Skip to main content

Advertisement

Log in

Factors associated with antimicrobial resistance among clinical isolates of Klebsiella pneumoniae: 1-year survey in a French university hospital

  • Article
  • Published:
European Journal of Clinical Microbiology and Infectious Diseases Aims and scope Submit manuscript

Abstract

Klebsiella pneumoniae is an opportunistic pathogen responsible for nosocomial infections. Both resistance to multiple antibiotics and the expression of virulence factors are likely to be involved in the physiopathological process. In this study, 227 isolates of K. pneumoniae collected over a 1-year period in a teaching hospital in Clermont-Ferrand, France, were investigated for their antibiotic resistance pattern and the presence of several potential virulence traits. Enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) indicated that most of the isolates were phylogenetically unrelated. When tested in an in vitro adhesion assay with Int-407 intestinal cells, the median adhesion index was 5.5×104 bacteria/cm2 (range, 2.0×102–3.4×105). Isolates resistant to cefoxitin, chloramphenicol, and quinolones showed significantly lower adhesion indexes. The frequency of mutagenesis conferring resistance to rifampicin was low for most of the isolates. The median mutagenesis frequency was 1.0×10−8 (range, 2.5×10−9–3.2×10−6) at 24 h and 1.1×10−8 (range, 1.8×10−9–1.2×10−5) at 7 days. In contrast, isolates resistant to cefoxitin, chloramphenicol, and tetracycline showed a significantly greater ability to mutate. These results suggest a link between adhesion capabilities and resistance to certain antibiotics. They furthermore indicate that strains with a high mutagenesis capacity are more likely to acquire antibiotic resistance genes. The high pathogenicity island of Yersinia was detected in 16.3% of the strains and was more often associated with isolates resistant to nalidixic acid and augmentin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Blot SI, Vandewoude KH, Colardyn FA (2002) Clinical impact of nosocomial Klebsiella bacteremia in critically ill patients. Eur J Clin Microbiol Infect Dis 21:471–473

    CAS  PubMed  Google Scholar 

  2. De Champs C, Rouby D, Guelon D, Sirot J, Sirot D, Beytout D, Gourgand JM (1991) A case-control study of an outbreak of infections caused by Klebsiella pneumoniae strains producing CTX-1 (TEM-3) beta-lactamase. J Hosp Infect 8:5–13

    Google Scholar 

  3. Gruteke P, Goessens W, van Gils J, Peerbooms P, Lemmens-den Toom N, van Santen-Verheuvel M, van Belkum A, Verbrugh H (2003) Patterns of resistance associated with integrons, the extended-spectrum β-lactamase SHV-5 gene, and a multidrug efflux pump of Klebsiella pneumoniae causing a nosocomial outbreak. J Clin Microbiol 41:1161–1166

    Article  CAS  PubMed  Google Scholar 

  4. Podschun R, Ullmann U (1998) Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev 11:589–603

    CAS  PubMed  Google Scholar 

  5. Tseng YC, Chiu YC, Wang JH, Lin HC, Lin HC, Su BH, Chiu HH (2002) Nosocomial bloodstream infections in a neonatal intensive care unit of a medical center: a three-year review. J Microbiol Immunol Infect 35:168–172

    PubMed  Google Scholar 

  6. Sirot D, Chanal C, Labia R, Meyran M, Sirot J, Cluzel R (1989) Comparative study of five plasmid-mediated ceftazidimases isolated in Klebsiella pneumoniae. J Antimicrob Chemother 24:509–521

    CAS  PubMed  Google Scholar 

  7. De Champs C, Sirot D, Chanal C, Poupart MC, Dumas MP, Sirot J (1991) Concomitant dissemination of three extended-spectrum beta-lactamases among different Enterobacteriaceae isolated in a French hospital. J Antimicrob Chemother 27:441–457

    PubMed  Google Scholar 

  8. Sirot J, Chanal C, Petit A, Sirot D, Labia R, Gerbaud G (1988) Klebsiella pneumoniae and other Enterobacteriaceae producing novel plasmid-mediated beta-lactamases markedly active against third-generation cephalosporins: epidemiologic studies. Rev Infect Dis 10:850–859

    CAS  PubMed  Google Scholar 

  9. Di Martino P, Livrelli V, Sirot D, Joly B, Darfeuille-Michaud A (1996) A new fimbrial antigen harbored by CAZ-5/SHV-4-producing Klebsiella pneumoniae strains involved in nosocomial infections. Infect Immun 64:2266–2273

