Candidaemia is the most common healthcare-associated invasive fungal infection. The evolution of the epidemiology of candidaemia in Italy has not been assessed, except at the local level. The primary objective of this study is monitoring changes in the epidemiology of candidaemia and in the susceptibility profiles of Candida isolates between 2015 and 2023. This retrospective multicentre study (2015–2023), involved 11 tertiary-care hospital microbiology laboratories across the Italian country. The confirmed candidaemia episodes were included and demographic data, hospital ward, species identification, and antifungal susceptibility profiles (Sensititre Yeast One) were collected. 6,927 candidaemia cases were identified; incidence increased from 1.1/1000 hospitalisations in 2017 to 2.3/1000 in 2020–2021, peaking during the COVID-19 pandemic, and declined in 2023 while remaining above prepandemic levels. Patients older than 65 years accounted for most infections. Medical wards represented the main setting of occurrence, followed by intensive care units, especially during pandemic years. C. albicans remained the most common species (45.4

Emergence of azole-resistant Aspergillus fumigatus represents a concern for public health worldwide. Here we applied a spatial analysis to a large number of records on A. fumigatus azole resistance in the Netherlands to evaluate the relationship of a set of environmental factors with the emergence of resistant isolates and to identify the potential risk areas. A total of 1850 aspergillosis cases were included in the analysis: 1559 caused by wild-type (WT) and 291 by azole-resistant (RES) strains. High-resolution maps containing environmental variables (climate, crop cultivations) were used as layers for spatial analysis. QGIS software was used for transformation and calculation of layers, and visualizing maps, whereas MaxEnt software was used to perform spatial analysis. A separate distribution map for WT and RES was generated using each layer, then the ratio between RES and WT suitability was calculated, and a new map was generated showing the areas where suitability of RES was higher than WT (ratio > 1). Layers presenting areas with a ratio > 1 were then used for a further analysis including all these layers together to generate a final risk map, to identify the most contributing environmental variables, and to estimate the number of people potentially exposed to the risk. Results showed that the areas with the highest RES/WT ratio were associated with the following variables: legume cultivations ratio 1.5–2.7; fruit tree plantations, ratio 2.1; dump sites and artificial sites, ratio 2.3–2.7; spring minimum and mean temperatures, ratio 1.6–1.8. Areas with medium, high, and very high risk covered a surface of about 2330 km2 and people exposed were >319,000, with Zeeland and Noord-Holland being the provinces with the highest risk. All together these results suggest that azole-resistance emergence is a complex phenomenon depending on a multitude of environmental variables that are not yet been fully explored.

Aspergillus fumigatus is a common fungus which has gained attention due to its resistance to azole compounds, substances used in both medical and agricultural settings. One of the genetic alterations responsible for this resistance is the mutation TR34/L98H in the cyp51A gene. The aim of this study was to understand the impact of azoles and non-azoles on Aspergillus fumigatus. By examining clinical samples, soil samples, and compost material, this research aims to provide insights into the susceptibility of these strains to antifungal substances. To deepen our understanding of the factors potentially involved in antifungal resistance, we combined in vitro studies of sixteen compounds against Aspergillus fumigatus with results from the sequencing of the cyp51 gene. We observed that compounds generally displayed a similar pattern activity against wild-type Aspergillus fumigatus. Non-azoles, except Pyrisoxazole and Amisulbrom, did not show any activity against Aspergillus fumigatus, while azole compounds displayed differential activity against the fungus, except for Tetraconazole. For the mutant strains, a generally similar activity was observed in both clinical and environmental samples, likely due to the same mutation in all the isolates. The implications of these findings may be relevant for better understanding the relationship between Aspergillus fumigatus and its ability to develop resistance to antifungal substances.

BACKGROUND:Starting from 2018 onwards, several outbreaks of fluconazole-resistant C. parapsilosis have been reported in many countries worldwide. OBJECTIVES:Here we report a retrospective study on C. parapsilosis blood isolates collected over 7 years (2018-2024) in two hospitals in Northern Italy. PATIENTS/METHODS:The study involved 169 C. parapsilosis isolates collected from individual hospitalised patients. We assessed the antifungal susceptibility of the isolates, evaluated the presence of mutations in the ERG11 gene and performed multilocus microsatellite typing to highlight the genetic relatedness of the strains. All isolates were also tested for their ability to produce biofilm. RESULTS:Among the 169 clinical isolates, 124 (73.4%) were classified as fluconazole-resistant C. parapsilosis (FRCP) and 45 (26.6%) as fluconazole-susceptible (FSCP). ERG11 sequencing highlighted that the most frequent mutation in FRCP is the Y132F (118/124, 95.2%). None of the FSCP carried the Y132F. Microsatellite genotyping showed five major clusters and 13 sub-clusters, formed by isolates sharing identical genotypes. Sub-cluster R1 included 96 FRCP carrying the Y132F substitution, isolated from 2018 to 2024 in both hospitals. Interestingly, 99.1% of the FRCP carrying the Y132F mutation were categorised as low biofilm formers, while FRCP carrying other ERG11 mutations were categorised as medium or high biofilm formers. CONCLUSIONS:Our results confirmed that Y132F may be mainly responsible for azole resistance in C. parapsilosis and inter-hospital spread. As we found, recent clinical studies indicate that FRCP isolates responsible for severe outbreaks produce thin biofilms. Mutated and therefore resistant strains may exhibit reduced biofilm production as a protective mechanism.

