Rifaximin use favoured micafungin-resistant Candida spp. infections in recipients of allogeneic hematopoietic cell transplantation.

Damage to gut mucosa following conditioning regimens may favour bacterial infections that can trigger graft versus host disease (GvHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Rifaximin, an oral and non-absorbable antibiotic, has been recently proposed as effective prophylaxis to reduce bacterial infections in the gut and consequently acute GvHD in this setting. The present study evaluated safety and outcomes of HSCT patients that were treated with rifaximin prophylaxis at Perugia University Hospital. Rifaximin prophylaxis was introduced as standard of care in HSCT patients in May 2018. We retrieved data from 118 consecutive transplants, and we compared the outcomes of rifaximin-treated patients with historical controls that did not receive antibiotic prophylaxis. While incidences of neutropenic fever, documented bacterial infections, and aGvHD were similar in the two groups, we found an increased frequency of invasive candidiasis and clinically relevant Candida spp. infections in rifaximin-treated patients (5 patients vs 1 patient, 25% [± 0.99%] vs 1% [± 0.01%], p < .0001). Three rifaximin-treated patients experienced life-threating candidemia (2 C. krusei, 1 C. orthopsilosis). Rifaximin was the only factor that increased the risk of Candida spp. infections. Rifaximin could have contributed to microbiome disruption which favoured an outbreak of life-threatening Candida infections. This important complication forced us to halt its use. Larger, prospective studies are needed to assess the impact of rifaximin prophylaxis on incidence of bacterial infections, aGvHD, and survival of HSCT patients.

Azole resistance in Aspergillus isolates by different types of patients and correlation with environment - An Italian prospective multicentre study (ARiA study).

BACKGROUND: A wide range of frequency of azole-resistance in A fumigatus in different patient populations worldwide was observed threatening to reduce therapeutic options. OBJECTIVES: Estimate the prevalence of azole-resistance, investigate the molecular mechanisms of resistance, compare the genotypes of resistant clinical isolates with those from the surrounding environment. METHODS: Aspergillus isolates were collected by seven Italian hospital microbiology laboratories. Strains were isolated from different clinical samples from unselected patients. The azole-resistance was evaluated using screening test and microdilution EUCAST method. The molecular mechanism of resistance was performed sequencing the cyp51A gene. Resistant isolates were genotyped by microsatellite analysis and their profiles compared with those of azole-resistant isolates from previous Italian studies. RESULTS: 425 Aspergillus isolates from 367 patients were analysed. The azole-resistance rates were 4.9% and 6.6% considering all Aspergillus spp. isolates and the A fumigatus sensu stricto, respectively. All resistant isolates except one were from a single hospital. Two rare azole-resistant species were identified: A thermomutatus and A lentulus. The predominant resistance mechanism was TR34 /L98H. No correlation between the clinical resistant strains and environmental isolates from patients' home/work/ward was observed. The analysis of the molecular correlation between the resistant clinical strains collected in the present study and those of environmental and clinical origin collected in previous Italian studies reveals a progressive diversification of azole-resistant genotypes starting from a founder azole-resistant genotype. CONCLUSIONS: This study confirms the trend of azole-resistance rate in Italy, showing a geographical difference. Data reinforce the importance of surveillance programmes to monitor the local epidemiological situation.

Yeast-like filamentous fungi: Molecular identification and in vitro susceptibility study.

Yeast-like filamentous fungi, collected in Italy from 1985 to 2018, were submitted to molecular identification and antifungal susceptibility testings. Clinical isolates were identified as Magnusiomyces capitatus (28), M. clavatus (18), and Geotrichum candidum (2). M. clavatus was prevalent among blood isolates (18/24), M. capitatus among isolates from other biological materials. The intrinsic echinocandin resistance was confirmed. Both species had low minimum inhibitory concentrations (MICs) of itraconazole, posaconazole, and voriconazole, while M. clavatus had lower MIC of flucytosine and higher MIC of isavuconazole than M. capitatus. The intrinsic resistance of these species to echinocandins could be the reason of the recent increase of M. clavatus bloodstream infections.

ECMM CandiReg-A ready to use platform for outbreaks and epidemiological studies.

