Correlation of MIC with outcome for Candida species tested against voriconazole: analysis and proposal for interpretive breakpoints

M A Pfaller; D J Diekema; J H Rex; A Espinel-Ingroff; E M Johnson; D Andes; V Chaturvedi; M A Ghannoum; F C Odds; M G Rinaldi; D J Sheehan; P Troke; T J Walsh; D W Warnock

doi:10.1128/JCM.44.3.819-826.2006

Back

Correlation of MIC with outcome for Candida species tested against voriconazole: analysis and proposal for interpretive breakpoints

Journal article

Open access

Peer reviewed

Correlation of MIC with outcome for Candida species tested against voriconazole: analysis and proposal for interpretive breakpoints

M A Pfaller, D J Diekema, J H Rex, A Espinel-Ingroff, E M Johnson, D Andes, V Chaturvedi, M A Ghannoum, F C Odds, M G Rinaldi, …

Journal of clinical microbiology, Vol.44(3), pp.819-826

03/2006

DOI: 10.1128/JCM.44.3.819-826.2006

PMCID: PMC1393146

PMID: 16517860

Files and links (1)

url

https://doi.org/10.1128/JCM.44.3.819-826.2006View

Published (Version of record) Open Access

Abstract

Developing interpretive breakpoints for any given organism-drug combination requires integration of the MIC distribution, pharmacokinetic and pharmacodynamic parameters, and the relationship between the in vitro activity and outcome from both in vivo and clinical studies. Using data generated by standardized broth microdilution and disk diffusion test methods, the Antifungal Susceptibility Subcommittee of the Clinical and Laboratory Standards Institute has now proposed interpretive breakpoints for voriconazole and Candida species. The MIC distribution for voriconazole was determined using a collection of 8,702 clinical isolates. The overall MIC90 was 0.25 microg/ml and 99% of the isolates were inhibited at < or = 1 microg/ml of voriconazole. Similar results were obtained for 1,681 Candida isolates (16 species) from the phase III clinical trials. Analysis of the available data for 249 patients from six phase III voriconazole clinical trials demonstrated a statistically significant correlation (P = 0.021) between MIC and investigator end-of-treatment assessment of outcome. Consistent with parallel pharmacodynamic analyses, these data support the following MIC breakpoints for voriconazole and Candida species: susceptible (S), < or = 1 microg/ml; susceptible dose dependent (SDD), 2 microg/ml; and resistant (R), > or = 4 microg/ml. The corresponding disk test breakpoints are as follows: S, > or = 17 mm; SDD, 14 to 16 mm; and R, < or = 13 mm.

Triazoles - administration & dosage

Data Interpretation, Statistical

Pyrimidines - administration & dosage

Humans

Fluconazole - administration & dosage

Microbial Sensitivity Tests - statistics & numerical data

Candidiasis - microbiology

Candida - isolation & purification

Candidiasis - drug therapy

Endpoint Determination

Voriconazole

Inhibitory Concentration 50

Candida - drug effects

Antifungal Agents - administration & dosage

Drug Resistance, Fungal

Microbial Sensitivity Tests - methods

Details

Title: Subtitle: Correlation of MIC with outcome for Candida species tested against voriconazole: analysis and proposal for interpretive breakpoints
Creators: M A Pfaller - Medical Microbiology Division, C606 GH, Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA. michael-pfaller@uiowa.edu
D J Diekema
J H Rex
A Espinel-Ingroff
E M Johnson
D Andes
V Chaturvedi
M A Ghannoum
F C Odds
M G Rinaldi
D J Sheehan
P Troke
T J Walsh
D W Warnock - Centers for Disease Control and Prevention
Resource Type: Journal article
Publication Details: Journal of clinical microbiology, Vol.44(3), pp.819-826
Publisher: United States
DOI: 10.1128/JCM.44.3.819-826.2006
PMID: 16517860
PMCID: PMC1393146
ISSN: 0095-1137
eISSN: 1098-660X
Language: English
Date published: 03/2006
Academic Unit: Infectious Diseases; Epidemiology; Pathology; Internal Medicine
Record Identifier: 9983986255602771

Metrics

13 Record Views

223 Times Cited - Web of Science