A holistic evaluation of patients with chronic Hepatitis D virus (HDV) infection enrolled in the Italian PITER-B and Delta cohort.

BACKGROUND AND AIMS: We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility. METHODS: This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model. RESULTS: Of 5,492 HBsAg-positive enrolled patients, 4,152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age≤40 years vs. 2.1%; p<0.001), more often females (males 43.0% vs. 68.6%; p<0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care. CONCLUSIONS: CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN.

The Clinical Characteristics of Bloodstream Infections Due to Candida spp. in Patients Hospitalized in Intensive Care Units during the SARS-CoV-2 Pandemic: The Results of a Multicenter Study.

Candidemia is a serious health threat. Whether this infection has a greater incidence and a higher mortality rate in patients with COVID-19 is still debated. In this multicenter, retrospective, observational study, we aimed to identify the clinical characteristics associated with the 30-day mortality in critically ill patients with candidemia and to define the differences in candidemic patients with and without COVID-19. Over a three-year period (2019-2021), we identified 53 critically ill patients with candidemia, 18 of whom (34%) had COVID-19 and were hospitalized in four ICUs. The most frequent comorbidities were cardiovascular (42%), neurological (17%), chronic pulmonary diseases, chronic kidney failure, and solid tumors (13% each). A significantly higher proportion of COVID-19 patients had pneumonia, ARDS, septic shock, and were undergoing an ECMO procedure. On the contrary, non-COVID-19 patients had undergone previous surgeries and had used TPN more frequently. The mortality rate in the overall population was 43%: 39% and 46% in the COVID-19 and non-COVID-19 patients, respectively. The independent risk factors associated with a higher mortality were CVVH (HR 29.08 [CI 95% 3.37-250]) and a Charlson's score of > 3 (HR 9.346 [CI 95% 1.054-82.861]). In conclusion, we demonstrated that candidemia still has a high mortality rate in patients admitted to ICUs, irrespective of infection due to SARS-CoV-2.

Candidemia in Internal Medicine: Facing the New Challenge.

Candidemia is an alarming problem in critically ill patients including those admitted in Internal Medicine Wards (IMWs). Here, we analyzed all cases of candidemia in adult patients hospitalized over nine years (2010-2018) in IMWs of a 980-bedded University Hospital of Ancona, Italy. During the study period, 218/505 (43%) episodes of candidemia occurred in IMWs patients. The cumulative incidence was 2.5/1000 hospital admission and increased significantly over time (p = 0.013). Patients were predominantly male, with a median age of 68 years. Cardiovascular diseases and solid tumors were the most frequent comorbidities. Candida albicans accounted for 51% of the cases, followed by C. parapsilosis (25%), C. tropicalis (9%) and C. glabrata (7%). Thirty-day mortality was 28% and did not increased significantly over time. By multivariate logistic regression analysis, the presence of neutropenia (OR 7.247 [CI95% 1,368-38,400; p = 0.020]), pneumonia (OR 2.323 [CI95% 1,105-4,884; p = 0.026]), and being infected with C. albicans (OR 2.642 [95% CI 1,223-5,708; p = 0.013) emerged as independent predictors of mortality. The type of antifungal therapy did not influence the outcome. Overall, these data indicate that patients admitted to IMWs are increasingly at higher risk of developing candidemia. Mortality rate remains high and significantly associated with both microbiologic- and host-related factors.

Effectiveness of remdesivir in patients with COVID-19 under mechanical ventilation in an Italian ICU.

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 < 0.001). Cox regression analysis showed that the Charlson Comorbidity Index was the only factor that had a significant association with higher mortality (OR 1.184; 95% CI 1.027-1.365; P = 0.020), while the use of remdesivir was associated with better survival (OR 3.506; 95% CI 1.768-6.954; P < 0.001). 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.

A proposal for a comprehensive approach to infections across the surgical pathway.

