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This study analyzed the epidemiology of bloodstream infections due to Candida spp. in a tertiary referral hospital of Ancona, Italy, and their susceptibility to antifungals. The retrospective observational study from January 2010 to December 2018 identified 504 episodes of candidemia in 461 patients. Although Candida albicans remained the species most frequently isolated, Candida spp. other than C. albicans caused 49% of the overall episodes of candidemia. According to CLSI interpretation, most of the isolates resulted susceptible to antifungals. Azoles vs Candida tropicalis represented an exception. Echinocandin non-susceptibility was rare across the species. In conclusion, with the exception of C. tropicalis, the isolation of a non-susceptible Candida strains against azoles, echinocandins and amphotericin B was a rare event.

Objectives Terbinafine resistance is increasingly reported in Trichophyton, rendering susceptibility testing particularly important in non-responding cases. We performed a multicentre evaluation of six EUCAST-based methods. Methods Ten laboratories susceptibility tested terbinafine, itraconazole, voriconazole and amorolfine against a blinded panel of 38 terbinafine WT and target gene mutant isolates. E.Def 9.3.1 modifications included: medium with/without addition of chloramphenicol and cycloheximide (CC), incubation at 25°C to 28°C for 5–7 days and three MIC endpoints [visually and spectrophotometrically (90%/50% inhibition)], generating 7829 MICs. Quality control (QC) strains were Aspergillus flavus ATCC 204304 and CNM-CM1813. Eyeball, ECOFFinder (where ECOFF stands for epidemiological cut-off) and derivatization WT upper limits (WT-ULs), very major errors (VMEs; mutants with MICs ≤WT-ULs) and major errors (MEs; WT isolates with MICs >WT-ULs) were determined. Results MICs fell within the QC ranges for ATCC 204304/CNM-CM1813 for 100%/96% (voriconazole) and 84%/84% (itraconazole), respectively. Terbinafine MICs fell within 0.25–1 mg/L for 96%/92%, suggesting high reproducibility. Across the six methods, the number of terbinafine MEs varied from 2 to 4 (2.6%–5.2%) for Trichophyton rubrum and from 0 to 2 (0%–2.0%) for Trichophyton interdigitale. Modes for WT and mutant populations were at least seven 2-fold dilutions apart in all cases. Excluding one I121M/V237I T. rubrum mutant and two mixed WT/mutant T. interdigitale specimens, the numbers of VMEs were as follows: T. rubrum: CC visual, 1/67 (1.5%); CC spectrophotometric 90% inhibition, 3/59 (5.1%); and CC spectrophotometric 50% inhibition, 1/67 (1.5%); and T. interdigitale: none. Voriconazole and amorolfine MICs were quite uniform, but trailing growth complicated determination of itraconazole visual and spectrophotometric 90% inhibition MIC. Conclusions Although none of the laboratories was experienced in dermatophyte testing, error rates were low. We recommend the CC spectrophotometric 50% inhibition method and provide QC ranges and WT-ULs for WT/non-WT classification.

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.

Objectives To analyse the impact of cefiderocol use on outcome in patients admitted to the ICU for severe COVID-19 and further diagnosed with carbapenem-resistant Acinetobacter baumannii (CR-Ab) infection. Methods Retrospective multicentre observational study was performed at four Italian hospitals, from January 2020 to April 2021. Adult patients admitted to ICU for severe COVID-19 and further diagnosed with CR-Ab infections were enrolled. Patients treated with cefiderocol, as compassionate use, for at least 72 h were compared with those receiving alternative regimens. Primary endpoint was all-cause 28 day mortality. The impact of cefiderocol on mortality was evaluated by multivariable Cox regression model. Results In total, 107 patients were enrolled (76% male, median age 65 years). The median time from ICU admission to CR-Ab infection diagnosis was 14 (IQR 8–20) days, and the main types of CR-Ab infections were bloodstream infection (58%) and lower respiratory tract infection (41%). Cefiderocol was administered to 42 patients within a median of 2 (IQR 1–4) days after CR-Ab infection diagnosis and as monotherapy in all cases. The remaining patients received colistin, mostly (82%) administered as combination therapy. All-cause 28 day mortality rate was 57%, without differences between groups (cefiderocol 55% versus colistin 58% P = 0.70). In multivariable analysis, the independent risk factor for mortality was SOFA score (HR 1.24, 95% CI 1.15–1.38, P Conclusions Our study confirms the potential role of cefiderocol in the treatment of CR-Ab infection, but larger clinical studies are needed.

