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Prevalence and pathogenesis of extended-spectrum beta-lactamase producing Escherichia coli causing urinary tract infection in hospitalized patients

  • A. Gündoğdu
  • Y. B. Long
  • M. KatouliEmail author
Article

Abstract

A total of 296 E. coli strains isolated from hospitalized patients with urinary tract infection were included in this study. These strains were tested for their resistance to 22 antimicrobial drugs and the presence of ESBLs genes coding for TEM, SHV, OXA, and CTX-M. We further characterized them for their interaction with a renal cell line (A-498) and a gastrointestinal cell line (Caco-2). Strains were also typed using a combination of RAPD-PCR, PhP-typing and phylogenetic grouping. Only eight strains (2.7 %) were confirmed as ESBLs producers. The most common clonal type contained 35 isolates and only two of them were ESBLs producers and both showed a high degree of adhesion to both cell lines but only one was able to translocate in Caco-2 cells. These strains belonged to phylogenetic group B2, were resistant to nine antibiotics and carried CTX-M-type of ESBL. The remaining six strains belonged to single clones with different phylogenetic groups and ESBL genotypes and were resistant to between 12 and 15 antibiotics. They also showed a high rate of adhesion to A-498 cells (19 ± 2 to 35 ± 3 CFU/cell) and all translocated in this cell line. The rate of adhesion of ESBL-producing strains to Caco-2 cells (11 ± 3.4 CFU/cell) was significantly lower than A-498 cells (26 ± 8 CFU/cell) (p = 0.0002) and only four of them translocated in Caco-2 cells. Our results suggest that the ESBL-producing clones of E. coli have a potential to translocate and cause septicemia in hospitalized patients with UTI.

Keywords

Urinary Tract Infection Phylogenetic Group Cefpodoxime Ertapenem Cefotetan 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgement

We thank Professor S. M. Bell for providing us with positive controls for ESBL genes. This study was financially supported by the PhD scholarship program of the Turkish Government.

Conflict of interest

The authors declare that there is no conflict of interest with the organization that sponsored this research and publications arising from this research.