BACKGROUND: Recent outbreaks of Candida auris further exemplify that invasive Candida infections are a substantial threat to patients and healthcare systems. Even short treatment delays are associated with higher mortality rates. Epidemiological shifts towards more resistant Candida spp. require careful surveillance. OBJECTIVES: Triggered by the emergence of C auris and by increasing antifungal resistance rates the European Confederation of Medical Mycology developed an international Candida Registry (FungiScope™ CandiReg) to allow contemporary multinational surveillance. METHODS: CandiReg serves as platform for international cooperation to enhance research regarding invasive Candida infections. CandiReg uses the General Data Protection Regulation compliant data platform ClinicalSurveys.net that holds the electronic case report forms (eCRF). Data entry is supported via an interactive macro created by the software that can be accessed via any Internet browser. RESULTS: CandiReg provides an eCRF for invasive Candida infections that can be used for a variety of studies from cohort studies on attributable mortality to evaluations of guideline adherence, offering to the investigators of the 28 ECMM member countries the opportunity to document their cases of invasive Candida infection. CandiReg allows the monitoring of epidemiology of invasive Candida infections, including monitoring of multinational outbreaks. Here, we describe the structure and management of the CandiReg platform. CONCLUSION: CandiReg supports the collection of clinical information and isolates to improve the knowledge on epidemiology and eventually to improve management of invasive Candida infections. CandiReg promotes international collaboration, improving the availability and quality of evidence on invasive Candida infection and contributes to improved patient management.

Epidemiological trends of cryptococcosis in Italy: Molecular typing and susceptibility pattern of Cryptococcus neoformans isolates collected during a 20-year period.

In the present study clinical data and isolates from cases of cryptococcosis recorded during clinical surveys carried out in Italy from 1997 to 2016, were investigated. Molecular typing and antifungal susceptibility testing were performed in order to delineate the epidemiological trend of cryptococcosis in Italy and to define wild-type population for four different antifungal compounds. During the studied period, a total of 302 cases collected from 32 centers of 11 Italian regions were recorded. Analysis of clinical data showed a significant increase of frequency (from 7% to 38%) of cryptococcosis in human immunodeficiency virus (HIV)-negative patients primarily with hematologic malignancies and solid organ transplantations. The prevalence of the molecular types has significantly changed during the study period, showing an increase of VNIII isolates from 11% to 41% in HIV-negative patients, and a decrease of VNIV isolates from 36% to 16%. Antifungal susceptibility testing allowed us to calculate the epidemiological cut-off for flucytosine (1 mg/l), fluconazole (8 mg/l), itraconazole (0.5 mg/l), and voriconazole (0.25 mg/l). Most of the isolates were wild-type strains. Comparison of the MIC distributions according to molecular types showed that VNIV isolates had lower MICs for fluconazole and itraconazole than the VNI and VIII isolates. The current study emphasizes that the epidemiology of cryptococcosis in Italy has significantly changed over the last decades.

Azole Resistance in Aspergillus fumigatus Clinical Isolates from an Italian Culture Collection.

The aims of the study were to investigate the prevalence of azole resistance among Aspergillus fumigatus clinical isolates. A total of 533 clinical isolates that had been collected between 1995 and 2006, from 441 patients, were screened. No resistance was detected in isolates collected between 1995 and 1997. Starting in 1998, the resistance rate was 6.9%; a total of 24 patients (6.25%) harbored a resistant isolate. The TR34/L98H substitution was found in 21 of 30 tested isolates.

Multilocus sequence typing analysis reveals that Cryptococcus neoformans var. neoformans is a recombinant population.

Cryptococcus neoformans var. neoformans (serotype D) represents about 30% of the clinical isolates in Europe and is present less frequently in the other continents. It is the prevalent etiological agent in primary cutaneous cryptococcosis as well as in cryptococcal skin lesions of disseminated cryptococcosis. Very little is known about the genotypic diversity of this Cryptococcus subtype. The aim of this study was to investigate the genotypic diversity among a set of clinical and environmental C. neoformans var. neoformans isolates and to evaluate the relationship between genotypes, geographical origin and clinical manifestations. A total of 83 globally collected C. neoformans var. neoformans isolates from Italy, Germany, France, Belgium, Denmark, Greece, Turkey, Thailand, Japan, Colombia, and the USA, recovered from different sources (primary and secondary cutaneous cryptococcosis, disseminated cryptococcosis, the environment, and animals), were included in the study. All isolates were confirmed to belong to genotype VNIV by molecular typing and they were further investigated by MLST analysis. Maximum likelihood phylogenetic as well as network analysis strongly suggested the existence of a recombinant rather than a clonal population structure. Geographical origin and source of isolation were not correlated with a specific MLST genotype. The comparison with a set of outgroup C. neoformans var. grubii isolates provided clear evidence that the two varieties have different population structures.

