High rates of susceptibility to ceftazidime among globally prevalent CTX-M-producing Escherichia coli: potential clinical implications of the revised CLSI interpretive criteria

  • D. A. Williamson
  • S. A. Roberts
  • M. Smith
  • H. Heffernan
  • A. Tiong
  • C. Pope
  • J. T. Freeman
Article

Abstract

The CTX-M family of extended-spectrum β-lactamases (ESBLs) is a significant global public health threat. The prevalence of specific bla CTX-M genes varies geographically, but bla CTX-M-15 and bla CTX-M-14 dominate in most countries. We applied the latest Clinical Laboratory Standards Institute (CLSI) interpretive criteria (M100-S20) to a diverse collection of ESBL-producing Escherichia coli strains obtained from clinical specimens in our laboratory. Whereas under previous CLSI recommendations all isolates in this strain collection would have been reported as ceftazidime-resistant, under the new recommendations, approximately 11% of CTX-M-15-producing E. coli and 93% of CTX-M-14-producing E. coli respectively tested as ceftazidime-susceptible. We also found that, whilst many CTX-M-14-producers had minimum inhibitory concentrations (MICs) less than the breakpoint of 4 mg/L, the MIC distribution for these strains was higher than that of wild-type E. coli, with one CTX-M-14-producing isolate having an MIC of >64 mg/L. Although the new CLSI recommendations imply that ceftazidime can be safely used to treat serious infections due to CTX-M-producing E. coli, clinical outcome data are lacking. Consequently, the widespread use of ceftazidime in this setting could have profound clinical implications.

Keywords

Minimum Inhibitory Concentration Ceftriaxone Ceftazidime Boronic Acid ESBL Production 
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

Conflict of interest

All authors report no conflict of interests.

Funding

No specific funding was required for this study.

References

  1. 1.
    Bonnet R (2004) Growing group of extended-spectrum β-lactamases: the CTX-M enzymes. Antimicrob Agents Chemother 48:1–14PubMedCrossRefGoogle Scholar
  2. 2.
    Peirano G, Pitout JD (2010) Molecular epidemiology of Escherichia coli producing CTX-M beta-lactamases: the worldwide emergence of clone ST131 O25:H4. Int J Antimicrob Agents 35:316–321PubMedCrossRefGoogle Scholar
  3. 3.
    Lewis JS, Herrera M, Wickes B, Patterson JE, Jorgensen JH (2007) First report of the emergence of CTX-M-type extended-spectrum beta-lactamases (ESBLs) as the predominant ESBL isolated in a U.S. health care system. Antimicrob Agents Chemother 51:4015–4021PubMedCrossRefGoogle Scholar
  4. 4.
    McGettigan SE, Hu B, Andreacchio K, Nachamkin I, Edelstein PH (2009) Prevalence of CTX-M β-lactamases in Philadelphia, Pennsylvania. J Clin Micro 47:2970–2974CrossRefGoogle Scholar
  5. 5.
    Clinical and Laboratory Standards Institute (CLSI) (2010) Performance standards for antimicrobial susceptibility testing; CLSI document M100-S20. CLSI, Wayne, PAGoogle Scholar
  6. 6.
    Song W, Bae IK, Lee YN et al (2007) Detection of extended-spectrum β-lactamases by using boronic acid as an AmpC β-lactamase inhibitor in clinical isolates of Klebsiella spp. and Escherichia coli. J Clin Microbiol 45(4):1180–4PubMedCrossRefGoogle Scholar
  7. 7.
    Jeong SH, Bae IK, Kwon SB et al (2005) Dissemination of transferable CTX-M-type extended-spectrum β-lactamase-producing Escherichia coli in Korea. J Appl Microbiol 98:921–7PubMedCrossRefGoogle Scholar
  8. 8.
    European Committee on Antimicrobial Susceptibility Testing (EUCAST). Antimicrobial wild type distributions of microorganisms. Home page at: http://www.escmid.org
  9. 9.
    Gniadkowski M (2008) Evolution of extended-spectrum β-lactamases by mutation. Clin Microbiol Infect 14(Suppl 1):11–32PubMedCrossRefGoogle Scholar
  10. 10.
    Andes D, Craig WA (2005) Treatment of infections with ESBL-producing organisms: pharmacokinetic and pharmacodynamic considerations. Clin Microbiol Infect 11(Suppl 6):10–17PubMedCrossRefGoogle Scholar
  11. 11.
    Turnidge J, Paterson DL (2007) Setting and revising antibacterial susceptibility breakpoints. Clin Microbiol Rev 20:391–408PubMedCrossRefGoogle Scholar
  12. 12.
    Roberts JA, Kirkpatrick CM, Lipman J (2011) Monte Carlo simulations: maximizing antibiotic pharmacokinetic data to optimize clinical practice for critically ill patients. J Antimicrob Chemother 66:227–231PubMedCrossRefGoogle Scholar
  13. 13.
    Tumbarello M, Sali M, Trecarichi EM et al (2008) Bloodstream infections caused by extended-spectrum-β-lactamase-producing Escherichia coli: risk factors for inadequate initial antimicrobial therapy. Antimicrob Agents Chemother 52:3244–3252PubMedCrossRefGoogle Scholar
  14. 14.
    Wong-Beringer A, Hindler J, Loeloff M et al (2002) Molecular correlation for the treatment outcomes in bloodstream infections caused by Escherichia coli and Klebsiella pneumoniae with reduced susceptibility to ceftazidime. Clin Infect Dis 34(2):135–146PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • D. A. Williamson
    • 1
  • S. A. Roberts
    • 1
  • M. Smith
    • 1
  • H. Heffernan
    • 2
  • A. Tiong
    • 1
  • C. Pope
    • 2
  • J. T. Freeman
    • 1
  1. 1.Department of Clinical MicrobiologyAuckland City HospitalAucklandNew Zealand
  2. 2.Institute of Environmental Science and ResearchPoriruaNew Zealand

Personalised recommendations