Systemic infections due to Candida spp. is common among immunocompromised patients, including those with solid tumors (ST). Clinical characteristics of candidemia in 114 patients with ST were compared with those of 249 candidemic patients without ST (non-ST). Patients with ST were more likely to be hospitalized in medical departments, to have a significantly higher Charlson’s score and to undergo a significantly later central venous catheter (CVC) removal (P

Objectives To analyse the impact of cefiderocol use on outcome in patients admitted to the ICU for severe COVID-19 and further diagnosed with carbapenem-resistant Acinetobacter baumannii (CR-Ab) infection. Methods Retrospective multicentre observational study was performed at four Italian hospitals, from January 2020 to April 2021. Adult patients admitted to ICU for severe COVID-19 and further diagnosed with CR-Ab infections were enrolled. Patients treated with cefiderocol, as compassionate use, for at least 72 h were compared with those receiving alternative regimens. Primary endpoint was all-cause 28 day mortality. The impact of cefiderocol on mortality was evaluated by multivariable Cox regression model. Results In total, 107 patients were enrolled (76% male, median age 65 years). The median time from ICU admission to CR-Ab infection diagnosis was 14 (IQR 8–20) days, and the main types of CR-Ab infections were bloodstream infection (58%) and lower respiratory tract infection (41%). Cefiderocol was administered to 42 patients within a median of 2 (IQR 1–4) days after CR-Ab infection diagnosis and as monotherapy in all cases. The remaining patients received colistin, mostly (82%) administered as combination therapy. All-cause 28 day mortality rate was 57%, without differences between groups (cefiderocol 55% versus colistin 58% P = 0.70). In multivariable analysis, the independent risk factor for mortality was SOFA score (HR 1.24, 95% CI 1.15–1.38, P

Objective: To assess the efficacy of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Methods: A multicentre observational study was performed from 22 February through 30 June 2020. We included consecutive adult patients with severe COVID-19, defined as respiratory rate ≥30 breath per minute, oxygen saturation ≤93% on ambient air or arterial partial pressure of oxygen to fraction of inspired oxygen ≤300 mm Hg. We excluded patients being treated with other immunomodulant drugs, receiving low-dose corticosteroids and receiving corticosteroids 72 hours after admission. The primary endpoint was 30-day mortality from hospital admission. The main exposure variable was corticosteroid therapy at a dose of ≥0.5 mg/kg of prednisone equivalents. It was introduced as binomial covariate in a logistic regression model for the primary endpoint and inverse probability of treatment weighting using the propensity score. Results: Of 1717 patients with COVID-19 evaluated, 513 were included in the study, and of these, 170 (33%) were treated with corticosteroids. During hospitalization, 166 patients (34%) met the criteria of the primary outcome (60/170, 35% in the corticosteroid group and 106/343, 31% in the noncorticosteroid group). At multivariable analysis corticosteroid treatment was not associated with lower 30-day mortality rate (adjusted odds ratio, 0.59; 95% confidence interval (CI), 0.20–1.74; p 0.33). After inverse probability of treatment weighting, corticosteroids were not associated with lower 30-day mortality (average treatment effect, 0.05; 95% CI, −0.02 to 0.09; p 0.12). However, subgroup analysis revealed that in patients with PO2/FiO2 < 200 mm Hg at admission (135 patients, 52 (38%) treated with corticosteroids), corticosteroid treatment was associated with a lower risk of 30-day mortality (23/52, 44% vs. 45/83, 54%; adjusted odds ratio, 0.20; 95% CI, 0.04–0.90; p 0.036). Conclusions: The effect of corticosteroid treatment on mortality might be limited to critically ill COVID-19 patients.