    PubMed  Google Scholar 

  10. Di Martino P, Bertin Y, Girardeau JP, Livrelli V, Joly B, Darfeuille-Michaud A (1995) Molecular characterization and adhesive properties of CF29K, an adhesin of Klebsiella pneumoniae strains involved in nosocomial infections. Infect Immun 63:4336–4344

    PubMed  Google Scholar 

  11. Favre-Bonte S, Licht TR, Forestier C, Krogfelt KA (1999) Klebsiella pneumoniae capsule expression is necessary for colonization of large intestines of streptomycin-treated mice. Infect Immun 67:6152–6156

    CAS  PubMed  Google Scholar 

  12. De Champs C, Sauvant MP, Chanal C, Sirot D, Gazuy N, Malhuret R, Baguet JC, Sirot J (1989) Prospective survey of colonization and infection caused by expanded-spectrum beta-lactamase-producing members of the family Enterobacteriaceae in an intensive care unit. J Clin Microbiol 27:2887–2890

    PubMed  Google Scholar 

  13. Selden R, Lee S, Wang WL, Bennett JV, Eickhoff TC (1971) Nosocomial Klebsiella infections: intestinal colonization as a reservoir. Ann Intern Med 74:657–664

    CAS  PubMed  Google Scholar 

  14. Denamur E, Bonacorsi S, Giraud A, Duriez P, Hilali F, Amorin C, Bingen E, Andremont A, Picard B, Taddei F, Matic I (2002) High frequency of mutator strains among human uropathogenic Escherichia coli isolates. J Bacteriol 184:605–609

    Article  CAS  PubMed  Google Scholar 

  15. Oliver A, Canton R, Campo P, Baquero F, Blazquez J (2000) High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science 288:1251–1254

    CAS  PubMed  Google Scholar 

  16. Carniel E (1999) The Yersinia high-pathogenicity island. Int Microbiol 2:161–167

    CAS  PubMed  Google Scholar 

  17. Versalovic J, Koeuth T, Lupski JR (1991) Distribution of repetitive DNA sequences in eubacteria and application to fingerprinting of bacterial genomes. Nucleic Acids Res 19:6823–6831

    CAS  PubMed  Google Scholar 

  18. Gutmann L, Williamson R, Moreau N, Kitzis MD, Collatz E, Acar JF, Goldstein FW (1985) Cross-resistance to nalidixic acid, trimethoprim, and chloramphenicol associated with alterations in outer membrane proteins of Klebsiella, Enterobacter, and Serratia. J Infect Dis 151:501–507

    CAS  PubMed  Google Scholar 

  19. Favre-Bonte S, Darfeuille-Michaud A, Forestier C (1995) Aggregative adherence of Klebsiella pneumoniae to human intestine-407 cells. Infect Immun 63:1318–1328

    CAS  PubMed  Google Scholar 

  20. Taddei F, Matic I, Radman M (1995) cAMP-dependent SOS induction and mutagenesis in resting bacterial populations. Proc Natl Acad Sci USA 92:11736–11740

    CAS  PubMed  Google Scholar 

  21. Bach S, de Almeida A, Carniel E (2000) The Yersinia high-pathogenicity island is present in different members of the family Enterobacteriaceae. FEMS Microbiol Lett 183:289–294

    Article  CAS  PubMed  Google Scholar 

  22. Martinez-Martinez L, Hernandez-Alles S, Alberti S, Tomas JM, Benedi VJ, Jacoby G (1996) In vivo selection of porin-deficient mutants of Klebsiella pneumoniae with increased resistance to cefoxitin and expanded-spectrum cephalosporins. Antimicrob Agents Chemother 40:342–348

    CAS  PubMed  Google Scholar 

  23. Andersson DI, Levin BR (1999) The biological cost of antibiotic resistance. Curr Opin Microbiol 2:489–493

    Article  CAS  PubMed  Google Scholar 

  24. Levin BR, Perrot V, Walker N (2000) Compensatory mutations, antibiotic resistance and the population genetics of adaptive evolution in bacteria. Genetics 154:985–997

    CAS  PubMed  Google Scholar 

  25. Nagaev I, Bjorkman J, Andersson DI, Hughes D (2001) Biological cost and compensatory evolution in fusidic acid-resistant Staphylococcus aureus. Mol Microbiol 40:433–439

    Article  CAS  PubMed  Google Scholar 

  26. Philippon A, Arlet G, Jacoby GA (2002) Plasmid-determined AmpC-type beta-lactamases. Antimicrob Agents Chemother 46:1–11

    Article  CAS  PubMed  Google Scholar 

  27. Yong D, Park R, Yum JH, Lee K, Choi EC, Chong Y (2002) Further modification of the Hodge test to screen AmpC-lactamase (CMY-1)-producing strains of Escherichia coli and Klebsiella pneumoniae. J Microbiol Methods 51:407–410

