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Emerging Infectious Diseases logoLink to Emerging Infectious Diseases
. 2001 Sep-Oct;7(5):862–871. doi: 10.3201/eid0705.017515

Rapid emergence of ciprofloxacin-resistant enterobacteriaceae containing multiple gentamicin resistance-associated integrons in a Dutch hospital.

A van Belkum 1, W Goessens 1, C van der Schee 1, N Lemmens-den Toom 1, M C Vos 1, J Cornelissen 1, E Lugtenburg 1, S de Marie 1, H Verbrugh 1, B Löwenberg 1, H Endtz 1
PMCID: PMC2631872  PMID: 11747700

Abstract

In a hematology unit in the Netherlands, the incidence of ciprofloxacin-resistant Enterobacter cloacae and Escherichia coli increased from from 1996 to 1999. Clonal spread of single genotypes of both ciprofloxacin-resistant E. coli and Enterobacter cloacae from patient to patient was documented by pulsed-field gel electrophoresis and random amplification of polymorphic DNA. In addition, genetically heterogeneous strains were isolated regularly. Integrons associated with gentamicin resistance were detected in Enterobacter cloacae and E. coli strains. Integron-containing E. coli were detected in all hematology wards. In contrast, in Enterobacter cloacae strains two integron types were encountered only in the isolates from one ward. Although in all patients identical antibiotic regimens were used for selective decontamination, we documented clear differences with respect to the nosocomial emergence of ciprofloxacin-resistant bacterial strains and gentamicin resistance-associated integrons.

