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Dengue is the most common arboviral disease globally. It is caused by four distinct but closely related Dengue viruses (DENV-1, -2, -3, and - 4) transmitted through bites of infected Aedes species mosquito vectors. In the last 50 years, incidence has increased 30-fold with increasing geographic expansion to new countries. Here we report the most important autochthonous Dengue epidemic in Italy ever recorded with a total of 86 confirmed cases occurring in September 2024 in Fano. They were caused by DENV-2. They were 61 Dengue fever, 21 Dengue with warning signs and no cases of severe Dengue. Our data underline the importance of considering Dengue not only as imported disease and rapidly testing all those patients with suggestive clinical pictures even if they have no travel history., Competing Interests: Declarations. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent to publish declarations: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background & Aims: Bulevirtide (BLV) 2 mg/day is EMA approved for the treatment of compensated chronic HDV infection; however, real-world data in large cohorts of patients with cirrhosis are lacking., Methods: Consecutive HDV-infected patients with cirrhosis starting BLV 2 mg/day from September 2019 were included in a European retrospective multicenter real-world study (SAVE-D). Patient characteristics before and during BLV treatment were collected. Virological, biochemical, combined responses, adverse events and liver-related events (hepatocellular carcinoma [HCC], decompensation, liver transplant) were assessed., Results: A total of 244 patients with HDV-related cirrhosis receiving BLV monotherapy for a median of 92 (IQR 71-96) weeks were included: at BLV start, median (IQR) age was 49 (40-58) years and 61% were men; median ALT, LSM and platelet count were 80 (55-130) U/L, 18.3 (13.0-26.3) kPa, and 94 (67-145) x10 3 /mm 3 , respectively; 54% had esophageal varices, 95% Child-Pugh A cirrhosis, and 10% HIV coinfection; 92% were on nucleos(t)ide analogues; median HDV RNA and HBsAg were 5.4 (4.1-6.5) log 10 IU/ml and 3.8 (3.4-4.1) log 10 IU/ml, respectively. At weeks 48 and 96, virological, biochemical and combined responses were observed in 65% and 79%, 61% and 64%, 44% and 54% of patients, respectively. AST, GGT, albumin, IgG and LSM values significantly improved throughout treatment. Serum bile acid levels increased in most patients, but only 10% reported mild and transient pruritus, which was independent of bile acid levels. The week 96 cumulative risks of de novo HCC and decompensation were 3.0% (95% CI 2-6%) and 2.8% (95% CI 1-5%), respectively. Thirteen (5%) patients underwent liver transplantation (n = 11 for HCC, n = 2 for decompensation)., Conclusion: BLV 2 mg/day monotherapy for up to 96 weeks was safe and effective in patients with HDV-related cirrhosis. Virological and clinical responses increased over time, while the incidence of liver-related complications was low., Impact and Implications: Bulevirtide 2 mg/day is EMA approved for the treatment of compensated chronic hepatitis delta; however, real-world data in large cohorts of patients with cirrhosis are lacking. Bulevirtide 2 mg/day monotherapy for up to 96 weeks was safe and effective (week 96: 79% virological, 64% biochemical and 54% combined response) in a large real-world cohort of patients with HDV-related cirrhosis, including patients with clinically significant portal hypertension. Liver function tests and liver stiffness improved, suggesting a potential clinical benefit in patients with advanced liver disease, while the incidence of de novo liver-related events (hepatocellular carcinoma and decompensation) was low during the 96-week study period., Competing Interests: Conflict of interest Elisabetta Degasperi: Advisory Board: AbbVie, Roche; Speaking and teaching: Gilead, Intercept, AbbVie; Travel Grant: AbbVie, Intercept, Gilead; Research grant: Gilead. Stanislas Pol: Consulting and lecturing fees from Gilead, MSD, AbbVie, Biotest, Shinogui, Viiv, LFB and grants from Bristol-Myers Squibb, Gilead, Roche and MSD. George Papatheodoridis: Advisor/lecturer: AbbVie, Albireo, Amgen, Astellas, Bayer, Elpen, Genesis, Gilead, GlaxoSmithKline, Ipsen, Janssen, Merck Sharp & Dohme, Novo Nordisk, Roche and Takeda; Research grants: AbbVie, Gilead and Takeda. Victor De Ledinghen: Advisory board and Speaking: Gilead. Dominique Roulot: Advisory board and Speaking: Gilead. Mathias Jachs: Speaking: Gilead. Thomas Reiberger: Speaker and/or consultant and/or advisory board member speaking honoraria from AbbVie, Bayer, Boehringer-Ingelheim, Gilead, Intercept, MSD, Roche, Siemens, and W. L. Gore & Associates; Travel support from AbbVie, Boehringer-Ingelheim, Gilead, and Roche; Grants/research support from AbbVie, Boehringer-Ingelheim, Gilead, Intercept, MSD, Myr Pharmaceuticals, Philips Healthcare, Pliant, Siemens, and W. L. Gore & Associates. Maurizia Brunetto: Speakers Bureau: AbbVie, Gilead, EISAI-MSD; Advisory: Gilead, AstraZeneca, Roche. Nasser Semmo: Grants from Gilead; speaker: Gilead; consulting fees from Gilead and AbbVie. Heiner Wedemeyer: Grants from AbbVie, Biotest, Gilead, Merck/MSD, Roche; consulting fees from AbbVie, Aligos, Altimmune, Biotest, BMS, BTG, Dicerna, Enanta, Gilead, Janssen, Merck/MSD, MYR GmbH, Roche, Vir Biotechnology; Speaker for AbbVie, Biotest, Gilead, Merck/MSD. Christopher Dietz-Fricke: Grant and travel support by Gilead. Fabien Zoulim: consultant for Aligos, Assembly, Evotec, GSK; speaker for Gilead; research grants: Assembly, Beam, Blue Jay, Janssen. Frank Tacke: research funding from AstraZeneca, MSD, Gilead (funding to the institution); honoraria for consulting or lectures from AstraZeneca, Gilead, AbbVie, BMS, Boehringer, Intercept, Falk, Orphalan, Inventiva, Merz, Pfizer, Alnylam, CSL Behring, Novo Nordisk, Novartis, GSK, MSD. Soo Aleman: Lectures for Gilead, advisory board for Gilead and Ribocure. Research grants from Gilead. Alessandra Mangia: Lectures for Gilead, Roche, Madrigal, Grants: Gilead, Angelini. Pietro Lampertico: Roche Pharma/Diagnostics, Gilead Sciences, Gsk, AbbVie, Janssen, Myr, Eiger, Antios, Aligos, Vir, Grifols, Altona, Roboscreen. Other authors have nothing to disclose. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2025 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