Fusarium verticillioides is an important plant pathogen in maize and other cereals that is seldom detected as the cause of human fusariosis. Here, we provide the analysis of the available diversity of F. verticillioides sequenced worldwide and report the first two genome assemblies and annotations (including mitochondrial DNA) of Fusarium verticillioides from clinical settings. Fusarium verticillioides 05-0160 (IUM05-0160) and Fusarium verticillioides 09-1037 (IUM09-1037) strains were obtained from the bone marrow and blood of two immunocompromised patients, respectively. The phylogenomic analysis confirmed the species identity of our two strains. Comparative genomic analyses among the reannotated F. verticillioides genomes (n = 46) did not lead to the identification of unique genes specific to the clinical samples. Two subgroups in the F. verticillioides clade were also identified and confirmed by a mitochondrial diversity study. Clinical strains (n = 4) were positioned in the multigene phylogenetic tree without any correlation between the host and the tree branches, grouping with plant-derived strains. To investigate the existence of a potential fitness advantage of our two clinical strains, we compared demethylase inhibitor fungicides susceptibility against the reference Fusarium verticillioides 7600, showing, on average, lower susceptibility to agricultural and medical-used antifungals. A significant reduction in susceptibility was observed for itraconazole and tetraconazole, which might be explained by structural changes in CYP51A and CYP51C sequences. By providing the first two annotated genomes of F. verticillioides from clinical settings comprehensive of their mitogenomes, this study can serve as a base for exploring the fitness and adaptation capacities of Fusarium verticillioides infecting different kingdoms.

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 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.

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM Objectives The present study employed data collected during the Mycosands survey to investigate the environmental factors influencing yeasts and molds distribution along European shores by applying a species distribution modeling approach. Methods Occurrence data were compared to climatic datasets (temperature, precipitation, and solar radiation), soil datasets (chemical and physical properties), and water datasets (temperature, salinity, and chlorophyll concentration) downloaded from web databases. All dataset layers were edited and formatted by QGIS software and analyses were performed by MaxEnt software. Results The distribution maps inferred comparing occurrence data on shores for Aspergillus spp., Aspergillus fumigatus, A. flavus, A. niger, Fusarium spp., dematiaceous fungi, and considering all molds, to climatic datasets showed the highest probability of presence along Eastern and South-Central Mediterranean coasts, whereas comparison of water occurrence data to water features identified a high suitability along Eastern Mediterranean coasts, Gulf of Lion, Southern coasts of Spain, and Southern and Central Atlantic coast of Portugal, Southern Atlantic coast of France, Netherlands coasts, the mouth of Danube, coasts of the Ireland sea, and Kuri Lagoon in Lithuania. The main variables contributing to the models were minimum temperatures in winter, water temperature during spring, and chlorophyll concentration. The comparison with soil datasets showed a high tolerance of soils with a high concentration of CaCO3 and basic pH. Nitrogen concentration was tolerated at values below 1 g/kg and phosphorus concentration at values <20 mg/kg and >40 mg/kg. In addition, the model identified a high tolerance to soils rich in nickel. The same analyses were performed for the following groups of occurrence data: Candida spp., Rhodotorula spp., and all yeasts. Results showed the highest probability of presence on shores located along the coasts of Eastern Mediterranean Sea, Southern-Central Mediterranean Sea, Northern Adriatic Sea coasts, Kuri Lagoon, and Northern European coasts from France to Denmark. In waters, high suitability areas were located along the coasts of Northern Black Sea, Northern Adriatic Sea, coasts of Ireland Sea, Western Atlantic coast of France, and the Northern European coasts from France to western Denmark. The most relevant variables contributing to the model were minimum temperatures during winter and water chlorophyll concentration. The comparison with soil features showed similar results to those obtained for molds, except a high tolerance for soils rich in cadmium. Conclusions All together our results suggest a different probability of distribution of yeasts and molds along European shores. Yeasts seem to tolerate low temperatures better during winter than molds and this reflects a higher suitability for the Northern European coasts. This difference is more evident considering suitability in waters. Both distributions of molds and yeasts are influenced by basic soil pH, probably because acidic soils are more favorable to bacterial growth. Soils with high nitrogen concentrations are not suitable for fungal growth, which, in contrast, are optimal for plant growth, favored by this environment. Finally, molds show affinity with soil rich in nickel and yeasts with soils rich in cadmium resulting in a distribution mainly at the mouths of European rivers or lagoons, where these metals accumulate in river sediments.

