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An abstract of the article "ECMM Survey of Candidemia in Italy: In Vitro Susceptibility of Non-Albicans Candida Species," by E. Biraghi and colleagues is presented.

In this exploratory study, we measured for the first-time human exposure to about 90 semi-volatile organic chemicals (SVOCs) in France and Italy using silicone wristbands. Participants in France (n = 40) and in Italy (n = 31) wore a silicone wristband for five days during 2018 and 2019. Samples were analyzed for 39 polybrominated diphenyl ethers (PBDEs), 10 novel brominated flame retardants (nBFRs), 25 organophosphate esters (OPEs), and 18 polycyclic aromatic hydrocarbons (PAHs). In both groups, the most commonly detected chemicals were BDE-209, BEHTBP, tris[(2R)-1-chloro-2-propyl] phosphate (TCIPP), and phenanthrene among PBDEs, nBFRs, OPEs, and PAHs, respectively. The concentrations of ∑ 39 PBDEs, ∑ 10 nBFRs, ∑ 25 OPEs, ∑ 18 PAHs, and of most individual chemicals were generally significantly higher in samples from France than in those from Italy, except for BDE-209 and TCIPP. On a broader scale, the chemical concentrations were generally significantly lower in this study than those measured in the United States in previous studies using the same type of wristbands. Efforts to standardize the protocols for the use of silicone wristbands are still needed but this study shows that wristbands are capable of capturing regional differences in human exposure to a large variety of SVOCs and, therefore, can be used as personal exposure monitor for studies with global coverage., Competing Interests: Declaration of competing interest The work submitted here has not been published previously, it is not under consideration for publication elsewhere, its publication is approved by all authors, and if accepted, it will not be published elsewhere in the same form, in English or in any other language, including electronically without the written consent of the copyright-holder., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The aims of the study were to analyze the clinical and epidemiological characteristics and treatments for patients who developed zygomycosis enrolled in Italy during the European Confederation of Medical Mycology of medical mycology survey. This prospective multicenter study was performed between 2004 and 2007 at 49 italian Departments. 60 cases of zygomycosis were enrolled: the median age was 59.5 years (range 1-87), with a prevalence of males (70%). The majority of cases were immunocompromised patients (42 cases, 70%), mainly hematological malignancies (37). Among non-immunocompromised (18 cases, 30%), the main category was represented by patients with penetrating trauma (7/18, 39%). The most common sites of infection were sinus (35%) with/without CNS involvement, lung alone (25%), skin (20%), but in 11 cases (18%) dissemination was observed. According to EORTC criteria, the diagnosis of zygomycosis was proven in 46 patients (77%) and in most of them it was made in vivo (40/46 patients, 87%); in the remaining 14 cases (23%) the diagnosis was probable. 51 patients received antifungal therapy and in 30 of them surgical debridement was also performed. The most commonly used antifungal drug was liposomal amphotericin B (L-AmB), administered in 44 patients: 36 of these patients (82%) responded to therapy. Altogether an attributable mortality rate of 32% (19/60) was registered, which was reduced to 18% in patients treated with L-AmB (8/44). Zygomycosis is a rare and aggressive filamentous fungal infection, still associated with a high mortality rate. This study indicates an inversion of this trend, with a better prognosis and significantly lower mortality than that reported in the literature. It is possible that new extensive, aggressive diagnostic and therapeutic procedures, such as the use of L-AmB and surgery, have improved the prognosis of these patients.

At the Istituto Ricovero Cura Carattere Scientifico, Ospedale Maggiore di Milano, Italy, Candida pelliculosa accounted for 3.3 and 4.4 % of all Candida species other than Candida albicans collected during 1996 and 1998, respectively. Genetic variability was investigated by electrophoretic karyotyping and inter-repeat PCR, and the susceptibility to five antifungal agents of 46 strains isolated from 37 patients during these 2 years was determined. Combination of the two typing methods yielded 14 different DNA types. Although the majority of DNA types were randomly distributed among different units, one DNA type was significantly more common in patients hospitalized in a given unit compared with those from other wards (P=0.034), whereas another DNA type was more frequently isolated in patients hospitalized during 1996 than in those hospitalized during 1998 (P=0.002). Fluconazole, itraconazole and posaconazole MIC90 values were 16, 1 and 4 microg ml-1, respectively. All isolates but three were susceptible in vitro to flucytosine. All isolates were susceptible in vitro to amphotericin B. These data suggest that there are possible relationships among strains of C. pelliculosa, wards and time of isolation. Amphotericin B seems to be the optimal drug therapy in infections due to this yeast species.

