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Abstract Introduction Cefiderocol is a siderophore cephalosporin showing activity against various carbapenem-resistant Gram-negative bacteria (CR-GNB). No data currently exist about real-world use of cefiderocol in terms of types of therapy (e.g., empirical or targeted, monotherapy or combined regimens), indications, and patient characteristics. Methods In this multicenter, prospective study, we aimed at describing the use of cefiderocol in terms of types of therapy, indications, and patient characteristics. Results Cefiderocol was administered as empirical and targeted therapy in 27.5% (55/200) and 72.5% (145/200) of cases, respectively. Overall, it was administered as monotherapy in 101/200 cases (50.5%) and as part of a combined regimen for CR-GNB infections in the remaining 99/200 cases (49.5%). In multivariable analysis, previous isolation of carbapenem-resistant Acinetobacter baumannii odds ratio (OR) 2.56, with 95% confidence interval (95% CI) 1.01–6.46, p = 0.047] and previous hematopoietic stem cell transplantation (OR 8.73, 95% CI 1.05–72.54, p = 0.045) were associated with administration of cefiderocol as part of a combined regimen, whereas chronic kidney disease was associated with cefiderocol monotherapy (OR 0.38 for combined regimen, 95% CI 0.16–0.91, p = 0.029). Cumulative 30-day mortality was 19.8%, 45.0%, 20.7%, and 22.7% in patients receiving targeted cefiderocol for infections by Enterobacterales, A. baumannii, Pseudomonas aeruginosa, and any metallo-β-lactamase producers, respectively. Conclusions Cefiderocol is mainly used for targeted treatment, although empirical therapies account for more than 25% of prescriptions, thus requiring dedicated standardization and guidance. The almost equal distribution of cefiderocol monotherapy and cefiderocol-based combination therapies underlines the need for further study to ascertain possible differences in efficacy between the two approaches.

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 5492 HBsAg-positive enrolled patients, 4152 (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.

Baricitinib, a reversible Janus-associated kinase-inhibitor, is approved for treating COVID-19, combined with Dexamethasone and, eventually, with Remdesivir (RDV). This retrospective cohort study assesses the real-life advantages and limits of Baricitinib in the current pandemic scenario. Data of all patients consecutively hospitalized with moderate/severe COVID-19 between 1 October 2021 and 31 March 2022 were retrospectively collected and described according to the treatment received (Baricitinib, Baricitinib + RDV, none). We performed survival analyses to estimate the 21-day probability of Intensive Care Unit (ICU) admission, death, and composite. We built multivariate Cox regression models to identify ICU admission/death predictors among patients’ features. Of 111 subjects, 28 received Baricitinib, 21 received Baricitinib + RDV, and 62 could not be treated due to pre-existing conditions. Treated patients had a comparable risk of death (HR 0.50, 95% C.I. 0.20–1.26, p = 0.14) but remarkably lower risk of 21-day ICU admission (H.R., 0.10, 95% C.I., 0.01–0.86, p = 0.03), regardless of the type of treatment received. At multivariable analysis, older age was the only predictor of ICU admission/death (HR 1.14, 95% C.I. 1.03–1.26, p ≤ 0.01).Although effective, the high prevalence of elderly, co-morbid patients limits Baricitinib use in the current pandemic setting.

Despite the availability of vaccines and antivirals and the biological evolution of SARS-CoV-2, the rate of hospitalizations and deaths from COVID-19 remains high in Italy. It is crucial to understand whether and how the clinical characteristics of patients hospitalized for COVID-19 have changed over 2021–2022 and which risk factors are currently associated with adverse outcomes to develop targeted interventions. In this study, we present and compare the characteristics and outcomes of 310 patients with COVID-19 who were hospitalized between 1 August and 9 December 2021, when the Delta SARS-CoV-2 variant was prevalent (Group A), and between 3 January and 30 June 2022, when the Omicron variant was predominant (Group B). Using Survival Analysis, we estimated the cumulative 28-day hazard ratio (H.R.) of Intensive Care Unit (ICU) admission/death of patients in Group B vs. A. We built uni- and multivariate Cox regression models for the overall population and each group to identify risk factors for ICU admission/death among patient features. We found that Group B had a comparable risk of ICU admission/death (HR 1.60, 95% Confidence Interval, C.I. 1.00–2.58, p = 0.05) but a higher prevalence of elderly and co-morbid subjects than Group A. Non-invasive ventilation requirement was associated with adverse outcomes in both Group A (HR 21.03, 95% C.I. 5.34–82.80, p < 0.001) and Group B (HR 4.53, 95% C.I. 2.39–8.59, p < 0.001), as well as in the overall population (HR 3.88, 95% C.I. 2.49–6.06, p < 0.001). During the Omicron wave, elderly and co-morbid subjects had the highest risk of hospitalization and poor outcomes.

