Multicenter Brazilian study of oral Candida species isolated from AIDS patients

Oropharyngeal candidiasis continues to be considered the most common opportunistic disease in Aids patients. This study was designed to investigate species distribution, serotype and antifungal susceptibility profile among Candida spp. isolated from the oral cavity of Aids patients recruited from six Brazilian university centers. Oral swabs from 130 Aids patients were plated onto CHROMagar Candida medium and 142 isolates were recovered. Yeast isolates were identified by classical methods and serotyped using the Candida Check or target system-Iatron. Antifungal susceptibility testing was performed according to the NCCLS microbroth assay. C. albicans was the most frequently isolated species (91%), and 70% of the isolates belonged to serotype A. We detected 12 episodes of co-infection (9%), including co-infection with both serotypes of C. albicans. Non-albicans species were isolated from 12 episodes, 50% of them exhibited DDS or resistance to azoles. Otherwise, only 8 out 130 isolates of C. albicans exhibited DDS or resistance to azoles. Brazilian Aids patients are infected mainly by C. albicans serotype A, most of them susceptible to all antifungal drugs.     

In vitro antifungal resistance in Candida albicans from HIV-infected patients with and without oral candidosis.

The main purpose of this study has been to determine the in vitro antifungal susceptibility of clinical isolates from HIV-infected or AIDS patients, depending on the presence of oral candidosis. The oral cavity of 307 HIV-infected or AIDS patients was examined and an oral swab was cultured on Sabouraud glucose agar and studied by conventional mycological methods. In vitro antifungal susceptibility to amphotericin B, nystatin, fluconazole, itraconazole and ketoconazole was tested by disk diffusion with Neo-Sensitabs tablets (Rosco Diagnostica, Dinamarca). One hundred and thirty five Candida albicans isolates (91 serotype A, 38 serotype B, three C. albicans variety stellatoidea and three untyped isolates), three Candida krusei and two Candida glabrata were obtained. All the isolates were susceptible to nystatin and amphotericin B. However, 7.9% isolates were resistant to fluconazole and 2.9% isolates were resistant to ketoconazole or itraconazole. Nearly all C. krusei and C. glabrata isolates, 31% patients with candidosis and 20% Candida-colonized patients showed decreased susceptibility to azoles. This study shows that polyenes had a great in vitro efficacy against clinical isolates from HIV-infected patients and that in vitro resistance to azoles is not as high as observed in other countries.     

Prevalence of Candida albican serotypes in blood isolates in Chile, and first report of Candida dubliniensis candidemia

Our main goal was to determine the prevalence of C. albicans serotypes isolates from blood cultures and identify the presence of C. dubliniensis. We studied 47 strains identified as C. albicans by conventional methods, 28 were isolated from children and 19 from adult patients. The strains were re-identified by standard methods and phenotypic screening as xylose assimilation and growth at 42 degrees C. API ID 32C (bioMérieux) was employed with the C. dubliniensis suspected strains and confirmation was made by molecular fingerprinting using random amplified polymorphic DNA (RAPD). The C. albicans serotype was determined by agglutination with antiserum anti-antigen 6 from cell wall (Candida Check, Iatron Inc., Japan) and the in vitro susceptibilities were evaluated by a microdilution method. From 47 strains, 46 were confirmed as C. albicans, 31 of them (67%) were serotype A. Adult patients presented a high prevalence of serotype A (95%) and children presented a frequency of 52% of the serotype B (p<0.05). We confirmed the identification of C. dubliniensis in one strain isolated from an infant. All serotype B strains were susceptible to fluconazole, itraconazole and amphotericin B. On the other hand, 3% and 6% of serotype A strains were "susceptible dose dependent" to fluconazole and itraconazole, respectively. C. albicans serotype A was predominant in adult candidemia and its distribution was homogenous in children patients. All strains were highly susceptible to antifungals. We report here the first case of C. dubliniensis candidemia in South America.     