Purpose: Candidemia is an alarming problem in critically ill patients including those admitted in intensive care units (ICUs). We aimed to describe the clinical and microbiological characteristics of bloodstream infections (BSIs) due to Candida spp. in patients admitted to ICUs of an italian tertiary referral university hospital over nine years. Methods: A retrospective observational study of all cases of candidemia in adult patients was carried out from January 1, 2010 to December 31, 2018 at a 980-bedded University Hospital in Ancona, Italy, counting five ICUs. The incidence, demographics, clinical and microbiologic characteristics, therapeutic approaches and outcomes of ICU-patients with candidemia were collected. Early (7 days from the occurrence of the episode of Candida BSI) and late (30 days) mortality rates were calculated. Results: During the study period, 188/505 (36%) episodes of candidemia occurred in ICU patients. Incidence rate was 9.9/1000 ICU admission and it showed to be stable over time. Candida albicans accounted for 52% of the cases, followed by C. parapsilosis (24%), and C. glabrata (14%). With the exception of isolates of C. tropicalis which showed to be fluconazole resistant in 25% of the cases, resistance to antifungals was not of concern in our patients. Early and late mortality rates were 19% and 41%, respectively and did not increased significantly over time. Independent risk factors for higher mortality were septic shock, acute kidney failure, pulmonary embolism and lack of antifungal therapy. The type of antifungal therapy did not influence the outcome. Conclusion: Neither incidence rate nor crude mortality of candidemia in ICU patients increased over time at our institution. However, mortality rate remained high and significantly associated with specific host-related factors.

Background The outbreak of COVID-19 has rapidly spread to Italy, including Pesaro-Urbino province. Data on young to middle age adults with COVID-19 are lacking. We report the characteristics, management and health-related quality of life (HRQoL) in patients with COVID-19 aging ≤50 years. Methods A retrospective analysis was performed in all patients ≤50 years with a confirmed diagnosis of COVID-19 admitted to Emergency department (ED) of San Salvatore Hospital in Pesaro from February 28th to April 8th, 2020. Data were collected from electronical medical records. HRQoL was investigated after 1 month from hospital discharge using the SF-36 questionnaire. Outcomes were evaluated between hospitalized and not hospitalized patients. Results Among 673 patients admitted to the ED and diagnosed with COVID-19, 104 (15%) were ≤ 50 years old: 74% were discharged at home within 48 h, 26% were hospitalized. Fever occurred in 90% of the cases followed by cough (56%) and dyspnoea (34%). The most frequent coexisting conditions were hypertension (11%), thyroid dysfunction (8%) and neurological and/or mental disorders [NMDs] (6%). Mean BMI was 27. Hypokalaemia and NMDs were significantly more common in patients who underwent mechanical ventilation. Regardless of hospitalization, there was an impairment in both the physical and mental functioning. Conclusions Overweight and hypertension are frequent conditions in young to middle age adults with COVID-19. Hypokalaemia and NMDs are commonly associated with progressive disease. A significant impact on HRQoL in the early stage of post-discharge is common in this population.

Background Remdesivir is a prodrug with in vitro activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Its clinical efficacy in patients with COVID-19 under mechanical ventilation remains to be evaluated. Methods This study includes patients under mechanical ventilation with confirmed SARS-CoV-2 infection admitted to the ICU of Pesaro hospital between 29 February and 20 March 2020. During this period, remdesivir was provided on a compassionate use basis. Clinical characteristics and outcome of patients treated with remdesivir were collected retrospectively and compared with those of patients hospitalized in the same time period. Results A total of 51 patients were considered, of which 25 were treated with remdesivir. The median (IQR) age was 67 (59–75.5) years, 92% were men and symptom onset was 10 (8–12) days before admission to ICU. At baseline, there was no significant difference in demographic characteristics, comorbidities and laboratory values between patients treated and not treated with remdesivir. Median follow-up was 52 (46–57) days. Kaplan–Meier curves showed significantly lower mortality among patients who had been treated with remdesivir (56% versus 92%, P Conclusions In this study the mortality rate of patients with COVID-19 under mechanical ventilation is confirmed to be high. The use of remdesivir was associated with a significant beneficial effect on survival.

