 17]. In accordance to our findings, there are several reports that indicate to a high prevalence of fluoroquinolones resistant E. coli in Iran. Studies in the United States show that E. coli antibiotic resistance increased from 3 percent to 17.1 percent between 2002 and 2010 [18]. But the global data suggest that the rate of fluoroquinolones resistance is on the rise, due to multifactorial causes including the antibiotic over abuse, and emergence of multidrug-resistant clone [19-21]. Due to the retrospective nature of this study, the main limitations of the present study are the existence of a defect in the records and the lack of some clinical. Also, due to the limited study area, the results can not be generalized to the whole region and thus require more extensive studies to determine the overall status of medical and educational centers in the future. The results of recent study determined a regional pattern of E. coli antibiotic resistance that causes UTIs. The results showed an alarming rate of cephalosporin and ciprofloxacin resistance among E. coli causing UTI in our region. These studies could lead to improved infection control programs in regional health centers as well as optimization of laboratory reports to help treat patients. Prevention of resistant isolates requires targeted optimization of treatment protocols based on laboratory results or the pattern of antibiotic resistance in the area. Due to changes in the susceptibility pattern of E. coli, as well as the time and place of increasing the rate of antibiotic resistance of this bacterium, continuous antibiogram tests are recommended. Also, designing prospective studies to investigate the effect of targeted use of antibiotics based on laboratory results in the process of reporting multidrug-resistant isolates can be helpful. References 1. Gómez-De Rueda F, Martinez-Nogueras R, Tena- Sempere ME, Elosegui-Horno I, Robles-Rodríguez L, Horno-Ureña F. Epidemiological aspects and prevalence study of nosocomial infections in a general hospital of specialties: retrospective analysis 2012-2017. Eur J Hosp Pharm. 2019; 26(6):339-42. 2. Willyard C. The drug-resistant bacteria that pose the greatest health threats. Nature. 2017; 543(7643):15. 3. 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. 2015; 8(2):190-7. 4. Ghashghaee A, Behzadifar M, Azari S, Farhadi Z, Luigi Bragazzi N, Behzadifar M, et al. Prevalence of nosocomial infections in Iran: A systematic review and meta-analysis. Med J Islam Repub Iran. 2018; 32:48. 5. Spatenkova V, Bradac O, Fackova D, Bohunova Z, Suchomel P. Low incidence of multidrug-resistant bacteria and nosocomial infection due to a preventive multimodal nosocomial infection control: a 10-year single centre prospective cohort study in neurocritical care. BMC Neurol. 2018; 18(1):23. 6. Li D, Liu B, Chen M, Guo D, Guo X, Liu F, et al. A multiplex PCR method to detect 14 Escherichia coli serogroups associated with urinary tract infections. J Microbiol Methods. 2010; 82(1):71-7. 7. Farajnia S, Alikhani MY, Ghotaslou R, Naghili B, Nakhlband A. Causative agents and antimicrobial susceptibilities of urinary tract infections in the northwest of Iran. Int J Infect Dis. 2009; 13(2):140-4. 