The presence of fluconazole-resistant Candida dubliniensis strains among Candida albicans isolates from immunocompromised or otherwise debilitated HIV-negative Turkish patients

The newly described species Candida dubliniensis phenotipically resembles Candida albicans in many respects and so it could be easily misidentified. The present study aimed at determining the frequency at which this new Candida species was not recognized in the authors' university hospital clinical laboratory and to assess antifungal susceptibility. In this study, six identification methods based on significant phenotypic characteristics each proposed as reliable tests applicable in mycology laboratories for the differentiation of the two species were performed together to assess the clinical strains that were initially identified as C. albicans. Only the isolates which have had the parallel results in all methods were assessed as C. dubliniensis. One hundred and twenty-nine C. albicans strains isolated from deep mycosis suspected patients were further examined. Three of 129 C. albicans (2 from oral cavity, 1 from sputum) were reidentified as C. dubliniensis. One of the strains isolated from oral cavity and that from the sputum were obtained at two months intervals from the same patient with acute myeloid leukemia, while the other oral cavity strain was obtained from a patient who had previously been irradiated for a laryngeal malignancy. Isolates were all susceptible in vitro to amphotericin B, with the MIC range 0.125 to 0.5 &mgr;g/ml, resistant to fluconazole, with MICs >/=64 &mgr;g/ml, and resistant to ketoconazole, with MICs >/=16 &mgr;g/ml, dose-dependent to itraconazole with a MIC range 0.25-0.5 &mgr;g/ml, and susceptible to flucytosine, with a MIC range 1-4 &mgr;g/ml.     

In vitro resistance to fluconazole and itraconazole in clinical isolates of Candida spp and Cryptococcus neoformans

An in vitro susceptibility testing of 181 strains of six species of Candida and 21 strains of Cryptococcus neoformans was carried out in order to investigate the resistance to new antifungal drugs. We have studied clinical isolates from 200 different patients of Hospital del Mar (Barcelona) and Hospital La Inmaculada (Almería). An agar diffusion method (NeoSensitabs, Rosco, Taastrup, Denmark), was employed with fluconazole, itraconazole, and reference drugs amphotericin B, flucytosine, tioconazole and ketoconazole. A high level of susceptibility was found for amphotericin B in C. neoformans strains while 19% of them were resistant to flucytosine. All the strains of C. neoformans and Candida guilliermondii were susceptible to the new azoles derivatives and also Candida parapsilosis and Candida albicans had a great susceptibility to this antifungals. A greater level of resistance was found for Candida krusei, Candida tropicalis and Candida glabrata to fluconazole, itraconazole and ketoconazole, but resistance to fluconazole and itraconazole is not always linked because ten resistant strains for fluconazole were susceptible to itraconazole, and two other resistant to itraconazole were susceptible to fluconazole.     

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

From March 1999 to March 2000, we conducted a prospective multicenter study of candidemia involving five tertiary care hospitals from four countries in Latin America. Yeast isolates were identified by classical methods and the antifungal susceptibility profile was determined according to the National Committee for Clinical Laboratory Standards microbroth assay method. During a 12 month-period we were able to collect a total of 103 bloodstream isolates of Candida spp. C. albicans was the most frequently isolated species accounting for 42% of all isolates. Non-albicans Candida species strains accounted for 58% of all episodes of candidemia and were mostly represented by C. tropicalis (24.2%) and C. parapsilosis (21.3%). It is noteworthy that we were able to identify two cases of C. lusitaniae from different institutions. In our casuistic, non-albicans Candida species isolates related to candidemic episodes were susceptible to fluconazole. Continuously surveillance programs are needed in order to identify possible changes in the species distribution and antifungal susceptibility patterns of yeasts that may occurs after increasing the use of azoles in Latin American hospitals.     

Point prevalence, microbiology and antifungal susceptibility patterns of oral Candida isolates colonizing or infecting Mexican HIV/AIDS patients and healthy persons

We have conducted a longitudinal study over a 3-year period to address the point prevalence, microbiological characteristics and antifungal susceptibility patterns of yeast isolates colonizing or infecting the oral cavities of 111 HIV-infected (51 adults, 60 children) and 201 non HIV-infected (109 adults, 92 children) Mexican persons. Regarding the epidemiology of oral candidiasis, Candida albicans was the most frequent species isolated. Seventy-one out of 85 isolates from colonized persons were C. albicans (83.5%), 27 isolates of them were from HIV-infected children and 44 from non HIV-infected patients. Sixty-two isolates belonged to serotype A which was the most prevalent serotype of C. albicans. Non-albicans species (Candida glabrata, Candida tropicalis and Candida parapsilosis, and Saccharomyces cerevisiae) were isolated from 16.5% of colonized patients and from 38.5% patients with candidiasis or Candida-related lesions. There were nine episodes of infection or colonization by at least 2 different yeast species. In the case of HIV/AIDS patients, it was determined that yeast carriage was not associated with the number of CD4+ cells or the viral load, but HAART reduced the prevalence of oral candidiasis. Overall, most patients harbored strains in vitro susceptible to fluconazole, however 10.8% of the yeasts were resistant to one or more azole antifungal agents and 29% were intermediate susceptible to them. On the contrary, 5-fluorocytosine was very active against all isolates tested, and amphotericin B was active against 97.9% of them.     