Objectives: We aimed to develop and validate a risk score to predict severe respiratory failure (SRF) among patients hospitalized with coronavirus disease-2019 (COVID-19). Methods: We performed a multicentre cohort study among hospitalized (>24 hours) patients diagnosed with COVID-19 from 22 February to 3 April 2020, at 11 Italian hospitals. Patients were divided into derivation and validation cohorts according to random sorting of hospitals. SRF was assessed from admission to hospital discharge and was defined as: SpO2 30 breaths/min or respiratory distress. Multivariable logistic regression models were built to identify predictors of SRF, β-coefficients were used to develop a risk score. Trial Registration NCT04316949. Results: We analysed 1113 patients (644 derivation, 469 validation cohort). Mean (±SD) age was 65.7 (±15) years, 704 (63.3%) were male. SRF occurred in 189/644 (29%) and 187/469 (40%) patients in the derivation and validation cohorts, respectively. At multivariate analysis, risk factors for SRF in the derivation cohort assessed at hospitalization were age ≥70 years (OR 2.74; 95% CI 1.66–4.50), obesity (OR 4.62; 95% CI 2.78–7.70), body temperature ≥38°C (OR 1.73; 95% CI 1.30–2.29), respiratory rate ≥22 breaths/min (OR 3.75; 95% CI 2.01–7.01), lymphocytes ≤900 cells/mm3 (OR 2.69; 95% CI 1.60–4.51), creatinine ≥1 mg/dL (OR 2.38; 95% CI 1.59–3.56), C-reactive protein ≥10 mg/dL (OR 5.91; 95% CI 4.88–7.17) and lactate dehydrogenase ≥350 IU/L (OR 2.39; 95% CI 1.11–5.11). Assigning points to each variable, an individual risk score (PREDI-CO score) was obtained. Area under the receiver-operator curve was 0.89 (0.86–0.92). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 71.6% (65%–79%), 89.1% (86%–92%), 74% (67%–80%) and 89% (85%–91%), respectively. PREDI-CO score showed similar prognostic ability in the validation cohort: area under the receiver-operator curve 0.85 (0.81–0.88). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 80% (73%–85%), 76% (70%–81%), 69% (60%–74%) and 85% (80%–89%), respectively. Conclusion: PREDI-CO score can be useful to allocate resources and prioritize treatments during the COVID-19 pandemic.

This study analyzed the epidemiology of bloodstream infections due to

Introduction Fungal infections are a significant and increasing public health problem worldwide, that range in severity from mild superficial infections that affect a large proportion of the otherwise healthy population to life-threatening invasive diseases limited mostly to vulnerable immunosuppressed patients (1). Patients that are at risk for fungal infections, those hospitalised with serious underlying diseases, such as those with HIV infection, haemato-oncological malignancies, recipients of immunosuppressive therapies, solid-organ or hematopoietic stem cell transplant (HSCT) recipients (2). The incidence of fungaemia is growing and has dramatically increased within the past two decades. Such infections have been attributed to the common practice of prolonged hospitalisation of highly susceptible patients receiving advanced medical treatment; such conditions render patients more susceptible to invasive fungal infections (3,4)The populations of patients at risk have expanded to include those with usually multiple underlying medical conditions, such as diabetes mellitus, chronic obstructive pulmonary diseases and those receiving corticosteroids (3,4) The current number of fungal infections occurring each year in Italy is not known. The aim of this work was to estimate the burden of fungal infections in Italy, a country, with a population of 61 millions. As invasive fungal infections are not reportable, exact data are not available. For this reason, we have taken different approaches to explore the current number of invasive fungal infections. First, we have estimated fungal infections based on populations at risk, with data from published Italian or international cohort studies and clinical trials.Material and methodsThe burden of serious fungal infections was estimated for general healthy population and for specific at-risk groups, including patients affected by HIV infection, respiratory diseases (COPD, asthma and tuberculosis), solid organ or hematologic malignancy and critical illness.Demographic data regarding Italian population were obtained from the Italian National Statistical Institute (ISTAT) (5).Data on the HIV/AIDS population were obtained from the Epicentro-National Institute of Health (Istituto Superiore di Sanità-ISS) (6) and recent published data estimating adult HIV prevalence in Italy (7).Tuberculosis statistics were taken from the Epicentro-National Institute of Health (ISS) (6) and World Health Organization (WHO) reports (8). COPD and asthma prevalence in Italy were obtained from the Health Examination Survey (OEC/HES) 2008-2012(9).Solid organ cancer and haematological diseases cases were taken from Associazione Italiana Oncologia Medica (AIOM) (10) and Associazione Italiana dei Registri Tumori (AIRTUM) reports (11).Country’s profile, populations and rates required to calculate burden of serious fungal infections are reported in Table 1.We conducted an extensive literature review and published epidemiology papers reporting fungal infections incidence and/or prevalence in Italy were identified.Where no national data existed, authors reviewed data from published single-center or multicentre trials and from public health institutions in Italy. Moreover, in selected cases, when Italian data were not available, we calculated Italian fungal burden based on fungal infection incidence in other European countries. RESULTSCountry profile Italy is a country with an estimated population of 61 million people, represented by adults ( 14 years) in up to 85% of cases. Of the general population, approximately 13 million (22%) are older than 65 years. Chronic obstructive pulmonary disease prevalence has been estimated in 3.5-5% in men and 2.3 - 3.3% in women overall among adult population, with the large majority of patients in classified as GOLD stage I. The number of HIV-infected patients ranged between 114.000 and 156.000 people, with approximately 84% of patients receiving ARV (7). Solid organ cancer prevalence is 3.037.127 cases, accounting for approximately 5% of overall population (11). The exact prevalence of patients with hematological malignancies is not available, but an estimated number of 31.300 new diagnosis per year, mainly represented by non-Hodgkin lymphoma and acute leukemia has been reported in Italian registries (11). The number of autologous and allogeneic HSCTs is available at the registry of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) and accounted in 2016 for 2905 and 1796 transplants, respectively (www.gitmo.it). Country’s profile, populations and rates required to calculate burden of serious fungal infections are reported in Table 1. Prevalence rates previously reported used to estimate the burden of serious fungal infections are reported in Table 2.

