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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

Angeby, K. A.; Jureen, P.; Giske, C. G.; Chryssanthou, E.; Sturegård, Erik LU ; Nordvall, M.; Johansson, A. G.; Werngren, J.; Kahlmeter, G. and Hoffner, S. E., et al. (2010) In Journal of Antimicrobial Chemotherapy 65(5). p.946-952
Abstract
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... (More)
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. (Less)
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publication status
published
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keywords
levofloxacin, moxifloxacin, ciprofloxacin, ofloxacin, susceptibility, testing
in
Journal of Antimicrobial Chemotherapy
volume
65
issue
5
pages
946 - 952
publisher
Oxford University Press
external identifiers
  • wos:000276527500019
  • scopus:77953726929
ISSN
1460-2091
DOI
10.1093/jac/dkq091
language
English
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yes
id
4b4a6f7e-08d2-43be-b529-dbee4bceccfd (old id 1603852)
date added to LUP
2010-05-19 08:11:11
date last changed
2018-07-01 03:12:22
@article{4b4a6f7e-08d2-43be-b529-dbee4bceccfd,
  abstract     = {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) &lt; 1.0 mg/L as the tentative epidemiological cut-off (ECOFF) for ofloxacin and ciprofloxacin, and S &lt; 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 &lt; 2.0 mg/L for ciprofloxacin, ofloxacin and levofloxacin, and S &lt; 0.5 mg/L could be considered as a clinical breakpoint for moxifloxacin, provided other investigators can confirm our findings.},
  author       = {Angeby, K. A. and Jureen, P. and Giske, C. G. and Chryssanthou, E. and Sturegård, Erik and Nordvall, M. and Johansson, A. G. and Werngren, J. and Kahlmeter, G. and Hoffner, S. E. and Schon, T.},
  issn         = {1460-2091},
  keyword      = {levofloxacin,moxifloxacin,ciprofloxacin,ofloxacin,susceptibility,testing},
  language     = {eng},
  number       = {5},
  pages        = {946--952},
  publisher    = {Oxford University Press},
  series       = {Journal of Antimicrobial Chemotherapy},
  title        = {Wild-type MIC distributions of four fluoroquinolones active against Mycobacterium tuberculosis in relation to current critical concentrations and available pharmacokinetic and pharmacodynamic data},
  url          = {http://dx.doi.org/10.1093/jac/dkq091},
  volume       = {65},
  year         = {2010},
}