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Talaromyces marneffei is a dimorphic fungus that causes substantial disease in Asia, especially among persons infected with the human immunodeficiency virus. In this randomized, controlled trial, initial therapy with amphotericin B was found to be superior to itraconazole. The dimorphic fungus Talaromyces (previously Penicillium ) marneffei causes a life-threatening mycosis in immunocompromised persons living in or traveling to Southeast Asia, China, and India. 1 Talaromycosis (previously penicilliosis) is a major cause of human immunodeficiency virus (HIV)–related death; its prevalence is surpassed only by the prevalence of tuberculosis and cryptococcosis, 2 and it leads to 4 to 15% of HIV-related hospital admissions in regions in which the disease is endemic. 3 – 7 Talaromycosis is increasingly diagnosed among patients who are not infected with HIV but who have other immunodeficiency conditions 8 and is reported to be the second most common cause of all . . .

Eumycetoma is an implantation mycosis characterised by a large subcutaneous mass in the extremities commonly caused by the fungus Madurella mycetomatis. Despite the long duration of treatment, commonly a minimum of 12 months, treatment failure is frequent and can lead to amputation. We aimed to compare the efficacy of two doses of fosravuconazole, a synthetic antifungal designed for use in onychomycosis and repurposed for mycetoma, with standard-of-care itraconazole, both in combination with surgery. This phase 2, randomised, double-blind, active-controlled, superiority trial was conducted in a single centre in Sudan. Patients with eumycetoma caused by M mycetomatis, who were aged 15 years or older, with a set lesion diameter (>2 cm and ≤16 cm) requiring surgery were included. There was a limit of 20 female patients in the initial enrolment, owing to preclinical toxicity concerns. Exclusion criteria included previous surgical or medical treatment for eumycetoma; presence of loco-regional lymphatic extension; osteomyelitis, or other bone involvement; pregnancy or lactation; severe concomitant diseases; a BMI under 16 kg/m2; contraindication to use of the study drugs; pre-existing liver disease; lymphatic extension; osteomyelitis; transaminase levels more than two times the laboratory's upper limit of normal, or elevated levels of alkaline phosphatase or bilirubin; or any history of hypersensitivity to any azole antifungal drug. Patients were randomly allocated in a 1:1:1 ratio to 300 mg fosravuconazole weekly for 12 months (group 1); 200 mg fosravuconazole weekly for 12 months (group 2); or 400 mg itraconazole daily for 12 months (group 3) using a random number list with non-disclosed fixed blocks of size 12, with equal allocation to each of the three arms within a block. To ensure masking between groups, placebo pills were used to disguise the difference in dosing schedules. All groups took pills twice daily with meals. In all groups, surgery was performed at 6 months. The primary outcome was complete cure at end of treatment at the month 12 visit, as evidenced by absence of mycetoma mass, sinuses, and discharge; normal ultrasonography or MRI examination of the eumycetoma site; and, if a mass was present, negative fungal culture from the former mycetoma site. The primary outcome was assessed in the modified intention-to-treat (mITT) population (all patients who received one or more treatment dose with one or more primary efficacy assessment). Safety was assessed in all patients who received one or more doses of the study drug. This study is registered with ClinicalTrials.gov (NCT03086226) and is complete. Between May 9, 2017, and June 10, 2021, 104 patients were randomly allocated (34 in group 1 and 2, respectively, and 36 in group 3). 86 (83%) of 104 patients were male and 18 (17%) patients were female. After an unplanned second interim analysis, the study was terminated early for futility. Complete cure at 12 months in the mITT population was 17 (50%) of 34 (95% CI 32–68) for group 1, 22 (65%) of 34 (47–80) for group 2, and 27 (75%) of 36 (58–88) in group 3. Neither dose of fosravuconazole was superior to itraconazole (p=0·35 for 200 mg fosravuconazole vs p=0·030 for 300 mg fosravuconazole). 83 patients had a total of 205 treatment-emergent adverse events, and two patients had serious adverse events that led to discontinuation, neither related to treatment. Treatment with either dose of fosravuconazole was not superior to itraconazole, and the two doses had a numerically lower efficacy. However, fosravuconazole presented no new safety signals, and its lower pill burden and reduced risk of drug–drug interactions compared with the relatively expensive and inaccessible itraconazole suggests further research into effective treatments with a shorter duration and higher cure rate, without the need for surgery are warranted. Drugs for Neglected Diseases initiative.