Background: A significant spread of Coronavirus Disease 19 (COVID-19) has been observed in Western countries. The aim of the study was to analyze whether obesity (BMI ≥ 30 kg/m2) was a risk factor for respiratory failure and death. Methods: Retrospective multicentric cohort study of 296 COVID-19 patients admitted to the hospital between February 28 and March 28, 2020. Demographic characteristics, laboratory findings and clinical scores were compared in obese and non-obese patients. Multivariable analysis was carried out to identify the risk factors for respiratory failure and mortality. Findings: Of 296 patients, 70 (23·6%) had a BMI ≥ 30 kg/m2. Obese patients were significantly older (68±13·5 vs. 63±16·8, p=0·0052) and reported a higher rate of hypertension (77.9% vs. 40.2%, p

The global emergence of antibiotic-resistance, together with the lack of/reduced development of new antibiotic molecules, currently represents a serious public health problem as it can mean the return to a pre-antibiotic era in which infections caused by multiple-resistant pathogens are intractable. Since the beginnings, the interest of the Institutes of Microbiology, Hygiene and Public Health, and Infectious Diseases was focused on antibiotic resistance: from molecular mechanisms, through epidemiology and clinical issues, to prevention. Future perspectives include the search of new strategies and/or new compounds for prevention and control of difficult-to-treat pathogens in a multidisciplinary approach.

Background: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-associated coronavirus disease-2019 (COVID-19) is spreading worldwide challenging healthcare resources. To provide the best possible care for patients, efficient prognosis is needed. Methods: We performed a multicentre cohort study to develop and validate a risk score for severe respiratory failure (SRF) among hospitalized patients diagnosed with COVID-19. Study population included all adult patients with RT-PCR on nasopharyngeal swab positive for SARS-CoV-2, hospitalized from February 22 to April 3 2020, at 11 hospitals from four Italian Regions. Exclusion criteria were early ( 30bpm, or respiratory distress. Findings: Of the 1265 included patients, 1044 patients were analyzed, (581 derivation, 463 validation cohort). Mean age was 65.7±15 years, 661 (63·3%) were male. SRF rates were 29% and 38% in derivation and validation cohort, respectively. At multivariate analysis, risk factors for SRF in the derivation cohort were age ≥70 years, obesity, body temperature ≥38°C, RR ≥22bpm, lymphocytes ≤900/mm3, creatinine ≥ 1 mg/dl, C-reactive protein ≥10mg/dl, and lactate dehydrogenase ≥350IU/L at hospitalization. Area under receiver-operator curve (AUROC) was 0·90 (95%CI 0.86-0.93). Assigning points to each variable an individual risk score (PREDICO score) was obtained. At risk score of >3, sensitivity, specificity, positive and negative predictive values were 71·6% (64-78), 89·1% (85-92), 72·9% (65-79), and 88·4% (85-91), respectively; positive and negative likelihood ratios were 6·56 (95% CI 4·9-8·77) and 0·31 (95%CI 0·25-0·40), respectively. PREDICO score showed similar prognostic ability in the validation cohort: AUROC 0·80 (0·74-0·88). Interpretation: Using eight variables, easy to obtain at hospitalization, patients with COVID-19 could be classified according to their probability of developing SRF during hospitalization. PREDICO score can be useful to allocate resources and prioritize treatments during COVID-19 pandemic. Trial Registration: NCT04316949. Funding Statement: None. Declaration of Interests: Authors state no conflict of interest related to the content of the present study. Ethics Approval Statement: The study was approved by the Ethic Committee of the promoting center (Comitato Etico Indipendente di Area Vasta Emilia Centro, n. 283/2020/Oss/AOUBo).

