Species distribution and antifungal susceptibility of 358 Trichosporon clinical isolates collected in 24 medical centres.

OBJECTIVES: To provide species distribution and antifungal susceptibility profiles of 358 Trichosporon clinical isolates collected from 24 tertiary-care hospitals. METHODS: Species identification was performed by sequencing the IGS1 region of rDNA. Antifungal susceptibility testing for amphotericin B, fluconazole, voriconazole and posaconazole followed the Clinical and Laboratory Standards Institute reference method. Tentative epidemiologic cutoff values (97.5% ECVs) of antifungals for Trichosporon asahii were also calculated. RESULTS: Isolates were cultured mostly from urine (155/358, 43.3%) and blood (82/358, 23%) samples. Trichosporon asahii was the most common species (273/358, 76.3%), followed by T. inkin (35/358, 9.7%). Isolation of non-T. asahii species increased substantially over the last 11 years [11/77 (14.2%) from 1997 to 2007 vs. 74/281, (26.3%) from 2008 to 2018, p0.03]. Antifungal susceptibility testing showed high amphotericin B minimum inhibitory concentrations against Trichosporon isolates, with higher values for T. faecale. The ECV for amphotericin B and T. asahii was set at 4 µg/mL. Among the triazole derivatives, fluconazole was the least active drug. The ECVs for fluconazole and posaconazole against T. asahii were set at 8 and 0.5 µg/mL, respectively. Voriconazole showed the strongest in vitro activity against the Trichosporon isolates; its ECV for T. asahii was set at 0.25 µg/mL after 48 hours' incubation. CONCLUSIONS: Trichosporon species diversity has increased over the years in human samples, and antifungal susceptibility profiles were species specific. Trichosporon asahii antifungal ECVs were proposed, which may be helpful to guide antifungal therapy.

Candida and invasive mould diseases in non-neutropenic critically ill patients and patients with haematological cancer.

Critically ill patients and patients with haematological cancer are HIV-negative populations at high risk of invasive fungal infections. In intensive-care units, candidaemia and intra-abdominal candidiasis predominate, but aspergillosis has emerged as a lethal, under-recognised cause of pneumonia. In patients with haematological malignancies or who have undergone stem-cell transplantations, pulmonary disease due to aspergillus and other mould diseases predominate. In this Series paper, we provide an update on risk assessment, new diagnostic strategies, and therapeutic approaches. New concepts have emerged for use of risk prediction rules and an evidence base now exists for inclusion of biomarkers (eg, galactomannan, 1,3-ß-D-glucan, and PCR assays for Aspergillus spp) into early diagnostic and therapeutic strategies. Imaging techniques remain helpful for early diagnosis of pulmonary mould diseases, with PET techniques offering potential improvements in diagnostic specificity and evaluation of clinical response. Echinocandins and triazoles have been validated extensively for prophylaxis, empirical therapy, and targeted therapy, but an increase in intrinsically resistant fungi and emergence of secondary resistance as a result of drug-induced selection pressure are of major concern. Echinocandins remain a major component of treatment of invasive candidiasis and new triazoles are the best alternative for prophylaxis and therapy of invasive aspergillosis.

Multicenter, International Study of MIC/MEC Distributions for Definition of Epidemiological Cutoff Values for Sporothrix Species Identified by Molecular Methods.

Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic Sporothrix species to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates of Sporothrixschenckii sensu lato and some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents and Sporothrix species and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for the species. We collected available CLSI MICs/minimal effective concentrations (MECs) of amphotericin B, five triazoles, terbinafine, flucytosine, and caspofungin for 301 Sporothrix schenckii sensu stricto, 486 S. brasiliensis, 75 S. globosa, and 13 S. mexicana molecularly identified isolates. Data were obtained in 17 independent laboratories (Australia, Europe, India, South Africa, and South and North America) using conidial inoculum suspensions and 48 to 72 h of incubation at 35°C. Sufficient and suitable data (modal MICs within 2-fold concentrations) allowed the proposal of the following ECVs for S. schenckii and S. brasiliensis, respectively: amphotericin B, 4 and 4 µg/ml; itraconazole, 2 and 2 µg/ml; posaconazole, 2 and 2 µg/ml; and voriconazole, 64 and 32 µg/ml. Ketoconazole and terbinafine ECVs for S. brasiliensis were 2 and 0.12 µg/ml, respectively. Insufficient or unsuitable data precluded the calculation of ketoconazole and terbinafine (or any other antifungal agent) ECVs for S. schenckii, as well as ECVs for S. globosa and S. mexicana These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy.