    Article  CAS  PubMed  Google Scholar 

  28. Pérez-Pérez FJ, Hanson ND (2002) Detection of plasmid-mediated AmpC β-lactamase genes in clinical isolates by using multiplex PCR. J Clin Microbiol 40:2153–2162

    Article  CAS  PubMed  Google Scholar 

  29. Simonet V, Malléa M, Pagès JM (2000) Substitutions in the eyelet region disrupt cefepime diffusion through the Escherichia coli OmpF channel. Antimicrob Agents Chemother 44:311–315

    Article  CAS  PubMed  Google Scholar 

  30. Nikaido H, Basina M, Nguyen VY, Rosenberg EY (1998) Multidrug efflux pump AcrAB of Salmonella typhimurium excretes only those β-lactam antibiotics containing lipophilic side chains. J Bacteriol 180:4686–4692

    PubMed  Google Scholar 

  31. Achouak W, Pages JM, De Mot R, Molle G, Heulin T (1998) A major outer membrane protein of Rahnella aquatilis functions as a porin and root adhesin. J Bacteriol 180:909–913

    CAS  PubMed  Google Scholar 

  32. Hernandez-Alles S, Conejo M, Pascual A, Tomas JM, Benedi VJ, Martinez-Martinez L (2000) Relationship between outer membrane alterations and susceptibility to antimicrobial agents in isogenic strains of Klebsiella pneumoniae. J Antimicrob Chemother 46:273–277

    Article  CAS  PubMed  Google Scholar 

  33. Schnappinger D, Hillen W (1996) Tetracyclines: antibiotic action, uptake, and resistance mechanisms. Arch Microbiol 165:359–369

    Article  CAS  PubMed  Google Scholar 

  34. Kohler T, van Delden C, Curty LK, Hamzehpour MM, Pechere JC (2001) Overexpression of the MexEF-OprN multidrug efflux system affects cell-to-cell signaling in Pseudomonas aeruginosa. J Bacteriol 183:5213–5222

    Article  CAS  PubMed  Google Scholar 

  35. Hirakata Y, Srikumar R, Poole K, Gotoh N, Suematsu T, Kohno S, Kamihira S, Hancock RE, Speert DP (2002) Multidrug efflux systems play an important role in the invasiveness of Pseudomonas aeruginosa. J Exp Med 196:109–118

    Article  CAS  PubMed  Google Scholar 

  36. Vila J, Simon K, Ruiz J, Horcajada JP, Velasco M, Barranco M, Moreno A, Mensa J (2002) Are quinolone-resistant uropathogenic Escherichia coli less virulent? J Infect Dis 186:1039–1042

    Article  CAS  PubMed  Google Scholar 

  37. Hatfield GW, Benham CJ (2002) DNA topology-mediated control of global gene expression in Escherichia coli. Annu Rev Genet 36:175–203

    Article  CAS  PubMed  Google Scholar 

  38. Alekshun MN, Levy SB (1997) Regulation of chromosomally mediated multiple antibiotic resistance: the mar regulon. Antimicrob Agents Chemother 41:2067–2075

    CAS  PubMed  Google Scholar 

  39. Chollet R, Bollet C, Chevalier J, Malléa M, Pagès JM, Davin-Regli A (2002) mar operon involved in multidrug resistance of Enterobacter aerogenes. Antimicrob Agents Chemother 46:1093–1097

    Article  CAS  PubMed  Google Scholar 

  40. Muhldorfer I, Hacker J (1994) Genetic aspects of Escherichia coli virulence. Microb Pathog 16:171–181

    Article  CAS  PubMed  Google Scholar 

  41. Carniel E, Mercereau-Puijalon O, Bonnefoy S (1989) The gene coding for the 190,000-dalton iron-regulated protein of Yersinia species is present only in the highly pathogenic strains. Infect Immun 57:1211–1217

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the “PRFMMIP—Réseau Infections Nosocomiales.” We thank Dominique Rubio for her technical assistance, Vincent Bige for helpful advice and Jeff Watts for revision of the English manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to C. Forestier.

Rights and permissions

Reprints and permissions

About this article

Cite this article

De Champs, C., Rich, C., Chandezon, P. et al. Factors associated with antimicrobial resistance among clinical isolates of Klebsiella pneumoniae: 1-year survey in a French university hospital. Eur J Clin Microbiol Infect Dis 23, 456–462 (2004). https://doi.org/10.1007/s10096-004-1144-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-004-1144-2

Keywords

Navigation