Candidemia can complicate major surgical procedures. However, literature data are scanty on this topic. In this study, we evaluated the epidemiology, clinical and microbiologic characteristics and outcome of candidemia in adult patients with recent surgery hospitalised in a single University Hospital in Central Italy from 2010 to 2016. Of the 304 episodes of candidemia, 160 (53%) occurred in surgical patients (SPs) while the remaining 144 (47%) in patients without history of recent surgery (non-SPs). Although either underlying chronic comorbidities (ie haematological malignancies, neurological and gastrointestinal diseases) or acute complications (ie pneumonia and septic shock) were less likely to occur in SPs than in non-SPs, 30-day mortality did not differ between groups being 38% and 42%, respectively. The specific risk factors significantly more common in SPs who died within 30 days were as follows: male gender, older age, being hospitalised in ICU rather than in other wards, having a higher Charlson's score, undergoing previous invasive procedures, haemodialysis, the presence of pneumonia, septic shock, acute kidney failure and the type of surgery. In particular, either gastrointestinal or cardiovascular surgeries were characterised by the highest mortality rates. Multivariate analysis showed that the occurrence of septic shock (HR 10.3131 [CI95% 1.176-90.466; P = .035] and ICU stay (HR 2.016 [CI95% 1.178-3.448; P = .011] was independently associated with higher mortality in SPs. Overall, these data show that candidemia in SPs is characterised by significant mortality and distinctive features.

We report the sharp reduction in the incidence of AIDS defining cancers in a multicentric, retrospective study carried out since 1991 and involving six Infectious Diseases Units spread across Italy. However, due to the parallel increase in non-AIDS defining cancers, cancer incidence was not reduced. Focusing on predictors of death in HIV-positive patients with neoplastic disease, multivariate models revealed that males as well as drug abusers were independently associated with a poor clinical outcome.

OBJECTIVES The aim of the present study was to evaluate the effects of delayed antifungal therapy on the outcome of invasive aspergillosis due to Aspergillus fumigatus in experimental models of infection. METHODS A clinical isolate of A. fumigatus susceptible to amphotericin B (MIC 0.5 mg/L) and micafungin [minimum effective concentration (MEC) 0.03 mg/L] was used in all experiments. Two models of infection were investigated in immunosuppressed mice: disseminated infection and pulmonary infection. Twenty-four hours (early therapy) and 48 h (delayed therapy) post-infection, the mice were given vehicle, liposomal amphotericin B, micafungin or liposomal amphotericin B plus micafungin (combination). Drug efficacy was assessed by either survival or tissue burden experiments. RESULTS In disseminated infection, any drug regimen given early significantly prolonged survival. When therapy was delayed, only micafungin and the combination were effective. In pulmonary infection, although there was a trend towards a prolongation of survival of mice treated early with liposomal amphotericin B, only the combination was effective. Similarly, when therapy was delayed, only the combination was effective. In disseminated infection, any drug regimen given early was effective at reducing the cfu in kidney tissue. In pulmonary infection, only liposomal amphotericin B and the combination given early were effective at reducing the cfu in lung tissue. Conversely, when therapy was delayed, no regimen was effective at reducing the tissue burden, regardless of the type of infection. CONCLUSIONS Our data indicate that delayed initiation of antifungal therapy is deleterious in experimental models of invasive aspergillosis. A combination regimen seems to have some advantages over a single-drug approach when the therapy is started late.

Background Bloodstream infections (BSI) due to Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) have become an important problem and they are associated with a high mortality rate. The aim of our study was to evaluate the clinical and epidemiological characteristics of KPC-Kp from BSIs. Methods In this retrospective cohort study, conducted in a tertiary referral center in Italy, 112 patients with KPC-Kp BSIs diagnosed between February 2011 and December 2015 were identified. We evaluated the mortality at 30 days from the first positive blood culture. Survivor and non-survivor subgroups were compared to identify predictors of mortality. Results The overall crude mortality was 35%. APACHE II score ≥ 15, septic shock at BSI onset, immunosuppressive therapy during the 30 days before the BSI onset, and the lack of a combination therapy with at least 2 active drugs emerged as independent predictors of mortality. Excluding patients with inadequate therapy, the mortality decreased to 25% while an APACHE II score ≥ 15 and the presence of septic shock remained independently associated with a negative outcome. Two different pulsotypes were identified: pulsotype A belonged to ST512 and carried KPC-3 and pulsotype B belonged to ST307 and carried KPC-2. Conclusions This study confirmed a high mortality rate of KPC-Kp BSIs. The outcome is heavily influenced by the patient’s clinical conditions. A therapeutic approach including a combination with at least two active drugs in vitro can improve the prognosis, unless patients received an appropriate therapy.