CAND-LO 2014-15 study: changing epidemiology of candidemia in Lombardy (Italy).

PURPOSE: The aim of this study was to monitor recent changes in the epidemiology of candidemia and in the antifungal susceptibility profiles of Candida isolates in one Italian region (Lombardy) in 2014-2015 in comparison with two other studies performed in the same area in 1997-1999 and in 2009. METHODS: A laboratory-based surveillance was conducted in 11 microbiology laboratories. Identification of Candida isolates from 868 episodes and antifungal susceptibility testing (YeastOne) was performed locally. RESULTS: A progressive increase in the rate of candidemia up to 1.27/1000 admissions and 1.59/10,000 patient days was documented. In all the three surveys, Candida albicans remains the most frequently isolated species, ranging from 52 to 59 % of the etiology of BSIs. The epidemiological shift to the more resistant C. glabrata, observed between 1997-1999 and 2009 surveys, was not confirmed by our more recent data. The pattern of etiology of BSIs occurred in 2014-2015 overlaps that of the 90s. Acquired antifungal resistance is a rare event. No isolate had an amphoterin B minimal inhibitory concentration (MIC, mg/L) value higher than the epidemiological cutoff. All the echinocandin MIC distributions are typical for wild-type organisms except for those of two C. glabrata isolates. Fluconazole resistance declined from 24.9 % in the 2009 survey to 5.4 % in the recent one. CONCLUSIONS: Data from regional surveys may highlight the influence of therapeutic practices on the epidemiology of Candida BSIs and may optimize empirical therapies.

Acute isolated appendicitis due to Aspergillus carneus in a neutropenic child with acute myeloid leukemia.

We describe a case of isolated acute appendicitis due to Aspergillus carneus in a neutropenic child with acute myeloid leukemia (AML) treated according to the AIEOP AML 2002/01 protocol. Despite prophylaxis with acyclovir, ciprofloxacin and fluconazole administered during the neutropenic phase, 16 days after the end of chemotherapy the child developed fever without identified infective foci, which prompted a therapy shift to meropenem and liposomial amphotericin B. After five days of persisting fever he developed ingravescent abdominal lower right quadrant pain. Abdominal ultrasound was consistent with acute appendicitis and he underwent appendectomy with prompt defervescence. PAS+ fungal elements were found at histopathology examination of the resected vermiform appendix, and galactomannan was low positive. A. carneus, a rare species of Aspergillus formerly placed in section Flavipedes and recently considered a member of section Terrei, was identified in the specimen. Treatment with voriconazole was promptly started with success. No other site of Aspergillus localization was detected. Appendicitis is rarely caused by fungal organisms and isolated intestinal aspergillosis without pulmonary infection is unusual. To our knowledge, this is the first report of infection due to A. carneus in a child and in a primary gastrointestinal infection.

Knowledge about tuberculosis among undergraduate health care students in 15 Italian universities: a cross-sectional study.

BACKGROUND: The Italian Study Group on Hospital Hygiene of the Italian Society of Hygiene, Preventive Medicine and Public Health conducted a multicentre survey aiming to evaluate undergraduate health care students' knowledge of tuberculosis and tuberculosis control measures in Italy. METHODS: In October 2012-June 2013, a sample of medical and nursing students from 15 Italian universities were enrolled on a voluntary basis and asked to complete an anonymous questionnaire investigating both general knowledge of tuberculosis (aetiology, clinical presentation, outcome, screening methods) and personal experiences and practices related to tuberculosis prevention. Data were analysed through multivariable regression using Stata software. RESULTS: The sample consisted of 2,220 students in nursing (72.6%) and medicine (27.4%) courses. Our findings clearly showed that medical students had a better knowledge of tuberculosis than did nursing students.Although the vast majority of the sample (up to 95%) answered questions about tuberculosis aetiology correctly, only 60% of the students gave the correct responses regarding clinical aspects and vaccine details. Overall, 66.9% of the students had been screened for tuberculosis, but less than 20% of those with a negative result on the tuberculin skin test were vaccinated. Multivariable regression analysis showed that age and type of study programme (nursing vs. medical course) were determinants of answering the questions correctly. CONCLUSIONS: Although our data showed sufficient knowledge on tuberculosis, this survey underlines the considerable need for improvement in knowledge about the disease, especially among nursing students. In light of the scientific recommendations concerning tuberculosis knowledge among students, progress of current health care curricula aimed to develop students' skills in this field is needed.