References

  1. 1.
    Foxman B, Brown P (2003) Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Infect Dis Clin North Am 17(2):227–478PubMedCrossRefGoogle Scholar
  2. 2.
    Gupta K, Hooton TM, Stamm WE (2001) Increasing antimicrobial resistance and the management of uncomplicated community-acquired urinary tract infections. Ann Intern Med 135(1):41–50PubMedGoogle Scholar
  3. 3.
    Solomkin JS, Mazuski JE, Baron EJ, Sawyer RG, Nathens AB, DiPiro JT, Buchman T, Dellinger EP, Jernigan J, Gorbach S, Chow AW, Bartlett J (2003) Guidelines for the selection of anti-infective agents for complicated intra-abdominal infections. Clin Infect Dis 37:997–1005PubMedCrossRefGoogle Scholar
  4. 4.
    Hooton TM (2012) Uncomplicated urinary tract infection. N Engl J Med 366(11):1028–1037PubMedCrossRefGoogle Scholar
  5. 5.
    Rodriguez-Bano J, Navarro MD, Romero L, Martinez-Martinez L, Muniain MA, Perea EJ, Perez-Cano R, Pascual A (2004) Epidemiology and clinical features of infections caused by extended-spectrum beta-lactamase-producing Escherichia coli in nonhospitalized patients. J Clin Microbiol 42(3):1089–1094PubMedCrossRefGoogle Scholar
  6. 6.
    Pitout JDD, Nordmann P, Laupland KB, Poirel L (2005) Emergence of Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) in the community. J Antimicrob Chemother 56:52–59PubMedCrossRefGoogle Scholar
  7. 7.
    Woodford N, Ward ME, Kaufmann ME, Turton J, Fagan EJ, James D, Johnson PA, Pike R, Warner M, Cheasty T, Pearson A, Harry S, Leach JB, Loughrey A, Lowes JA, Warren RE, Livermore DM (2004) Community and hospital spread of Escherichia coli producing CTX-M extended-spectrum beta-lactamases in the UK. J Antimicrob Chemother 54:735–743PubMedCrossRefGoogle Scholar
  8. 8.
    Paterson DL, Bonomo RA (2005) Extended-spectrum beta-lactamases: a clinical update. Clin Microbiol Rev 18:657–686PubMedCrossRefGoogle Scholar
  9. 9.
    Romero L, Lopez L, Rodriguez-Bano J, Hernandez JR, Martinez-Martinez L, Pascual A (2005) Long-term study of the frequency of Escherichia coli and Klebsiella pneumoniae isolates producing extended-spectrum beta-lactamases. Clin Microbiol Infect 11:625–631PubMedCrossRefGoogle Scholar
  10. 10.
    Xiong Z, Zhu D, Wang F, Zhang Y, Okamoto R, Inoue M (2002) Investigation of extended-spectrum beta-lactamase in Klebsiella pneumoniae and Escherichia coli from China. Diagn Microbiol Infect Dis 44:195–200PubMedCrossRefGoogle Scholar
  11. 11.
    Ho P-L, Chan W-M, Tsang KWT, Wong SSY, Young K (2002) Bacteremia caused by Escherichia coli producing extended-spectrum beta-lactamase: a case-control study of risk factors and outcomes. Scand J Infect Dis 34:567–573PubMedCrossRefGoogle Scholar
  12. 12.
    Diekema DJ, Pfaller MA, Jones RN, Doern GV, Winokur PL, Gales AC, Sader HS, Kugler K, Beach M (1999) Survey of bloodstream infections due to gram-negative bacilli: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada and Latin America for the SENTRY Antimicrobial Surveillance Program, 1997. Clin Infect Dis 29:595–607PubMedCrossRefGoogle Scholar
  13. 13.
    Rodriguez-Bano J, Navarro MD, Romero L, Muniain MA, Perea EJ, Perez-Cano R, Hernandez JR, Pascual A (2006) Clinical and molecular epidemiology of extended-spectrum beta-lactamase-producing Escherichia coli as a cause of nosocomial infection or colonization: implications for control. Clin Infect Dis 42:37–45PubMedCrossRefGoogle Scholar
  14. 14.
    Wagenlehner FME, Pilatz A, Naber KG, Weidner W (2008) Therapeutic challenges of urosepsis. Eur J Clin Invest 38(2):45–49PubMedCrossRefGoogle Scholar
  15. 15.
    Wagenlehner FME, Pilatz A, Weidner W (2011) Urosepsis—from the view of the urologist. Int J Antimicrob Agents 38S:51–57CrossRefGoogle Scholar
  16. 16.