Ceftobiprole is a fifth-generation cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA). One-year surveillance at the Regional Hospital of Ancona (Italy) disclosed a 12% ceftobiprole resistance rate (12/102 isolates; MIC, ≥4 mg/liter). Epidemiological characterization demonstrated that the resistant isolates all belonged to different clones. Penicillin-binding protein (PBP) analysis showed substitutions in all PBPs and a novel insertion in PBP2a. The mecB and mecC genes were not detected. Ceftobiprole susceptibility screening is essential to avoid therapeutic failure and the spread of ceftobiprole-resistant strains.

Ceftobiprole is a fifth-generation cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA). One-year surveillance at the Regional Hospital of Ancona (Italy) disclosed a 12% ceftobiprole resistance rate (12/102 isolates; MIC, ≥4 mg/liter). Epidemiological characterization demonstrated that the resistant isolates all belonged to different clones. Penicillin-binding protein (PBP) analysis showed substitutions in all PBPs and a novel insertion in PBP2a. The mecB and mecC genes were not detected. Ceftobiprole susceptibility screening is essential to avoid therapeutic failure and the spread of ceftobiprole-resistant strains.

Background Histoplasmosis is a fungal infection highly endemic in the American continent. The disease can be severe in immunocompromised subjects. In immunocompetent subjects the clinical manifestations are variable. Aim of this work was to review the cases of acute histoplasmosis in immunocompetent travelers reported in literature. Methods A systematic review of literature was conducted. Electronic search was performed in Pubmed and LILACS. Two reviewers independently extracted data on demographic, clinical and radiological features, and treatment. Cases were classified according to Wheat’s definitions. Results Seventy-one studies were included in the analysis, comprising a total of 814 patients. Twenty-one patients diagnosed at the Centre of Tropical Diseases, Negrar (VR), Italy were also included. The most common travel destination was Central America (168 people, 29.8%); the most common way of exposure to histoplasma was the exploration of caves and/or contact with bat guano (349 people, 60.9%). The multivariate logistic regression model showed association between the development of disseminated histoplasmosis (DH) and activities that involved the exploration of caves and/or the contact with bats’ guano (adjusted OR: 34.20 95% CI: 5.29 to 220.93) or other outdoor activities (adjusted OR: 4.61 95% CI: 1.09 to 19.56). No significant difference in the attack rate between countries of destination was observed (p-value: 0.8906, Kruskal-Wallis test). Conclusions Histoplasmosis often causes no or mild symptoms in immunocompetent individuals, although a severe syndrome may occur. The infection can mimic other diseases, and the epidemiological risk of exposure is an important clue to raise the index of suspicion. Electronic supplementary material The online version of this article (10.1186/s12879-018-3476-z) contains supplementary material, which is available to authorized users.

Monitoring of liver fibrosis (LF) is an essential tool for preventing liver-related complications in HIV/HCV co-infected patients. In this study, we compared LF progression by transient elastometry (TE) in 50 HIV/HCV co-infected and 115 HCV mono-infected patients followed in our institution between June 2006 and December 2011. Patients naive to interferon therapy and with at least two measurements of liver stiffness by TE were included. In all, 76% of HIV/HCV co-infected and 75% of HCV mono-infected patients remained in the same stage of LF over time. Conversely, 19% and 15% of HIV/HCV co-infected and HCV mono-infected subjects, respectively, had progression to advanced LF (≥ F3). Our study found a similar proportion of HIV/HCV co-infected and HCV mono-infected patients that developed an advanced LF during the follow-up time considered. Alcohol abuse was the only factor significantly associated with the progression as evidenced by multiple quantile regression analysis.