In this randomized trial of patients undergoing treatment for acute myelogenous leukemia or the myelodysplastic syndrome, prophylaxis with posaconazole resulted in fewer fungal infections and longer survival than did prophylaxis with fluconazole or itraconazole. The difference was primarily due to a lower rate of invasive aspergillosis in the posaconazole group. In patients undergoing treatment for acute myelogenous leukemia or the myelodysplastic syndrome, prophylaxis with posaconazole resulted in fewer fungal infections and longer survival than did prophylaxis with fluconazole or itraconazole. Invasive fungal infections remain a major cause of illness and death in patients with neutropenia who have hematologic cancers, despite the availability of new antifungal agents. The incidence of proven or probable mold and yeast infections can reach 24% among patients with leukemia. 1 , 2 Reported mortality from candidiasis or aspergillosis ranges from 40 to 50%, and mortality from fusariosis or zygomycosis is 70% or more. 3 – 8 Prophylaxis is a commonly used treatment strategy, because the diagnosis of fungal infection is often delayed or difficult to establish with certainty, and a delay in antifungal treatment increases mortality. 9 – 11 Antifungal prophylaxis with . . .

Some patients with severe asthma are immunologically sensitized to one or more fungi, a clinical entity categorized as severe asthma with fungal sensitization (SAFS). It is not known whether SAFS responds to antifungal therapy. To evaluate the response of SAFS to oral itraconazole. Patients with severe asthma sensitized to at least one of seven fungi by skin prick or specific IgE testing were recruited. All had total IgE less than 1,000 IU/ml and negative Aspergillus precipitins. They were treated with oral itraconazole (200 mg twice daily) or placebo for 32 weeks, with follow-up for 16 weeks. The primary end point was change in the Asthma Quality of Life Questionnaire (AQLQ) score, with rhinitis score, total IgE, and respiratory function as secondary end points. Fifty-eight patients were enrolled, of whom 41% had been hospitalized in the previous year. Baseline mean AQLQ score was 4.13 (range, 1-7). At 32 weeks, the improvement (95% confidence interval) in AQLQ score was +0.85 (0.28, 1.41) in the antifungal group, compared with a -0.01 (-0.43, 0.42) change in the placebo group (P = 0.014). Rhinitis score improved (-0.43) in the antifungal, and deteriorated (+0.17) in the placebo group (P = 0.013). Morning peak flow improved (20.8 L/minute, P = 0.028) in the antifungal group. Total serum IgE decreased in the antifungal group (-51 IU/ml) but increased in placebo group (+30 IU/ml) (P = 0.001). No severe adverse events were observed, but seven patients developed adverse events requiring discontinuation, five in the antifungal group. SAFS responds to oral antifungal therapy as judged by large improvements in quality of life in about 60% of patients.

The global burden of mycetoma, a debilitating, neglected tropical disease, is unknown, and patients struggle to complete treatment due to limited accessibility and affordability of medications. This communication highlights a landmark clinical trial conducted by the Mycetoma Research Center (MRC) at the University of Khartoum, Sudan, in partnership with the Drugs for Neglected Diseases initiative (DNDi) and Eisai Co., Ltd. (Eisai). Published in The Lancet Infectious Diseases, this clinical trial marks a significant advancement in mycetoma research and treatment. As the first randomised clinical trial assessing a new mycetoma treatment, it compared fosravuconazole with the current standard of care, itraconazole. While the trial found no dose of fosravuconazole to be superior to itraconazole, it did reveal that fosravuconazole presented no new safety concerns. Moreover, its lower pill burden, reduced risk of drug–drug interactions, and the fact that it can be taken without food make it a more feasible alternative to the relatively expensive and less accessible itraconazole for treating eumycetoma. This clinical trial, conducted in a difficult socio-political situation in Sudan, was only made possible by the exceptional efforts of the MRC. This groundbreaking study not only advances treatment options for mycetoma but also enhances research capacity in an endemic region, paving the way for future investigations into neglected tropical diseases.