8. Chin BS, Kim MS, Han SH, Shin SY, Choi HK, Chae YT, et al. Risk factors of all-cause in-hospital mortality among Korean elderly bacteremic urinary tract infection (UTI) patients. Arch Gerontol Geriatr. 2011; 52(1):e50-5. 9. Foxman B. Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect Dis Clin North Am. 2014; 28(1):1-13. 10. Nikokar I, Tishayar A, Flakiyan Z, Alijani K, Rehana- Banisaeed S, Hossinpour M, et al. Antibiotic resistance and Table 1. Antibiotic resistance pattern Type of antibiotic Resistance Susceptibility Amikacin 25.2 % 74.8 % Gentamicin 83 % 17 % Imipenem 85.9 % 14.1 % Nitrofurantoin 32.5 % 67.5 % https://pubmed.ncbi.nlm.nih.gov/31798858/ https://pubmed.ncbi.nlm.nih.gov/31798858/ https://pubmed.ncbi.nlm.nih.gov/31798858/ https://pubmed.ncbi.nlm.nih.gov/31798858/ https://pubmed.ncbi.nlm.nih.gov/31798858/ https://pubmed.ncbi.nlm.nih.gov/31798858/ https://pubmed.ncbi.nlm.nih.gov/28252092/ https://pubmed.ncbi.nlm.nih.gov/28252092/ https://pubmed.ncbi.nlm.nih.gov/26383222/ https://pubmed.ncbi.nlm.nih.gov/26383222/ https://pubmed.ncbi.nlm.nih.gov/26383222/ https://pubmed.ncbi.nlm.nih.gov/26383222/ https://pubmed.ncbi.nlm.nih.gov/30159299/ https://pubmed.ncbi.nlm.nih.gov/30159299/ https://pubmed.ncbi.nlm.nih.gov/30159299/ https://pubmed.ncbi.nlm.nih.gov/30159299/ https://pubmed.ncbi.nlm.nih.gov/29514600/ https://pubmed.ncbi.nlm.nih.gov/29514600/ https://pubmed.ncbi.nlm.nih.gov/29514600/ https://pubmed.ncbi.nlm.nih.gov/29514600/ https://pubmed.ncbi.nlm.nih.gov/29514600/ https://pubmed.ncbi.nlm.nih.gov/29514600/ https://pubmed.ncbi.nlm.nih.gov/20434495/ https://pubmed.ncbi.nlm.nih.gov/20434495/ https://pubmed.ncbi.nlm.nih.gov/20434495/ https://pubmed.ncbi.nlm.nih.gov/20434495/ https://pubmed.ncbi.nlm.nih.gov/18703368/ https://pubmed.ncbi.nlm.nih.gov/18703368/ https://pubmed.ncbi.nlm.nih.gov/18703368/ https://pubmed.ncbi.nlm.nih.gov/18703368/ https://pubmed.ncbi.nlm.nih.gov/20579748/ https://pubmed.ncbi.nlm.nih.gov/20579748/ https://pubmed.ncbi.nlm.nih.gov/20579748/ https://pubmed.ncbi.nlm.nih.gov/20579748/ https://pubmed.ncbi.nlm.nih.gov/24484571/ https://pubmed.ncbi.nlm.nih.gov/24484571/ https://pubmed.ncbi.nlm.nih.gov/24484571/ https://pubmed.ncbi.nlm.nih.gov/23466812/ https://pubmed.ncbi.nlm.nih.gov/23466812/ Shalibeik et al. 4 frequency of class 1 integrons among Pseudomonas aeruginosa, isolated from burn patients in Guilan, Iran. Iran J Microbiol. 2013; 5(1):36-41. 11. Bush K, Jacoby GA, Medeiros AA. A functional classification scheme for beta-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother. 1995; 39(6):1211-33. 12. Zhao L, Chen X, Zhu X, Yang W, Dong L, Xu X, et al. Prevalence of virulence factors and antimicrobial resistance of uropathogenic Escherichia coli in Jiangsu province (China). Urology. 2009; 74(3):702-7. 13. Kawamura-Sato K, Yoshida R, Shibayama K, Ohta M. Virulence genes, quinolone and fluoroquinolone resistance, and phylogenetic background of uropathogenic Escherichia coli strains isolated in Japan. Jpn J Infect Dis. 2010; 63(2):113-5. 14. CLSI. Performance Standards for Antimicrobial Susceptibility Testing; 30th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2020. 15. Alizade H. Escherichia coli in Iran: An Overview of Antibiotic Resistance: A Review Article. Iran J Public Health. 