Abstract Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Objectives In Italy, a prevalence of 16.9% of resistance to clinical azoles was observed among Aspergillus fumigatus isolates from an agricultural environment. This spread of azole-resistance is attributed to the widespread use of 14a-demethylase inhibitors (DMIs). The aims of the present study were to investigate: the DMIs resistance in Italian A. fumigatus strains of clinical and environmental origin, both susceptible and resistant to clinical azoles; the molecular mechanism of resistance in strains susceptible to clinical azoles but resistant to at least one of the tested DMIs; the in vitro DMI resistance induced by prolonged exposure to DMIs in susceptible clinical and environmental strains, and the molecular mechanism of resistance. Methods A total of 54 A. fumigatus strains were selected: 23 susceptible to clinical azoles (CAS) and 31 resistant (CAR) with and without mutations in the CYP51A gene (TR34/L98H, F219I, G54R, G54E, D269Y, M220I, or F46Y/M172V/N248T/D255E/E427K). Antifungal susceptibility testing was performed for 8 DMIs (tebuconazole, epoxiconazole, difenoconazole, propiconazole, tetraconazole, flusilazole, fenbuconazole, and prochloraz) using broth microdilution method according to EUCAST and CLSI methods. Mutations in CYP51A, CYP51B, and HMG1 genes were investigated in CAS with DMI high MIC values. In vitro induction of resistance was performed using the 8 DMIs on 11 (6 clinical and 5 environmental) A. fumigatus strains susceptible both to clinical azoles and DMIs. A suspension of 106 conidia was inoculated on glucose-yeast extract-peptone agar plates containing different DMIs at different concentrations and incubated at 37°C for 72 h for six repeated passages. Results Comparable results were obtained using EUCAST and CLSI methods. Resistance (MIC ≥16) to tetraconazole and fenbuconazole was observed in 100% of isolates, both CAR and CAS. On the contrary, a statistically significant difference in tebuconazole, epoxiconazole, difenoconazole, propiconazole, and flusilazole MICs between CAR strains and CAS strains was observed with higher geometric means (GM) in CAR (range 4.9-9.3 mg/L) than in CAS (1.5-2.7 mg/L) strains. Prochloraz showed the lowest GMs: 0.6 and 0.25 mg/L in CAR and CAS strains, respectively. A significant difference of the GMs for all the DMIs tested, except prochloraz, was observed between the isolates harboring a TR34/L98H or a M220I mutation (GM range 10.4-16 mg/L) and those with other CYP51A mutations (GM range 1-4.6 mg/L). In the CAS showing high DMI MICs, the absence of CYP51A mutations was confirmed, while a synonymous mutation P394P, was identified in CYP51B. No mutations in HMG1 gene were found. In the induction tests, the prolonged exposure to DMIs showed an induced phenotypic resistance of 100% (11/11 isolates) for epoxiconazole, of 72.7% (8/11) for propiconazole, of 54% (6/11) for tebuconazole and difenoconazole, and of 9.1% (1/11) for prochloraz. Molecular analysis to understand if the phenotypic resistance corresponds to induced mutations in CYP51A, CYP51B, and HMG1 genes is in progress. Conclusions Preliminary results confirm cross-resistance between clinical azoles and DMIs, with MIC differences between CAR and CAS and between strains with different mutations in the CYP51A gene. Furthermore, the ability of DMIs to induce resistance in vitro was highlighted.

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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.

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/MIC 50 s (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 .

Millerozyma farinose is a halotolerant yeast that has recently been described as an emerging human pathogen, especially in immunocomprom ised patients. Both the diagnostic process and treatment options are still unclear. Here, we report a case of an immunocompetent oncological patient who developed a catheter -related bloodstream infection (CRBSI) with a concomitant respiratory tract infection caused by M. farinosa. In this report, we discuss how prompt microbiological identification and attentive evaluation of the patient's clinical status can play a significant role in the appropriate management of infections caused by uncommon fungi. MALDI-TOF technology has also substantially improved the timely diagnosis of rare fungi. Furthermore, our diagnosis was subsequently confirmed by 5.8S rRNA sequencing. In our patient, the rapid diagnosis of fungaemia was crucial, together with catheter removal and the initiation of antifungal treatment, for the patient's clinical improvement.