In vitro antifungal susceptibility of clinical isolates of Candida spp. obtained from patients with different predisposing factors to candidosis

The increase in the number of infections caused by Candida species and the consequent use of antifungal agents favours an increase of resistant isolates. The aim of this study was to evaluate the antifungal susceptibility of Candida spp. isolates from patients with different systemic predisposing factors to candidosis. Seventy-nine Candida spp. isolates were assayed for in vitro susceptibility to amphotericin B, fluconazole, 5-flucytosine and itraconazole using the technique proposed by the Clinical and Laboratory Standards Institute (CLSI). Four C. albicans, one C. guilliermondii, four C. parapsilosis and two C. tropicalis isolates were resistant to amphotericin B. Only two isolate was resistant to itraconazole. All the isolates tested were susceptible to fluconazole and flucytosine. It could be concluded that the most efficient drugs against the Candida isolates studied were fluconazole and flucytosine and that all of the antifungal agents used in this study were effective against the Candida spp. isolates tested.     

Multicenter survey of in vitro antifungal resistance in yeasts of medical importance isolated from Spanish patients

Twelve Spanish laboratories collected 325 yeast clinical isolates during a 30 day's period, among them 224 Candida albicans, 30 Candida glabrata, and 27 Candida parapsilosis. In vitro antifungal susceptibility to amphotericin B, ketoconazole, fluconazole and itraconazole was determined by an agar diffusion test (Neo-Sensitabs, Rosco, Denmark). All the isolates tested were susceptible in vitroto amphotericin B and nearly all (97.2%) to itraconazole. In vitrosusceptibility to fluconazole and ketoconazole was high (90.2% and 91.4% of isolates, respectively) but showed variations depending on the species tested. Resistance to fluconazole and ketoconazole was low in C. albicans (4% and 3%, respectively), but 30% of Candida guilliermondii and 36% of C. glabrata isolates were resistant to fluconazole. Ketoconazole resistance was observed in 40% of C. glabrata, and 17% of Candida tropicalis. Resistance to antifungal drugs is very low in Spain and it is related to non-C. albicans isolates.     

ATB FUNGUS2法在念珠菌属和新生隐球菌抗真菌药敏试验中应用的评价

目的评价ATBFUNGUS2半固体培养基法在测定念珠菌属和新生隐球菌对4种常用抗真菌药物敏感性中的应用价值。方法利用CLSIM27．A2微量液基稀释法和ATBFUNGUS2法同时测定131株念珠菌和20株新生隐球菌对两性霉素B（AmB）、氟康唑（FLC）、氟胞嘧啶（5-Fc）和伊曲康唑（ITC）的敏感性。结果①两种方法对于AmB、5-FC、FLC和ITC的一致性分别为98％、89．4％、78．8％和78．1％;②所有受试菌株中两种方法的一致性为80％,但ATBFUNGUS2法将2／5株M27-A2法检查为FLC耐药的白念珠菌判断为敏感或剂量依赖,将8／10株M27-A2法检查为FLC剂量依赖的白念珠菌判断为敏感或耐药。③ATBFUNGUS2法中AmB的MIC值判读范围偏高,以致于实际工作中不能读出准确的值。结论ATBFUNGUS2半固体培养基法在测定念珠菌属和新生隐球菌对4种常用抗真菌药物的敏感性时不失为简单、快速而且重复性好的方法。     

In vitro activity of essential oils extracted from plants used as spices against fluconazole-resistant and fluconazole-susceptible Candida spp