A prospective international Aspergillus terreus survey: an EFISG, ISHAM and ECMM joint study.

OBJECTIVES: A prospective international multicentre surveillance study was conducted to investigate the prevalence and amphotericin B susceptibility of Aspergillus terreus species complex infections. METHODS: A total of 370 cases from 21 countries were evaluated. RESULTS: The overall prevalence of A. terreus species complex among the investigated patients with mould-positive cultures was 5.2% (370/7116). Amphotericin B MICs ranged from 0.125 to 32 mg/L, (median 8 mg/L). CONCLUSIONS: Aspergillus terreus species complex infections cause a wide spectrum of aspergillosis and the majority of cryptic species display high amphotericin B MICs.

Melanized fungal infections in kidney transplant recipients: contributions to optimize clinical management.

OBJECTIVES: This is a retrospective and observational study addressing clinical and therapeutic aspects of melanized fungal infections in kidney transplant recipients. METHODS: We retrospectively reviewed medical records of all patients admitted between January 1996 and December 2013 in a single institution who developed infections by melanized fungi. RESULTS: We reported on 56 patients aged between 30 and 74 years with phaeohyphomycosis or chromoblastomycosis (0.54 cases per 100 kidney transplants). The median time to diagnosis post-transplant was 31.2 months. Thirty-four (60.8%) infections were reported in deceased donor recipients. Fifty-one cases of phaeohyphomycosis were restricted to subcutaneous tissues, followed by two cases with pneumonia and one with brain involvement. Most dermatological lesions were represented by cysts (23/51; 45.1%) or nodules (9/51; 17.9%). Exophiala spp. (34.2%) followed by Alternaria spp. (7.9%) were the most frequent pathogens. Graft loss and death occurred in two patients and one patient, respectively. Regarding episodes of subcutaneous phaeohyphomycosis, a complete surgical excision without antifungal therapy was possible in 21 of 51 (41.2%) patients. Long periods of itraconazole were required to treat the other 30 (58.8%) episodes of subcutaneous disease. All four cases of chromoblastomycosis were treated only with antifungal therapy. CONCLUSIONS: Melanized fungal infections should be considered in the differential diagnosis of all chronic skin lesions in transplant recipients. It is suggested that the impact of these infections on graft function and mortality is low. The reduction in immunosuppression should be limited to severely ill patients.

Predictors of choice of initial antifungal treatment in intraabdominal candidiasis.

Intraabdominal candidiasis (IAC) is the second most frequent form of invasive candidiasis, and is associated with high mortality rates. This study aims to identify current practices in initial antifungal treatment (IAT) in a real-world scenario and to define the predictors of the choice of echinocandins or azoles in IAC episodes. Secondary analysis was performed of a multinational retrospective cohort at 13 teaching hospitals in four countries (Italy, Greece, Spain and Brazil), over a 3-year period (2011-2013). IAC was identified in 481 patients, 323 of whom received antifungal therapy (classified as the treatment group). After excluding 13 patients given amphotericin B, the treatment group was further divided into the echinocandin group (209 patients; 64.7%) and the azole group (101 patients; 32.3%). Median APACHE II scores were significantly higher in the echinocandin group (p 0.013), but IAT did not differ significantly with regard to the Candida species involved. Logistic multivariate stepwise regression analysis, adjusted for centre effect, identified septic shock (adjusted OR (aOR) 1.54), APACHE II >15 (aOR 1.16) and presence in surgical ward at diagnosis (aOR 1.16) as the top three independent variables associated with an empirical echinocandin regimen. No differences in 30-day mortality were observed between groups. Echinocandin regimen was the first choice for IAT in patients with IAC. No statistical differences in mortality were observed between regimens, but echinocandins were administered to patients with more severe disease. Some disagreements were identified between current clinical guidelines and prescription of antifungals for IAC at the bedside, so further educational measures are required to optimize therapies.

International Evaluation of MIC Distributions and Epidemiological Cutoff Value (ECV) Definitions for Fusarium Species Identified by Molecular Methods for the CLSI Broth Microdilution Method.