Background and aimHepatitis C virus (HCV) infection is a major global public health concern, being a leading cause of chronic liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The virus is classified into 8 genotypes and 93 subtypes, each displaying distinct geographic distributions. Genotype 4 is the most predominant in the Middle East and Eastern Mediterranean and is associated with high rates of hepatitis C infection worldwide. This study used next-generation sequencing to fully characterize the HCV genome and identify a novel subtype within genotype 4 isolated from a 64-year-old Saudi man diagnosed with hepatitis C.MethodsWe analyzed the complete genome of the 141-HCV isolate using whole-genome sequencing.ResultsOur phylogenetic reconstructions, based on the entire genome of HCV-4 strains, revealed that the 141-HCV isolate formed a distinct group within the genotype 4 classification, providing valuable new insights into the variability of HCV.ConclusionThis discovery of a previously unclassified HCV subtype within genotype 4 sheds light on the ongoing evolution and diversity of the virus. Such knowledge has significant implications for diagnostic and therapeutic approaches, as different subtypes may exhibit varying drug sensitivities and resistance profiles.

Objectives: The study measures trends in the profile of patients with chronic hepatitis B virus linked to care in Italy. Methods: A cross-sectional, multicenter, observational cohort (PITER cohort) of consecutive patients with hepatitis B surface antigen (HBsAg) over the period 2019-2021 from 46 centers was evaluated. The reference was the MASTER cohort collected over the years 2012-2015. Standard statistical methods were used. Results: The PITER cohort enrolled 4583 patients, of whom 21.8% were non-Italian natives. Compared with those in MASTER, the patients were older and more often female. The prevalence of hepatitis B e antigen (HBeAg) declined (7.2% vs 12.3; P

BackgroundThe current prevalence and clinical burden of Hepatitis Delta Virus (HDV) infection in Apulia are unknown. This study aimed to define the current epidemiological scenario of delta infection and to detect difficulties in the diagnosis and clinical management of HDV patients in Apulia.MethodsFrom May to September 2022, a fact-finding survey was conducted at eight Infectious Diseases Units of the Apulian region; each Unit was asked to complete a questionnaire on screening and diagnosis of HDV infection and demographic, virological, and clinical characteristics of HDV patients.ResultsA total of 1,461 HBsAg-positive subjects were followed up on an outpatient basis. Screening for HDV ranged from 30 to 90% of HBsAg + carriers in a single center. Overall, 952 HBsAg ± subjects (65%) were tested for HDV, and 80/952 (8.4%) were anti-HDV positive. Serum HDV RNA was detected only in 15/80 (19%) anti-HDV-positive subjects, and 12/15 patients (80%) were viremic. Sixty-five anti-HDV-positive subjects (81%) were from Italy; risk factors for HDV acquisition included the presence of HDV infection in the family (29/80 = 36%), drug addiction (12/80 = 15%), and co-infection with HCV or HIV (7/80 = 9%). Liver cirrhosis and hepatocellular carcinoma were diagnosed in 41 (51%) and 4 (5%) patients, respectively. Fifty-seven patients (71%) received nucleos(t)ide analog treatment.ConclusionsThe results of this survey show that HDV screening is variable and insufficient, thus real prevalence data on delta infection are lacking in Apulia. Moreover, the HDV RNA test is not available in most laboratories and is not provided by the national health system. These results underline the need for an organizational model to optimize the management of HDV patients throughout the Apulian region.

