What do We Know about Cryptic Aspergillosis?

Cryptic Aspergillus species are increasingly recognized as pathogens involved in human disease. They are ubiquitarian fungi with high tenacity in their environment and can express various resistance mechanisms, often due to exposure to antifungal agents employed in agriculture and farming. The identification of such species is increasing thanks to molecular techniques, and a better description of this type of pathogen is granted. Nevertheless, the number of species and their importance in the clinical setting still need to be well studied. Furthermore, their cross-sectional involvement in animal disease, plants, and human activities requires a multidisciplinary approach involving experts from various fields. This comprehensive review aims to provide a sharp vision of the cryptic Aspergillus species, from the importance of correct identification to the better management of the infections caused by these pathogens. The review also accentuates the importance of the One Health approach for this kind of microorganism, given the interconnection between environmental exposure and aspergillosis, embracing transversely the multidisciplinary process for managing the cryptic Aspergillus species. The paper advocates the need for improving knowledge in this little-known species, given the burden of economic and health implications related to the diffusion of these bugs.

HBV in Italian Women's Jail: An Underestimated Problem?

BACKGROUND: There is little information regarding the hepatitis B virus (HBV), vaccination status, and hepatitis B exposure in Italian women's jails. We aimed to describe the HBV exposure and HBs antibody (anti-HBs) protection levels in female prisoners. MATERIAL AND METHODS: A retrospective multicentric study was performed in Italian prisons from 2021 to 2023. Univariate and multivariate analyses were conducted to identify risk factors for HBc antibody (anti-HBc) seropositivity and non-protective anti-HBs titer. RESULTS: We included 156 patients. The median age was 41.0 (IQR 34.0-48.0). Of the studied subjects, 31 (19.9%) had anti-HBc positive titer. Two women were HBsAg positive. In the multivariate analysis, older age [OR 1.06 (CI 1.01-1.11), p = 0.011], North-Eastern European [OR 11.67 (3.29-41.30), p < 0.001] and African origin [OR 6.92 (CI 1.51-31.60), p = 0.013], and drug use [OR 6.55 (CI 1.96-21.9), p = 0.002] were risk factors for HBV exposure. Thirty-seven (32%) women had no history of HBV vaccination. Forty-four (38%) had an anti-HBs non-protective titer. In the multivariate analysis, North-Eastern European origin [OR 4.55 (CI 1.19-17.50), p = 0.027] was associated with unprotective anti-HBs titer. CONCLUSION: Our results show both the low prevalence of HBV and protection in female prisoners. Age, North-Eastern European and African origin, and drug use have a role in exposure risk to HBV.

Successful control measures to treat the transmission of Candida auris in Northern Italian Hospital.

Candida auris has emerged globally as a multidrug-resistant health care-associated fungal pathogen. In the literature, nosocomial outbreaks are reported worldwide. In addition, C. auris diffusion occurs in high-dependency settings with infections typically affecting critically ill patients, resulting in life-threatening disease. We describe the first documented case of C. auris in northeastern Italy and the measures applied to contain the transmission that led to zero collateral infections.

Differences in HCV Seroprevalence, Clinical Features, and Treatment Outcomes between Female and Male Incarcerated Population: Results from a Matched Cohort Study.

BACKGROUND: Women represent less than 5% of the incarcerated population in Italy, with very limited data on HCV infection. Higher HCV seroprevalence and active infection rates have been described among incarcerated females in available studies. Our aim is to compare the prevalence and cascade of care of HCV between male and female populations in Italian penitentiaries. METHODS: We conducted a multicentre, retrospective study comparing HCV seroprevalence, active infections, treatment, and SVR rates between female (Group A) and male (Group B) populations in Italian prison settings. RESULTS: No significant differences were found between the two groups regarding PWIDs (p = 0.16), nor in people living with HIV (p = 0.35) or HBV co-infection (p = 0.36). HCV seroprevalence was higher in Group A (p = 0.002). There was no statistically significant difference between the two groups regarding active infections (p = 0.41). Both groups showed a low level of fibrosis, and the dominant genotype was 3a. Almost all patients underwent antiviral treatment. All treated patients achieved SVR12. CONCLUSIONS: Our findings illuminate the importance of recognizing and addressing gender differences in HCV seroprevalence within penitentiary settings. Moving forward, addressing the unique needs of incarcerated females and optimizing HCV care for all incarcerated individuals are essential steps in the pursuit of achieving HCV micro-elimination goals.