A case of systemic infection due to Saprochaete capitata in a patient with chronic lymphocytic leukemia is described. A review of the literature was conducted to identify all reported cases of this infection described between 1977 and August 2013. One hundred and four cases (included the present one) were identified. The median age of the patients was 56 years and 56 % were males. Comorbidities included acute myeloid leukemia (52 %), acute lymphoid leukemia (22 %), other hematological malignancies (13 %) and non-hematological diseases (9 %). At the time of the infection, 82 % of the patients were neutropenic. In 75 % of the cases, the yeast was isolated from blood culture, in 25 % from other sterile sites. Empirical treatment was done in 36 % of the cases. Fifty-eight percent of the individual cases were treated with a combination or a sequential antifungal therapy. Amphotericin B was the antifungal drug most commonly used, followed by voriconazole and itraconazole. The overall crude mortality was 60 %. Saprochaete capitata causes life-threatening infections in neutropenic patients. This comprehensive literature review may help the clinician to optimize the management of this rare infection.

Aspergillus osteomyelitis is a rare infection. We reviewed 310 individual cases reported in the literature from 1936 to 2013. The median age of patients was 43 years (range, 0–86 years), and 59% were males. Comorbidities associated with this infection included chronic granulomatous disease (19%), haematological malignancies (11%), transplantation (11%), diabetes (6%), pulmonary disease (4%), steroid therapy (4%), and human immunodeficiency virus infection (4%). Sites of infection included the spine (49%), base of the skull, paranasal sinuses and jaw (18%), ribs (9%), long bones (9%), sternum (5%), and chest wall (4%). The most common infecting species were Aspergillus fumigatus (55%), Aspergillus flavus (12%), and Aspergillus nidulans (7%). Sixty-two percent of the individual cases were treated with a combination of an antifungal regimen and surgery. Amphotericin B was the antifungal drug most commonly used, followed by itraconazole and voriconazole. Several combination or sequential therapies were also used experimentally. The overall crude mortality rate was 25%.

Chronic hepatitis C virus (HCV) infection has become a leading cause of non-acquired immunodeficiency syndrome (AIDS)-related morbidity and mortality for human immunodeficiency virus (HIV)-infected persons in the highly active antiretroviral therapy (HAART) era. Despite injection drug use (IDU) remaining the main route of HCV infection, recent reports indicate outbreaks of acute HCV infection among HIV-infected men who have sex with men (MSM) and sexually transmitted infections in the absence of IDU.We conducted a retrospective observational study of behavioural and demographic factors of patients with and without incident HCV infection among HIV-infected individuals followed at the AIDS Clinic of the Infectious Disease Department of the University of Ancona from 1989 to 2011.Overall, 440 patients were considered; a total of 145 patients had initial positive HCV antibody test results (HCV+); a total of 295 patients had initial negative HCV antibody test results (HCV-). In the latter population, 14 seroconverted to HCV antibody (neoHCV), with an overall incidence of 0.59 per 100 person-years. While IDU was the principal risk factor of HCV+, the main route of transmission of incident HCV infection was sexual transmission. The HCV- group was significantly older than the other two groups and showed a significantly lower CD4 count at HIV diagnosis than neoHCV. Being Italian and having a low level of education were significantly more represented in HCV+. Younger age at HIV infection, IDU and additional risk factors other than sexual transmission significantly affected the probability of being HCV+. The cumulative probability of developing HCV infection in the HCV- group was calculated to be 6% at 15 years.The epidemiology of the newly acquired HCV in HIV+ persons is changing. Therefore, a frequent and constant counselling about HCV infection is desirable and a periodical screening test is mandatory.

Candida parapsilosis may be responsible for bloodstream infections (BSI) and it is characterised by an increased incidence of fluconazole resistance. A 75-year old woman with severe comorbidities received the insertion of a peripherally inserted central venous catheter. Fluconazole did not prevent a C. parapsilosis BSI hence caspofungin was started after a nephrotoxic first-line treatment with amphotericin B. The ratio of peak plasma concentration over the minimum inhibitory concentration (Cmax/MIC) was adopted to maximise efficacy of caspofungin. MIC and plasma Cmax values were obtained by broth microdilution and LC-MS, respectively. Interestingly, daily doses of 1 mg/kg (total daily dose, 50 mg) allowed the achievement of Cmax/MIC values > 10. The optimised regimen was safe and effective, leading to negative blood culture at day 8. The patient was discharged home at day 21. Therefore, individualised dosing regimens of caspofungin may be effective and safe even in the case of C. parapsilosis BSI.