IntroductionTuberculosis (TB) remains an unresolved global health problem and vulnerable groups such as migrants remain the most affected with a higher risk of worse outcomes. The aim of this study was to evaluate clinical features, outcomes, and adverse events in migrant and native Italian patients admitted to three Italian hospitals in Southern Italy in order to assess differences and targeted strategies.MethodsWe performed a retrospective study on TB patients admitted between January 1, 2013, and December 31, 2021, in three Apulia hospitals. Two logistic regression models were used, with the dependent variables being (I) unsuccessful treatment (died, loss to follow-up, and failed treatment) and (II) adverse events.ResultsWe enrolled 543 consecutive patients admitted at three Italian hospitals with a diagnosis of TB during the study period, of them 323 (59.5%) were migrants and 220 Italian patients. The treatment success rate in the migrant group was 44.9% (137/305), while in the non-migrant group was 97.1% (203/209). Independent factors of unsuccess treatment (death, failure or loss to follow up) were: migrant status (O.R. = 11.31; 95% CI 9.72–14.23), being male (O.R. = 4.63; 95% CI 2.16–6.10), homelessness (O.R. = 3.23; 95% CI 2.58–4.54), having a MDR (Multidrug-resistant) (O.R = 6.44; 95% CI 4.74–8.23), diagnostic delay (O.R. = 3.55; 95% CI 1.98–5.67), and length of hospitalization (O.R. = 3.43; 95% CI 1.88–5.87). While, age >65 ys (O.R. = 3.11; 95% CI 1.42–4.76), presence of extrapulmonary TB (O.R. = 1.51; 95% CI 1.31–2.18), monoresistance (O.R. = 1.45; 95% CI 1.25–3.14) and MDR pattern (O.R. = 2.44; 95% CI 1.74–5.03) resulted associated with adverse events.ConclusionMigrant population is at high risk of unsuccessful treatment (death, loss to follow-up, and treatment failure). Policies targeted specifically to this group are needed to really impact and improve their health status and also to contain the TB burden.

The oral mucosa is the first site of SARS-CoV-2 entry and replication, and it plays a central role in the early defense against infection. Thus, the SARS-CoV-2 viral load, miRNAs, cytokines, and neutralizing activity (NA) were assessed in saliva and plasma from mild (MD) and severe (SD) COVID-19 patients. Here we showed that of the 84 miRNAs analyzed, 8 were differently expressed in the plasma and saliva of SD patients. In particular: (1) miRNAs let-7a-5p, let-7b-5p, and let-7c-5p were significantly downregulated; and (2) miR-23a and b and miR-29c, as well as three immunomodulatory miRNAs (miR-34a-5p, miR-181d-5p, and miR-146) were significantly upregulated. The production of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, IL-9, and TNFα) and chemokines (CCL2 and RANTES) increased in both the saliva and plasma of SD and MD patients. Notably, disease severity correlated with NA and immune activation. Monitoring these parameters could help predict disease outcomes and identify new markers of disease progression.

BackgroundSARS-CoV-2 transmission mainly occurs through exposure of the upper airway mucosa to infected secretions such as saliva, which are excreted by an infected person. Thus, oral mucosal immunity plays a central role in the prevention of and early defense against SARS-CoV-2 infection. Although virus-specific antibody response has been extensively investigated in blood samples of SARS-CoV-2-infected patients and vaccinees, local humoral immunity in the oral cavity and its relationship to systemic antibody levels needs to be further addressed.Material and MethodsWe fine-tuned a virus neutralization assay (vNTA) to measure the neutralizing activity (NA) of plasma and saliva samples from 20 SARS-CoV-2-infected (SI), 40 SARS-CoV-2-vaccinated (SV), and 28 SARS-CoV-2-vaccinated subjects with a history of infection (SIV) using the “wild type” SARS-CoV-2 lineage B.1 (EU) and the Delta (B.1.617.2) strains. To validate the vNTA results, the presence of neutralizing antibodies (NAbs) to the spike receptor binding domain (RBD) was evaluated with an ELISA assay.ResultsNA to SARS-CoV-2 lineage B.1 (EU) was present in plasma samples from all the tested subjects, with higher titers in SIV compared to both SI and SV. Conversely, NA was detected in saliva samples from 10.3% SV, 45% SI, and 92.6% SIV, with significantly lower titers in SV compared to both SI and SIV. The detection of NAbs in saliva reflected its reduced NA in SV.DiscussionThe difference in NA of plasma vs. saliva was confirmed in a vNTA where the SARS-CoV-2 B.1 and Delta strains were tested head-to-head, which also revealed a reduced NA of both specimens compared to the B.1 variant.ConclusionsThe administration of SARS-CoV-2 vaccines was associated with limited virus NA in the oral cavity, as measured in saliva and in comparison to plasma. This difference was more evident in vaccinees without a history of SARS-CoV-2 infection, possibly highlighting the importance of local exposure at the site of virus acquisition to effectively prevent the infection and block its spread. Nevertheless, the presence of immune escape mutations as possibly represented by the SARS-CoV-2 Delta variant negatively affects both local and systemic efficacy of NA associated with vaccination.