In the present study, the antifungal activity of selected essential oils obtained from plants used as spices was evaluated against both fluconazole-resistant and fluconazole-susceptible Candida spp. The Candida species studied were Candida albicans, Candida dubliniensis, Candida tropicalis, Candida glabrata, and Candida krusei. For comparison purposes, they were arranged in groups as C. albicans, C. dubliniensis, and Candida non-albicans. The essential oils were obtained from Cinnamomum zeylanicum Breyn, Lippia graveolens HBK, Ocimum basilicum L., Origanum vulgare L., Rosmarinus officinalis L., Salvia officinalis L., Thymus vulgaris L., and Zingiber officinale. The susceptibility tests were based on the M27-A2 methodology. The chemical composition of the essential oils was obtained by gas chromatography-mass spectroscopy and by retention indices. The results showed that cinnamon, Mexican oregano, oregano, thyme, and ginger essential oils have different levels of antifungal activity. Oregano and ginger essential oils were found to be the most and the least efficient, respectively. The main finding was that the susceptibilities of fluconazole-resistant C. albicans, C. dubliniensis, and Candida non-albicans to Mexican oregano, oregano, thyme, and ginger essential oils were higher than those of the fluconazole-susceptible yeasts (P<0.05). In contrast, fluconazole-resistant C. albicans and Candida non-albicans were less susceptible to cinnamon essential oil than their fluconazole-susceptible counterparts (P<0.05). A relationship between the yeasts' susceptibilities and the chemical composition of the essential oils studied was apparent when these 2 parameters were compared. Finally, basil, rosemary, and sage essential oils did not show antifungal activity against Candida isolates at the tested concentrations.     

Susceptibility profile of vaginal yeast isolates from Brazil

Vaginal specimens for culture were obtained from two hundred and five immunocompetent, non-hospitalized patients selected among all women attending the Gynecology and Obstetric Ambulatory Clinic of the University of Espírito Santo, Brazil, during a 2-year period (From 1998 to 1999). Patients were checked for signs and symptoms of vulvovaginitis and previous use of topical and systemic antifungal drugs. Yeast isolates were identified by classical methods and the antifungal susceptibility profile was determined according to NCCLS microbroth assay. The prevalence of vaginal yeast isolates from asymptomatic women was 25% (30/121) and 60% (50/84) among patients with symptoms of vulvovaginitis. Candida albicans was the most frequently isolated species in both groups (46% and 90%, respectively), followed by C. glabrata (13% and 6%, respectively). All isolates were susceptible to amphotericin B. Only ten isolates had dose dependent susceptibility (DDS) or resistance to azoles; and seven of these were non-albicans species. Based on our results we suggest that species identification and antifungal susceptibility testing need not be routinely performed in immunocompetent women, and may be reasonable only for the minority of patients with complicated vulvovaginal candidiasis that fail to respond to therapy.     

男性尿道炎和包皮龟头炎致病真菌的分布与药敏分析

目的了解男性念珠菌性尿道炎和包皮龟头炎的菌群分布及体外抗真菌药敏试验情况。方法菌株分离均来自复旦大学附属华山医院皮肤性病门诊临床症状轻重不一、真菌直接镜检阳性的61例患者。用科玛嘉念珠菌显色培养基及API 20C AUX鉴定系统进行菌种鉴定;采用CLSIM27-A2肉汤微量稀释法对61株临床分离念珠菌作了氟康唑、两性霉素B、氟胞嘧啶、伊曲康唑、伏立康唑、特比萘芬6种抗真菌药物敏感性测定。结果对培养阳性的61例菌株,通过科玛嘉念珠菌显色培养基及API 20C AUX鉴定系统作菌种鉴定,白念珠菌52例（85.2%）,近平滑念珠菌3例,光滑念珠菌2例,热带念珠菌2例,季也蒙念珠菌1例,克柔念珠菌1例。对52株白念珠菌的药敏试验显示氟康唑98.1%敏感,1.9%剂量依赖性敏感;氟胞嘧啶96.2%敏感,3.8%耐药;伊曲康唑44.2%敏感,40.5%剂量依赖性敏感,15.3%耐药;伏立康唑84.6%敏感,15.4%耐药;两性霉素B全部敏感;特比萘芬的MIC范围为1-64μg/ml,MIC50和MIC90皆为64μg/ml。结论在男性念珠菌性尿道炎和包皮龟头炎中,白念珠菌仍是第一位致病菌,体外药敏试验显示氟康唑、伏立康唑、氟胞嘧啶、两性霉素B对男性念珠菌性尿道炎均有较好的敏感性。     

Comparison of the epidemiology, drug resistance mechanisms, and virulence of Candida dubliniensis and Candida albicans

