Document Type : Original Article


1 Department of Clinical Pharmacy and Pharmacy Practice, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Infectious Diseases, Isfahan University of Medical Sciences, Isfahan, Iran

3 Nosocomial Infection Research Center, Isfahan University of Medical Sciences, Isfahan, Iran


Objective: Gram‑negative bacilli are the most important cause of nosocomial urinary 
tract infections (UTIs). The production of extended‑spectrum β‑lactamase (ESBL) enzymes 
is a common mechanism of resistance among these bacteria. The aim of this study was to 
determine the rate of ESBL producing Gram‑negative bacteria causing nosocomial UTI in a 
referral hospital as well as their susceptibility pattern to the most commonly used antibiotics.
Methods: In a prospective cross‑sectional study performed over a 6‑month period, urinary 
specimens obtained from hospitalized patients with documented culture‑proved nosocomial 
UTI (age range of 1-87 years). Isolated aerobic Gram‑negative bacteria underwent further 
microbiologic tests for detection of ESBL, as well as antimicrobial susceptibility test using 
Kirby-Bauer (disk diffusion) and E‑test methods.
Findings: During the study period, 213 urine samples were detected to have growth of 
Gram‑negative organism. Escherichia coli was the most frequently isolated organism (61%). 
ESBL was detected in 102 isolates including 38.5% of E. coli, 39.5% of Klebsiella pneumonia, 
88.5% of Pseudomonas aeruginosa, and 100% of Acinetobacter baumannii strains. Imipenem 
and meropenem were the most effective antibiotics on E. coli and K. pneumoniae strains. P.
aeruginosa and A. baumannii strains showed high resistance to all tested antibiotics.
Conclusion: Large numbers of Gram‑negative bacteria causing nosocomial UTIs produce 
ESBL with most being multidrug‑resistant. Therefore, routine ESBL detection testing and 
subsequent antibiogram with disk diffusion method could be useful to determine the best 
treatment options for UTI.


