This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pfaller, M. A.
Right arrow Articles by Warnock, D. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pfaller, M. A.
Right arrow Articles by Warnock, D. W.

 Previous Article  |  Next Article 

Journal of Clinical Microbiology, March 2006, p. 819-826, Vol. 44, No. 3
0095-1137/06/$08.00+0     doi:10.1128/JCM.44.3.819-826.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Correlation of MIC with Outcome for Candida Species Tested against Voriconazole: Analysis and Proposal for Interpretive Breakpoints

M. A. Pfaller,1* D. J. Diekema,1 J. H. Rex,2 A. Espinel-Ingroff,3 E. M. Johnson,4 D. Andes,5 V. Chaturvedi,6 M. A Ghannoum,7 F. C. Odds,8 M. G. Rinaldi,9 D. J. Sheehan,10 P. Troke,11 T. J. Walsh,12 and D. W. Warnock13

University of Iowa College of Medicine, Iowa City, Iowa,1 AstraZeneca, Macclesfield, Cheshire, United Kingdom,2 VCU Medical Center, Richmond, Virginia,3 HPA Centre for Infections, Kingsdown, Bristol, United Kingdom,4 University of Wisconsin, Madison, Wisconsin,5 New York State Department of Health, Albany, New York,6 Case Western Reserve University, Cleveland, Ohio,7 University of Aberdeen, Aberdeen, Scotland, United Kingdom,8 University of Texas Health Science Center, San Antonio, Texas,9 Pfizer, Inc., New York, New York,10 Pfizer Global Research and Development, Sandwich, Kent, United Kingdom,11 National Cancer Institute, Bethesda, Maryland,12 Centers for Disease Control and Prevention, Atlanta, Georgia,13

Received 24 October 2005/ Accepted 20 December 2005

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 µg/ml and 99% of the isolates were inhibited at ≤1 µg/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), ≤1 µg/ml; susceptible dose dependent (SDD), 2 µg/ml; and resistant (R), ≥4 µg/ml. The corresponding disk test breakpoints are as follows: S, ≥17 mm; SDD, 14 to 16 mm; and R, ≤13 mm.

* Corresponding author. Mailing address: Medical Microbiology Division, C606 GH, Department of Pathology, University of Iowa College of Medicine, Iowa City, IA 52242. Phone: (319) 384-9566. Fax: (319) 356-4916. E-mail: michael-pfaller{at}uiowa.edu.