Candida dubliniensis is a pathogenic yeast species that was first identified as a distinct taxon in 1995. Epidemiological studies have shown that C. dubliniensis is prevalent throughout the world and that it is primarily associated with oral carriage and oropharyngeal infections in human immunodeficiency virus (HIV)-infected and acquired immune deficiency syndrome (AIDS) patients. However, unlike Candida albicans, C. dubliniensis is rarely found in the oral microflora of normal healthy individuals and is responsible for as few as 2% of cases of candidemia (compared to approximately 65% for C. albicans). The vast majority of C. dubliniensis isolates identified to date are susceptible to all of the commonly used antifungal agents, however, reduced susceptibility to azole drugs has been observed in clinical isolates and can be readily induced in vitro. The primary mechanism of fluconazole resistance in C. dubliniensis has been shown to be overexpression of the major facilitator efflux pump Mdr1p. It has also been observed that a large number of C. dubliniensis strains express a non-functional truncated form of Cdr1p, and it has been demonstrated that this protein does not play a significant role in fluconazole resistance in the majority of strains examined to date. Data from a limited number of infection models reflect findings from epidemiological studies and suggest that C. dubliniensis is less pathogenic than C. albicans. The reasons for the reduced virulence of C. dubliniensis are not clear as it has been shown that the two species express a similar range of virulence factors. However, although C. dubliniensis produces hyphae, it appears that the conditions and dynamics of induction may differ from those in C. albicans. In addition, C. dubliniensis is less tolerant of environmental stresses such as elevated temperature and NaCl and H(2)O(2) concentration, suggesting that C. albicans may have a competitive advantage when colonising and causing infection in the human body. It is our hypothesis that a genomic comparison between these two closely-related species will help to identify virulence factors responsible for the far greater virulence of C. albicans and possibly identify factors that are specifically implicated in either superficial or systemic candidal infections.     

Susceptibilities of Candida albicans Mouth Isolates to Antifungal Agents, Essentials Oils and Mouth Rinses

Forty Candida albicans strains isolated from patient's mouth with fixed orthodontic appliances were analyzed to their susceptibilities to antifungal agents, mouth rinses and essential oils. Susceptibility to fluconazole, econazole, miconazole and ketoconazole, amphotericin B and nystatin was assessed by the disk diffusion (DD) method based on the Clinical and Laboratory Standards Institute M44-A protocol, and by Etest (fluconazole and amphotericin B). The susceptibilities to mouth rinses and essential oils were also determined by the DD technique. All isolates tested were susceptible (S) to amphotericin B, nystatin and fluconazole. The overall concordance between the DD and the Etest was 100% for amphotericin and fluconazole. One isolate was resistant to econazole (2.5%) and the other to ketoconazole (2.5%). Econazole and ketoconazole had the highest percentages of susceptible dose dependent (SDD), 55 and 95%, respectively. Regarding to the susceptibility isolates profile, seven phenotypes were detected, and the 3 more represented (90% of the isolates) of them were SDD to one, two or three azoles. The study of mouth rinses showed a high variability of efficacy against C. albicans. The results showed that the isolates susceptibility to essential oils differed (P < 0.05). The profile activity was: cinnamon > laurel > mint > eucalyptus > rosemary > lemon > myrrh > tangerine. The main finding was that the susceptibility to cinnamon and laurel varied among the three more representative antifungal phenotypes (P < 0.05). The susceptibility of econazole-SDD isolates to cinnamon and lemon was higher than those of the econazole-S yeasts (P < 0.05). In contrast, econazole-SDD isolates were less affected by laurel than econazole-S counterparts (P < 0.05).     

白念珠菌临床分离调查及基因分型研究

目的 了解白念珠菌临床分离情况,并探讨其药敏结果与基因分型的相关性.方法 回顾性分析本院2011年3～11月间临床分离白念珠菌分布及耐药性;随机选取232株,采用PCR方法扩增白念珠菌25S rDNA基因内含子区进行基因分型研究;采用ATB真菌药敏试剂条进行药敏分析;统计分析药敏结果与基因分型的相关性.结果 期间共检出酵母样真菌973例,占病原菌阳性样本数比率为15.7％ (973/6196);其中分离白念珠菌562株,占58％ (562/973),主要分布科室为呼吸科(39.1％)、老年科(13.2％)、ICU(7.7％)、神经内科(7.5％)、免疫科(6.0％)以及其他科室(26.5％);标本类型以下呼吸道为主(81.7％),其次为尿路(9.4％)、血液(1.8％)等.对氟胞嘧啶、两性霉素B、氟康唑、伊曲康唑及伏立康唑的耐药率分别为0.9％、0％、1.4％、1.6％和1.1％.随机选取的232株白念珠菌经PCR方法可分为3型:A型125株,B型96株,C型11株.各型在5种药物的耐药性上并无差异.结论 临床分离酵母样真菌以白念珠菌为主,感染部位以下呼吸道为主;临床分离株对5种抗真菌药物敏感度较高,主要基因型为A和B型,不同基因分型间药敏结果并无统计学差异.     