Candida auris as an Emergent Public Health Problem: A Current Update on European Outbreaks and Cases.

Candida auris is considered to be an emerging fungal pathogen and is related to high mortality rates, persistent candidemia, inconsistencies in susceptibility testing results and misidentification by available commercial identification systems. Multidrug-resistant (MDR) and pandrug-resistant (PDR) strains are increasingly detected. In Europe, hospital outbreaks caused by C. auris have been reported in the United Kingdom (UK), Italy and Spain; however, several cases have been sporadically detected in all European countries. C. auris is difficult to control despite enhanced control measures due to its ability to survive for a long time in environments and colonize patients for prolonged periods. An adequate laboratory diagnostic capacity and national surveillance are fundamental to rapidly detect new C. auris cases and to apply the correct measures to circumscribe them and prevent their spread. Our narrative review aims to highlight the primary C. auris outbreaks and case reports that have occurred in Europe.

Role of HBcAb Positivity in Increase of HIV-RNA Detectability after Switching to a Two-Drug Regimen Lamivudine-Based (2DR-3TC-Based) Treatment: Months 48 Results of a Multicenter Italian Cohort.

The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies (HBcAb positivity) could influence the control of HIV viremia in patients living with HIV (PLWH) who switch to two-drug antiretroviral therapy (2DR) containing lamivudine (3TC) (2DR-3TC-based). A retrospective multicentre observational study was conducted on 160 PLWH switching to the 2DR-3TC-based regimen: 51 HBcAb-positive and 109 HBcAb-negative patients. The HBcAb-positive PLWH group demonstrated a significantly lower percentage of subjects with HIV viral suppression with target not detected (TND) at all time points after switching (24th month: 64.7% vs. 87.8%, p < 0.0001; 36th month 62.7% vs. 86.8%, p = 0.011; 48th month 57.2% vs. 86.1%, p = 0.021 of the HBcAb-positive and HBcAb-negative groups, respectively). Logistic regression analysis showed that the presence of HBcAb positivity (OR 7.46 [95% CI 2.35−14.77], p = 0.004) could favour the emergence of HIV viral rebound by nearly 54% during the entire study follow-up after switching to 2DR-3TC.

A case of hepatic and bone marrow sarcoidosis with progressive renal failure: diagnostic and therapeutic challenges.

Sarcoidosis is a systemic granulomatous disease, sometimes characterized by an extrapulmonary localization in 30 - 50% of cases. We describe a 60-year-old Italian man with an unexplained history of fatigue, ascitis and progressive renal function impairment. Diagnosis of hepatic and bone marrow sarcoidosis was established by histology, and fast improvement of renal function was obtained after starting  corticosteroid therapy. Atypical presentation and simultaneous involvement of liver, bone marrow and kidneys make diagnosis of extrapulmonary sarcoidosis still a diagnostic challenge. Delayed diagnosis could lead to serious organ damage like a progressive severe kidney failure.

Treatment with cefiderocol in K. pneumoniae KPC nosocomial external ventricular drainage meningitis: A brief report.

We report the case of successful use of cefiderocol (FDC) in a Carbapenemase Producing K. pneumoniae (CPKP) post-surgical meningitis in a 44-year-old man treated with antimicrobial therapy and external ventricular drainage (EVD). The patient was known for being colonised by CPKP; for this reason, therapy with ceftazidime/avibactam (CZA) plus fosfomycin and linezolid was started. After an initial response a CZA resistant CPKP strain was isolated from CSF culture, so the antibiotic therapy was modified to FDC with trimethoprim/sulfamethoxazole for 14 days, and EVD was replaced. A complete recovery was obtained. This is the first case report describing FDC administration in CPKP meningitis.

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19.

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage.

Clinical efficacy of different monoclonal antibody regimens among non-hospitalised patients with mild to moderate COVID-19 at high risk for disease progression: a prospective cohort study.