2018; 47(1):1-12. 16. Haghighatpanah M, Mojtahedi A. Characterization of antibiotic resistance and virulence factors of Escherichia coli strains isolated from Iranian inpatients with urinary tract infections. Infect Drug Resist. 2019; 12:2747-54. 17. Mortazavi-Tabatabaei SAR, Ghaderkhani J, Nazari A, Sayehmiri K, Sayehmiri F, Pakzad I. Pattern of Antibacterial Resistance in Urinary Tract Infections: A Systematic Review and Meta-analysis. Int J Prev Med. 2019; 10:169. 18. Sanchez GV, Master RN, Karlowsky JA, Bordon JM. In vitro antimicrobial resistance of urinary Escherichia coli isolates among U.S. outpatients from 2000 to 2010. Antimicrob Agents Chemother. 2012; 56(4):2181-3. 19. Dalhoff A. Global fluoroquinolone resistance epidemiology and implictions for clinical use. Interdiscip Perspect Infect Dis. 2012; 2012:976273. 20. Stapleton AE, Wagenlehner FME, Mulgirigama A, Twynholm M. Escherichia coli Resistance to Fluoroquinolones in Community-Acquired Uncomplicated Urinary Tract Infection in Women: a Systematic Review. Antimicrob Agents Chemother. 2020; 64(10). 21. Jafari A, Falahatkar S, Delpasand K, Sabati H, Sedigh Ebrahim-Saraie H. Emergence of Escherichia coli ST131 Causing Urinary Tract Infection in Western Asia: A Systematic Review and Meta-Analysis. Microb Drug Resist. 2020; 26(11):1357-64. https://pubmed.ncbi.nlm.nih.gov/23466812/ https://pubmed.ncbi.nlm.nih.gov/23466812/ https://pubmed.ncbi.nlm.nih.gov/23466812/ https://pubmed.ncbi.nlm.nih.gov/7574506/ https://pubmed.ncbi.nlm.nih.gov/7574506/ https://pubmed.ncbi.nlm.nih.gov/7574506/ https://pubmed.ncbi.nlm.nih.gov/7574506/ https://pubmed.ncbi.nlm.nih.gov/19362346/ https://pubmed.ncbi.nlm.nih.gov/19362346/ https://pubmed.ncbi.nlm.nih.gov/19362346/ https://pubmed.ncbi.nlm.nih.gov/19362346/ https://pubmed.ncbi.nlm.nih.gov/20332573/ https://pubmed.ncbi.nlm.nih.gov/20332573/ https://pubmed.ncbi.nlm.nih.gov/20332573/ https://pubmed.ncbi.nlm.nih.gov/20332573/ https://pubmed.ncbi.nlm.nih.gov/20332573/ https://pubmed.ncbi.nlm.nih.gov/29318111 https://pubmed.ncbi.nlm.nih.gov/29318111 https://pubmed.ncbi.nlm.nih.gov/29318111 https://pubmed.ncbi.nlm.nih.gov/31564925/ https://pubmed.ncbi.nlm.nih.gov/31564925/ https://pubmed.ncbi.nlm.nih.gov/31564925/ https://pubmed.ncbi.nlm.nih.gov/31564925/ https://pubmed.ncbi.nlm.nih.gov/32133087/ https://pubmed.ncbi.nlm.nih.gov/32133087/ https://pubmed.ncbi.nlm.nih.gov/32133087/ https://pubmed.ncbi.nlm.nih.gov/32133087/ https://pubmed.ncbi.nlm.nih.gov/32133087/ https://pubmed.ncbi.nlm.nih.gov/22252813/ https://pubmed.ncbi.nlm.nih.gov/22252813/ https://pubmed.ncbi.nlm.nih.gov/22252813/ https://pubmed.ncbi.nlm.nih.gov/22252813/ https://pubmed.ncbi.nlm.nih.gov/23097666/ https://pubmed.ncbi.nlm.nih.gov/23097666/ https://pubmed.ncbi.nlm.nih.gov/23097666/ https://pubmed.ncbi.nlm.nih.gov/32747356/ https://pubmed.ncbi.nlm.nih.gov/32747356/ https://pubmed.ncbi.nlm.nih.gov/32747356/ https://pubmed.ncbi.nlm.nih.gov/32747356/ https://pubmed.ncbi.nlm.nih.gov/32747356/ https://pubmed.ncbi.nlm.nih.gov/32380906/ https://pubmed.ncbi.nlm.nih.gov/32380906/ https://pubmed.ncbi.nlm.nih.gov/32380906/ https://pubmed.ncbi.nlm.nih.gov/32380906/ https://pubmed.ncbi.nlm.nih.gov/32380906/