Molecular Analysis and Susceptibility Profiling of Candida albicans Isolates from Immunocompromised Patients in South India

The genetic diversity and in vitro antifungal susceptibility profiles of 55 Candida albicans from immunocompromised patients were studied. PCR based analysis of the transposable intron in the 25S rDNA revealed 39 genotype A, 4 genotype B and 12 genotype C isolates. Serotype analysis categorized 52 isolates as serotype A and 3 as serotype B. All strains were susceptible to micafungin, 5-flucytosine and miconazole, whereas resistance against amphotericin B (3.6%), fluconazole (3.6%), itraconazole (7.3%) and voriconazole (5.5%) was observed. No association was seen between antifungal resistance and genotype/serotype status.     

Biotypes, genotypes and ketoconazole susceptibility of Candida albicans isolates from a group of Thai AIDS patients

A total of eighty-seven Candida albicans isolates from a group of Thai AIDS patients were characterized for phenotypic and genotypic profiles and antifungal susceptibility to ketoconazole. Phenotyping of the isolates was carried out by a biotyping method based on the enzyme profiles, carbohydrate assimilation patterns and boric acid resistance of the yeasts. Genotyping was performed through randomly amplified polymorphic DNA (RAPD) analysis. Antifungal susceptibility of ketoconazole was performed using the NCCLS broth microdilution method. Combination of the biotypic tests revealed a total of 49 different biotypes. The most predominant was A1S (31%), the remaining biotypes represented only few isolates in each. RAPD profiles identified 14 clusters of genotype among the 87 isolates. Almost every individual harboured his/her own specific isolate and in 25 of 26 (96.2%) harboured more than one clonal type. The heterogeneity of both phenotypic and genotypic profiles of C. albicans isolates in this study was similar to previous reports from other oral sources in different geographic areas. All isolates were susceptible to ketoconazole. The findings may be useful as baseline information of oral C. albicans colonization in Thai population living in the south of Thailand.     

Variation of cell surface hydrophobicity and biofilm formation among genotypes of Candida albicans and Candida dubliniensis under antifungal treatment

Candida infections are frequently associated with formation of biofilms on artificial medical devices. This work studied variation of cell surface hydrophobicity (CSH) and formation of biofilm in relation to Candida albicans and Candida dubliniensis genotypes and an effect of some conventional antifungal agents on both CSH and biofilm. The 50 isolates of C. albicans and C. dubliniensis were classified into genotypes A, B, C, and D, genotype D being exclusively represented by C. dubliniensis. No significant differences between CSH of genotypes A and B and B and C were observed with respect to cultivation temperature 25 or 37 degrees C. Candida dubliniensis showed increased CSH in comparison with other C. albicans genotypes (p < 0.001) regardless of temperature used. Using XTT reduction assay and dry masses, genotypes B and C showed reduced ability to form biofilm in comparison with genotype A (p < 0.05) and C. dubliniensis (p < 0.001). Fluconazole reduced biofilm in C. albicans genotypes A, B, and C (p < 0.05) but not CSH. The opposite effect was observed in C. dubliniensis. Voriconazole effectively reduced both biofilm formation and CSH in all tested genotypes of C. albicans and C. dubliniensis (p < 0.05).     

In Candida albicans, resistance to flucytosine and terbinafine is linked to MAT locus homozygosity and multilocus sequence typing clade 1

A panel of 637 isolates of Candida albicans that had been typed by multilocus sequence typing (MLST) and tested for susceptibility to amphotericin B, caspofungin, fluconazole, flucytosine, itraconazole, ketoconazole, miconazole, terbinafine and voriconazole was the material for a statistical analysis of possible associations between antifungal susceptibility and other properties. For terbinafine and flucytosine, the greatest proportion of low-susceptibility isolates, judged by two resistance breakpoints, was found in MLST clade 1 and among isolates homozygous at the MAT locus, although only three isolates showed cross-resistance to the two agents. Most instances of low susceptibility to azoles, flucytosine and terbinafine were among oropharyngeal isolates from HIV-positive individuals. Statistically significant correlations were found between terbinafine and azole minimal inhibitory concentrations (MICs), while correlations between flucytosine MICs and azole MICs were less strong. It is concluded that a common regulatory mechanism may operate to generate resistance to the two classes of agent that inhibit ergosterol biosynthesis, terbinafine and the azoles, but that flucytosine resistance, although still commonly associated with MAT homozygosity, is differently regulated.