Journal of Clinical Microbiology, March 2006, p. 819-826, Vol. 44, No. 3
0095-1137/06/$08.00+0     doi:10.1128/JCM.44.3.819-826.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Pfaller, M. A., Messer, S. A., Hollis, R. J., Boyken, L., Tendolkar, S., Kroeger, J., Diekema, D. J. (2009). Variation in Susceptibility of Bloodstream Isolates of Candida glabrata to Fluconazole According to Patient Age and Geographic Location in the United States in 2001 to 2007. J. Clin. Microbiol. 47: 3185-3190 [Abstract] [Full Text]  
  • Diekema, D. J., Messer, S. A., Boyken, L. B., Hollis, R. J., Kroeger, J., Tendolkar, S., Pfaller, M. A. (2009). In Vitro Activity of Seven Systemically Active Antifungal Agents against a Large Global Collection of Rare Candida Species as Determined by CLSI Broth Microdilution Methods. J. Clin. Microbiol. 47: 3170-3177 [Abstract] [Full Text]  
  • Dennis, D., Robertson, D., Curtis, L., Black, J. (2009). Fungal exposure endocrinopathy in sinusitis with growth hormone deficiency: Dennis-Robertson syndrome. Toxicol Ind Health 25: 669-680 [Abstract]  
  • Espinel-Ingroff, A., Canton, E., Peman, J., Rinaldi, M. G., Fothergill, A. W. (2009). Comparison of 24-Hour and 48-Hour Voriconazole MICs as Determined by the Clinical and Laboratory Standards Institute Broth Microdilution Method (M27-A3 Document) in Three Laboratories: Results Obtained with 2,162 Clinical Isolates of Candida spp. and Other Yeasts. J. Clin. Microbiol. 47: 2766-2771 [Abstract] [Full Text]  
  • Ghebremedhin, B., Bluemel, A., Neumann, K.-H., Koenig, B., Koenig, W. (2009). Peritonitis due to Neosartorya pseudofischeri in an elderly patient undergoing peritoneal dialysis successfully treated with voriconazole. J Med Microbiol 58: 678-682 [Abstract] [Full Text]  
  • Andes, D., Pascual, A., Marchetti, O. (2009). Antifungal Therapeutic Drug Monitoring: Established and Emerging Indications. Antimicrob. Agents Chemother. 53: 24-34 [Full Text]  
  • Pfaller, M. A., Diekema, D. J., Gibbs, D. L., Newell, V. A., Bijie, H., Dzierzanowska, D., Klimko, N. N., Letscher-Bru, V., Lisalova, M., Muehlethaler, K., Rennison, C., Zaidi, M., the Global Antifungal Surveillance Group, (2009). Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: 10.5-Year Analysis of Susceptibilities of Noncandidal Yeast Species to Fluconazole and Voriconazole Determined by CLSI Standardized Disk Diffusion Testing. J. Clin. Microbiol. 47: 117-123 [Abstract] [Full Text]  
  • Howard, A., Hoffman, J., Sheth, A. (2008). Clinical Application of Voriconazole Concentrations in the Treatment of Invasive Aspergillosis. The Annals of Pharmacotherapy 42: 1859-1864 [Abstract] [Full Text]  
  • Gygax, S. E., Vermitsky, J.-P., Chadwick, S. G., Self, M. J., Zimmerman, J. A., Mordechai, E., Adelson, M. E., Trama, J. P. (2008). Antifungal Resistance of Candida glabrata Vaginal Isolates and Development of a Quantitative Reverse Transcription-PCR-Based Azole Susceptibility Assay. Antimicrob. Agents Chemother. 52: 3424-3426 [Abstract] [Full Text]  
  • Gonzalez, G. M., Elizondo, M., Ayala, J. (2008). Trends in Species Distribution and Susceptibility of Bloodstream Isolates of Candida Collected in Monterrey, Mexico, to Seven Antifungal Agents: Results of a 3-Year (2004 to 2007) Surveillance Study. J. Clin. Microbiol. 46: 2902-2905 [Abstract] [Full Text]  
  • Ruan, S.-Y., Chu, C.-C., Hsueh, P.-R. (2008). In Vitro Susceptibilities of Invasive Isolates of Candida Species: Rapid Increase in Rates of Fluconazole Susceptible-Dose Dependent Candida glabrata Isolates. Antimicrob. Agents Chemother. 52: 2919-2922 [Abstract] [Full Text]  
  • Pfaller, M. A., Diekema, D. J., Ostrosky-Zeichner, L., Rex, J. H., Alexander, B. D., Andes, D., Brown, S. D., Chaturvedi, V., Ghannoum, M. A., Knapp, C. C., Sheehan, D. J., Walsh, T. J. (2008). Correlation of MIC with Outcome for Candida Species Tested against Caspofungin, Anidulafungin, and Micafungin: Analysis and Proposal for Interpretive MIC Breakpoints. J. Clin. Microbiol. 46: 2620-2629 [Abstract] [Full Text]  
