Abstract Background Hepatitis C virus (HCV) remains a global public health concern. Despite the availability of direct-acting antivirals (DAAs), many infections remain undiagnosed—particularly in older adults excluded from national screening programs. This study aimed to assess the prevalence of unrecognized HCV infections in surgical patients over 55 years of age through an opportunistic hospital-based screening approach. Methods A single-center, retrospective observational study was conducted at “Federico II” University Hospital in Naples, Italy, from January 1 to December 31, 2023. All patients aged ≥ 18 years undergoing surgery or hospital admission were screened for anti-HCV antibodies. Reflex testing of samples with a signal-to-cut off (s/co) ratio ≥ 11 was performed with Elecsys® HCV Duo assay to confirm active infection via antigen detection. The primary endpoint was the prevalence of undiagnosed active infections in patients over 55. Secondary endpoints included distribution by age, sex, and hospital department. Results Of 33,658 patients screened, 768 (2.3%) tested positive for anti-HCV antibodies; 178 (23.2%) were antigen-positive. Active infections were most common in patients aged 55–79 (66%) and ≥ 80 (21.7%), with the highest positivity (36.5%) in those over 80. In non–high-risk departments, HCV antigen positivity reached 21.2%. No significant sex differences were observed. All antigen-positive patients received DAA treatment. Conclusions Opportunistic screening in surgical patients over 55 is effective, feasible, and cost-efficient. The high rate of undiagnosed infections in this age group supports expanding screening efforts to include older adults. These results support the national implementation of opportunistic screening programs targeting older adults to achieve HCV elimination goals. Further multicenter studies are needed to support broader implementation.

INTRODUCTION:Hepatocellular carcinoma represents a relevant cause of cancer mortality globally, with hepatitis C virus infection accounting for 25-30% of cases. The advent of direct-acting antivirals has transformed HCV management, yet treatment of patients with concurrent or prior HCC presents unique pharmacotherapeutic challenges. AREAS COVERED:This review examines DAA efficacy and safety in HCC patients, addressing the now-resolved controversy regarding potential increased HCC recurrence. We analyze drug-drug interactions between DAAs and systemic HCC therapies, including tyrosine kinase inhibitors and immune checkpoint inhibitors. The impact of sustained virological response on oncological outcomes is evaluated, alongside practical guidance for special populations. EXPERT OPINION:Current evidence supports universal HCV treatment in HCC patients, with SVR rates approaching 90% and demonstrated reductions in both recurrence and mortality. The recurrence controversy has been definitively resolved through rigorous meta-analyses. Future research should prioritize prospective pharmacokinetic studies and optimization of treatment sequencing.

INTRODUCTION:Pregnant women represent a vulnerable population during the COVID-19 pandemic, facing increased risks of severe disease and adverse obstetric outcomes, yet they have been largely excluded from pivotal therapeutic clinical trials, leaving a critical evidence gap for treatment decisions. AREAS COVERED:This review examines the available evidence on the safety and efficacy of COVID-19 therapies during pregnancy, including oral antivirals (nirmatrelvir/ritonavir, molnupiravir), intravenous remdesivir, monoclonal antibodies, corticosteroids, and immunomodulators (tocilizumab, baricitinib). A literature search was conducted using MEDLINE/PubMed for English-language articles published from March 2020 to December 2023, including studies of any design reporting maternal and neonatal outcomes. EXPERT OPINION:The COVID-19 pandemic exposed a critical gap in clinical research through the systematic exclusion of pregnant women from therapeutic trials. Current evidence, though largely observational, supports vaccination as the primary preventive strategy, nirmatrelvir/ritonavir for outpatients at risk of progression, and remdesivir plus corticosteroids for hospitalized patients requiring oxygen supplementation.