    Duell BL, Carey AJ, Tan CK, Cui X, Webb RI, Totsika M, Schembri MA, Derrington P, Irving-Rodgers H, Brooks AJ, Cripps AW, Crowley M, Ulett GC (2012) Innate transcriptional networks activated in bladder in response to uropathogenic Escherichia coli drive diverse biological pathways and rapid synthesis of IL-10 for defense against bacterial urinary tract infection. J Immunol 188:781–792PubMedCrossRefGoogle Scholar
  17. 17.
    Schiappa DA, Hayden MK, Matushek MG, Hashemi FN, Sullivan J, Smith KY, Miyashiro D, Quinn JP, Weinstein RA, Trenholme GM (1996) Ceftazidime-resistant Escherichia coli and Klebsiella pneumoniae blood stream infection: a case control and molecular epidemiologic investigation. J Infect Dis 174:529–536PubMedCrossRefGoogle Scholar
  18. 18.
    Jepsen OB, Larsen SO, Dankert J, Daschner F, Gronroos P, Meers PD, Nystrom B, Rotter M, Sander J (1982) Urinary-tract infection and bacteraemia in hospitalized medical patients—a European multicentre prevalence survey on nosocomial infection. J Hospit Infect 3(3):241–252CrossRefGoogle Scholar
  19. 19.
    Leblebicioglu H, Esen S, Turkish Nosocomial Urinary Tract Infection Study Group (2003) Hospital-acquired urinary tract infections in Turkey: a nationwide multicentre point prevelence study. J Hospit Infect 53:207–210CrossRefGoogle Scholar
  20. 20.
    Yamamoto S, Tsukamoto T, Terai A, Kurazono H, Takeda Y, Yoshida O (1997) Genetic evidence supporting the faecal-perineal-urethral hypothesis in cystitis caused by Escherichia coli. J Urol 157(3):1127–1129PubMedCrossRefGoogle Scholar
  21. 21.
    Katouli M, Ramos NL, Nettelbladt CG, Ljungdahl M, Robinson W, Ison HM, Brauner A, Möllby R (2009) Host species-specific translocation of Escherichia coli. Eur J Clin Microbiol Infect Dis 28:1095–1103PubMedCrossRefGoogle Scholar
  22. 22.
    Nettelbladt CG, Katouli M, Bark T, Svenberg T, Möllby R, Ljunquvist O (2003) Orally inoculated Escherichia coli strains colonise the gut and increase bacterial translocation after stress in rats. Shock 20:251–256PubMedCrossRefGoogle Scholar
  23. 23.
    Ljungdahl M, Lundholm M, Katouli M, Rasmussen I, Engstrand L, Haglund U (2000) Bacterial translocation in experimental shock is dependent on the strains in the intestinal flora. Scand J Gasteroentrol 35:389–397CrossRefGoogle Scholar
  24. 24.
    Mabbett AN, Ulett GC, Watts RE, Tree JJ, Totsika M, Ong CY, Wood JM, Monaghan W, Looke DF, Nimmo GR, Svanborg C, Schembri MA (2009) Virulence properties of asymptomatic bacteriuria Escherichia coli. Int J Med Microbiol 299:53–63PubMedCrossRefGoogle Scholar
  25. 25.
    Chen J, Griffiths MW (1998) PCR differentiation of Escherichia coli from other Gram-negative bacteria using primers derived from the nucleotide sequences flanking the gene encoding the universal stress protein. Lett Appl Microbiol 27:369–371PubMedCrossRefGoogle Scholar
  26. 26.
    Ramos NL, Saayman ML, Chapman TA, Tucker JR, Smith HV, Faoagali J, Chin JC, Brauner A, Katouli M (2010) Genetic relatedness and virulence gene profiles of Escherichia coli strains isolated from septicaemic and uroseptic patients. Eur J Clin Microbiol Infect Dis 29:15–23PubMedCrossRefGoogle Scholar
  27. 27.
    Landgren M, Oden H, Kuhn I, Osterlund A, Kahlmeter G (2005) Diversity among 2481 Escherichia coli from women with community-acquired lower urinary tract infections in 17 countries. J Antimicrob Chemother 55:928–937PubMedCrossRefGoogle Scholar
  28. 28.
    Sneath PHA, Sokal RR (1973) Numerical taxonomy. The principles and practice of numerical classification. W. H. Freeman & Co., San FranciscoGoogle Scholar
  29. 29.
    Saeedi B, Tarnberg M, Gill H, Hallgren A, Jonasson J, Nilsson LE, Isaksson B, Kuhn I, Hanberger H (2005) Phene Plate (PhP) biochemical fingerprinting; a screening method for epidemiological typing of enterococcal isolates? APMIS 113(9):603–612PubMedCrossRefGoogle Scholar
  30. 30.
    Clermont O, Bonacorsi S, Bingen E (2000) Rapid and simple determination of the Escherichia coli phylogenetic group. Appl Environ Microbiol 66:4555–4558PubMedCrossRefGoogle Scholar
  31. 31.