This study aimed to compare the clinical progression of COVID-19 in high-risk outpatients treated with the monoclonal antibodies (mAb) bamlanivimab, bamlanivimab-etesevimab and casirivimab-imdevimab. This is an observational, multi-centre, prospective study conducted from 18 March to 15 July 2021 in eight Italian tertiary-care hospitals including mild-to-moderate COVID-19 outpatients receiving bamlanivimab (700 mg), bamlanivimab-etesevimab (700-1400 mg) or casirivimab-imdevimab (1200-1200 mg). All patients were at high risk of COVID-19 progression according to Italian Medicines Agency definitions. In a patient subgroup, SARS-CoV-2 variant and anti-SARS-CoV-2 serology were analysed at baseline. Factors associated with 28-day all-cause hospitalisation were identified using multivariable multilevel logistic regression (MMLR) and summarised with adjusted odds ratio (aOR) and 95% confidence interval (CI). A total of 635 outpatients received mAb: 161 (25.4%) bamlanivimab, 396 (62.4%) bamlanivimab-etesevimab and 78 (12.2%) casirivimab-imdevimab. Ninety-five (15%) patients received full or partial SARS-CoV-2 vaccination. The B.1.1.7 (Alpha) variant was detected in 99% of patients. Baseline serology showed no significant differences among the three mAb regimen groups. Twenty-eight-day all-cause hospitalisation was 11.3%, with a significantly higher proportion (p 0.001) in the bamlanivimab group (18.6%), compared to the bamlanivimab-etesevimab (10.1%) and casirivimab-imdevimab (2.6%) groups. On MMLR, aORs for 28-day all-cause hospitalisation were significantly lower in patients receiving bamlanivimab-etesevimab (aOR 0.51, 95% CI 0.30-0.88 p 0.015) and casirivimab-imdevimab (aOR 0.14, 95% CI 0.03-0.61, p 0.009) compared to those receiving bamlanivimab. No patients with a history of vaccination were hospitalised. The study suggests differences in clinical outcomes among the first available mAb regimens for treating high-risk COVID-19 outpatients. Randomised trials are needed to compare efficacy of mAb combination regimens in high-risk populations and according to circulating variants.

Epidemiology, aetiology and treatment of skin and soft tissue infections: final report of a prospective multicentre national registry.

Skin and soft tissue infections (SSTIs) represent a heterogenous group of pathological conditions involving the skin or the underlying subcutaneous tissues, fascia and muscle, characterised by a considerable variety of clinical presentations, severity and possible aetiological pathogens. Although previous analyses on restricted types of SSTIs and population have already been published, we conducted a large nationwide surveillance program on behalf of the Italian Society of Infectious and Tropical Diseases to assess the clinical and microbiological characteristics of the whole SSTI spectrum, from mild to severe life-threatening infections, in both inpatients and outpatients and their management. Twenty-nine Infectious Diseases (ID) Centres throughout Italy collected prospectively data concerning both the clinical and microbiological diagnosis of patients affected by SSTIs via an electronic case report form. We included in our database all cases managed by ID specialists participating to the study, independently from their severity or the setting of consultation. Here, we integrated previous preliminary results analysing and reporting data referring to a 3-year period (October 2016-October 2019). During this period, the study population included 478 adult patients with diagnosis of SSTI. The type of infection diagnosed, the aetiological agent involved and some notes on antimicrobial susceptibilities were collected and reported herein. We also analysed the most common co-morbidities, the type and duration of therapy executed, before and after ID intervention and the length of stay. The results of our study provide information to better understand the national epidemiologic data and the current clinical management of SSTIs in Italy.

The serious threat of late presenters HIV-infected patients in the context of the COVID-19 pandemic.

The impact of current SARS-CoV-2 pandemic on the healthcare services had serious consequences, especially for the most fragile populations such as HIV-positive subjects. In the period April to September 2020 we reported four cases of HIV-infected late presenters with an AIDS-defining life-threatening condition that, due to the difficult access to the hospital during the pandemic, were characterized by a delayed HIV recognition and institution of correct treatment. Even after two decades of highly active antiretroviral therapy late presenters HIV-infected patients still represent a serious clinical challenge.

HBcAb Positivity Is a Risk Factor for an Increased Detectability of HIV RNA after Switching to a Two-Drug Regimen Lamivudine-Based (2DR-3TC-Based) Treatment: Analysis of a Multicenter Italian Cohort.

The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies (HBcAb positivity) could influence the control of Human Immunodeficiency Virus (HIV) viremia in patients living with HIV (PLWH) who switch a to two-drug antiretroviral therapy (2DR) containing lamivudine (3TC) (2DR-3TC). A retrospective observational multicenter study was conducted on 166 PLWH switching to the 2DR-3TC-based regimen: 58 HBcAb-positive and 108 HBcAb-negative patients. The HBcAb-positive PLWH group demonstrated a significantly higher percentage of subjects with very low-level viremia at all time points after switching (6th month: <31% vs. 17.6%, p = 0.047; 12th month 34% vs. 27.5%, p = 0.001; 24th month 37% vs. 34.2, p = 0.003 of the HBcAb-positive and HBcAb-negative groups, respectively) and a higher percentage of subjects with detectable HIV RNA greater than 20 copies/mL 12 and 24 months after switching (12 months 32% vs. 11%, p = 0.001; 24 months 37% vs. 13.9%, p = 0.003 of the HBcAb-positive and HBcAb-negative groups, respectively). Logistic regression analysis showed that an increase in age of ten years (OR 2.48 (95% CI 1.58-3.89), p < 0.0001) and the presence of HBcAb positivity (OR 2.7 (5% CI 1.05-6.9), p = 0.038) increased the risk of detectability of HIV RNA by nearly three-fold after switching to 2DR-3TC.