Background: Difficult-to-treat resistant Pseudomonas aeruginosa (DTR-PA) infections are associated with high morbidity and mortality, but data on prognostic factors remain limited. Given the limited real-world data on outcomes of DTR-PA infections, we aimed to identify clinical predictors of mortality and response to therapy in this setting. Methods: We conducted a single-center retrospective cohort study of 51 patients with DTR-PA infections. The primary endpoint was 30-day all-cause mortality; secondary endpoints were clinical and microbiological cure at end of therapy. An exploratory analysis evaluated 30-day infection-related mortality. Logistic regression models (univariable, multivariable and Firth bias-reduced) were used to identify independent predictors. Results: Median age was 64 years (IQR 22); 63% were male and 71% were in the ICU at infection onset. Sepsis occurred in 80% and septic shock in 45%. Thirty-day all-cause mortality was 49% (25/51). According to multivariable analysis, septic shock was an independent predictor of mortality (aOR 5.52, 95% CI 1.04-29.27; p = 0.045) as younger age (aOR 1.06, 95% CI 1.00-1.12; p = 0.052), whereas targeted therapy with ceftazidime/avibactam or ceftolozane/tazobactam is a protective factor (aOR 0.15, 95% CI 0.02-1.17; p = 0.070) did not reach significance in the final model. Clinical cure occurred in 33% (17/51) and was negatively associated with device burden and bloodstream infection, whereas microbiological cure (45%, 23/51) was more likely with targeted therapy and absence of sepsis. The exploratory analysis of infection-related mortality (35%) showed similar predictors. Conclusions: DTR-PA infections are associated with high mortality. Septic shock and older age predict death, while the use of novel β-lactam/β-lactamase inhibitors is associated with improved outcomes. Early recognition of severe illness and timely administration of active therapy may improve survival in these infections.

This subgroup analysis of the FORTRESS study aimed to evaluate clinical and microbiological outcomes, treatment patterns, and safety of intravenous fosfomycin (FOS)-containing regimens for the treatment of infections due to carbapenem-resistant (CR) Gram-negative bacteria in a real-world setting. Interim data from patients treated with FOS for infections due to CR pathogens were analyzed from the ongoing prospective, multicenter, multinational, observational FORTRESS study. Key outcomes included patient demographics, clinical and infection characteristics at baseline, treatment patterns, and indications of FOS use, as well as clinical, microbiological, and safety outcomes. Exploratory Firth univariate and multivariate logistic regression were performed to identify factors associated with successful clinical response. The subgroup included 161 patients (median age 60 years, 30.4

Machine learning (ML) models have been increasingly applied to support the diagnosis of bloodstream infections (BSI), particularly through the analysis of large routinely collected healthcare datasets. However, it remains uncertain whether large sample sizes alone are sufficient to achieve high diagnostic accuracy. We performed a systematic review and meta-analysis to evaluate the diagnostic performance of ML-based models for BSI in large cohorts. MEDLINE, Embase, and Web of Science were systematically searched from inception to December 31, 2025 (Prospero registration CRD420251080948). We included observational studies evaluating ML models for BSI diagnosis with ≥ 1000 patients or BSI episodes and reporting sufficient data to reconstruct diagnostic accuracy measures. Pooled sensitivity and specificity were estimated using a bivariate random-effects Reitsma model. Secondary analyses included pooled area under the summary receiver operating characteristic curve (SROC-AUC), predictive values, subgroup analyses, and meta-regression. Twenty-four retrospective studies were included. Most studies evaluated adult hospitalized patients and used routinely collected structured data, including laboratory, vital sign, and administrative variables. Tree-based ensemble algorithms were the most commonly used architectures. The pooled sensitivity and specificity were 76.6

BackgroundIntravenous hyper-immune anti-cytomegalovirus immunoglobulins (CMV-IG) therapy are licensed for prophylaxis, yet their therapeutic value in established CMV disease remains poorly defined. We aimed to evaluate the clinical and virological impact of adjunctive CMV-IG in combination with standard antiviral therapy in immunocompromised patients with CMV disease, compared with standard antiviral therapy alone.MethodsWe performed a single-center retrospective case-control study at A.O.U. "Federico II" University Hospital, Naples, Italy, including consecutive immunocompromised patients with CMV disease between March 2021 and November 2024. Cases received standard antiviral therapy plus CMV-IG (100 IU kg-1 day-1 for three consecutive days). Controls received antivirals only.ResultsThirty-four patients were analyzed (15 cases, 19 controls). Thirty-day survival was 93% vs 95% (p=>0.9) and composite outcome (combination of 30-day mortality and clinical response) occurred in 93% vs 90% (p=>0.9) in cases and controls, respectively. Median time-to-virological response in days was achieved 4 vs 7 days (p=<0.001), as was median duration of antiviral therapy in days 12 vs 16 days (p=0.001) and hospitalization 14 vs 19 days (p=0.004) in cases and controls, respectively. Adverse-event rates were low and comparable in the 2 groups.ConclusionsIn this real-world cohort, adjunctive CMV-IG did not affect mortality, but was associated with faster virological clearance and shorter antiviral and hospital courses, without additional toxicity.