    Bell SM, Gatus BJ, Pham JN, Rafferty DL (2006) Antibiotic susceptibility testing by the CDS method: a manual for medical and veterinary laboratories. Arthur Productions Pty. Ltd., Sydney, AustraliaGoogle Scholar
  32. 32.
    Vahaboglu H, Ozturk R, Akbal H, Saribas S, Tansel O, Coskunkan F (1998) Practical approach for detection and identification of OXA-10-derived ceftazidime-hydrolyzing ESBL. J Clin Microbiol 36(3):827–829PubMedGoogle Scholar
  33. 33.
    Cruz N, Qi L, Alvarez X, Berg RD, Deitch EA (1994) The CaCo-2 cell monolayer system as an in vitro model for studying bacterial-enterocyte interactions and bacterial translocation. J Burn Care Rehabil 15:207–212PubMedCrossRefGoogle Scholar
  34. 34.
    Bonnet R (2004) Growing group of extended-spectrum beta-lactamases: the CTX-M enzymes. Antimicrob Agents Chemother 48:1–14PubMedCrossRefGoogle Scholar
  35. 35.
    Moland ES, Black JA, Hossain A, Hanson ND, Thomson KS, Pottumarthy S (2003) Discovery of CTX-M-like extended-spectrum beta-lactamases in Escherichia coli isolates from five U.S. states. Antimicrob Agents Chemother 47:2382–2383PubMedCrossRefGoogle Scholar
  36. 36.
    Perez F, Endimiani A, Hujer MK, Bonomo RA (2007) The continuing challenge of ESBLs. Curr Opin Pharmacol 7:496–469CrossRefGoogle Scholar
  37. 37.
    Arslan H, Azap OK, Ergonul O, Timurkaynak F (2005) Risk factors for ciprofloxacin resistance among Escherichia coli strains isolated from community-acquired urinary tract infections in Turkey. J Antimicrob Chemother 56:914–918PubMedCrossRefGoogle Scholar
  38. 38.
    Ena J, Arjona F, Martinez-Peinado C, Lopez-Perezaqua M, Amador C (2006) Epidemiology of urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli. Urology 68(6):1169–1174PubMedCrossRefGoogle Scholar
  39. 39.
    Gales AC, Jones RN, Gordon KA, Sader HS, Wilke WW, Beach ML, Pfaller MA, Doern GV (2000) Activity and spectrum of 22 antimicrobial agents tested against urinary tract infection pathogenes in hospitalized patients in Latin America: report from the second year of the SENTRY Antimicrobial Surveillance Program (1998). J Antimicrob Chemother 45:295–303PubMedCrossRefGoogle Scholar
  40. 40.
    Bell JM, Turnidge JD, Gales AC, Pfaller MA, Jones RN (2002) Prevalence of extended spectrum beta-lactamase (ESBL)-producing clinical isolates in the Asia-Pasific region and South Africa: regional results from SENTRY Antimicrobial Surveillance Program (1998-99). Diagn Microbiol Infect Dis 42(3):193–198PubMedCrossRefGoogle Scholar
  41. 41.
    Stuart RL, Kotsanas D, Webb B, Vandergraaf S, Gillespie EE, Hogg GG, Korman TM (2011) Prevalence of antimicrobial-resistant organisms in residental aged care facilities. Med J Aust 195(9):530–533PubMedCrossRefGoogle Scholar
  42. 42.
    Pitout JDD, Hanson ND, Deirdre LC, Laupland KB (2004) Population-based laboratory surveillance for Escherichia coli-producing extended-spectrum beta-lactamases: importance of community isolates with blaCTX-M genes. Clin Infect Dis 38:1736–1741PubMedCrossRefGoogle Scholar
  43. 43.
    Valverde A, Coque TM, Sanchez-Moreno MP, Rollan A, Baquero F, Canton R (2004) Dramatic increase in prevalence of fecal carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae during nonoutbreak situations in Spain. J Clin Microbiol 42(10):4769–4775PubMedCrossRefGoogle Scholar
  44. 44.
    Pitout JDD, Gregson DB, Church DL, Elsayed S, Laupland KB (2005) Community-wide outbreaks of clonally related CTX-M-14 beta-lactamase-production Escherichia coli strains in the Calgary health region. J Clin Microbiol 43:2844–2849PubMedCrossRefGoogle Scholar
  45. 45.
    Johnson J, Delavari P, Kuskowski M, Stell AL (2001) Phylogenetic distribution of extra-intestinal virulence-associated traits in Escherichia coli. J Infect Dis 183(1):78–88PubMedCrossRefGoogle Scholar
  46. 46.
    Bingen E, Picard B, Brahimi N, Mathy S, Desjardins P, Elion J, Demanur E (1998) Phylogenetic analysis of Escherichia coli strains causing neonatal meningitis suggests horizontal gene transfer from a predominant pool of highly virulence B2 group strains. J Infect Dis 177:642–650PubMedCrossRefGoogle Scholar