Deep-seated candidosis is a major problem in critically ill patients. Colonization with candida has been identified as an important independent risk factor for the development of candidaemia. Since the 1980s routine surveillance cultures have been performed on patients admitted for six or more days to the 'E. Vecla' intensive care unit (ICU) of the IRCCS Ospedale Maggiore di Milano. Colonization was observed on admission to the ICU in 59 of 117 (50%) patients in 2000 and 10 others developed colonization during their stay on the unit. A similar colonization rate was found in a survey performed 16 years earlier. The incidence of non-albicans Candida species, however, increased in 2000. In particular, 24 patients were culture positive for Candida glabrata at some point during their hospital stay, whereas this species was isolated from only one patient in 1983-1984. Antifungal susceptibility testing performed by Sensititre Yeast One revealed no resistance among 19 C. albicans strains tested. In contrast, fluconazole resistance was observed in two of 39 (5%) C. glabrata isolates from 23 patients. In the period 1983-2002, 28 candida bloodstream infections were identified and 12 were considered to be ICU-acquired (2.6/1000 hospitalized patients; 0.33/1000 patient days). The low rate of ICU-acquired candidaemia despite the inclusion of severely compromised patients in this study confirms the usefulness of routine mycological surveillance in preventing deep-seated candidosis.

Aspergillus fumigatus infection in hospitalized immunocompromised patients often raises suspicion regarding the potential for hospital acquisition. Hospital staff have an important responsibility in implementing preventive measures, especially since the advent of current legislation concerning hospital-acquired infections. There have been high expectations that molecular typing methods might determine the source of Aspergillus fumigatus, a ubiquitous mould. The aim of the present epidemiological study, was therefore, to identify the origin(s) of Aspergillus infection in six well-documented patients. All the clinical strains (N=33), and those from hospital (N=14) and home environments (N=34) were isolated according to a standardized protocol and typed by sequence-specific DNA primer analysis. The results confirmed the huge biodiversity of the A. fumigatus population, and consequently the difficulty in ascertaining a hospital source of the infection, as opposed to infections due to other Aspergillus species less frequently encountered.

Cryptococcus neoformans is a heterothallic basidiomycete which possesses a bipolar mating system based on two mating type alleles, MATa and MATalpha. In the type variety, C. neoformans var. neoformans, both mating types have been found among strains of one serotype, serotype D, whereas only MATalpha was identified after extensive survey of serotype A strains. Serotype A MA Ta appeared to be extinct or to exist only in a vestigial, non-functional form. We report the isolation of a C. n. var. neoformans serotype A MATa strain from the Italian environment. The strain was serotyped by slide agglutination test, genotyped by polymerase chain reaction (PCR) fingerprinting using the (GACA)4 primer, and its haploid state was determined by flow cytometry. The mating type was identified by PCR amplification of the pheromone a gene. In addition, the amplification of the four STE20 alleles, specific for the mating type of serotypes A and D, showed that the strain contains only the MATa locus. By crossing experiments the strain was found to be fertile. The interest in the finding of this fertile isolate is related to the possibility to construct a congenic pair of serotype A MATa/MATalpha strains to be used in genetic and pathogenesis studies.

Histoplasmosis is endemic in some areas of United States and in South America, and generally causes an acute self-limiting respiratory infection. In elderly and immunosuppressed patients the infection can spread through the blood, causing a severe systemic illness. Here we describe two cases of disseminated histoplasmosis in AIDS patients. The first was observed in an Italian woman who had never visited endemic countries, and was recognized only at autopsy; the second was observed in a trans-sexual patient, arrived in Italy from Brazil. Clinical suspicion of histoplasmosis is important in immunocompromised patients of non-endemic areas as symptoms are often aspecific and misdiagnosis is frequent.

We report a case of bilateral adrenal incidentaloma caused by the capsulatum variety of Histoplasma capsulatum diagnosed in a 74 years old man born in and a life time resident of Treviso, Italy, with the exception of two years spent in Pakistan (1964-1966) as a well-driller. The patient was hospitalized in 1995 for alcoholic chronic hepatitis, chronic Helicobacter pylori gastritis and post-infarction ischemic cardiomyopathy. Abdominal ultrasound incidentally showed bilateral adrenal masses (the right one 6.3 cm in diameter) confirmed by computed tomography, with adrenal function within normal limits. After three months, the patient was again hospitalized due to evening fever, asthenia, anorexia, weight loss and occasional hyperhidrosis. Abdominal ultrasound showed an increase of the right adrenal lesion with normal adrenal function. Ultrasound-guided fine needle aspiration did not prove useful for diagnosis. Accordingly, a laparotomy with bilateral biopsy was performed; histology showed the presence of numerous tissue form cells of H. capsulatum variety capsulatum. Serum anti-H. capsulatum antibodies were negative. Since March, 1996, the patient was given itraconazole and his symptoms quickly regressed but the computed tomography findings, however, have not changed and the patient has adrenal hypofunction that is being treated with cortisone acetate.