Background: Refractory cytomegalovirus (CMV) infection remains a major challenge after solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT). Maribavir has demonstrated efficacy and a favorable safety profile in clinical trials, but real-world data on virological endpoints, treatment duration, and recurrence remain limited. Methods: We retrospectively reviewed all consecutive transplant recipients treated with maribavir for refractory CMV infection/disease at a tertiary referral center in Naples, Italy. Clinical and laboratory information were extracted from medical records. Results: Six patients were included: five SOT recipients and one autologous HSCT recipient. Maribavir was administered at 400 mg twice daily for a median of 43.5 days (IQR 23–56 days). At the end of treatment, five patients had detectable CMV DNA < 1000 IU/mL without confirmed clearance. Patient 6 was the only patient to achieve confirmed clearance (

Patients with inflammatory bowel disease(IBD)have a higher risk of varicella zoster virus infection (VZI) than the general population, largely due to immunosuppressive-biologic therapies. Preventing viral reactivation is a relevant clinical goal. The recombinant zoster vaccine (RZV, Shingrix) has shown high efficacy and good tolerability in the general population,but data in IBD are limited. Real-world evidence on its effectiveness and safety is needed to support vaccination strategies and guide clinical practice. The objective of the study was to assess the effectiveness and safety of the RZV in IBD. From March 2023 to September 2024, consecutive IBDpatients who received the RZV Shingrix before starting or with ongoing biologics were prospectively enrolled across 9 tertiary IBDcenters. Effectiveness was assessed clinically and defined as the absence of VZI or HZ reactivation during the observation period. Safety outcomes included the occurrence of vaccine-related adverse events (AEs)—such as fever, arthralgia, and others—systematically recorded during the follow-up after each vaccine dose. A total of 420 IBD cases were included, comprising 215 (51.2%) with UC and 205 (48.8%) with CD. Most patients (95.8%) completed the VZV vaccination cycle. Biologic therapy was ongoing in 319 (75.9%) patients, more frequently in CD than UC (p < 0.001). During a mean follow-up of 11.0 ± 1.2 months, VZV reactivation occurred in only 0.7% of patients, confirming a high clinical effectiveness of RZV in IBD. Overall, AEs were reported in 52.4% of cases, with the most common being arm pain (37.1%), followed by asthenia (16.0%) and fever (13.8%). No significant differences between UC and CD (54.4% vs 50.2%, p = 0.448), as for gender (p = 0.96), were found. AE occurrence was significantly associated with ongoing biologic therapy (56.9% vs 29.3% without, p = 0.009) and lower age (median 42 vs 45.5 years, p = 0.047). However, analyzing therapies by specific mechanism of action, no class of drug was associated with a higher AE risk compared to others. Logistic regression confirmed only biologics as an independent risk factor (OR1.84; 95%; p = 0.009). In the subgroup analysis comparing biologics to conventional or no therapy, only asthenia and joint pain were more common in patients on biologics (p < 0.001 and p = 0.04, respectively). No serious AEs were reported. RZV demonstrated a favorable safety profile in IBD patients, with only mild and self-limiting adverse events, more frequently observed in those receiving biologics. Notably, the very low rate of VZV reactivation (0.7%) over a mean follow-up of 11 months confirms the high effectiveness of RZV in this high-risk population. These findings support the integration of RZV into preventive strategies in IBD, particularly before or during immunosuppressive therapy. References: 1. Din S, Selinger CP, Black CJ, Ford AC. Systematic review with network meta-analysis: Risk of Herpes zoster with biological therapies and small molecules in inflammatory bowel disease. Aliment Pharmacol Ther. 2023 Mar; 57 (6): 666-675. 2. Nugent Z, Singh H, Targownik LE, Bernstein CN. Herpes Zoster Infection and Herpes Zoster Vaccination in a Population-Based Sample of Persons With IBD: Is There Still an Unmet Need? Inflamm Bowel Dis. 2019 Feb 21; 25 (3): 532-540. Conflict of interest: Castiglione, Fabiana: Honoraria from: Takeda, AbbVie, Celltrion, Johnsson Johnsson, Cadigroup, Sandoz, Pfizer, Lilly, Lionhealth, Nestlè Guarino, Alessia Dalila: No conflict of interest Pinchera, Biagio: No conflict of interest Spadaro, Giuseppe: No conflict of interest Zappulo, Emanuela: No conflict of interest Calabrese, Giulio: No conflict of interest Rispo, Antonio: None Testa, Anna: Consultant /Advisory board for Abbvie, J & J, Takeda, Ferring Nardone, Olga Maria: Advisory board fees from Eli Lilly, Nestlè, Janssen Speaker fees from AbbVie, Janssen, Eli Lilly, Ferring, Alfa Sigma, Recordati, Noòs, and Pfizer Mucherino, Caterina: Takeda, Pfizer, Alfasigma, Galapagos, Johnson & Johnson, Miranda, Agnese: No conflict of interest Vespere, Giuliana: none Imperatore, Nicola: None to declare Capone, Pietro: No conflict of interest Patturelli, Marta: No conflict of interest Gravina, Antonietta Gerarda: Gravina AG has conducted training activities [e.g. educational continuing medical activities (ECM), preceptorship] for Pfizer, Galapagos Biopharma, and AbbVie. Pellegrini, Lucienne: No conflict of interest Gentile, Ivan: No conflict of interest