Millerozyma farinose is a halotolerant yeast that has recently been described as an emerging human pathogen, especially in immunocompromised patients. Both the diagnostic process and treatment options are still unclear. Here, we report a case of an immunocompetent oncological patient who developed a catheter-related bloodstream infection (CRBSI) with a concomitant respiratory tract infection caused by M. farinosa. In this report, we discuss how prompt microbiological identification and attentive evaluation of the patient's clinical status can play a significant role in the appropriate management of infections caused by uncommon fungi. MALDI-TOF technology has also substantially improved the timely diagnosis of rare fungi. Furthermore, our diagnosis was subsequently confirmed by 5.8S rRNA sequencing. In our patient, the rapid diagnosis of fungaemia was crucial, together with catheter removal and the initiation of antifungal treatment, for the patient's clinical improvement.

Fusarium musae belongs to the Fusarium fujikuroi species complex. It causes crown rot disease in banana but also keratitis and skin infections as well as systemic infections in immunocompromised patients. Antifungal treatments in clinical and agricultural settings rely mostly on molecules belonging to the azole class. Given the potential risk of pathogen spread from food to clinical settings, the goal of the work was to define the level of susceptibility to different azoles of a worldwide population of F. musae. Eight fungicides used in agriculture and five antifungals used in clinical settings (4 azoles and amphotericin B) were tested using the CLSI (Clinical and Laboratory Standards Institute) protocol methodology on 19 F. musae strains collected from both infected patients and bananas. The level of susceptibility to the different active molecules was not dependent on the source of isolation with the exception of fenbuconazole and difenoconazole which had a higher efficiency on banana-isolated strains. Minimal inhibitory concentrations (MICs) of the different molecules ranged from 0.12–0.25 mg/L for prochloraz to more than 16 mg/L for tetraconazole and fenbuconazole. Compared to the F. verticillioides, F. musae MICs were higher suggesting the importance of monitoring the potential future spread of this species also in clinical settings.

Scientific communication is facilitated by a data-driven, scientifically sound taxonomy that considers the end-user's needs and established successful practice. In 2013, the Fusarium community voiced near unanimous support for a concept of Fusarium that represented a clade comprising all agriculturally and clinically important Fusarium species, including the F. solani species complex (FSSC). Subsequently, this concept was challenged in 2015 by one research group who proposed dividing the genus Fusarium into seven genera, including the FSSC described as members of the genus Neocosmospora, with subsequent justification in 2018 based on claims that the 2013 concept of Fusarium is polyphyletic. Here, we test this claim and provide a phylogeny based on exonic nucleotide sequences of 19 orthologous protein-coding genes that strongly support the monophyly of Fusarium including the FSSC. We reassert the practical and scientific argument in support of a genus Fusarium that includes the FSSC and several other basal lineages, consistent with the longstanding use of this name among plant pathologists, medical mycologists, quarantine officials, regulatory agencies, students, and researchers with a stake in its taxonomy. In recognition of this monophyly, 40 species described as genus Neocosmospora were recombined in genus Fusarium, and nine others were renamed Fusarium. Here the global Fusarium community voices strong support for the inclusion of the FSSC in Fusarium, as it remains the best scientific, nomenclatural, and practical taxonomic option available.

Candidemia and invasive candidiasis are the most common healthcare-associated invasive fungal infections, with a crude mortality rate of 25-50%. Candida albicans remains the most frequent etiology, followed by C. glabrata, C. parapsilosis and C. tropicalis. With the exception of a limited number of species (ie: C. krusei, C. glabrata and rare Candida species), resistance to fluconazole and other triazoles are quite uncommon. However, recently fluconazole-resistant C. parapsilosis, echinocandin-resistant C. glabrata and the multidrug resistant C. auris have emerged. Resistance to amphotericin B is even more rare due to the reduced fitness of resistant isolates. The mechanisms of antifungal resistance in Candida (altered drug-target interactions, reduced cellular drug concentrations, and physical barriers associated with biofilms) are analyzed. The choice of the antifungal therapy for candidemia must take into account several factors such as type of patient, presence of devices, severity of illness, recent exposure to antifungals, local epidemiology, organs involvement, and Candida species. The first-line therapy in non-neutropenic critical patient is an echinocandin switching to fluconazole in clinically stable patients with negative blood cultures and azole susceptible isolate. Similarly, an echinocandin is the drug of choice also in neutropenic patients. The treatment duration is 14 days after the first negative blood culture or longer in cases of organ involvement. An early removal of vascular catheter improves the outcome. The promising results of new antifungal molecules, such as the terpenoid derivative ibrexafungerp, the novel echinocandin with an enhanced half-life rezafungin, oteseconazole and fosmanogepix, representative of new classes of antifungals, are discussed.

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.