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JAC Advance Access published online on January 12, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki489
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received September 24, 2005
Revised December 14, 2005
Accepted December 20, 2005

Original article

Epidemiological MIC cut-off values for tigecycline calculated from Etest MIC values using normalized resistance interpretation

Göran Kronvall 1 *, Inga Karlsson 1, Mats Walder 2, Mikael Sörberg 3, and Lennart E. Nilsson 4

1 Clinical Microbiology--MTC, Karolinska Institute, Karolinska Hospital L2:02, 17176 Stockholm, Sweden
2 Clinical Microbiology, Malmö University Hospital, Malmö, Sweden
3 Department of Infectious Diseases, Karolinska Hospital, Karolinska Institute, SE-17176 Stockholm, Sweden
4 Division of Clinical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, SE-58185 Linköping, Sweden

* To whom correspondence should be addressed.
Göran Kronvall, E-mail: goran.kronvall{at}ki.se


  Abstract

Objectives: To apply the normalized resistance interpretation (NRI) method to Etest MIC results which have higher precision than conventional log2 dilution MIC tests due to the inclusion of intermediate values. If successful, NRI might provide an objective tool for the definition of epidemiological MIC cut-off values.

Methods: MICs of tigecycline and other antimicrobial agents were determined for 4771 clinical isolates comprising five Gram-positive and 13 Gram-negative species or species groups using the Etest. Histograms of MIC values were constructed for each species and NRI calculations were applied to them. An upper MIC limit of 2.5 SD above the theoretical mean of the normalized distribution was used for setting the epidemiological cut-off values.

Results: Calculated cut-off values for wild-type strains were between 0.11 and 0.96 mg/L for Gram-positive species, and between 0.44 and 8.3 mg/L for Gram-negative species, except for Pseudomonas aeruginosa, which had a cut-off value of 450 mg/L, consistent with earlier reports on the lack of activity of tigecycline against this species.

Conclusions: NRI offers an objective method for the analysis of MICs produced using Etests and the determination of epidemiological MIC cut-off values.

Keywords: antimicrobial susceptibility tests; MIC breakpoints; drug resistance; clinical microbiology; wild-type MIC distributions.
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