  1. Sharifi Y, Hasani A, Ghotaslou R, Naghili B, Aghazadeh M, 
    Milani M, et al. Virulence and antimicrobial resistance in 
    Enterococci isolated from urinary tract infections. Adv Pharm 
    Bull 2013;3:197‑201.
    2. Gaynes R, Edwards JR, National Nosocomial Infections 
    Surveillance System. Overview of nosocomial infections 
    caused by gram‑negative bacilli. Clin Infect Dis 2005;41:848‑54.
    3. P i t o u t J D , L a u p l a n d K B . E x t e n d e d ‑ s p e c t r u m 
    beta‑lactamase‑producing Enterobacteriaceae: An emerging 
    public‑health concern. Lancet Infect Dis 2008;8:159‑66.
    4. Jain A, Roy I, Gupta MK, Kumar M, Agarwal SK. Prevalence of 
    extended‑spectrum beta‑lactamase‑producing Gram‑negative 
    bacteria in septicaemic neonates in a tertiary care hospital. J 
    Med Microbiol 2003;52:421‑5.
    5. Livermore DM. Current epidemiology and growing 
    resistance of gram‑negative pathogens. Korean J Intern Med 
    6. Hawser SP, Badal RE, Bouchillon SK, Hoban DJ. Trending 
    eight years of in vitro activity of ertapenem and comparators 
    against Escherichia coli from intra‑abdominal infections 
    in North America - SMART 2002‑2009. J Chemother 
    7. Nakamura T, Komatsu M, Yamasaki K, Fukuda S, 
    Miyamoto Y, Higuchi T, et al. Epidemiology of Escherichia 
    coli, Klebsiella species, and Proteus mirabilis strains producing 
    extended‑spectrum β‑lactamases from clinical samples in the 
    Kinki Region of Japan. Am J Clin Pathol 2012;137:620‑6.
    8. Hawser SP, Badal RE, Bouchillon SK, Hoban DJ, 
    Biedenbach DJ, Cantón R, et al. Monitoring the global in 
    vitro activity of ertapenem against Escherichia coli from 
    intra‑abdominal infections: SMART 2002‑2010. Int J Antimicrob 
    Agents 2013;41:224‑8.
    9. P i t o u t J D . I n f e c t i o n s w i t h e x t e n d e d ‑ s p e c t r u m 
    beta‑lactamase‑producing enterobacteriaceae: Changing 
    epidemiology and drug treatment choices. Drugs 2010;70:313‑33.
    10. Sievert DM, Ricks P, Edwards JR, Schneider A, Patel J, 
    Srinivasan A, et al. Antimicrobial‑resistant pathogens 
    associated with healthcare‑associated infections: Summary 
    of data reported to the National Healthcare Safety Network 
    at the Centers for Disease Control and Prevention, 2009‑2010. 
    Infect Control Hosp Epidemiol 2013;34:1‑14.
    11. Zilberberg MD, Shorr AF. Secular trends in gram‑negative 
    resistance among urinary tract infection hospitalizations in 
    the United States, 2000‑2009. Infect Control Hosp Epidemiol 
    12. Schaberg DR, Culver DH, Gaynes RP. Major trends in 
    the microbial etiology of nosocomial infection. Am J Med 
    13. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance 
    definition of health care‑associated infection and criteria for 
    specific types of infections in the acute care setting. Am J Infect 
    Control 2008;36:309‑32.
    14. Clinical and Laboratory Standards Institute. Performance 
    Standard for Antimicrobial Susceptibility Testing. Document 
    M100‑S24. Vol. 34, No. 1. PA, USA: CLSI; 2009.
    15. Livermore DM, Brown DF. Detection of β‑lactamase mediated 
    resistance. J Antimicrob Chemother 2001;35:281‑94.
    16. Jiang X, Zhang Z, Li M, Zhou D, Ruan F, Lu Y. Detection 
    of extended‑spectrum beta‑lactamases in clinical isolates 
    of Pseudomonas aeruginosa. Antimicrob Agents Chemother 
    17. Tzelepi E, Giakkoupi P, Sofianou D, Loukova V, Kemeroglou 
    A, Tsakris A. Detection of extended‑spectrum beta‑lactamases 
    in clinical isolates of Enterobacter cloacae and Enterobacter 
    aerogenes. J Clin Microbiol 2000;38:542‑6.
  2. 18. Talebi Taher M, Golestanpour A. Symptomatic nosocomial 
    urinary tract infection in ICU patients: Identification of 
    antimicrobial resistance pattern. Iran J Clin Infect Dis 
    19. Saffar MJ, Enayti AA, Abdolla IA, Razai MS, Saffar H. 
    Antibacterial susceptibility of uropathogens in 3 hospitals, 
    Sari, Islamic Republic of Iran, 2002‑2003. East Mediterr Health 
    J 2008;14:556‑63.
    20. Bouza E, San Juan R, Muñoz P, Voss A, Kluytmans J, 
    Co‑operative Group of the European Study Group on 
    Nosocomial Infections. A European perspective on nosocomial 
    urinary tract infections I. Report on the microbiology workload, 
    etiology and antimicrobial susceptibility (ESGNI‑003 study). 
    European Study Group on Nosocomial Infections. Clin 
    Microbiol Infect 2001;7:523‑31.
    21. Tankhiwale SS, Jalgaonkar SV, Ahamad S, Hassani U. 
    Evaluation of extended spectrum beta lactamase in urinary 
    isolates. Indian J Med Res 2004;120:553‑6.
    22. Hosain Zadegan H, Ramazanzadeh R, Hasany A. 
    Cross‑sectional study of extended spectrum beta‑lactamase 
    producing gram‑negative bacilli from clinical cases in 
    Khorramabad, Iran. Iran J Microbiol 2009;1:16‑9.
    23. Irajian G, Jazayeri‑Moghadas A, Beheshti A. Prevalence of 
    extended‑spectrum beta‑lactamase positive and multidrug 
    resistance pattern of Escherichia coli and Klebsiella pneumonia
    isolates, Semnan, Iran. Iran J Microbiol 2009;1:49‑53.
    24. Shahid M, Malik A, Akram M, Agrawal LM, Khan AU, 
    Agrawal M. Prevalent phenotypes and antibiotic resistance 
    in Escherichia coli and Klebsiella pneumoniae at an Indian 
    tertiary care hospital: Plasmid‑mediated cefoxitin resistance. 
    Int J Infect Dis 2008;12:256‑64.
    25. Durmaz R, Durmaz B, Koroglu M, Tekerekoglu MS. Detection 
    and typing of extended‑spectrum beta‑lactamases in clinical 
    isolates of the family Enterobacteriaceae in a medical center in 
    Turkey. Microb Drug Resist 2001;7:171‑5.
    26. Lagacé‑Wiens PR, Nichol KA, Nicolle LE, Decorby 
    MR, McCracken M, Alfa MJ, et al. ESBL genotypes in 
    fluoroquinolone‑resistant and fluoroquinolone‑susceptible 
    ESBL‑producing Escherichia coli urinary isolates in Manitoba. 
    Can J Infect Dis Med Microbiol 2007;18:133‑7.
    27. Khalili H, Soltani R, Negahban S, Abdollahi A, Gholami K. 
    Reliability of disk diffusion test results for the antimicrobial 
    susceptibility testing of nosocomial gram‑positive 
    microorganisms: Is E‑test method better? Iran J Pharm Res 
    28. Katz OT, Peled N, Yagupsky P. Evaluation of the current 
    National Committee for Clinical Laboratory standards 
    guidelines for screening and confirming extended‑spectrum 
    beta‑lactamase production in isolates of Escherichia coli and 
    Klebsiella species from bacteremic patients. Eur J Clin Microbiol 
    Infect Dis 2004;23:813‑7.
    29. Rahbar M, Yaghoobi M, Fattahi A. Comparison of different 
    laboratory methods for detection of methicillin resistant 
    Staphylococcus aureus. Pak J Med Sci 2006;22:442‑5.
    30. Hsueh PR, Chang JC, Teng LJ, Yang PC, Ho SW, Hsieh WC, 
    et al. Comparison of Etest and agar dilution method for 
    antimicrobial susceptibility testing of Flavobacterium isolates. 
    J Clin Microbiol 1997;35:1021‑3.
    31. Erfani Y, Rasti A, Mirsalehian A, Mirafshar SM, Ownegh V. 
    E‑test versus disk diffusion method in determining multidrug 
    resistant strains of Escherichia coli in urinary tract infection. Afr 
    J Microbiol Res 2011;5:608‑11.