Despite evidence supporting the effectiveness of best practices in infection prevention and management, many healthcare workers fail to implement them and evidence-based practices tend to be underused in routine practice. Prevention and management of infections across the surgical pathway should always focus on collaboration among all healthcare workers sharing knowledge of best practices. To clarify key issues in the prevention and management of infections across the surgical pathway, a multidisciplinary task force of experts convened in Ancona, Italy, on May 31, 2019, for a national meeting. This document represents the executive summary of the final statements approved by the expert panel.

Characterisation of candidemia in patients with recent surgery: A 7-year experience.

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.

Central venous catheter unrelated candidemia influences the outcome of infection in patients with solid tumors.

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 < 0.001). Similarly, the use of total parenteral nutrition was more common in ST patients (P = 0.026). Although there was a trend toward a more appropriate use of antifungal therapy in ST (60%) than in non-ST patients (49%), the difference was not statistically significant (P = 0.059). Thirty-day mortality was significantly higher in ST (49%) than in non-ST patients (36%, P = 0.016). Multivariate analysis showed that either higher age or septic shock was an independent risk factor for mortality in both groups of patients. Conversely, a CVC-unrelated candidemia represented an independent risk factor for mortality in ST patients (HR 3.581 [CI 95% 1.412-9.087, P = 0.007]). Overall, these data show that candidemia in ST patients is characterized by an extremely high mortality rate.

Prevalence and predictors of malignancies in HIV patients: results of a retrospective multicentric Italian cohort.

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.

Epidemiology, clinical characteristics, and outcome of candidemia in a tertiary referral center in Italy from 2010 to 2014.

PURPOSE: We evaluated the epidemiology, clinical characteristics and outcome of candidemia in a single institution from 2010 to 2014. METHODS: A retrospective observational study of all cases of candidemia was carried out at a University Hospital in Central Italy including five intensive care units (ICUs), 11 medical and 11 surgical wards. Data regarding demographic characteristics and clinical risk factors were collected from the patient's medical records. Antifungal susceptibility testing was performed and MIC results were interpreted according to species-specific clinical breakpoints. RESULTS: A total of 270 episodes of candidemia were identified. Overall incidence rate was 1.5 episodes/1000 hospital admissions. Although Candida albicans represented the most commonly isolated species, its percentage significantly decreased from 68 to 48 % (p = 0.040). The overall 30-day mortality was 35 %. The variables independently associated with a significant higher risk of mortality were: older age; being hospitalized in ICU or in medical wards vs surgical wards; being infected with C. albicans vs other species; the occurrence of septic shock, pneumonia and acute renal failure; the presence of a solid organ tumor or a chronic pulmonary disease. Conversely, an appropriate treatment was confirmed to be significantly associated with a lower risk of mortality. The overall resistance was low and it was noted only among triazoles. CONCLUSIONS: Our study shows that candidemia is a significant source of morbidity and mortality. The identification of risk factors associated with mortality along with the knowledge of local susceptibility may lead to a better management in terms of preventive and therapeutic measures.

Prevalence and predictors of malignancies in a polycentric cohort of HIV patients from Italy.