Acquired echinocandin resistance in a Candida krusei blood isolate confirmed by mutations in the fks1 gene.

We describe a case of bloodstream infection caused by a Candida krusei strain that developed echinocandin resistance during caspofungin therapy. Three mutations were found in the HS1 region of the fks1 gene, two of them have never been reported either in C. krusei nor in C. albicans.

Molecular epidemiology of Italian clinical Cryptococcus neoformans var. grubii isolates.

Cryptococcus neoformans variety grubii is the major etiological agent of cryptococcal meningitis in both immunocompromised and immunocompetent patients. The current PCR-based molecular methods are not sufficient to discriminate among the different populations of this yeast. Therefore, the aim of the present study was to investigate the genotypes of the Italian clinical C. neoformans var. grubii isolates by multilocus sequence typing (MLST). A total of 53 isolates, each representative of a single case, were studied. Genotyping was performed using the ISHAM Cryptococcus MLST consensus scheme and the results were compared to the publically available global C. neoformans var. grubii MLST dataset. A total of 16 genotypes were identified; 14 were new genotypes, one was identical to sequence type (ST) ST81, which had been previously reported from Thailand, and one to ST23 already identified in Uganda, the USA and Korea. Sequence type ST61 was the most numerous, including 16 isolates. Network phylogenetic analysis showed that the Italian isolates could be divided into at least three clusters with similarities with those recovered in Africa, Asia and Americas. Distribution of the STs among the isolates could not be correlated to the hospital in which they were recovered or to the HIV status of the patients. The majority of the isolates belonged to the molecular type VNI; three belonged to the rare molecular type VNII and one to the VNB group, which until now had not been described in Europe. The results reveal that the Italian C. neoformans var. grubii population presents a distinct variability, displaying a high number of new genotypes, and probably recombines sexually.

Yeast Bloodstream Infections in the COVID-19 Patient: A Multicenter Italian Study (FiCoV Study).

Fungemia is a co-infection contributing to the worsening of the critically ill COVID-19 patient. The multicenter Italian observational study FiCoV aims to estimate the frequency of yeast bloodstream infections (BSIs), to describe the factors associated with yeast BSIs in COVID-19 patients hospitalized in 10 hospitals, and to analyze the antifungal susceptibility profiles of the yeasts isolated from blood cultures. The study included all hospitalized adult COVID-19 patients with a yeast BSI; anonymous data was collected from each patient and data about antifungal susceptibility was collected. Yeast BSI occurred in 1.06% of patients, from 0.14% to 3.39% among the 10 participating centers. Patients were mainly admitted to intensive or sub-intensive care units (68.6%), over 60 years of age (73%), with a mean and median time from the hospitalization to fungemia of 29 and 22 days, respectively. Regarding risk factors for fungemia, most patients received corticosteroid therapy during hospitalization (61.8%) and had a comorbidity (25.3% diabetes, 11.5% chronic respiratory disorder, 9.5% cancer, 6% haematological malignancies, 1.4% organ transplantation). Antifungal therapy was administered to 75.6% of patients, mostly echinocandins (64.5%). The fatality rate observed in COVID-19 patients with yeast BSI was significantly higher than that of COVID-19 patients without yeast BSI (45.5% versus 30.5%). Candida parapsilosis (49.8%) and C. albicans (35.2%) were the most fungal species isolated; 72% of C. parapsilosis strains were fluconazole-resistant (range 0-93.2% among the centers). The FiCoV study highlights a high prevalence of Candida BSIs in critically ill COVID-19 patients, especially hospitalized in an intensive care unit, a high fatality rate associated with the fungal co-infection, and the worrying spread of azole-resistant C. parapsilosis.