A broth microdilution method was used for testing amphotericin B against 33 clinical isolates of Candida tropicalis. All isolates were in vitro susceptible to the polyene (MIC [minimal inhibitory concentration] < or = 1.0 microg/mL). However, when the isolates were cultured in a medium containing amphotericin B at a concentration of 1.5 microg/mL, a wide interstrain variation of growth rate was observed. Five isolates (15%) proved to be highly tolerant to the drug and grew at a frequency ranging from 1 x 10(-1) to 2 x 10(-2). Twenty-three isolates (70%) grew at a frequency ranging from 1 x 10(-5) to 1 x 10(-8). The remaining five isolates (15%) failed to grow in drug-containing medium. In general, this growth variation was not associated with amphotericin B MICs displayed by the single isolates. In addition, the strains grown in drug-containing medium did not represent amphotericin B-resistant mutants, as shown by the maintenance of MICs similar to those of their respective parent isolates. Killing experiments conducted in selected isolates confirmed a variation of fungicidal activity of amphotericin B. To see whether this phenomenon was associated with a variation of amphotericin B response in vivo, we established an experimental model of systemic murine candidiasis in CD1 mice by intravenous injection of cells belonging to Candida tropicalis 3147 (growth rate at a frequency of 1 x 10(-1) in amphotericin B medium) and Candida tropicalis 4055 (no growth). Low (0.3 mg/kg/day) and high (1 mg/kg/day) doses of amphotericin B were both effective at reducing the fungal burdens in the kidneys of mice infected with either strain (p, 0.01 to 0.02). However, whereas the burden of mice infected with isolate 3147 and treated with the polyene at 0.3 mg/kg/day was reduced by 1.2 +/- 0.25 (mean +/- standard deviation) log10 cfu/g compared to untreated mice, the same dosing regimen yielded a burden reduction of 2.6 +/- 0.07 log10 cfu/g in mice infected with isolate 4055 (p < 0.001). Similarly, amphotericin B at 1 mg/kg/day yielded a burden reduction of 1.8 +/- 0.20 vs. 2.5 +/- 0.30 log10 cfu/g in mice infected with isolates 3147 and 4055, respectively (p < 0.001). Our data revealed a variable pattern of tolerance to amphotericin B among isolates of Candida tropicalis and showed that this phenomenon might influence the rate of organ clearance during therapy.

