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 Diekema, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pfaller, M. A.
Right arrow Articles by Diekema, D. J.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, November 2002, p. 3518-3521, Vol. 46, No. 11
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.11.3518-3521.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

In Vitro Activities of 5-Fluorocytosine against 8,803 Clinical Isolates of Candida spp.: Global Assessment of Primary Resistance Using National Committee for Clinical Laboratory Standards Susceptibility Testing Methods

M. A. Pfaller,1,2* S. A. Messer,1 L. Boyken,1 H. Huynh,1 R. J. Hollis,1 and D. J. Diekema1,3

Departments of Pathology,1 Epidemiology,2 Medicine, University of Iowa College of Medicine, and College of Public Health, Iowa City, Iowa 522423

Received 10 May 2002/ Returned for modification 16 July 2002/ Accepted 5 August 2002

We determined the in vitro activity of flucytosine (5-fluorocytosine [5FC]) against 8,803 clinical isolates of Candida spp. (18 species) obtained from more than 200 medical centers worldwide between 1992 and 2001. The MICs were determined by broth microdilution tests performed according to NCCLS guidelines by using RPMI 1640 as the test medium and the following interpretive breakpoints: susceptible (S), <=4 µg/ml; intermediate (I), 8 to 16 µg/ml; resistant (R), >=32 µg/ml. 5FC was very active against the 8,803 Candida isolates (MIC90, 1 µg/ml), 95% S. A total of 99 to 100% of C. glabrata (MIC90, 0.12 µg/ml), C. parapsilosis (MIC90, 0.25 µg/ml), C. dubliniensis (MIC90, 0.12 µg/ml), C. guilliermondii (MIC90, 0.5 µg/ml), and C. kefyr (MIC90, 1 µg/ml) were susceptible to 5FC at the NCCLS breakpoint. C. albicans (MIC90, 1 µg/ml; 97% S) and C. tropicalis (MIC90, 1 µg/ml; 92% S) were only slightly less susceptible. In contrast, C. krusei was the least susceptible species: 5% S; MIC90, 32 µg/ml. Primary resistance to 5FC is very uncommon among Candida spp. (95% S, 2% I, and 3% R), with the exception of C. krusei (5% S, 67% I, and 28% R). The in vitro activity of 5FC, combined with previous data demonstrating a prolonged post-antifungal effect (2.5 to 4 h) and concentration-independent activity (optimized at 4x MIC), suggest that 5FC could be used in lower doses to reduce host toxicity while maintaining antifungal efficacy.

* 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.