  • Guinea, J., Pelaez, T., Recio, S., Torres-Narbona, M., Bouza, E. (2008). In Vitro Antifungal Activities of Isavuconazole (BAL4815), Voriconazole, and Fluconazole against 1,007 Isolates of Zygomycete, Candida, Aspergillus, Fusarium, and Scedosporium Species. Antimicrob. Agents Chemother. 52: 1396-1400 [Abstract] [Full Text]  
  • Pfaller, M. A., Diekema, D. J., Gibbs, D. L., Newell, V. A., Ng, K. P., Colombo, A., Finquelievich, J., Barnes, R., Wadula, J., the Global Antifungal Surveillance Group, (2008). Geographic and Temporal Trends in Isolation and Antifungal Susceptibility of Candida parapsilosis: a Global Assessment from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005. J. Clin. Microbiol. 46: 842-849 [Abstract] [Full Text]  
  • Espinel-Ingroff, A., Johnson, E., Hockey, H., Troke, P. (2008). Activities of voriconazole, itraconazole and amphotericin B in vitro against 590 moulds from 323 patients in the voriconazole Phase III clinical studies. J Antimicrob Chemother 61: 616-620 [Abstract] [Full Text]  
  • Andes, D., Diekema, D. J., Pfaller, M. A., Prince, R. A., Marchillo, K., Ashbeck, J., Hou, J. (2008). In Vivo Pharmacodynamic Characterization of Anidulafungin in a Neutropenic Murine Candidiasis Model. Antimicrob. Agents Chemother. 52: 539-550 [Abstract] [Full Text]  
  • Pfaller, M. A., Diekema, D. J., Gibbs, D. L., Newell, V. A., Nagy, E., Dobiasova, S., Rinaldi, M., Barton, R., Veselov, A., the Global Antifungal Surveillance Group, (2008). Candida krusei, a Multidrug-Resistant Opportunistic Fungal Pathogen: Geographic and Temporal Trends from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005. J. Clin. Microbiol. 46: 515-521 [Abstract] [Full Text]  
  • Pfaller, M. A., Messer, S. A., Boyken, L., Tendolkar, S., Hollis, R. J., Diekema, D. J. (2008). Selection of a Surrogate Agent (Fluconazole or Voriconazole) for Initial Susceptibility Testing of Posaconazole against Candida spp.: Results from a Global Antifungal Surveillance Program. J. Clin. Microbiol. 46: 551-559 [Abstract] [Full Text]  
  • Johnson, E. M. (2008). Issues in antifungal susceptibility testing. J Antimicrob Chemother 61: i13-i18 [Abstract] [Full Text]  
  • Pfaller, M. A., Diekema, D. J., Procop, G. W., Rinaldi, M. G. (2007). Multicenter Comparison of the VITEK 2 Antifungal Susceptibility Test with the CLSI Broth Microdilution Reference Method for Testing Amphotericin B, Flucytosine, and Voriconazole against Candida spp.. J. Clin. Microbiol. 45: 3522-3528 [Abstract] [Full Text]  
  • Zepelin, M. B.-v., Kunz, L., Ruchel, R., Reichard, U., Weig, M., Gross, U. (2007). Epidemiology and antifungal susceptibilities of Candida spp. to six antifungal agents: results from a surveillance study on fungaemia in Germany from July 2004 to August 2005. J Antimicrob Chemother 60: 424-428 [Abstract] [Full Text]  
  • Li, Y., Nguyen, M. H., Derendorf, H., Cheng, S., Clancy, C. J. (2007). Measurement of Voriconazole Activity against Candida albicans, C. glabrata, and C. parapsilosis Isolates Using Time-Kill Methods Validated by High-Performance Liquid Chromatography. Antimicrob. Agents Chemother. 51: 2985-2987 [Abstract] [Full Text]  
  • Arendrup, M. C., Denning, D. W., Pfaller, M. A., Diekema, D. J., Rex, J. H. (2007). Does One Voriconazole Breakpoint Suit All Candida Species?. J. Clin. Microbiol. 45: 2093-2094 [Full Text]  
  • Pfaller, M. A., Diekema, D. J., Gibbs, D. L., Newell, V. A., Meis, J. F., Gould, I. M., Fu, W., Colombo, A. L., Rodriguez-Noriega, E., and the Global Antifungal Surveillance Group, (2007). Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2005: an 8.5-Year Analysis of Susceptibilities of Candida Species and Other Yeast Species to Fluconazole and Voriconazole Determined by CLSI Standardized Disk Diffusion Testing. J. Clin. Microbiol. 45: 1735-1745 [Abstract] [Full Text]  
  • Tumbarello, M., Posteraro, B., Trecarichi, E. M., Fiori, B., Rossi, M., Porta, R., de Gaetano Donati, K., La Sorda, M., Spanu, T., Fadda, G., Cauda, R., Sanguinetti, M. (2007). Biofilm Production by Candida Species and Inadequate Antifungal Therapy as Predictors of Mortality for Patients with Candidemia. J. Clin. Microbiol. 45: 1843-1850 [Abstract] [Full Text]  