Hepatitis B virus infection occurs in approximately 7% of people living with HIV (PLWH), with substantial regional variation and higher prevalence among intravenous drug users. Early studies on the natural history of HIV/HBV coinfection demonstrated that in coinfected patients, chronic hepatitis B (CHB) has a more rapid progression than in HBV-monoinfected patients, leading to end-stage liver disease complications, including hepatocellular carcinoma. Therefore, the adequate management of CHB is considered a priority in HIV-coinfected patients. Several guidelines have highlighted this issue and have provided recommendations for preventing and treating HBV infection. This article discusses the management of liver disease in patients with HIV/HBV coinfection and summarizes the current and future therapeutic options for treating chronic hepatitis B in this setting.

Is it possible to achieve a collaboration between Infectious Diseases (ID) Specialists and General Practitioners (GPs) in the management of chronic HIV infection? A cross sectional survey was conducted among People Living with HIV (PLWHIV) attending the outpatient services of four Italian Infectious Diseases Centers to understand to which extent patients trust their GPs and involve them in the management of their chronic condition. Information about level of communication with GPs, subjective perception of the disease, and presence of co-medications were collected and matched with socio-demographic data using χ2statistics. A p50 years. Overall, 508 patients (76%) had informed GPs about HIV-positivity. Communication of diagnosis was significantly associated with age >50years, lower education level, history of disease >10 years and residency in Northern Italy. The "Undetectable = Untrasmittable" (U = U) concept was investigated as an indirect measure of perceived stigma. 23% of subjects was unaware of its meaning. Despite undetectable status, 50% of PLWHIV found difficult to communicate their condition to GPs, especially married (52% vs 48% of unmarried, p = 0.003), well-educated patients (51% vs 48, p = 0.007), living in Southern vs Northern Italy (52% vs 46%, p< 0.001). More than 75% of the participants consulted the ID specialist for co-medications and DDIs management, often complaining a lack of communication of the former with GPs. Overall, a good level of communication between PLWHIV and GPs was outlined, even if a wider involvement of the latter in HIV care is desirable.

The aim of this study is to describe the features, the outcomes, and the clinical issues related to Remdesivir administration of a cohort of 220 patients (pts) with COVID-19 hospitalized throughout the last two pandemic waves in Italy. One hundred and nine pts were enrolled from 1 September 2020, to 28 February 2021 (Group A) and 111 from 1 March to 30 September 2021 (Group B). Notably, no differences were reported between the two groups neither in the timing of hospitalization. nor in the timing of Remdesivir administration from symptoms onset. Remarkably, a higher proportion of pts with severe COVID-19 was observed in Group B (25% vs. 10%, p < 0.001). At univariate and multivariate analysis, rather than the timing of Remdesivir administration, age, presence of coexisting conditions, D-dimers, and O2 flow at admission correlated positively to progression to non-invasive ventilation, especially for patients in Group B. However, the rate of admission in the Intensive Care Unit and/or death was comparable in the two groups (7% vs. 4%). Negligible variations in serum GOT, GPT, GGT, and eGFR levels were detected. A mean reduction in heart rate was noticed within the first three days of antiviral treatment (p < 0.001). Low rate of ICU admission, high rate of clinical recovery, and good drug safety were observed in COVID-19 patients treated with Remdesivir during two diverse pandemic waves.

The reason behind the high inter-individual variability in response to SARS-CoV-2 infection and patient’s outcome is poorly understood. The present study targets the sphingolipid profile of twenty-four healthy controls and fifty-nine COVID-19 patients with different disease severity. Sera were analyzed by untargeted and targeted mass spectrometry and ELISA. Results indicated a progressive increase in dihydrosphingosine, dihydroceramides, ceramides, sphingosine, and a decrease in sphingosine-1-phosphate. These changes are associated with a serine palmitoyltransferase long chain base subunit 1 (SPTLC1) increase in relation to COVID-19 severity. Severe patients showed a decrease in sphingomyelins and a high level of acid sphingomyelinase (aSMase) that influences monosialodihexosyl ganglioside (GM3) C16:0 levels. Critical patients are characterized by high levels of dihydrosphingosine and dihydroceramide but not of glycosphingolipids. In severe and critical patients, unbalanced lipid metabolism induces lipid raft remodeling, leads to cell apoptosis and immunoescape, suggesting active sphingolipid participation in viral infection. Furthermore, results indicated that the sphingolipid and glycosphingolipid metabolic rewiring promoted by aSMase and GM3 is age-dependent but also characteristic of severe and critical patients influencing prognosis and increasing viral load. AUCs calculated from ROC curves indicated ceramides C16:0, C18:0, C24:1, sphingosine and SPTLC1 as putative biomarkers of disease evolution.

