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Wild-type MIC distributions of four fluoroquinolones active against Mycobacterium tuberculosis in relation to current critical concentrations and available pharmacokinetic and pharmacodynamic data

In English

Författare

  • K. A. Angeby
  • P. Jureen
  • C. G. Giske
  • E. Chryssanthou
  • Erik Sturegård
  • M. Nordvall
  • A. G. Johansson
  • J. Werngren
  • G. Kahlmeter
  • S. E. Hoffner
  • T. Schon
Visa allt

Summary, in English

To describe wild-type distributions of the MIC of fluoroquinolones for Mycobacterium tuberculosis in relation to current critical concentrations used for drug susceptibility testing and pharmacokinetic/pharmacodynamic (PK/PD) data. A 96-stick replicator on Middlebrook 7H10 medium was used to define the MICs of ciprofloxacin, ofloxacin, moxifloxacin and levofloxacin for 90 consecutive clinical strains and 24 drug-resistant strains. The MICs were compared with routine BACTEC 460 susceptibility results and with MIC determinations in the BACTEC MGIT 960 system in a subset of strains using ofloxacin as a class representative. PK/PD data for each drug were reviewed in relation to the wild-type MIC distribution. The wild-type MICs of ciprofloxacin, ofloxacin, moxifloxacin and levofloxacin were distributed from 0.125 to 1, 0.25 to 1, 0.032 to 0.5 and 0.125 to 0.5 mg/L, respectively. The MIC data correlated well with the BACTEC 960 MGIT and BACTEC 460 results. PD indices were the most favourable for levofloxacin, followed by moxifloxacin, ofloxacin and ciprofloxacin. We propose S (susceptible) < 1.0 mg/L as the tentative epidemiological cut-off (ECOFF) for ofloxacin and ciprofloxacin, and S < 0.5 mg/L for levofloxacin and moxifloxacin, although it is possible that adding more MIC data could shift the ECOFFs for ofloxacin and levofloxacin one dilution upwards. The proposed ECOFFs may be more appropriate if used as clinical breakpoints on Middlebrook 7H10 agar than the current critical concentrations of S < 2.0 mg/L for ciprofloxacin, ofloxacin and levofloxacin, and S < 0.5 mg/L could be considered as a clinical breakpoint for moxifloxacin, provided other investigators can confirm our findings.

Publiceringsår

2010

Språk

Engelska

Sidor

946-952

Publikation/Tidskrift/Serie

Journal of Antimicrobial Chemotherapy

Volym

65

Issue

5

Dokumenttyp

Artikel i tidskrift

Förlag

Oxford University Press

Ämne

  • Pharmacology and Toxicology

Nyckelord

  • levofloxacin
  • moxifloxacin
  • ciprofloxacin
  • ofloxacin
  • susceptibility
  • testing

Status

Published

Forskningsgrupp

  • Clinical Microbiology, Malmö

ISBN/ISSN/Övrigt

  • ISSN: 1460-2091