Candida glabrata has recently emerged as a significant pathogen involved in both superficial and deep-seated infections. In the present study, a checkerboard broth microdilution method was performed to investigate the in vitro activities of voriconazole (VOR) in combination with terbinafine (TRB), amphotericin B (AMB), and flucytosine (5FC) against 20 clinical isolates of C. glabrata. Synergy, defined as a fractional inhibitory concentration (FIC) index of < or = 0.50, was observed in 75% of VOR-TRB, 10% of VOR-AMB, and 5% of VOR-5FC interactions. None of these combinations yielded antagonistic interactions (FIC index > 4). When synergy was not achieved, there was still a decrease in the MIC of one or both drugs used in the combination. In particular, the MICs were reduced to < or = 1.0 microg/ml as a result of the combination for all isolates for which the AMB MIC at the baseline was > or = 2.0 microg/ml. By a disk diffusion assay, the halo diameters produced by antifungal agents in combination were greater that those produced by each drug alone. Finally, killing curves showed that VOR-AMB exhibited synergistic interactions, while VOR-5FC sustained fungicidal activities against C. glabrata. These studies demonstrate that the in vitro activity of VOR against this important yeast pathogen can be enhanced upon combination with other drugs that have different modes of action or that target a different step in the ergosterol pathway. Further studies are warranted to elucidate the potential beneficial effects of such combination regimens in vivo.

To investigate the effects of posaconazole (POS) and amphotericin B (AMB) combination therapy in cryptococcal infection, we established an experimental model of systemic cryptococcosis in CD1 mice by intravenous injection of three distinct clinical isolates of Cryptococcus neoformans. Therapy was started 24 h after the infection and continued for 10 consecutive days. POS was given at 3 and 10 mg/kg of body weight/day, while AMB was given at 0.3 mg/kg/day. Combination therapy consisted of POS given at a low (combo 3) or at a high (combo 10) dose plus AMB. Survival studies showed that combo 3 was significantly more effective than POS at 3 mg/kg for two isolates tested (P value, < or = 0.001), while combo 10 was significantly more effective than POS at 10 mg/kg for all three isolates (P values ranging from <0.001 to 0.005). However, neither combination regimen was more effective than AMB alone. For two isolates, combination therapy was significantly more effective than each single drug at reducing the fungal burden in the brain (P values ranging from 0.001 to 0.015) but not in the lungs. This study demonstrates that the major impact of POS and AMB combination therapy is on brain fungal burden rather than on survival.

A broth microdilution method following the NCCLS recommendations was used for testing fluconazole, itraconazole, posaconazole, 5-fluorocytosine and amphotericin B against 83 yeast isolates causing bloodstream infections in 59 patients hospitalized between January 1998 and June 2001 at the University Hospital of Bari, Italy. Isolates belonged to four species of Candida and three other yeast genera. Of the isolates, 97%, 95% and 100% were susceptible to fluconazole, itraconazole and posaconazole, respectively. Similarly, 97% and 100% of the isolates were susceptible to 5-fluorocytosine and amphotericin B, respectively.

We conducted a prospective study to address the prevalence and microbiological characteristics of yeast isolates colonizing the oral cavities of HIV-infected patients undergoing highly active antiretroviral therapy. Sixty-eight patients (67%) from a total of 102 were found to be colonized with yeasts. Sixty-five patients carried a single species (60 Candida albicans, three Candida glabrata and two Candida krusei) and three patients had mixed colonization of C. albicans and C. krusei. The status of yeast carrier was not associated with the number of CD4 cells or the viral load. Similarly, the type of antiretroviral regimen was not associated with the carriage of Candida spp. The only predictor of Candida colonization was a previous history of oropharyngeal candidiasis (P = 0.009). Although many patients in this series had already been treated with repeated courses of fluconazole therapy for previous episodes of oropharyngeal candidiasis, fluconazole susceptibility patterns showed that 93% of yeasts were susceptible to this triazole in vitro (MIC < or = 8.0 mg/L).