Abstract Background Migrants in Italy are prevalently young adults, with a higher risk of sexual transmitted infections (STI) and HIV infection. Promoting consistent as well as correct use of condoms could reduce failure rate due to their improper use. The aim of our study was to evaluate Condom Use Skills among a migrant population recently landed in Italy, hosted in a government center for asylum seekers. Methods The study sample was composed of 80 male migrants. Sanitary trained interviewers submitted a questionnaire to participants to investigate age, provenience, marital status, educational level and knowledge about transmission and prevention of HIV/STI. Then, we assessed participants’ level of condom use skill with the Condom Use Skills (CUS) measure by using a wooden penile model. The interviewer filled in a checklist and assigned 1 point for correct demonstration of each behavior that may prevent condom failure during sex. Results Participants’ median age was 26 years and the sample was composed of 54 migrants from sub-Saharan Africa and 26 from Middle East. Most of them were married, with a lower middle level of education, up to 8 or 5 years. Half of the sample achieved the highest score in the questionnaire and our CUS showed a large number of people with middle high score classes. The Spearman’s rho was 0.30, therefore answers to the questionnaire and CUS score appeared correlated (p

Few data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure.To evaluate DAA failure incidence and the retreatment clinical impact in patients treated in the advanced liver disease stage.Data on HCV genotype, liver disease severity, and first and second line DAA regimens were prospectively collected in consecutive patients who reached the 12-week post-treatment and retreatment evaluations from January 2015 to December 2016 in 23 of the PITER network centers.Among 3,830 patients with advanced fibrosis (F3) or cirrhosis, 139 (3.6%) failed to achieve SVR. Genotype 3, bilirubin levels >1.5mg/dl, platelet count

Chronic hepatitis B (CHB) is a complex disease with significant social impact both on the patients’ quality of life of and the economic resources involved. Its chronicity affects considerably not only the clinical management of the disease (for the need for drugs with proven long-term safety and low rate of resistance), but also the economic impact (for the high costs of treatment, the management of complications, and the constant monitoring of therapy). Since, as is well known, the main problem of modern health care systems is the general scarcity of available resources in the face of growing demand for health, the issue of economic evaluation of therapies for the treatment of chronic hepatitis B has been addressed in numerous national and international studies. In fact, clinicians find a strong support for the choice of the most suitable therapeutic pathway in the major scientific societies’ guidelines (European Association for the Study of The Liver – EASL, American Association for the Study of Liver Diseases – AASLD, Associazione Italiana per lo Studio del Fegato – AISF), while the analysis of the economic implications is rather more difficult, even for the methodological differences and peculiarities of the different countries. The aim of this paper is to present a brief summary of some of the recently conducted cost-effectiveness analyses and extrapolate some data to support the economic evidence related to the treatment of CHB with nucleos(t)ide analogs. In particular, the article focuses on the comparison between entecavir (ETV) and tenofovir (TDF), the two oral antiviral therapies recommended for first-line treatment. In the selected studies, the comparison between the different treatment options was conducted in order to assess the incremental cost-effectiveness ratio (ICER) and the results were expressed in terms of QALYs (Quality Adjusted Life Years) gained. Despite the methodological differences among the selected studies, tenofovir is found to be, in the context of first-line oral antiviral therapies, the most cost-effective treatment for patients with chronic hepatitis B.

Treatment of chronic hepatitis B (CHB) has markedly improved in the last 15 years due to the availability of direct antivirals which greatly increase therapeutic options. Currently, there are two classes of agents licensed for CHB treatment: standard or pegylated interferon alpha (IFN or Peg-IFN) and five nucleoside/nucleotide analogues (NAs). Long-term treatment with NAs is the treatment option most often used in the majority of CHB patients. Entecavir and tenofovir, the most potent NAs with high barrier to resistance, are recommended as first-line monotherapy by all major treatment guidelines and can lead to long-lasting virological suppression, resulting in histological improvement or reversal of advanced fibrosis and reduction in disease progression and liver-related complications. In this review, we focus on current treatment strategies of chronic hepatitis B and discuss the most recent efficacy and safety data from clinical trials and real life clinical practice. Recent findings of response-guided approaches are also discussed.