Primary resistance to flucytosine among clinical isolates of Candida spp.

F. Barchiesi*, D. Arzeni, F. Caselli and G. Scalise

Istituto di Malattie Infettive e Medicina Pubblica, Università degli Studi di Ancona, Ospedale Umberto I, largo Cappelli 1, 60121 Ancona, Italy

Sir,

Fungal infections caused by common new and emerging yeast and mould pathogens are increasing in frequency, largely as a result of greater numbers of immunocompromised patients.1 Azole drugs are commonly used as treatment for patients with superficial and mild to moderate systemic mycoses, but 5-flucytosine (5FC) is administered, almost always in combination with amphotericin B, to most of those with severe systemic yeast and mould infections.2,3 The present study was undertaken to determine the susceptibilities to 5FC of 179 Candida spp. strains.

The isolates studied included 97 strains of Candida albicans, 30 of Candida tropicalis, 22 each of Candida parapsilosis and Candida glabrata and eight of Candida krusei. The strains were non-replicate and none of the patients from whom they were isolated had recently received antifungal therapy. Eighty-one strains (52 C. albicans, 22 C. glabrata and eight C. krusei) were isolated from human immunodeficiency virus (HIV)-infected patients, and the remaining 98 strains were recovered from HIV-negative patients. Susceptibility to 5FC was determined by a microbroth dilution method recommended by the National Committee for Clinical Laboratory Standards (NCCLS).4 5FC was tested at concentrations ranging from 0.125 to 64 mg/L and C. albicans ATCC 76615 and C. krusei ATCC 6258 were used as controls. Each strain was assigned to a susceptibility category according to the following MIC breakpoints recommended by the NCCLS:4 susceptible <=4 mg/L; intermediate susceptibility 8–16 mg/L; and resistant >=32 mg/L.

The results are summarized in the TableGo. Overall, 173/ 179 (97%) of the isolates were susceptible to 5FC, but 2/179 (1%) and 4/179 (2%) were intermediately susceptible and resistant, respectively. There was no statistically significant difference between isolates recovered from HIV-positive and HIV-negative patients in terms of susceptibility to 5FC (Mann–Whitney U test; P = 0.16).


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Table. In vitro susceptibilities of 179 clinical isolates of Candida spp. to 5FC
 
Although we have evaluated a relatively small number of clinical isolates, we have shown that 5FC possesses excellent in vitro activity against the most common Candida spp. The relationship between resistance to 5FC in C. albicans and serological type has been investigated by Drouhet et al., who reported that the percentage of 5FC-resistant strains isolated from patients in Africa was higher than that recovered from patients in Europe.5 They suggested that the high incidence of resistance (85%) among the former strains was related to the predominance of serotype B isolates, which are recovered more frequently from black people, in contrast to the low incidence of resistance (1%) among serotype A isolates, which are encountered predominantly in white people.5,6 The absence in this study of C. albicans strains resistant to 5FC on primary isolation can be explained by the fact that all of our isolates belonged to serotype A.

We identified two species, C. glabrata and C. krusei, whose isolates exhibited reduced susceptibility to 5FC. This observation suggests that the use of 5FC as treatment for patients with fungal infections caused by strains belonging to these species should be avoided unless they are known to be susceptible. To our knowledge this is the first report describing the patterns of susceptibility to 5FC among common clinical yeast isolates based on NCCLS interpretative breakpoints.

Notes

J Antimicrob Chemother 2000; 45: 408–409

* Corresponding author. Tel: +39-71-596-3467; Fax: +39-71-596-3468; E-mail: cmalinf{at}popcsi.unian.it Back

References

1 . Anaissie, E. J., Bodey, G. P. & Rinaldi, M. G. (1989). Emerging fungal pathogens. European Journal of Clinical Microbiology and Infectious Diseases 8, 323–30.[ISI][Medline]

2 . Rex, J. H., Pfaller, M. A., Galgiani, J. N., Bartlett, M. S., Espinel-Ingroff, A. & Ghannoum, M. A. (1997). Development of interpretative breakpoints for antifungal susceptibility testing: conceptual framework and analysis of in vitro–in vivo correlation data for fluconazole, itraconazole, and Candida infections. Clinical Infectious Diseases 24, 235–47.[ISI][Medline]

3 . Grillot, R., Slavov, R., Grayal, J. P., Buissière, J. & Ambroise-Thomas, P. (1975). Sensibilité de 250 souches de leuvres à la flucytosine et à l’amphotéricin B. Bullettin Societé Française Mycologie Medicine 4, 173–6.

4 . National Committee for Clinical Laboratory Standards. (1997). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts: Approved Standard M27-A. NCCLS, Wayne, PA.

5 . Drouhet, E., Mercier-Soucy, L. & Montplaisir, S. (1975). Sensitivity and resistance of pathogenic yeasts to 5-fluoropyrimidines. I. Relation between the phenotypes of resistance to 5-fluorocytosine, the serotype of Candida albicans and the ecology of various species of Candida of human origin. Annales de Microbiologie (Paris) 126B, 25–39.

6 . Iwata, K. (1992). Drug resistance in human pathogenic fungi. European Journal of Epidemiology 8, 407–21.[ISI][Medline]