Rhino-orbital mucormycosis is a rare, life-threatening opportunistic fungal infection, typically affecting immunocompromised patients. During the COVID-19 pandemic, increased cases were mainly linked to SARS-CoV-2 infection, diabetes, and corticosteroid exposure. We report a severe case in a previously healthy 44-year-old immunocompetent man who developed acute left-sided exophthalmos, ophthalmoplegia, severe visual loss, and systemic deterioration 10 days after AZD1222 COVID-19 vaccination. Clinical and radiologic findings suggested invasive rhino-orbital fungal disease, prompting immediate liposomal amphotericin B, broad-spectrum antibiotics, urgent endoscopic sinus surgery, and repeated orbital-sinonasal debridements with amphotericin B irrigation. Histopathological examination demonstrated broad aseptate hyphae with tissue necrosis, consistent with mucormycosis, while fungal culture and ITS sequencing identified Rhizopus arrhizus as the causative species. Therapy was later adjusted to include isavuconazole and antibacterial coverage for persistent inflammation and secondary colonization. Orbital and systemic improvement occurred within the first week, with globe preservation and marked proptosis reduction at 6 months, despite persistent ophthalmoplegia and residual light perception. Isavuconazole was continued for 2 years, with no recurrence during 3 years of follow-up. Although causality with vaccination cannot be established, the temporal association and biological plausibility warrant further investigation. Early suspicion and prompt combined medical-surgical management are essential in rapidly progressive orbital cellulitis.

Several years after its emergence, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [...]