The first Italian case report of leg ulcer and sepsis caused by Shewanella algae in a immunocompetent patient.

We describe the first Italian case of Shewanella algae septicemia in an immunocompetent patient with chronic leg ulcers. The patient had been exposed to seawater before the onset of symptoms. Despite the absence of severe underlying diseases, the primary soft tissue infection of the leg was complicated by hematogenous dissemination.

Role of pretreatment variables on plasma HIV RNA value at the sixth month of antiretroviral therapy including all first line drugs in HIV naïve patients: A path analysis approach.

BACKGROUND AND AIMS: We investigated the conditioning roles of viral tropism and other variables on plasma HIV RNA levels after 6 months of combination antiretroviral therapy (cART) in an HIV-infected Italian naïve population using regression tree, random forest regression, and path analysis (PA). Patients in this multicenter observational study were treated with all antiviral drugs that are currently recommended as first-line therapies. METHODS: Adult patients with chronic HIV infection were enrolled at the beginning of first-line cART (T0). The main variables were age, gender, tropism, "lcd4_0" and "lcd4_6" (log10 CD4+counts at T0 and after 6 months of cART, respectively), and "lrna0" (log10 HIV RNA at T0). Regression tree and random forest analyses were applied. The predictive effect on lrna6 (log10-transformed plasma HIV RNA after 6 months of cART) was also investigated via PA (x4->lcd4_0->lrna0->lrna6) with a treatment selection step included as a dependent (mediator) variable for each third drug and, as predictive covariates, age, female, x4_10, x4_5, lcd4_0, and lrna0. Tropism was assessed in plasma using the Geno2pheno algorithm with 2 false positive rate (FPR) cut-offs: 5% (x4_5) and 10% (x4_10). RESULTS: The study included 571 subjects (21% x4_10 and 10.7% x4_5). The only important predictor of lrna6 was lrna0, and a positive indirect effect of bearing X4 virus in plasma was suggested. A significant direct positive effect of protease inhibitors on lrna6 was found (p = 0.022), and a significant negative effect of integrase strand transfer inhibitor (INSTI) was also detected (p = 0.003 for FPR ≤ 5% and p = 0.01 for FPR < 10%). PA predicted mean residual viremias of 40 copies/mL without INSTI and 3 copies/mL with INSTI. CONCLUSIONS: PA indicated a possible indirect role of HIV tropism on lrna6 with both FPR < 10% and ≤ 5%. Patients treated with INSTI had a predicted residual viremia of 3 copies/mL.

Epidemiology and Microbiology of Skin and Soft Tissue Infections: Preliminary Results of a National Registry.

Skin and soft tissue infections (SSTIs) represent a wide range of clinical conditions characterized by a considerable variety of clinical presentations and severity. Their aetiology can also vary, with numerous possible causative pathogens. While other authors previously published analyses on several types of SSTI and on restricted types of patients, we conducted a large nationwide surveillance programme on behalf of the Italian Society of Infectious and Tropical Diseases to assess the clinical and microbiological characteristics of the whole SSTI spectrum, from mild to severe life-threatening infections, in both inpatients and outpatients. Twenty-five Infectious Diseases (ID) Centres throughout Italy collected prospectively data concerning both the clinical and microbiological diagnosis of patients affected by SSTIs via an electronic case report form. All the cases included in our database, independently from their severity, have been managed by ID specialists joining the study while SSTIs from other wards/clinics have been excluded from this analysis. Here, we report the preliminary results of our study, referring to a 12-month period (October 2016-September 2017). During this period, the study population included 254 adult patients and a total of 291 SSTI diagnoses were posed, with 36 patients presenting more than one SSTIs. The type of infection diagnosed, the aetiological micro-organisms involved and some notes on their antimicrobial susceptibilities were collected and are reported herein. The enrichment of our registry is ongoing, but these preliminary results suggest that further analysis could soon provide useful information to better understand the national epidemiologic data and the current clinical management of SSTIs in Italy.

Newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with DAAs: A prospective population study.

BACKGROUND & AIMS: Direct-acting antiviral agents (DAAs) are safe and effective in patients with hepatitis C. Conflicting data were reported on the risk of hepatocellular carcinoma (HCC) during/after therapy with DAAs. The aim of this study was to evaluate the incidence of newly diagnosed HCC and associated risk factors in patients with advanced hepatitis C treated with DAAs. METHODS: The study is based on the NAVIGATORE platform, a prospectively recording database of all patients with hepatitis C receiving DAAs in the Veneto region of Italy. The inclusion criteria were: fibrosis stage ≥F3. The exclusion criteria were: Child-Turcotte-Pugh (CTP)-C, liver transplantation before DAAs, history or presence of HCC, follow-up <4 weeks after starting DAAs. A total of 3,917 out of 4,234 consecutive patients were included, with a mean follow-up of 536.2 ±â€¯197.6 days. RESULTS: Overall, HCC was diagnosed in 55 patients. During the first year, HCC incidence was 0.46% (95% CI 0.12-1.17) in F3, 1.49% (1.03-2.08) in CTP-A and 3.61% (1.86-6.31) in CTP-B cirrhotics; in the second year, HCC incidences were 0%, 0.2%, and 0.69%, respectively. By multivariate analysis, HCC was significantly associated with an aspartate aminotransferase to platelet ratio ≥2.5 (hazard ratio [HR] 2.03; 95% CI 1.14-3.61; p = 0.016) and hepatitis B virus infection (HR 3.99; 1.24-12.91; p = 0.021). Failure to achieve a sustained virological response was strongly associated with development of HCC (HR 9.09; 5.2-16.1; p = 0.0001). A total of 29% of patients with HCC had an aggressive tumor, often seen in the early phase of treatment. CONCLUSIONS: These data, obtained in a large, prospective, population-based study, indicate that in patients with advanced hepatitis C receiving DAAs, the risk of "de novo" hepatocarcinoma during the first year is not higher, and might be lower, than that of untreated patients. The risk further declines thereafter. Early hepatocarcinoma appearance may reflect pre-existing, microscopic, undetectable tumors. LAY SUMMARY: Hepatocellular carcinoma is one of the complications of hepatitis C related cirrhosis. Treating patients with advanced hepatitis C with the new interferon-free direct-acting antiviral agents has been associated with improvement in liver function and survival, while more conflicting data have been reported regarding the risk of hepatocellular carcinoma. We report the results of a prospective population study on the incidence of newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with direct-acting antiviral agents, clearly indicating that the residual hepatocellular carcinoma risk is reduced and declines progressively with time after a sustained virological response. Development of a liver tumor during/after therapy was associated with known risk factors and with virological failure.

Drug resistance in B and non-B subtypes amongst subjects recently diagnosed as primary/recent or chronic HIV-infected over the period 2013-2016: Impact on susceptibility to first-line strategies including integrase strand-transfer inhibitors.

OBJECTIVES: To characterize the prevalence of transmitted drug resistance mutations (TDRMs) by plasma analysis of 750 patients at the time of HIV diagnosis from January 1, 2013 to November 16, 2016 in the Veneto region (Italy), where all drugs included in the recommended first line therapies were prescribed, included integrase strand transfer inhibitors (InNSTI). METHODS: TDRMs were defined according to the Stanford HIV database algorithm. RESULTS: Subtype B was the most prevalent HIV clade (67.3%). A total of 92 patients (12.3%) were expected to be resistant to one drug at least, most with a single class mutation (60/68-88.2% in subtype B infected subjectsand 23/24-95.8% in non-B subjects) and affecting mainly NNRTIs. No significant differences were observed between the prevalence rates of TDRMs involving one or more drugs, except for the presence of E138A quite only in patients with B subtype and other NNRTI in subjects with non-B infection. The diagnosis of primary/recent infection was made in 73 patients (9.7%): they had almost only TDRMs involving a single class. Resistance to InSTI was studied in 484 subjects (53 with primary-recent infection), one patient had 143C in 2016, a total of thirteen 157Q mutations were detected (only one in primary/recent infection). CONCLUSIONS: Only one major InSTI-TDRM was identified but monitoring of TDRMs should continue in the light of continuing presence of NNRTI-related mutation amongst newly diagnosed subjects, sometime impacting also to modern NNRTI drugs recommended in first-line therapy.