INTRODUCTION: HIV infected patients have a higher risk of developing cancer than the general population. Kaposi's sarcoma, non-Hodgkin's lymphoma, primary CNS lymphoma and invasive cervical cancers are considered as AIDS defining [1]. An increased incidence in recent years has been reported also for other malignancies after the introduction of cART [2,3]. MATERIALS AND METHODS: We performed a retrospective multicentric evaluation of all HIV infected patients with both AIDS and non-AIDS defining neoplasms at six Infectious Disease Units spread throughout Italy since 1991 through 2013. Cases were compared with equal number of controls without neoplasia followed at the same institutions, matched for length of HIV infection. RESULTS: Since 1991, 339 consecutive cases of malignancy were collected from the six convening centres, including approximately an equal proportion of AIDS (51.2%) and non-AIDS defining tumours. Mean prevalence of tumours among centres was 8.3% (r. 6.1%-9.6%). Mean age at tumour diagnosis was significantly lower than in controls (42.6±11.0 vs 46.8±10.6 years, respectively, p<0.0001). As to risk factors for HIV infection, approximately 1/4 (26.1%) of patients were drug abusers, in equal proportion as in controls. A remarkable higher proportion of cancer patients had CD4 T-cell counts <200 c/mmc at time of diagnosis (45.2% vs 13.3%, p<0.0001). Seventy percent of tumours occurred in males; 52.8% of tumour patients were diagnosed with AIDS before and 19.0% at the time of tumour diagnosis. Ninety (28.1%) tumour patients were dead at the time of data collection, a much higher proportion than among cases (12.9%, p<0.0001). Deaths among non-AIDS (20.8%) and AIDS defining tumour patients (35.0%) were significantly different (p=0.005). Predictors of AIDS defining tumours at the time of data collection were: male sex (57.9% vs 40.6%, p=0.004), CD4 T-cell counts <200 c/mmc (63.6% vs 44.1%, p<0.0001), whereas being cART treated at the time of tumour diagnosis was protective (38.0% vs 68.0%, p<0.0001). In the final multivariate model of logistic regression, male sex (OR=2.0, p=0.03) and not being cART treated (OR=2.5, p=0.001) held as independent predictors. CONCLUSIONS: Our retrospection revealed a considerably high proportion of non-AIDS defining tumours, apparently at rise in recent years. We registered high prevalence of tumours in each centre. Absence of cART seemed related with AIDS defining tumours: once more prevention of late presentation appeared the way to avoid worse prognosis in this setting.

Comparison of liver fibrosis progression in HIV/HCV co-infected and HCV mono-infected patients by transient elastometry.

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.

Candida guilliermondii fungemia in patients with hematologic malignancies.

The microbiological, clinical, and epidemiological features of most non-Candida albicans Candida species are well known, but much less is known about species such as Candida guilliermondii, an uncommon pathogen causing a variety of deep-seated infections in immunocompromised hosts. To characterize C. guilliermondii fungemia in patients with hematological malignancies and its susceptibility to antifungal drugs, all cases of C. guilliermondii fungemia diagnosed in our department between 1983 and 2005 were retrospectively analyzed and the literature was reviewed. C. guilliermondii caused 29/243 (11.7%) candidemia episodes diagnosed during the study period. Central venous catheters were the documented sources of candidemia in 19/29 episodes (65.5%), and invasive tissue infections were documented in 2 (6.9%). In the remaining eight, the catheter was not removed and the source of the fungemia remained obscure. Seven episodes ended in death, but only one could be attributed to invasive C. guilliermondii infection. Molecular typing data reveal no evidence of common infection sources. Isolates displayed high rates of in vitro susceptibility to amphotericin B (100%), voriconazole (95%), and fluconazole (90%) and lower rates of in vitro susceptibility to flucytosine (86%), itraconazole (76%), and caspofungin (33%). Our literature review confirms that C. guilliermondii is a significantly more frequent cause of candidemia among cancer patients compared with the general hospital population. It accounted for <1% of the total number of Candida bloodstream isolates reported in the articles we reviewed, with higher rates in Europe (1.4%) and Asia (1.8%) compared with North America (0.3%).

In vitro effect of short-term exposure to two synthetic peptides, alone or in combination with clarithromycin or rifabutin, on Cryptosporidium parvum infectivity.

The viability of Cryptosporidium parvum after exposure to peptide antibiotics was studied by two different methods, a cell culture system and a double fluorogenic staining. The peptides KFFKFFKFF and IKFLKFLKFL exerted high cytotoxic effects on sporozoites, as demonstrated by cell cultures (complete inhibition after 60 min at 100 microg/ml) and flow cytometry (30% after 20 min at 100 microg/ml), but did not affect consistently the oocysts. Clarithromycin and rifabutin demonstrated less activity against sporozoites but higher activity against oocysts (30% after 180 min at 10 microg/ml). The combination between peptides and azithromycin or rifabutin exerted the highest activities.