The CLSI epidemiological cutoff values (ECVs) of antifungal agents are available for various Candida spp., Aspergillus spp., and the Mucorales. However, those categorical endpoints have not been established for Fusarium spp., mostly due to the difficulties associated with collecting sufficient CLSI MICs for clinical isolates identified according to the currently recommended molecular DNA-PCR-based identification methodologies. CLSI MIC distributions were established for 53 Fusarium dimerum species complex (SC), 10 F. fujikuroi, 82 F. proliferatum, 20 F. incarnatum-F. equiseti SC, 226 F. oxysporum SC, 608 F. solani SC, and 151 F. verticillioides isolates originating in 17 laboratories (in Argentina, Australia, Brazil, Canada, Europe, Mexico, and the United States). According to the CLSI guidelines for ECV setting, ECVs encompassing ≥97.5% of pooled statistically modeled MIC distributions were as follows: for amphotericin B, 4 µg/ml (F. verticillioides) and 8 µg/ml (F. oxysporum SC and F. solani SC); for posaconazole, 2 µg/ml (F. verticillioides), 8 µg/ml (F. oxysporum SC), and 32 µg/ml (F. solani SC); for voriconazole, 4 µg/ml (F. verticillioides), 16 µg/ml (F. oxysporum SC), and 32 µg/ml (F. solani SC); and for itraconazole, 32 µg/ml (F. oxysporum SC and F. solani SC). Insufficient data precluded ECV definition for the other species. Although these ECVs could aid in detecting non-wild-type isolates with reduced susceptibility to the agents evaluated, the relationship between molecular mechanisms of resistance (gene mutations) and MICs still needs to be investigated for Fusarium spp.

Evidence of genotypic diversity among Candida auris isolates by multilocus sequence typing, matrix-assisted laser desorption ionization time-of-flight mass spectrometry and amplified fragment length polymorphism.

Candida auris is a multidrug-resistant nosocomial bloodstream pathogen that has been reported from Asian countries and South Africa. Herein, we studied the population structure and genetic relatedness among 104 global C. auris isolates from India, South Africa and Brazil using multilocus sequence typing (MLST), amplified fragment length polymorphism (AFLP) fingerprinting and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). RPB1, RPB2 and internal transcribed spacer (ITS) and D1/D2 regions of the ribosomal DNA were sequenced for MLST. Further, genetic variation and proteomic assessment was carried out using AFLP and MALDI-TOF MS, respectively. Both MLST and AFLP typing clearly demarcated two major clusters comprising Indian and Brazilian isolates. However, the South African isolates were randomly distributed, suggesting different genotypes. MALDI-TOF MS spectral profiling also revealed evidence of geographical clustering but did not correlate fully with the genotyping methods. Notably, overall the population structure of C. auris showed evidence of geographical clustering by all the three techniques analysed. Antifungal susceptibility testing by the CLSI microbroth dilution method revealed that fluconazole had limited activity against 87% of isolates (MIC90, 64 mg/L). Also, MIC90 of AMB was 4 mg/L. Candida auris is emerging as an important yeast pathogen globally and requires reproducible laboratory methods for identification and typing. Evaluation of MALDI-TOF MS as a typing method for this yeast is warranted.

Initial serum (1,3)-ß-D-glucan as a predictor of mortality in proven candidaemia: findings from a retrospective study in two teaching hospitals in Italy and Brazil.

A retrospective study was conducted to assess the role of initial serum (1,3)-ß-d-glucan (BDG) values in predicting mortality in proven candidaemia. The study was conducted in two large teaching hospitals in Italy and Brazil. From January 2009 to June 2014, all patients with proven candidaemia who underwent a BDG test within 96 hours before or after the first positive blood culture were included in the study. The primary end point was 28-day mortality, with the role of initial BDG being assessed by univariate and multivariate analyses. A total of 104 patients met the inclusion criteria. Overall, the crude 28-day mortality was 30% (31/104). In the final multivariate model, an initial BDG of >287 pg/mL (odds ratio (OR) 4.40, 95% confidence interval (CI) 1.56-12.39, p 0.005), haemodialysis (OR 4.33, 95% CI 1.24-15.17, p 0.022) and a Pitt score of ≥ 2 (OR 4.10, 95% CI 1.24-13.54, p 0.021) were significant predictors of 28-day mortality. The >287 pg/mL cutoff predicted 28-day mortality with 65% sensitivity and 70% specificity. Centre of enrolment (p for interaction 0.012), haemodialysis (p for interaction 0.062) and timing of BDG test of more than 24 hours before or after the positive culture (p for interaction 0.143) appeared to interact with BDG's ability to predict mortality. Although not statistically significant, the last two of these interactions might partially explain why BDG's ability to predict mortality was present only in the Italian cohort.

Cryptic and rare Aspergillus species in Brazil: prevalence in clinical samples and in vitro susceptibility to triazoles.