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Selected References

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  1. Bennett P. M. Integrons and gene cassettes: a genetic construction kit for bacteria. J Antimicrob Chemother. 1999 Jan;43(1):1–4. [PubMed] [Google Scholar]
  2. Blandino G., Caccamo F., Di Marco R., Speciale A., Nicoletti G. Epidemiology of antibiotic resistance in human isolates of Enterobacteriaceae in Sicily. J Chemother. 1990 Feb;2(1):40–44. doi: 10.1080/1120009x.1990.11738979. [DOI] [PubMed] [Google Scholar]
  3. Boom R., Sol C. J., Salimans M. M., Jansen C. L., Wertheim-van Dillen P. M., van der Noordaa J. Rapid and simple method for purification of nucleic acids. J Clin Microbiol. 1990 Mar;28(3):495–503. doi: 10.1128/jcm.28.3.495-503.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bornet C., Davin-Regli A., Bosi C., Pages J. M., Bollet C. Imipenem resistance of enterobacter aerogenes mediated by outer membrane permeability. J Clin Microbiol. 2000 Mar;38(3):1048–1052. doi: 10.1128/jcm.38.3.1048-1052.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bosi C., Davin-Regli A., Bornet C., Mallea M., Pages J. M., Bollet C. Most Enterobacter aerogenes strains in France belong to a prevalent clone. J Clin Microbiol. 1999 Jul;37(7):2165–2169. doi: 10.1128/jcm.37.7.2165-2169.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brown H. J., Stokes H. W., Hall R. M. The integrons In0, In2, and In5 are defective transposon derivatives. J Bacteriol. 1996 Aug;178(15):4429–4437. doi: 10.1128/jb.178.15.4429-4437.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Carratala J., Fernandez-Sevilla A., Tubau F., Dominguez M. A., Gudiol F. Emergence of fluoroquinolone-resistant Escherichia coli in fecal flora of cancer patients receiving norfloxacin prophylaxis. Antimicrob Agents Chemother. 1996 Feb;40(2):503–505. doi: 10.1128/aac.40.2.503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Carratalá J., Fernández-Sevilla A., Tubau F., Callis M., Gudiol F. Emergence of quinolone-resistant Escherichia coli bacteremia in neutropenic patients with cancer who have received prophylactic norfloxacin. Clin Infect Dis. 1995 Mar;20(3):557–563. doi: 10.1093/clinids/20.3.557. [DOI] [PubMed] [Google Scholar]
  9. Chiew Y. F., Yeo S. F., Hall L. M., Livermore D. M. Can susceptibility to an antimicrobial be restored by halting its use? The case of streptomycin versus Enterobacteriaceae. J Antimicrob Chemother. 1998 Feb;41(2):247–251. doi: 10.1093/jac/41.2.247. [DOI] [PubMed] [Google Scholar]
  10. Collis C. M., Hall R. M. Expression of antibiotic resistance genes in the integrated cassettes of integrons. Antimicrob Agents Chemother. 1995 Jan;39(1):155–162. doi: 10.1128/aac.39.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cruciani M., Rampazzo R., Malena M., Lazzarini L., Todeschini G., Messori A., Concia E. Prophylaxis with fluoroquinolones for bacterial infections in neutropenic patients: a meta-analysis. Clin Infect Dis. 1996 Oct;23(4):795–805. doi: 10.1093/clinids/23.4.795. [DOI] [PubMed] [Google Scholar]
  12. De Gheldre Y., Maes N., Rost F., De Ryck R., Clevenbergh P., Vincent J. L., Struelens M. J. Molecular epidemiology of an outbreak of multidrug-resistant Enterobacter aerogenes infections and in vivo emergence of imipenem resistance. J Clin Microbiol. 1997 Jan;35(1):152–160. doi: 10.1128/jcm.35.1.152-160.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Diekema D. J., Pfaller M. A., Jones R. N., Doern G. V., Winokur P. L., Gales A. C., Sader H. S., Kugler K., Beach M. 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. 1999 Sep;29(3):595–607. doi: 10.1086/598640. [DOI] [PubMed] [Google Scholar]
  14. Digranes A., Solberg C. O., Sjursen H., Skovlund E., Sander J. Antibiotic susceptibility of blood culture isolates of Enterobacteriaceae from six Norwegian hospitals 1991-1992. APMIS. 1997 Nov;105(11):854–860. doi: 10.1111/j.1699-0463.1997.tb05094.x. [DOI] [PubMed] [Google Scholar]
  15. Emre S., Sebastian A., Chodoff L., Boccagni P., Meyers B., Sheiner P. A., Mor E., Guy S. R., Atillasoy E., Schwartz M. E. Selective decontamination of the digestive tract helps prevent bacterial infections in the early postoperative period after liver transplant. Mt Sinai J Med. 1999 Oct-Nov;66(5-6):310–313. [PubMed] [Google Scholar]
  16. Fluit A. C., Schmitz F. J. Class 1 integrons, gene cassettes, mobility, and epidemiology. Eur J Clin Microbiol Infect Dis. 1999 Nov;18(11):761–770. doi: 10.1007/s100960050398. [DOI] [PubMed] [Google Scholar]
  17. Garau J., Xercavins M., Rodríguez-Carballeira M., Gómez-Vera J. R., Coll I., Vidal D., Llovet T., Ruíz-Bremón A. Emergence and dissemination of quinolone-resistant Escherichia coli in the community. Antimicrob Agents Chemother. 1999 Nov;43(11):2736–2741. doi: 10.1128/aac.43.11.2736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Haertl R., Bandlow G. Epidemiological fingerprinting of Enterobacter cloacae by small-fragment restriction endonuclease analysis and pulsed-field gel electrophoresis of genomic restriction fragments. J Clin Microbiol. 1993 Jan;31(1):128–133. doi: 10.1128/jcm.31.1.128-133.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hsieh W. J., Lin H. C., Hwang S. J., Hou M. C., Lee F. Y., Chang F. Y., Lee S. D. The effect of ciprofloxacin in the prevention of bacterial infection in patients with cirrhosis after upper gastrointestinal bleeding. Am J Gastroenterol. 1998 Jun;93(6):962–966. doi: 10.1111/j.1572-0241.1998.00288.x. [DOI] [PubMed] [Google Scholar]
