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; S A Messer; L Boyken; H Huynh; R J Hollis; D J Diekema

doi:10.1128/AAC.46.11.3518-3521.2002

Back

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

Journal article

Open access

Peer reviewed

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, S A Messer, L Boyken, H Huynh, R J Hollis and D J Diekema

Antimicrobial agents and chemotherapy, Vol.46(11), pp.3518-3521

11/2002

DOI: 10.1128/AAC.46.11.3518-3521.2002

PMCID: PMC128740

PMID: 12384359

Files and links (1)

url

https://doi.org/10.1128/AAC.46.11.3518-3521.2002View

Published (Version of record) Open Access

Abstract

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), < or =4 micro g/ml; intermediate (I), 8 to 16 micro g/ml; resistant (R), > or =32 micro g/ml. 5FC was very active against the 8,803 Candida isolates (MIC(90), 1 micro g/ml), 95% S. A total of 99 to 100% of C. glabrata (MIC(90), 0.12 micro g/ml), C. parapsilosis (MIC(90), 0.25 micro g/ml), C. dubliniensis (MIC(90), 0.12 micro g/ml), C. guilliermondii (MIC(90), 0.5 micro g/ml), and C. kefyr (MIC(90), 1 micro g/ml) were susceptible to 5FC at the NCCLS breakpoint. C. albicans (MIC(90), 1 micro g/ml; 97% S) and C. tropicalis (MIC(90), 1 micro g/ml; 92% S) were only slightly less susceptible. In contrast, C. krusei was the least susceptible species: 5% S; MIC(90), 32 micro g/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.

Antifungal Agents - pharmacology

Microbial Sensitivity Tests - standards

Humans

Candida - drug effects

Flucytosine - pharmacology

Candidiasis - microbiology

Drug Resistance, Fungal

Details

Title: Subtitle: 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
Creators: M A Pfaller - Departments of Pathology. Epidemiology. Medicine, University of Iowa College of Medicine, and College of Public Health, Iowa City, Iowa 52242, USA. michael-pfaller@uiowa.edu
S A Messer
L Boyken
H Huynh
R J Hollis
D J Diekema
Resource Type: Journal article
Publication Details: Antimicrobial agents and chemotherapy, Vol.46(11), pp.3518-3521
DOI: 10.1128/AAC.46.11.3518-3521.2002
PMID: 12384359
PMCID: PMC128740
NLM abbreviation: Antimicrob Agents Chemother
ISSN: 0066-4804
eISSN: 1098-6596
Publisher: United States
Language: English
Date published: 11/2002
Academic Unit: Infectious Diseases; Epidemiology; Pathology; Internal Medicine
Record Identifier: 9983986363202771

Metrics

14 Record Views

87 Times Cited - Web of Science