Fungal diversity in lake and sea beaches of Italy: Relevance to human health.

Fungal diseases correlated to beach sand or water have not yet been demonstrated due to the lack of epidemiological studies. This study aims to illustrate the fungal population in beach sands of the two largest Italian lakes and in sands and waters of Mediterranean coasts of Southern Italy to contribute to the identification and assessment of causes of microbiological pollution that might impair bathers health. A great difference was observed between the two lakes, where the total of colony-forming units (CFU) ranged from 33.3 to 1049.9 CFU/g. For coastal sands, the total CFU ranged from 216.7 to 538.8 CFU/g, and for coastal waters the total ranged from 185 to 368.7 CFU/ml. The survey revealed the prevalence of opportunistic pathogenic moulds, mainly Aspergillus spp. (A. niger and A. fumigatus) and Penicillium spp., both in freshwater and costal bathing sites. Dermatophytes and yeasts were not detected in the freshwater sands while they were found at low load in coastal waters (3.3 CFU/ml) and sands (1.7 CFU/g). Differences were observed between urban and non-urban coastal beaches with regard to isolation of dermatophytes only from one urban beach. The present study reports a great diversity of fungi in sand and water of bathing beaches confirming that the Mediterranean region has a greater variety of fungal species.

Cross-reactivity of Fusarium spp. in the Aspergillus Galactomannan enzyme-linked immunosorbent assay.

Nine of 11 hematological patients with disseminated/deep-seated Fusarium infection tested at least twice for Aspergillus galactomannan (GM) had repeated positive results in the absence of Aspergillus isolation in culture. The centrifuged supernatants of 12 Fusarium isolates were tested by a GM enzyme-linked immunosorbent assay (EIA). All the isolates produced positive reactions when tested undiluted. These results show cross-reactivity of Fusarium spp. with Aspergillus GM that may constitute a drawback with respect to the specificity of the Platelia EIA.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry-based method for discrimination between molecular types of Cryptococcus neoformans and Cryptococcus gattii.

We evaluated the usefulness of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for Cryptococcus identification at the species and subspecies levels by using an in-house database of 25 reference cryptococcal spectra. Eighty-one out of the 82 Cryptococcus isolates (72 Cryptococcus neoformans and 10 Cryptococcus gattii) tested were correctly identified with respect to their molecular type designations. We showed that MALDI-TOF MS is a practicable alternative to conventional mycology or DNA-based methods.

Invasive fungal infections in the intensive care unit: a multicentre, prospective, observational study in Italy (2006-2008).

Critically ill patients admitted to intensive care units (ICU) are highly susceptible to healthcare-associated infections caused by fungi. A prospective sequential survey of invasive fungal infections was conducted from May 2006 to April 2008 in 38 ICUs of 27 Italian hospitals. A total of 384 fungal infections (318 invasive Candida infections, three cryptococcosis and 63 mould infections) were notified. The median rate of candidaemia was 10.08 per 1000 admissions. In 15% of cases, the infection was already present at the time of admission to ICU. Seventy-seven percent of Candida infections were diagnosed in surgical patients. Candida albicans was isolated in 60% of cases, Candida glabrata and Candida parapsilosis in 13%, each. Candida glabrata had the highest crude mortality rate (60%). Aspergillus infection was diagnosed in 32 medical and 25 surgical patients. The median rate was 6.31 per 1000 admissions. Corticosteroid treatment was the major host factor. Aspergillosis was demonstrated to be more severe than candidiasis as the crude mortality rate was significantly higher (63% vs. 46%), given an equal index of severity, Simplified Acute Physiology Score (SAPS-II). The present large nationwide survey points out the considerable morbidity and mortality of invasive fungal infections in surgical as well as medical patients in ICU.

Heterozygosis and pathogenicity of Cryptococcus neoformans AD-hybrid isolates.