Aspergillus spp. are among the most common causes of opportunistic invasive fungal infections in tertiary care hospitals. Little is known about the prevalence and in vitro susceptibility of Aspergillus species in Latin America, because there are few medical centers able to perform accurate identification at the species level. The purpose of this study was to analyze the distribution of cryptic and rare Aspergillus species among clinical samples from 133 patients with suspected aspergillosis admitted in 12 medical centers in Brazil and to analyze the in vitro activity of different antifungal drugs. The identification of Aspergillus species was performed based on a polyphasic approach, as well as sequencing analysis of the internal transcribed spacer (ITS) region, calmodulin, and ß-tubulin genes and phylogenetic analysis when necessary. The in vitro susceptibility tests with voriconazole, posaconazole, and itraconazole were performed according to the CLSI M38-A2 document (2008). We demonstrated a high prevalence of cryptic species causing human infection. Only three isolates, representing the species Aspergillus thermomutatus, A. ochraceus, and A. calidoustus, showed less in vitro susceptibility to at least one of the triazoles tested. Accurate identifications of Aspergillus at the species level and with in vitro susceptibility tests are important because some species may present unique resistance patterns against specific antifungal drugs.

Epidemiology of candidemia in patients with hematologic malignancies and solid tumours in Brazil.

Candidemia in cancer patients may differ according to the type of cancer. To characterise the epidemiology and outcome of candidemia in cancer patients from Brazilian hospitals, we compared the characteristics of patients with hematologic malignancies (HM) and solid tumours (ST). A retrospective study was performed, based on data collected from laboratory-based surveillance studies in 18 tertiary care hospitals between March/2003 and December/2007. The characteristics of patients with HM (n = 117) were compared with patients with ST (n = 248). Predictors of 30-day mortality were identified by uni- and multivariate analyses. Candidemia in HM was more likely to occur in the setting of chemotherapy, corticosteroids, neutropenia, mucositis and tunnelled central venous catheter (CVC), whereas surgery, intensive care unit admission and invasive procedures (mechanical ventilation, parenteral nutrition and CVC) were more frequent in ST. The 30-day mortality rate was higher in the ST group (65% vs. 46%, P = 0.001). Factors significantly associated with 30-day mortality were older age and intensive care unit admission. Important differences in the epidemiology and outcome of candidemia in HM and ST were observed. The characterisation of the epidemiology is important to drive preventive measures and to select appropriate therapies.

Invasive fungal diseases in haematopoietic cell transplant recipients and in patients with acute myeloid leukaemia or myelodysplasia in Brazil.

Invasive fungal disease (IFD) shows distinct regional incidence patterns and epidemiological features depending on the geographic region. We conducted a prospective survey in eight centres in Brazil from May 2007 to July 2009. All haematopoietic cell transplant (HCT) recipients and patients with acute myeloid leukaemia (AML) or myelodysplasia (MDS) were followed from admission until 1 year (HCT) or end of consolidation therapy (AML/MDS). The 12-month cumulative incidence (CI) of proven or probable IFD was calculated, and curves were compared using the Grey test. Among 237 AML/MDS patients and 700 HCT recipients (378 allogeneic, 322 autologous), the 1-year CI of IFD in AML/MDS, allogeneic HCT and autologous HCT was 18.7%, 11.3% and 1.9% (p <0.001), respectively. Fusariosis (23 episodes), aspergillosis (20 episodes) and candidiasis (11 episodes) were the most frequent IFD. The 1-year CI of aspergillosis and fusariosis in AML/MDS, allogeneic HCT and autologous HCT were 13.4%, 2.3% and 0% (p <0.001), and 5.2%, 3.8% and 0.6% (p 0.01), respectively. The 6-week probability of survival was 53%, and was lower in cases of fusariosis (41%). We observed a high burden of IFD and a high incidence and mortality for fusariosis in this first multicentre epidemiological study of IFD in haematological patients in Brazil.

Comparison of Photodynamic Therapy versus conventional antifungal therapy for the treatment of denture stomatitis: a randomized clinical trial.