  20. Jamal W. Y., El-Din K., Rotimi V. O., Chugh T. D. An analysis of hospital-acquired bacteraemia in intensive care unit patients in a university hospital in Kuwait. J Hosp Infect. 1999 Sep;43(1):49–56. doi: 10.1053/jhin.1999.0608. [DOI] [PubMed] [Google Scholar]
  21. Kholodii G. Y., Mindlin S. Z., Bass I. A., Yurieva O. V., Minakhina S. V., Nikiforov V. G. Four genes, two ends, and a res region are involved in transposition of Tn5053: a paradigm for a novel family of transposons carrying either a mer operon or an integron. Mol Microbiol. 1995 Sep;17(6):1189–1200. doi: 10.1111/j.1365-2958.1995.mmi_17061189.x. [DOI] [PubMed] [Google Scholar]
  22. Klastersky J. Science and pragmatism in the treatment and prevention of neutropenic infection. J Antimicrob Chemother. 1998 Jun;41 (Suppl 500):13–24. doi: 10.1093/jac/41.suppl_4.13. [DOI] [PubMed] [Google Scholar]
  23. Lingnau W., Berger J., Javorsky F., Fille M., Allerberger F., Benzer H. Changing bacterial ecology during a five-year period of selective intestinal decontamination. J Hosp Infect. 1998 Jul;39(3):195–206. doi: 10.1016/s0195-6701(98)90258-4. [DOI] [PubMed] [Google Scholar]
  24. Lévesque C., Piché L., Larose C., Roy P. H. PCR mapping of integrons reveals several novel combinations of resistance genes. Antimicrob Agents Chemother. 1995 Jan;39(1):185–191. doi: 10.1128/aac.39.1.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Martinez-Freijo P., Fluit A. C., Schmitz F. J., Grek V. S., Verhoef J., Jones M. E. Class I integrons in Gram-negative isolates from different European hospitals and association with decreased susceptibility to multiple antibiotic compounds. J Antimicrob Chemother. 1998 Dec;42(6):689–696. doi: 10.1093/jac/42.6.689. [DOI] [PubMed] [Google Scholar]
  26. Martinez-Freijo P., Fluit A. C., Schmitz F. J., Verhoef J., Jones M. E. Many class I integrons comprise distinct stable structures occurring in different species of Enterobacteriaceae isolated from widespread geographic regions in Europe. Antimicrob Agents Chemother. 1999 Mar;43(3):686–689. doi: 10.1128/aac.43.3.686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mazel D., Davies J. Antibiotic resistance in microbes. Cell Mol Life Sci. 1999 Nov 30;56(9-10):742–754. doi: 10.1007/s000180050021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Oethinger M., Conrad S., Kaifel K., Cometta A., Bille J., Klotz G., Glauser M. P., Marre R., Kern W. V. Molecular epidemiology of fluoroquinolone-resistant Escherichia coli bloodstream isolates from patients admitted to European cancer centers. Antimicrob Agents Chemother. 1996 Feb;40(2):387–392. doi: 10.1128/aac.40.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Osterblad M., Pensala O., Peterzéns M., Heleniusc H., Huovinen P. Antimicrobial susceptibility of Enterobacteriaceae isolated from vegetables. J Antimicrob Chemother. 1999 Apr;43(4):503–509. doi: 10.1093/jac/43.4.503. [DOI] [PubMed] [Google Scholar]
  30. Ronveaux O., Gheldre Y., Glupczynski Y., Struelens M., Mol P. Emergence of Enterobacter aerogenes as a major antibiotic-resistant nosocomial pathogen in Belgian hospitals. Clin Microbiol Infect. 1999 Oct;5(10):622–627. doi: 10.1111/j.1469-0691.1999.tb00419.x. [DOI] [PubMed] [Google Scholar]
  31. Sallen B., Rajoharison A., Desvarenne S., Mabilat C. Molecular epidemiology of integron-associated antibiotic resistance genes in clinical isolates of enterobacteriaceae. Microb Drug Resist. 1995 Fall;1(3):195–202. doi: 10.1089/mdr.1995.1.195. [DOI] [PubMed] [Google Scholar]
  32. Shi Z. Y., Liu P. Y., Lau Y. J., Lin Y. H., Hu B. S. Epidemiological typing of isolates from an outbreak of infection with multidrug-resistant Enterobacter cloacae by repetitive extragenic palindromic unit b1-primed PCR and pulsed-field gel electrophoresis. J Clin Microbiol. 1996 Nov;34(11):2784–2790. doi: 10.1128/jcm.34.11.2784-2790.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sundström L. The potential of integrons and connected programmed rearrangements for mediating horizontal gene transfer. APMIS Suppl. 1998;84:37–42. doi: 10.1111/j.1600-0463.1998.tb05646.x. [DOI] [PubMed] [Google Scholar]
  34. Tenover F. C., Arbeit R. D., Goering R. V., Mickelsen P. A., Murray B. E., Persing D. H., Swaminathan B. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol. 1995 Sep;33(9):2233–2239. doi: 10.1128/jcm.33.9.2233-2239.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Versalovic J., Koeuth T., Lupski J. R. Distribution of repetitive DNA sequences in eubacteria and application to fingerprinting of bacterial genomes. Nucleic Acids Res. 1991 Dec 25;19(24):6823–6831. doi: 10.1093/nar/19.24.6823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. van Belkum A., van Leeuwen W., Kluytmans J., Verbrugh H. Molecular nosocomial epidemiology: high speed typing of microbial pathogens by arbitrary primed polymerase chain reaction assays. Infect Control Hosp Epidemiol. 1995 Nov;16(11):658–666. [PubMed] [Google Scholar]
  37. van Kraaij M. G., Dekker A. W., Peters E., Fluit A., Verdonck L. F., Rozenberg-Arska M. Emergence and infectious complications of ciprofloxacin-resistant Escherichia coli in haematological cancer patients. Eur J Clin Microbiol Infect Dis. 1998 Aug;17(8):591–592. doi: 10.1007/BF01708627. [DOI] [PubMed] [Google Scholar]
  38. van Nierop W. H., Duse A. G., Stewart R. G., Bilgeri Y. R., Koornhof H. J. Molecular epidemiology of an outbreak of Enterobacter cloacae in the neonatal intensive care unit of a provincial hospital in Gauteng, South Africa. J Clin Microbiol. 1998 Oct;36(10):3085–3087. doi: 10.1128/jcm.36.10.3085-3087.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]

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