Nineteen Cryptococcus neoformans AD-hybrid isolates were investigated to assess whether hybrid genomic background could affect virulence in a mouse model. The level of heterozygosity of each strain was analyzed using primers specific for allele A and D of 15 polymorphic genes. Virulence was tested in a mouse model of systemic infection by measuring time of survival. In addition, the putative virulence attributes, melanin, phospholipase, and capsule production, as well as growth at 39°C and UV sensitivity were investigated. Eight strains showed to be heterozygous in up to 70% of loci, other eight strains were heterozygous in less than 60% of loci, while the remaining three strains were homozygous at all tested loci. Mice infected with hybrids with a high percentage of heterozygosis showed significantly (P < 0.01) shorter survival than mice infected with the other hybrids. Mortality was not correlated with the mating-type locus pattern, as well as it was not correlated with the level of expression of the different virulence attributes investigated. The present study confirms that hybridization in C. neoformans could represent an important evolutionary driving force in increasing the fitness of this yeast in the environment and in the host.

Exploring Mitogenomes Diversity of Fusarium musae from Banana Fruits and Human Patients.

Fusarium musae has recently been described as a cross-kingdom pathogen causing post-harvest disease in bananas and systemic and superficial infection in humans. The taxonomic identity of fungal cross-kingdom pathogens is essential for confirming the identification of the species on distant infected hosts. Understanding the level of variability within the species is essential to decipher the population homogeneity infecting human and plant hosts. In order to verify that F. musae strains isolated from fruits and patients are part of a common population and to estimate their overall diversity, we assembled, annotated and explored the diversity of the mitogenomes of 18 F. musae strains obtained from banana fruits and human patients. The mitogenomes showed a high level of similarity among strains with different hosts' origins, with sizes ranging from 56,493 to 59,256 bp. All contained 27 tRNA genes and 14 protein-coding genes, rps3 protein, and small and large ribosomal subunits (rns and rnl). Variations in the number of endonucleases were detected. A comparison of mitochondrial endonucleases distribution with a diverse set of Fusarium mitogenomes allowed us to specifically discriminate F. musae from its sister species F. verticillioides and the other Fusarium species. Despite the diversity in F. musae mitochondria, strains from bananas and strains from human patients group together, indirectly confirming F. musae as a cross-kingdom pathogen.

In Vitro Antifungal Activity of Ibrexafungerp (SCY-078) Against Contemporary Blood Isolates From Medically Relevant Species of Candida: A European Study.

Background: Ibrexafungerp (SCY-078) is the newest oral and intravenous antifungal drug with broad activity, currently undergoing clinical trials for invasive candidiasis. Objective: The aim of this study was to assess the in vitro activity of ibrexafungerp and comparators against a collection of 434 European blood isolates of Candida. Methods: Ibrexafungerp, caspofungin, fluconazole, and micafungin minimum inhibitory concentrations (MICs) were collected from 12 European laboratories for 434 blood isolates, including 163 Candida albicans, 108 Candida parapsilosis, 60 Candida glabrata, 40 Candida tropicalis, 29 Candida krusei, 20 Candida orthopsilosis, 6 Candida guilliermondii, 2 Candida famata, 2 Candida lusitaniae, and 1 isolate each of Candida bracarensis, Candida catenulata, Candida dubliniensis, and Candida kefyr. MICs were determined by the EUCAST broth microdilution method, and isolates were classified according to recommended clinical breakpoints and epidemiological cutoffs. Additionally, 22 Candida auris from different clinical specimens were evaluated. Results: Ibrexafungerp MICs ranged from 0.016 to ≥8 mg/L. The lowest ibrexafungerp MICs were observed for C. albicans (geometric MIC 0.062 mg/L, MIC range 0.016-0.5 mg/L) and the highest ibrexafungerp MICs were observed for C. tropicalis (geometric MIC 0.517 mg/L, MIC range 0.06-≥8 mg/L). Modal MICs/MIC50s (mg/L) against Candida spp. were 0.125/0.06 for C. albicans, 0.5/0.5 for C. parapsilosis, 0.25/0.25 for C. glabrata, 0.5/0.5 for C. tropicalis, 1/1 for C. krusei, 4/2 for C. orthopsilosis, and 0.5/0.5 for C. auris. Ibrexafungerp showed activity against fluconazole- and echinocandin-resistant isolates. If adopting wild-type upper limits, a non-wild-type phenotype for ibrexafungerp was only observed for 16/434 (3.7%) isolates: 11 (4.6%) C. parapsilosis, 4 (5%) C. glabrata, and 1 (2.5%) C. tropicalis. Conclusion: Ibrexafungerp showed a potent in vitro activity against Candida.