Susceptibility to 5-fluorocytosine and prevalence of serotype in 402 Candida albicans isolates from the United States

Abstract

Candida albicans isolates from 402 patients with no prior history of treatment with 5-fluorocytosine were collected at five medical centers from different areas of the United States. Isolates could be separated into four groups based on their minimum inhibitory concentrations (MICs) to 5-fluorocytosine. Group I isolates (60%) had MICs less than or equal to 12.5 micrograms/ml after 7 days, whereas groups II (22%), III (14%), and IV (4%) demonstrated MICs greater than 12.5 micrograms/ml on days 7, 2, and 1, respectively. Serotypes A and B accounted for 50.7 and 49.3%, respectively, of the 398 isolates typed. Serotype B was less prevalent in group I (26%), but predominated in the more resistant groups, groups II (85%), III (86%), and IV (53%). The common practice of identifying as "resistant" those isolates with MICs greater than 12.5 micrograms/ml after 48 h of incubation would yield a resistance rate in the United States of 11.5 to 15.5% in four centers and 35% in the fifth. Although serotype B and small agar disk diffusion zone sizes correlated with poor 5-fluorocytosine susceptibility, their ability to predict tube dilution MICs was limited. The true predictive value of such tests awaits correlation with in vivo studies.

Susceptibility testing of fungi: current status of the standardization process

“…In the study by Fromtling et al (11), some of the C. neofornans strains were selected because of their previously recognized flucytosine resistance and were identified as resistant by the proposed method. In addition, some of the Candida strains demonstrated high-level resistance, as would be expected from previous studies of the prevalence of flucytosine resistance (27).…”

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

“…has been derived from studies conducted in the 1970s and 1980s (3,5,8,31,34) prior to the standardization of in vitro testing methods. Primary resistance among C. albicans has been reported to range from 6.5% in Europe to 33% in the United States, with an overall prevalence of 7 to 9% (3,31).…”

“…Although not used as monotherapy, 5FC may be a useful adjunct to amphotericin B or azoles in the treatment of hematogenous candidiasis (11,29,38). Despite a general consensus regarding the clinical efficacy of 5FC when used in combination with amphotericin B (11), clinicians are often hesitant to use 5FC due to concerns about toxicity (13,39) and either primary or secondary resistance (8,22,34,35,39). Although primary resistance to 5FC is stated to occur among 10 to 15% of Candida albicans isolates and even higher among other Candida species (31), there is very little recent data explicitly addressing this issue by using the standardized National Committee for Clinical Laboratory Standards (NCCLS) antifungal susceptibility testing method (24) against a large geographically diverse collection of contemporary clinical isolates of Candida spp.…”

Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem

“…Although not used as monotherapy, 5FC may be a useful adjunct to other systemically active antifungal agents in the treatment of hematogenous candidiasis (68, 189, 293). Despite a general consensus regarding the clinical efficacy of 5FC when used in combination with other agents (68), clinicians are often hesitant to use this antifungal agent due to concerns about toxicity (78,297) and either primary or secondary resistance (155,280,281,297). The older literature has stated that primary resistance to 5FC occurred among 10% to 15% of C. albicans isolates and was even higher among other species (265,280).…”

“…Despite a general consensus regarding the clinical efficacy of 5FC when used in combination with other agents (68), clinicians are often hesitant to use this antifungal agent due to concerns about toxicity (78,297) and either primary or secondary resistance (155,280,281,297). The older literature has stated that primary resistance to 5FC occurred among 10% to 15% of C. albicans isolates and was even higher among other species (265,280). However, more-recent studies using CLSI-based methods strongly refute these statements (17,46,104,206).…”