In this randomized clinical trial, the clinical and mycological efficacy of Photodynamic Therapy (PDT) was compared with that of topical antifungal therapy for the treatment of denture stomatitis (DS) and the prevalence of Candida species was identified. Patients were randomly assigned to one of two groups (n = 20 each); in the nystatin (NYT) group patients received topical treatment with nystatin (100,000 IU) four times daily for 15 days and in the PDT group the denture and palate of patients were sprayed with 500 mg/L of Photogem(®), and after 30 min of incubation, were illuminated by light emitting-diode light at 455 nm (37.5 and 122 J/cm(2), respectively) three times a week for 15 days. Mycological cultures taken from dentures and palates and standard photographs of the palates were taken at baseline (day 0), at the end of the treatment (day 15) and at the follow-up time intervals (days 30, 60 and 90). Colonies were quantified (CFU/mL) and identified by biochemical tests. Data were analysed by Fisher's exact test, analysis of variance and Tukey tests and κ test (α = 0.05). Both treatments significantly reduced the CFU/mL at the end of the treatments and on day 30 of the follow-up period (p <0.05). The NYT and PDT groups showed clinical success rates of 53% and 45%, respectively. Candida albicans was the most prevalent species identified. PDT was as effective as topical nystatin in the treatment of DS.

Prevalence rates and antifungal susceptibility profiles of the Candida parapsilosis species complex: results from a nationwide surveillance of candidaemia in Brazil.

The genetically heterogeneous taxon Candida parapsilosis was recently reclassified into three species: Candida parapsilosis, Candida orthopsilosis and Candida metapsilosis. The prevalences of these species among 141 bloodstream isolates tested in Brazil were 88% for C. parapsilosis, 9% for C. orthopsilosis, and 3% for C. metapsilosis. Except for three C. orthopsilosis isolates that were considered resistant to 5-flucytosine, all isolates representing the different species of this complex were susceptible to polyenes, triazoles and caspofungin.

Clinical and microbiological assessment of patients with a long-term diagnosis of human immunodeficiency virus infection and Candida oral colonization.

The objective of this study was to evaluate Candida oral colonization in human immunodeficiency virus (HIV)-infected patients undergoing long-term highly active antiretroviral therapy (ARV). The cross-sectional study included 331 HIV patients, diagnosed from 1983 to 2003. Oral swabs were performed, and Candida species were determined using ID 32C. Isolates were tested for antifungal susceptibility. Clinical and laboratory data were collected to identify the association with Candida colonization. In total, 161 Candida isolates were detected among 147 of the 331 patients (44%), independently of the time when HIV infection was diagnosed. Candida albicans strains represented 137 (85%) of the isolates, and were susceptible to all of the tested antifungal drugs. Among the non-C. albicans strains, six isolates were dose-dependently susceptible to fluconazole, nine to itraconazole, and seven to ketoconazole. The isolation of Candida was significantly higher in patients with virological failure (83/147; p 0.0002) and CD4(+) T-lymphocyte counts <200 cells/mm(3) (30/83; p 0.0003). Recovery of Candida in the oral cavity was independent of protease inhibitor (PI) usage (p 0.60). Colonized patients typically underwent salvage therapy (p 0.003), and had more episodes of opportunistic fungal infections (p 0.046) and malignancies (p 0.004).Oral Candida colonization in patients under ARV therapy was associated with the immunosupressed status of HIV-infected patients, i.e. low number of CD4(+) T-cells per cubic millimetre, failure of ARV therapy (salvage therapy), and higher number of opportunistic infections and malignancies. Despite the fact that PIs have in vitro antifungal activity, the use of this class of antiretroviral agent did not influence the presence of Candida in the oral cavity of AIDS patients.

Results from the ARTEMIS DISK Global Antifungal Surveillance study, 1997 to 2005: an 8.5-year analysis of susceptibilities of Candida species and other yeast species to fluconazole and voriconazole determined by CLSI standardized disk diffusion testing.

Fluconazole in vitro susceptibility test results for 205,329 yeasts were collected from 134 study sites in 40 countries from June 1997 through December 2005. Data were collected for 147,776 yeast isolates tested with voriconazole from 2001 through 2005. All investigators tested clinical yeast isolates by the CLSI M44-A disk diffusion method. Test plates were automatically read and results recorded with a BIOMIC image analysis system. Species, drug, zone diameter, susceptibility category, and quality control results were collected quarterly. Duplicate (same patient, same species, and same susceptible-resistant biotype profile during any 7-day period) and uncontrolled test results were not analyzed. Overall, 90.1% of all Candida isolates tested were susceptible (S) to fluconazole; however, 10 of the 22 species identified exhibited decreased susceptibility (<75% S) on the order of that seen with the resistant (R) species C. glabrata and C. krusei. Among 137,487 isolates of Candida spp. tested against voriconazole, 94.8% were S and 3.1% were R. Less than 30% of fluconazole-resistant isolates of C. albicans, C. glabrata, C. tropicalis, and C. rugosa remained S to voriconazole. The non-Candida yeasts (8,821 isolates) were generally less susceptible to fluconazole than Candida spp. but, aside from Rhodotorula spp., remained susceptible to voriconazole. This survey demonstrates the broad spectrum of these azoles against the most common opportunistic yeast pathogens but identifies several less common yeast species with decreased susceptibility to antifungal agents. These organisms may pose a future threat to optimal antifungal therapy and emphasize the importance of prompt and accurate species identification.