  • Fleck, R., Dietz, A., Hof, H. (2007). In vitro susceptibility of Candida species to five antifungal agents in a German university hospital assessed by the reference broth microdilution method and Etest. J Antimicrob Chemother 59: 767-771 [Abstract] [Full Text]  
  • da Matta, V. L. R., Melhem, M. d. S. C., Colombo, A. L., Moretti, M. L., Rodero, L., de Almeida, G. M. D., Martins, M. d. A., Costa, S. F., Souza Dias, M. B. G., Nucci, M., Levin, A. S. (2007). Antifungal Drug Susceptibility Profile of Pichia anomala Isolates from Patients Presenting with Nosocomial Fungemia. Antimicrob. Agents Chemother. 51: 1573-1576 [Abstract] [Full Text]  
  • Messer, S. A., Diekema, D. J., Hollis, R. J., Boyken, L. B., Tendolkar, S., Kroeger, J., Pfaller, M. A. (2007). Evaluation of Disk Diffusion and Etest Compared to Broth Microdilution for Antifungal Susceptibility Testing of Posaconazole against Clinical Isolates of Filamentous Fungi. J. Clin. Microbiol. 45: 1322-1324 [Abstract] [Full Text]  
  • Alexander, B. D., Byrne, T. C., Smith, K. L., Hanson, K. E., Anstrom, K. J., Perfect, J. R., Reller, L. B. (2007). Comparative Evaluation of Etest and Sensititre YeastOne Panels against the Clinical and Laboratory Standards Institute M27-A2 Reference Broth Microdilution Method for Testing Candida Susceptibility to Seven Antifungal Agents. J. Clin. Microbiol. 45: 698-706 [Abstract] [Full Text]  
  • Pfaller, M. A., Diekema, D. J. (2007). Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem. Clin. Microbiol. Rev. 20: 133-163 [Abstract] [Full Text]  
  • Pfaller, M. A., Messer, S. A., Boyken, L., Rice, C., Tendolkar, S., Hollis, R. J., Diekema, D. J. (2007). Use of Fluconazole as a Surrogate Marker To Predict Susceptibility and Resistance to Voriconazole among 13,338 Clinical Isolates of Candida spp. Tested by Clinical and Laboratory Standards Institute-Recommended Broth Microdilution Methods. J. Clin. Microbiol. 45: 70-75 [Abstract] [Full Text]  
  • Pascual, A., Nieth, V., Calandra, T., Bille, J., Bolay, S., Decosterd, L. A., Buclin, T., Majcherczyk, P. A., Sanglard, D., Marchetti, O. (2007). Variability of Voriconazole Plasma Levels Measured by New High-Performance Liquid Chromatography and Bioassay Methods. Antimicrob. Agents Chemother. 51: 137-143 [Abstract] [Full Text]  
  • Coen, M., Bodkin, J., Power, D., Bubb, W. A., Himmelreich, U., Kuchel, P. W., Sorrell, T. C. (2006). Antifungal Effects on Metabolite Profiles of Medically Important Yeast Species Measured by Nuclear Magnetic Resonance Spectroscopy. Antimicrob. Agents Chemother. 50: 4018-4026 [Abstract] [Full Text]  
  • Pfaller, M. A., Diekema, D. J., Mendez, M., Kibbler, C., Erzsebet, P., Chang, S.-C., Gibbs, D. L., Newell, V. A., the Global Antifungal Surveillance Group, (2006). Candida guilliermondii, an Opportunistic Fungal Pathogen with Decreased Susceptibility to Fluconazole: Geographic and Temporal Trends from the ARTEMIS DISK Antifungal Surveillance Program.. J. Clin. Microbiol. 44: 3551-3556 [Abstract] [Full Text]  
  • Pfaller, M. A., Diekema, D. J., Colombo, A. L., Kibbler, C., Ng, K. P., Gibbs, D. L., Newell, V. A., the Global Antifungal Surveillance Group, (2006). Candida rugosa, an Emerging Fungal Pathogen with Resistance to Azoles: Geographic and Temporal Trends from the ARTEMIS DISK Antifungal Surveillance Program.. J. Clin. Microbiol. 44: 3578-3582 [Abstract] [Full Text]  
  • Posteraro, B., Sanguinetti, M., Fiori, B., La Sorda, M., Spanu, T., Sanglard, D., Fadda, G. (2006). Caspofungin activity against clinical isolates of azole cross-resistant Candida glabrata overexpressing efflux pump genes. J Antimicrob Chemother 58: 458-461 [Abstract] [Full Text]  
  • Pfaller, M. A., Diekema, D. J., Sheehan, D. J. (2006). Interpretive Breakpoints for Fluconazole and Candida Revisited: a Blueprint for the Future of Antifungal Susceptibility Testing. Clin. Microbiol. Rev. 19: 435-447 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»