The genotypes of 50 isolates of Aspergillus fumigatus from 11 patients with invasive aspergillosis, obtained from three hospitals in different geographical areas, were determined by multilocus enzyme electrophoresis (MLEE). The study analysed the genetic polymorphism of multiple isolates from the first sample. Seven of the 14 enzymic loci studied were polymorphic, giving rise to eight different electrophoretic types. For nine of 11 patients studied, no polymorphism was observed in isolates within the first clinical sample. Analysis of genetic distance between electrophoretic types demonstrated a genetic heterogeneity within each geographical site. Moreover, some genotypes were preferentially found in a given area and this revealed a population structure within these geographical sites. Therefore, the epidemiology of A. fumigatus should be considered separately for each of these areas. The multiple discriminatory markers of MLEE seem to provide a powerful tool for increasing the understanding of the biology of this fungus.

This study investigated the source of infection and strain relatedness of Aspergillus fumigatus isolates from bronchial colonisation and invasive aspergillosis (IA) in four transplant patients. Environmental isolates from the patient's home and from the hospital and infecting isolates were obtained for patient A who developed IA. Clinic environmental and colonising isolates were obtained for patient B. Sequential isolates were obtained from various organs from patient C who developed IA and also from patient D who had a bronchitic aspergillosis that developed into IA. Ninety-one A. fumigatus isolates were analysed by three typing methods: multi-locus enzyme electrophoresis (MLEE), random amplified polymorphic DNA (RAPD) and sequence-specific DNA primers (SSDP). The three combined typing methods demonstrated a greater differentiation of isolates than the typing methods used separately or in pairs. This demonstrated the genotypic variability of A. fumigatus and facilitated better epidemiological analysis. Large polymorphisms were demonstrated for each patient isolate between and colonies within various samples. The relatedness of the isolates suggested nosocomially acquired aspergillosis for patient B, but the source of infection for patient A remained unclear. The results suggested at least three multiple infections among the four patients. This study enabled the identification of the source of infection and strain relatedness, which in turn facilitates the development of preventive measures for patient management in the future.

Cryptococcus neoformans strains isolated from 207 HIV positive and HIV negative patients hospitalized in Northern Italy were serotyped by slide agglutination. One Brazilian HIV negative woman was infected by var. gattii serotype B and all the other patients by var. neoformans, serotype D in 71%, serotype A in 24.6% and serotype AD in 3.4%. No difference was observed between subjects with serotypes A and D in HIV coinfection, exposure categories for AIDS, age, sex, and CD4 count of HIV positive patients. Meningeal and respiratory tract involvements and prostatic reservoir occurred with comparable frequency in AIDS patients infected by serotypes A and D. Skin lesions were observed only in serotype D infections, occurring in 12.6% of HIV positive and 58.3% of HIV negative patients infected by this serotype. Serotype A was found less susceptible to fluconazole than serotype D: 53.7% of serotype A strains had a MIC > or = 25 micrograms ml-1 compared to 17.7% of the serotype D isolates. On the other hand, both serotypes were highly susceptible to itraconazole.

A case of disseminated penicilliosis marneffei, the first to be diagnosed in Italy, is described in a male HIV-positive drug addict. The patient had visited Thailand several times in the two years prior to his hospitalization. The presenting signs were fever, productive cough, facial skin papules and pustules, nodules on both thumbs and oropharyngeal candidiasis. Penicillium marneffei was isolated from a series of blood specimens with the lysis centrifugation procedure. Septate, yeast-like cells were observed in histological sections of the nodules and sputum smears. The patient was treated for 6 weeks with amphotericin B (total dosage 1,400 mg) and flucytosine (150 mg/kg/die) for the first 3 weeks. Prompt clinical improvement and sterilization of all biological specimens were attained. Itraconazole was administered as maintenance therapy (400 mg/die for the first month and 200 mg afterward). During the follow-up period, no relapse was observed. The patient, however, did succumb to a variety of non-mycotic infections and died nine months after start of therapy. At autopsy, P. marneffei was not detected in his tissues. Serological studies were performed with a micro-immunodiffusion procedure using a mycelial culture filtrate antigen of P. marneffei. Sera taken early in the course of the disease gave positive antibody reactions. Whereas sera taken 3-5 months following therapy were negative. All known cases of penicilliosis marneffei in bamboo rats and in humans among the inhabitants and visitors to the endemic areas of P. marneffei in South East Asia and Indonesia are summarized.