Candida rugosa, an emerging fungal pathogen with resistance to azoles: geographic and temporal trends from the ARTEMIS DISK antifungal surveillance program.

Candida rugosa is a fungus that appears to be emerging as a cause of infection in some geographic regions. We utilized the extensive database of the ARTEMIS DISK Antifungal Surveillance Program to describe the geographic and temporal trends in the isolation of C. rugosa from clinical specimens and the in vitro susceptibilities of 452 isolates to fluconazole and voriconazole. C. rugosa accounted for 0.4% of 134,715 isolates of Candida, and the frequency of isolation increased from 0.03% to 0.4% over the 6.5-year study period (1997 to 2003). C. rugosa was most common in the Latin American region (2.7% versus 0.1 to 0.4%). Decreased susceptibility to fluconazole (40.5% susceptible) was observed in all geographic regions; however, isolates from Europe and North America were much more susceptible (97 to 100%) to voriconazole than those from other geographic regions (55.8 to 58.8%). C. rugosa was most often isolated from blood and urine in patients hospitalized at the Medical and Surgical inpatient services. Notably, bloodstream isolates were the least susceptible to both fluconazole and voriconazole. C. rugosa should be considered, along with the established pathogens Candida krusei and Candida glabrata, as a species of Candida with reduced susceptibility to the azole antifungal agents.

The ergosterol biosynthesis pathway, transporter genes, and azole resistance in Aspergillus fumigatus.

The continuous use of triazoles can result in the development of drug resistance. Azole-resistant clinical isolates, spontaneous and induced mutants of Aspergillus fumigatus have been documented. The azoles block the ergosterol biosynthesis pathway by inhibiting the enzyme 14-alpha-demethylase, product of the CYP51. Fungal azole resistance involves both amino acid changes in the target site that alter drug-target interactions and those that decrease net azole accumulation. The reduced intracellular accumulation has also been correlated with overexpression of multidrug resistance (MDR) efflux transporter genes of the ATP-binding cassette (ABC) and the major facilitator superfamily (MFS) classes. About 20 genes are involved in the A. fumigatus ergosterol biosynthesis pathway. There are several duplicated genes in this pathway. Interestingly, erg3 and erg11 showed two copies in A. fumigatus. In general, Aspergillus spp. have proportionally more MFS transporter encoding genes than Saccharomyces cerevisiae, S. pombe, and Neurospora crassa. The drug H+ (12 and 14 spanners) sub-families are also proportionally greater than in the other species. Although the numbers of ABC transporter encoding genes are comparable, again the Aspergillus spp. have more ABC transporters related to multidrug permease than the other fungal species.

Susceptibility profile of 200 bloodstream isolates of Candida spp. collected from Brazilian tertiary care hospitals.

We evaluated the antifungal susceptibility profile of 200 recent bloodstream isolates of Candida spp. sequentially obtained from patients admitted to five tertiary care hospitals in Brazil. Isolates were identified by classical methods and the antifungal susceptibility profile was determined by the NCCLS microbroth assay method. Candida albicans was the most frequent species (41.5%); followed by C. tropicalis (24%) and C. parapsilosis (20.5%). The frequency of C. glabrata and C. krusei was low (nine and two isolates, respectively). Only three strains were resistant to fluconazole (two C. krusei and one C. glabrata) and only one was resistant to itraconazole (the same C. glabrata strain that was resistant to fluconazole). Two strains were considered susceptible dose-dependent (SDD) to fluconazole and 13 isolates (6.5%) were SDD to itraconazole. Overall, the MIC50 value of non-C. albicans isolates for fluconazole was two dilutions higher than that of C. albicans isolates, and for itraconazole was one dilution higher. Resistance to amphotericin B (MIC > or = 2 microg ml(-1)) was observed in 2.5% of isolates (two strains of C. albicans, two of C. parapsilosis and one of C. krusei). This study showed that episodes of candidemia in Brazilian public hospitals are represented mainly by fluconazole-susceptible non-C. albicans species. This finding is probably related to the low use of fluconazole in these hospitals.