OBJECTIVES:Undernutrition remains one of the most powerful yet neglected determinants of tuberculosis (TB) incidence and progression. Although its impact on TB outcomes has been extensively described in low-income countries, limited evidence is available from high-income settings. This study aimed to assess the association between body mass index (BMI) strata at treatment initiation and TB-related outcomes in a large multicentre cohort from Italy. METHODS:We conducted a retrospective, multicentre observational study including all adults diagnosed with TB between January 2021 and August 2025 in 16 Infectious and Tropical Diseases Units across seven Italian regions. Patients were stratified by BMI at treatment initiation (<16, 16-16.99, 17-18.49, 18.5-24.99, and ≥25 kg/m2). Outcomes included time to sputum conversion, length of hospital stay, occurrence and severity of adverse events, incomplete treatment (including failure, death, and loss to follow-up), and loss to follow-up. Multilevel regression models adjusting for study centre and relevant confounders were used to assess associations between BMI strata and each outcome. RESULTS:A total of 709 people with TB were included (median age, 38 years [interquartile range 28-53]; 488/709, 75.5% male). Overall, 299 of 709 (42%) were underweight (BMI <18.5 kg/m2). Compared with people with TB with normal BMI (18.5-24.99 kg/m2), those with severe undernutrition (BMI <16 kg/m2) showed higher rates of adverse events (54/74 [73.0%] vs. 101/410 [24.6%]; adjusted OR [aOR] 12.17, 95% CI 6.41-23.08), incomplete treatment (53/74 [71.6%] vs. 87/410 [21.2%]; aOR 18.28, 95% CI 6.70-49.80), and loss to follow-up (41/74 [55.4%] vs. 81/410 [19.7%]; aOR 5.99, 95% CI 2.58-13.90). Median hospital stay was also longer in this group (50 days [interquartile range 24-66] vs. 30 days [interquartile range 18-60]), corresponding to a 23% adjusted increase. Weight gain during the first 6 months of treatment was not significantly associated with major outcomes. CONCLUSIONS:Severe underweight at treatment initiation is a major independent predictor of poor outcomes in TB. These findings highlight the need for systematic nutritional assessment and targeted interventions within TB programmes, even in high-income, low-incidence settings.

OBJECTIVES:Doxycycline postexposure prophylaxis (DoxyPEP) has emerged as a promising tool for reducing bacterial sexually transmitted infections (bSTIs), particularly among men who have sex with men. This study aims to investigate the attitudes and prescribing practices of Italian infectious disease (ID) physicians regarding DoxyPEP for the prevention of bSTIs. METHODS:This is a cross-sectional survey conducted between October 2024 and March 2025 among ID specialists registered with the Italian Society of Infectious and Tropical Diseases. An anonymous online questionnaire assessed demographics, prescribing behaviour, attitudes and concerns regarding DoxyPEP. Favourability was rated on a visual analogue scale from 0 to 100. Descriptive and non-parametric statistics were used, and a Poisson regression model for predictors of favourable attitude was weighted according to the inverse of the probability of being sampled for responding to the survey. RESULTS:Of 132 respondents, 44.0% reported prescribing DoxyPEP, primarily in STI or pre-exposure prophylaxis clinics and urban settings. Median favourability was 70/100 and was higher among DoxyPEP prescribers (80 vs 50, p<0.001). The main reasons for prescribing were repeated STIs and specific sexual behaviour. The most frequently cited concern was antimicrobial resistance (96.2%), followed by the perceived superiority of condoms in preventing bSTIs and DoxyPEP toxicity. Informal use of DoxyPEP without medical supervision was reported by 46.2%, but counselling was significantly lower among non-prescribers. Older age was independently associated with higher favourability (p=0.005). CONCLUSIONS:This national survey shows a favourable attitude towards DoxyPEP among Italian ID physicians. DoxyPEP prescription was reported by less than half of the respondents, suggesting limited real-world use in Italy, with a variability in physicians' concerns and attitudes towards this preventive strategy for bSTIs.

Sex disparities in tuberculosis (TB) outcomes are not well characterized, especially in high-income countries where social vulnerability and migration influence access to care. Although men globally experience a higher TB burden, the interaction between sex, migration, and social determinants is complex and extends beyond biological factors. This study evaluated sex differences in clinical and programmatic TB outcomes in a high-income European country with a significant substantial migrant population. A retrospective multicentre cohort study was conducted across 16 Infectious Diseases Units in seven Italian regions from (January 2021 to September 2025). Outcomes included time to sputum conversion (in pulmonary TB), length of hospital stay (LOS), adverse events (AEs) and their severity, incomplete treatment (defined as failure, death, or loss to follow-up), and loss to follow-up (LTFU). Mixed-effects models were applied using two prespecified adjustment sets: sex, centre, and core confounders (Model A); and sex, centre, and clinically relevant baseline imbalances (Model B). Sub-analyses examined the impact of migration status. Of 982 TB patients, 229 (23.3