  47. 47.
    Escobar-Paramo P, Grenet K, Menac’h AL, Salgado E, Amorin C, Gouriou S, Picard B, Rahimy MC, Andremont A, Denamur E, Ruimy R (2004) Large-scale population structure of human commensal Escherichia coli isolates. Appl Environ Microbiol 70(9):5698–5700PubMedCrossRefGoogle Scholar
  48. 48.
    Hamelin K, Bruant G, El-Shaarawi A, Hill T, Edge TA, Fairbrother J, Harel J, Maynard C, Masson L, Brousseau R (2007) Occurrence of virulence and antimicrobial resistance genes in Escherichia coli isolates from different aquatic ecosystems within the St. Clair River and Detroit River areas. Appl Environ Microbiol 73(2):477–484PubMedCrossRefGoogle Scholar
  49. 49.
    Ramos NL, Dzung DTN, Stopsack K, Janko V, Pourshafie MR, Katouli M, Brauner A (2011) Characterisation of uropathogenic Escherichia coli from children with urinary tract infection in different countries. Eur J Clin Microbiol Infect Dis 30(12):1587–1593PubMedCrossRefGoogle Scholar
  50. 50.
    Escobar-Paramo P, Menac’h AL, Gall TL, Amorin C, Gouriou S, Picard B, Skurnik D, Denamur E (2006) Identification of forces shaping the commensal E. coli genetic structure by comparing animal and human isolates. Environ Microbiol 8(11):1975–1984PubMedCrossRefGoogle Scholar
  51. 51.
    Blanc V, Mesa RJ, Saco M, Lavilla S, Prats G, Miro E, Navarro F, Cortes P, Llagostera M (2006) ESBL- and plasmidic class C beta-lactamase-producing E. coli strains isolated from poultry, pig and rabbit farms. Vet Microbiol 118:299–304PubMedCrossRefGoogle Scholar
  52. 52.
    Moore FA (1999) The role of the gastrointestinal tract in postinjury multiple organ failure. Am J Surg 178(6):449–453PubMedCrossRefGoogle Scholar
  53. 53.
    Rush BF, Sori AJ, Murphy TF, Smith S, Flanagan JJ, Machiedo GW (1988) Endotoxemia and bacteremia during hemorrhagic shock. The link between trauma and sepsis? Ann Surg 207:549–554PubMedCrossRefGoogle Scholar
  54. 54.
    Weinstein MP, Towns ML, Quartey SM, Mirrett S, Reimer LG, Parmigiani G, Reller LB (1997) The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin Infect Dis 24:584–602PubMedGoogle Scholar
  55. 55.
    Angus DC, Linde-Zwirble W, Lidicker J, Clermont G, Carcillo J, Pinksy MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29(7):1303–1310PubMedCrossRefGoogle Scholar
  56. 56.
    Brun-Busisson C (2000) The epidemiology of the systemic inflammatory response. Intensive Care Med 26(1):64–74CrossRefGoogle Scholar
  57. 57.
    Paterson DL, Ko WC, Van Gottberg A, Casellas JM, Mulazimoglu L, Klugnam KP, Bonomo RA, Rice LB, McCormack JG, Yu VL (2001) Outcome of cephalosporin treatment for serious infections due to apparently susceptible organisms producing extended-spectrum beta-lactamases: implication for the clinical microbiology laboratory. J Clin Microbiol 39:2206–2212PubMedCrossRefGoogle Scholar
  58. 58.
    Kim Y-K, Pai H, Lee H-J, Park S-E, Choi E-H, Kim J, Kim J-H, Kim E-C (2002) Bloodstream infections by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in children: epidemiology and clinical outcome. Antimicrob Agents Chemother 46(5):1481–1491PubMedCrossRefGoogle Scholar
  59. 59.
    Sidjabat HE, Paterson DL, Qureshi ZA, Adams-Haduch JM, O’Keefe A, Pascual A, Bano-Rodriguez J, Doi Y (2009) Clinical features and molecular epidemiology of CMY-type beta-lactamase-producing Escherichia coli. Clin Infect Dis 48:739–744PubMedCrossRefGoogle Scholar
  60. 60.
    Pitout JDD, Hossain A, Hanson ND (2004) Phenotypic and moleculer detection of CTX-M-beta-lactamases produced by Escherichia coli and Klebsiella spp. J Clin Microbiol 42(12):5715–5721PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Faculty of Science, Health and EducationUniversity of the Sunshine CoastMaroochydore DCAustralia

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