Drug resistance in human pathogenic fungi

Abstract

Since the therapy of the mycoses, particularly the systemic mycoses, is relatively long-term in nature, emergence of resistance to antifungal drugs during the treatment of period would be of considerable clinical importance. However, most reports of resistance to antifungal agents among human pathogenic fungi indicate that naturally-occurring resistance is very rare, and that the induction of resistant mutants or variants is much more difficult to achieve in vitro and in vivo than with bacteria. As a matter of fact, amphotericin B and some other classic antifungals have not as yet posed a broadly significant problem relative to drug resistance despite their widespread and frequent use. Fungal resistance has thus received little attention, in contrast to the critical importance of bacterial resistance frequently caused by a variety of antibacterial chemotherapeutic agents, until a single exception to this generalization arose with the advent of flucytosine. This new development has aroused great interest in the problem of fungal resistance among the scientists involved with medical mycology. It is generally believed that fungi, like bacteria, are intrinsically capable of developing resistance to antifungal agents. As illustrated by flucytosine, inherently resistant mutants to antifungals occur within sensitive strains of human pathogenic fungi with significant frequency. Given the relatively high degree of such primary resistance, these mutants should develop secondary resistance during therapy, thus resulting in considerable limitations in the clinical usefulness of the antifungals. Virtually, all unsuccessful cases of mycoses treated with some of the recently exploited antifungal drugs, albeit scarce to date, would obviously be attributable to the occurrence of secondary resistance. The exploitation of new antifungal drugs thus requires investigations of their resistance as one of the most important research projects to be undertaken before receiving approval for use on humans. This paper reviews from various aspects the literature on resistance to various classic and novel antifungal agents among human pathogenic fungi. The resistance of some nonpathogenic fungi to these agents will also be described from genetic and biochemical points of view.

Species distribution and antifungal susceptibility profile of Candida spp. bloodstream isolates from Latin American hospitals

“…However, we had one strain of C. albicans and other of C. lusitaniae that were resistant and intermediate, respectively, to 5-FC. Isolates of C. albicans primarily resistant to 5-FC have been identified in different clinical materials by several authors, varying in frequency between 0% and 38% (Iwata 1992, Barchiesi et al 2000. The relationship between resistance to 5-FC in C. albicans and serological type was investigated by Drouhet et al (1975), who reported that the percentage of 5FC-resistant strains isolated from patients in Africa was higher than that recovered from patients in Europe.…”

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

“…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). C. albicans serotype B, found mainly in Africans and among human immunodeficiency virus (HIV)-infected patients with thrush (18,37), is reported to be significantly more resistant (49%) than serotype A strains (11%) (5). These data were derived by nonstandardized testing methods that have been shown to vary by as much as 10,000-fold when used to determine 5FC MICs for Candida spp.…”

Antimicrobial Drug Resistance in Pathogens Causing Nosocomial Infections at a University Hospital in Taiwan, 1981-1999

“…Since 1990, Candida species have continued to be an important cause of nosocomial BSI in the United States, and the proportion (40%-50%) of these infections due to species of Candida other than C. albicans may be increasing ( 12 , 19 , 20 , 31 , 32 ) . Among the species of Candida other than C. albicans, C. glabrata (prone to be resistant to fluconazole) and C. krusei (intrinsically resistant to fluconazole) are of clinical importance 31 , 33 .…”