Antimicrobial Agents and Chemotherapy, November 2002, p. 3518-3521, Vol. 46, No. 11
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.11.3518-3521.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • 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., 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]  
  • Hope, W. W., Warn, P. A., Sharp, A., Reed, P., Keevil, B., Louie, A., Walsh, T. J., Denning, D. W., Drusano, G. L. (2007). Optimization of the Dosage of Flucytosine in Combination with Amphotericin B for Disseminated Candidiasis: a Pharmacodynamic Rationale for Reduced Dosing. Antimicrob. Agents Chemother. 51: 3760-3762 [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]  
  • Mokaddas, E. M., Al-Sweih, N. A., Khan, Z. U. (2007). Species distribution and antifungal susceptibility of Candida bloodstream isolates in Kuwait: a 10-year study. J Med Microbiol 56: 255-259 [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]  
  • Bergner, R., Hoffmann, M., Riedel, K.-D., Mikus, G., Henrich, D. M., Haefeli, W. E., Uppenkamp, M., Walter-Sack, I. (2006). Fluconazole dosing in continuous veno-venous haemofiltration (CVVHF): need for a high daily dose of 800 mg. Nephrol Dial Transplant 21: 1019-1023 [Abstract] [Full Text]  
  • Pfaller, M. A., Boyken, L., Messer, S. A., Tendolkar, S., Hollis, R. J., Diekema, D. J. (2005). Comparison of Results of Voriconazole Disk Diffusion Testing for Candida Species with Results from a Central Reference Laboratory in the ARTEMIS Global Antifungal Surveillance Program. J. Clin. Microbiol. 43: 5208-5213 [Abstract] [Full Text]  
  • Al Mosaid, A., Sullivan, D. J., Polacheck, I., Shaheen, F. A., Soliman, O., Al Hedaithy, S., Al Thawad, S., Kabadaya, M., Coleman, D. C. (2005). Novel 5-Flucytosine-Resistant Clade of Candida dubliniensis from Saudi Arabia and Egypt Identified by Cd25 Fingerprinting. J. Clin. Microbiol. 43: 4026-4036 [Abstract] [Full Text]  
  • Majoros, L., Kardos, G., Feiszt, P., Szabo, B. (2005). Efficacy of amphotericin B and flucytosine against fluconazole-resistant Candida inconspicua clinical isolates. J Antimicrob Chemother 56: 253-254 [Full Text]  
  • Cuenca-Estrella, M., Rodriguez, D., Almirante, B., Morgan, J., Planes, A. M., Almela, M., Mensa, J., Sanchez, F., Ayats, J., Gimenez, M., Salvado, M., Warnock, D. W., Pahissa, A., Rodriguez-Tudela, J. L., on behalf of the Barcelona Candidemia Project Stud, (2005). In vitro susceptibilities of bloodstream isolates of Candida species to six antifungal agents: results from a population-based active surveillance programme, Barcelona, Spain, 2002-2003. J Antimicrob Chemother 55: 194-199 [Abstract] [Full Text]  
  • Hope, W. W., Tabernero, L., Denning, D. W., Anderson, M. J. (2004). Molecular Mechanisms of Primary Resistance to Flucytosine in Candida albicans. Antimicrob. Agents Chemother. 48: 4377-4386 [Abstract] [Full Text]  
  • Pfaller, M. A., Diekema, D. J. (2004). Rare and Emerging Opportunistic Fungal Pathogens: Concern for Resistance beyond Candida albicans and Aspergillus fumigatus. J. Clin. Microbiol. 42: 4419-4431 [Full Text]  
  • Ahmad, S., Khan, Z., Mokaddas, E., Khan, Z. U. (2004). Isolation and molecular identification of Candida dubliniensis from non-human immunodeficiency virus-infected patients in Kuwait. J Med Microbiol 53: 633-637 [Abstract] [Full Text]  
  • Dodgson, A. R., Dodgson, K. J., Pujol, C., Pfaller, M. A., Soll, D. R. (2004). Clade-Specific Flucytosine Resistance Is Due to a Single Nucleotide Change in the FUR1 Gene of Candida albicans. Antimicrob. Agents Chemother. 48: 2223-2227 [Abstract] [Full Text]  
  • Hajjeh, R. A., Sofair, A. N., Harrison, L. H., Lyon, G. M., Arthington-Skaggs, B. A., Mirza, S. A., Phelan, M., Morgan, J., Lee-Yang, W., Ciblak, M. A., Benjamin, L. E., Thomson Sanza, L., Huie, S., Yeo, S. F., Brandt, M. E., Warnock, D. W. (2004). Incidence of Bloodstream Infections Due to Candida Species and In Vitro Susceptibilities of Isolates Collected from 1998 to 2000 in a Population-Based Active Surveillance Program. J. Clin. Microbiol. 42: 1519-1527 [Abstract] [Full Text]  
  • Favel, A., Michel-Nguyen, A., Datry, A., Challier, S., Leclerc, F., Chastin, C., Fallague, K., Regli, P. (2004). Susceptibility of clinical isolates of Candida lusitaniae to five systemic antifungal agents. J Antimicrob Chemother 53: 526-529 [Abstract] [Full Text]  
  • Pujol, C., Pfaller, M. A., Soll, D. R. (2004). Flucytosine Resistance Is Restricted to a Single Genetic Clade of Candida albicans. Antimicrob. Agents Chemother. 48: 262-266 [Abstract] [Full Text]  
  • Pfaller, M. A., Messer, S. A., Boyken, L., Rice, C., Tendolkar, S., Hollis, R. J., Diekema, D. J. (2003). Caspofungin Activity against Clinical Isolates of Fluconazole-Resistant Candida. J. Clin. Microbiol. 41: 5729-5731 [Abstract] [Full Text]  
  • Ostrosky-Zeichner, L., Rex, J. H., Pappas, P. G., Hamill, R. J., Larsen, R. A., Horowitz, H. W., Powderly, W. G., Hyslop, N., Kauffman, C. A., Cleary, J., Mangino, J. E., Lee, J. (2003). Antifungal Susceptibility Survey of 2,000 Bloodstream Candida Isolates in the United States. Antimicrob. Agents Chemother. 47: 3149-3154 [Abstract] [Full Text]  
  • Tortorano, A. M., Rigoni, A. L., Biraghi, E., Prigitano, A., Viviani, M. A., the FIMUA-ECMM candidaemia study group, (2003). The European Confederation of Medical Mycology ECMM) survey of candidaemia in Italy: antifungal susceptibility patterns of 261 non-albicans Candida isolates from blood. J Antimicrob Chemother 52: 679-682 [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»