BACKGROUND:Bloodstream infections (BSIs) by methicillin-susceptible Staphylococcus aureus (MSSA) are a significant cause of morbidity and mortality, traditionally treated with antistaphylococcal penicillins (ASPs) or cefazolin. Ceftriaxone has emerged as an alternative due to its once-daily dosing regimen and favourable safety profile; however, its efficacy compared to the standard of care (SoC) remains controversial. This evidence synthesis aimed to assess the role of ceftriaxone in treating MSSA-BSIs. METHODS:A systematic literature search was conducted in PubMed, Embase, and Scopus up to December 31, 2025 (PROSPERO protocol CRD42024595748). Studies comparing ceftriaxone to ASPs or cefazolin for MSSA-BSIs were included. Primary outcomes were 30-day and 90-day all-cause mortality . Pooled effect sizes with their 95% confidence intervals (CIs), were calculated using random-effects models, odds ratios (ORs) and mean differences (MDs) according to the type of outcome. RESULTS:Eleven studies totalling 2,568 patients were included. Ceftriaxone was associated with significantly increased 30-day mortality (OR 3.33; 95% CI: 2.17-5.10), although differences at 90 days were not significant (OR 1.71; 95% CI: 0.75-3.90). No significant differences were noted for clinical success (OR 0.49; 95% CI: 0.19-1.26), microbiological clearance (OR 1.66; 95% CI: 0.73-3.82). Adverse event rates were similar between groups. CONCLUSION:Given the availability of various alternatives and the consistent short-term mortality signal observed, routine use of ceftriaxone for MSSA-BSIs, especially as initial therapy, is not supported by current evidence. Only novel findings from randomized studies may change the place in therapy of the drug in this context.

To describe the clinical characteristics and outcomes of patients with nosocomial pneumonia (NP) caused by carbapenem-resistant Gram-negative bacilli (CR-GNB) and to compare them to patients with NP caused by carbapenem-susceptible (CS)-GNB. Prospective observational multicenter study including patients with bacteremic NP caused by GNB from the ALARICO Network (June 2018-January 2020). The primary outcome measure was 30-day mortality. A Cox regression analysis was performed to identify factors independently associated with 30-day mortality. Hazard ratio (HR) and 95

Refractory and resistant cytomegalovirus infections remain significant challenges in solid-organ transplant recipients. In this context, maribavir is a valuable therapeutic option for management of cytomegalovirus infection. Although the clinical efficacy and safety of maribavir are well established, the optimal approach for assessment of viremic response, which is defined as the clearance of viremia, still requires further clarification. Notably, some patients treated with maribavir do not achieve full viremia clearance, despite clinical improvement and a significant reduction in viral load. In this report, we shared our exploration of the potential for a new paradigm for management of the viremic response during maribavir therapy. Our experience suggested that the goal to achieve complete viremia clearance may not always be necessary if clinical resolution and stable viremic responses (ie, viral load <1000 IU/mL) are achieved. In such cases, discontinuation of therapy with close monitoring may be a viable option.

Background: Invasive fungal infections (IFIs) are a major complication in patients with acute myeloid leukemia (AML), particularly during chemotherapy-induced neutropenia. Posaconazole is the standard drug for primary antifungal prophylaxis (PAP), but its use is limited by oral bioavailability and CYP3A4 interactions. Study Objective: This study aims to evaluate the clinical efficacy and safety of intravenous caspofungin versus oral posaconazole as PAP in AML patients during their first cycle of chemotherapy and assess their subsequent impact on clinical outcomes. Methods: A retrospective, monocentric study was conducted on 75 consecutive AML patients treated at the Federico II University Medical School of Naples, Italy (2021-2025). Patients received either caspofungin or posaconazole as PAP based on the drug-drug interaction risk or clinical conditions. IFIs were diagnosed using EORTC/MSG criteria. Logistic and Cox regression models were used to assess risk factors and overall survival (OS). Results: IFI incidence was 13.3% overall (9.4% proven/probable). No significant difference was found between the caspofungin and posaconazole groups (six vs. four IFIs; p = 0.878). Post-chemotherapy refractory AML (OR = 11.9; p = 0.003) and liver disease (OR = 30.4; p = 0.004) independently predicted IFI development. Median OS did not significantly differ in patients receiving caspofungin versus posaconazole (29.3 vs. 32.1 months, p = 0.6). Conclusions: Caspofungin appears clinically comparable to posaconazole for PAP in AML during the induction phase, especially when azole use is contraindicated. Prospective studies are warranted to refine prophylactic strategies in the era of new AML therapies.