CoChat
Sign Up
Cited by 855Antifungal resistance and susceptibilityBacterial Identification and Susceptibility TestingFungal Plant Pathogen Control

Development of Interpretive Breakpoints for Antifungal Susceptibility Testing: Conceptual Framework and Analysis of In Vitro-In Vivo Correlation Data for Fluconazole, Itraconazole, and Candida Infections

Rex, J. H., Pfaller, M. A., Galgiani, J. N., Bartlett, M. S., Espinel-Ingroff, A., Ghannoum, M. A., Lancaster, M., Odds, F. C. +4 more·1997·Clinical Infectious Diseases
DOI 10.1093/clinids/24.2.235
Open this paper in CoChat — free account

Abstract

The availability of reproducible antifungal susceptibility testing methods now permits analysis of data correlating susceptibility in vitro with outcome in vivo in order to define interpretive breakpoints. In this paper, we have examined the conceptual framework underlying interpretation of antimicrobial susceptibility testing results and then used these ideas to drive analysis of data packages developed by the respective manufacturers that correlate fluconazole and itraconazole MICs with outcome of candidal infections. Tentative fluconazole interpretive breakpoints for MICs determined by the National Committee for Clinical Laboratory Standards' M27-T broth macrodilution methodology are proposed: isolates for which MICs are < or = 8 microg/mL are susceptible to fluconazole, whereas those for which MICs are > or = 64 microg/mL appear resistant. Isolates for which the MIC of fluconazole is 16-32 microg/mL are considered susceptible dependent upon dose (S-DD), on the basis of data indicating clinical response when > 100 mg of fluconazole per day is given. These breakpoints do not, however, apply to Candida krusei, as it is considered inherently resistant to fluconazole. Tentative interpretive MIC breakpoints for itraconazole apply only to mucosal candidal infections and are as follows: susceptible, < or = 0.125 microg/mL; S-DD, 0.25-0.5 microg/mL; and resistant, > or = 1.0 microg/mL. These tentative breakpoints are now open for public commentary.

Integrity signals

Registry

Crossref · 10.1093/clinids/24.2.235

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Analysis of trial data found that treatment efficacy for fluconazole in oropharyngeal candidiasis was maximal near a 24-hour AUC/MIC of 25.

    “Analysis of these trial data found that treatment efficacy was maximal with fluconazole exposures relative to the MIC of the infecting Candida species near a 24-hour AUC/ MIC value of 25.”

    From Fungal Sepsis: Optimizing Antifungal Therapy in the Critical Care Setting (2011) · cites this paper as [146]

  • When fluconazole AUC/MIC exceeded 25, clinical success was noted in 91% to 100% of patients with oropharyngeal candidiasis.

    “When the fluconazole AUC/MIC exceeded 25, clinical success was noted in 91% to 100% of patients.”

    From Fungal Sepsis: Optimizing Antifungal Therapy in the Critical Care Setting (2011) · cites this paper as [146]

  • When fluconazole AUC/MIC was less than 25, clinical failure was noted in 27% to 35% of patients with oropharyngeal candidiasis.

    “However, when AUC/MIC was less than 25, clinical failure was noted in 27% to 35% of patients.”

    From Fungal Sepsis: Optimizing Antifungal Therapy in the Critical Care Setting (2011) · cites this paper as [146]

  • Data-driven interpretive breakpoints using the M27-A method are available for testing the susceptibility of Candida species to fluconazole, itraconazole, and flucytosine.

    “Data-driven interpretive breakpoints using this method are available for testing the susceptibility of Candida species to fluconazole, itraconazole, and flucytosine [28][29][30][31].”

    From Guidelines for Treatment of Candidiasis (2004) · cites this paper as [30]

  • In the case of fluconazole, data for both human beings and animals suggest that S-DD isolates may be treated successfully with a dosage of 12 mg/kg per day.

    “In the case of fluconazole, data for both human beings and animals suggest that S-DD isolates may be treated successfully with a dosage of 12 mg/kg per day [30,32].”

    From Guidelines for Treatment of Candidiasis (2004) · cites this paper as [30]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Rex, J. H., Pfaller, M. A., Galgiani, J. N., Bartlett, M. S., Espinel-Ingroff, A., Ghannoum, M. A., Lancaster, M., Odds, F. C., Rinaldi, M. G., Walsh, T. J., Barry, A. L., & Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Laboratory Standards
Corresponding author
Rex, J. H.
ORCID
Venue
Clinical Infectious Diseases
Publisher
Oxford University Press (OUP)
Published
1997-02-01
Volume
24
Issue
2
Pages
235-247
ISSN
  • 1058-4838 (ISSN-L)
  • 1537-6591
DOI
10.1093/clinids/24.2.235
OpenAlex
W2134458167
Cited by
855
References
2
Citations by year
2025: 9 · 2024: 3 · 2023: 9 · 2022: 5 · 2021: 13 · 2020: 13 · 2019: 20 · 2018: 11 · 2017: 15 · 2016: 17 · 2015: 14 · 2014: 22 · 2013: 12 · 2012: 23
FWCI
56.24
Type
journal article
Language
en
Open access
closed
Locations
  • Clinical Infectious Diseases (publishedVersion)
  • PubMed (publishedVersion)
Funders
Pfizer
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
  • Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Keywords
interpretive breakpoints, antifungal susceptibility testing, fluconazole, itraconazole, candidiasis, in vitro-in vivo correlation, minimum inhibitory concentration, Candida krusei, mucosal candidiasis, antifungal resistance
MeSH terms
Animals, Antifungal Agents, Candidiasis, Drug Resistance, Microbial, Humans, Microbial Sensitivity Tests, Fluconazole, Itraconazole, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review