IntroductionTalaromycosis is a severe fungal infection caused by Talaromyces marneffei that predominantly affects people living with HIV (PLWH), particularly in southern China where it contributes substantially to AIDS-related mortality. While liposomal amphotericin B (L-AMB) is preferred for induction therapy due to its superior safety profile over conventional amphotericin B deoxycholate (AmBD), the efficacy of a single high-dose L-AMB regimen in talaromycosis remains unestablished. Furthermore, current guidelines recommend initiating antiretroviral therapy (ART) within 1 week of antifungal treatment, though real-world evidence in Chinese populations is limited. This study aims to evaluate the efficacy and safety of single high-dose L-AMB for AIDS-associated talaromycosis and provide clinical evidence on early initiation of bictegravir/emtricitabine/tenofovir alafenamide fumarate (B/F/TAF) in this population.Methods and analysisThis multicentre, randomised controlled phase II clinical trial compares the efficacy and safety of single high-dose L-AMB (10 mg/kg), followed by itraconazole capsule 200 mg every 12 hours for the remaining 13 days of induction therapy, versus AmBD (0.5 mg/kg/day for 14 days) as induction therapy for AIDS-associated talaromycosis in PLWH adults with microbiologically confirmed diagnosis. Eligible participants (n=116) will be randomly assigned (1:1) at four Chinese centres to receive either treatment, followed by 10 weeks of itraconazole capsule consolidation therapy and secondary prophylaxis until CD4+ T-lymphocyte counts exceed 100 cells/mm³ for ≥6 months, with ART initiated within 7 days of antifungal treatment according to current ART guidelines. The primary endpoint is clinical resolution rate after induction, while secondary endpoints include overall survival, organ function recovery and adverse event incidence.Ethics and disseminationThis study was approved by the Institutional Review Board of Shanghai Public Health Clinical Centre (Approval No. 2025-S039-01) and the ethics committees of all participating study centres: Guiyang Public Health Treatment Centre, Mengchao Hepatobiliary Hospital of Fujian Medical University and Chest Hospital of Guangxi Zhuang Autonomous Region. All procedures were conducted in accordance with the ethical standards of the Declaration of Helsinki and national regulations. Written informed consent was obtained from all participants prior to enrolment. The findings of this study will be disseminated through publications in international peer-reviewed journals and presentations at scientific conferences. Participants who express interest in the study results will be provided with a summary report following the release of the primary findings.Trial registration numberClinicalTrials. gov NCT06926569.

Background Current treatment options for Malassezia folliculitis (MF) are limited. Recent research has demonstrated the inhibitory effect of cold atmospheric plasma (CAP) on the growth of Malassezia pachydermatis in vitro, suggesting CAP as a potential therapeutic approach for managing MF. Objectives The objective of our study is to assess the in vitro antifungal susceptibility of Malassezia yeasts to CAP. Additionally, we aim to evaluate the efficacy and tolerability of CAP in treating patients with MF. Methods We initially studied the antifungal effect of CAP on planktonic and biofilm forms of Malassezia yeasts, using well‐established techniques such as zone of inhibition, transmission electron microscopy, colony count assay and 2,3‐bis(2‐methoxy‐4‐nitro‐5‐sulfophenyl)‐2H‐tetrazolium‐5‐carboxanilide salt assay. Subsequently, a randomized (1:1 ratio), active comparator‐controlled, observer‐blind study was conducted comparing daily CAP therapy versus itraconazole 200 mg/day for 2 weeks in 50 patients with MF. Efficacy outcomes were measured by success rate, negative microscopy rate and changes in Dermatology Life Quality Index (DLQI) and Global Aesthetic Improvement Scale (GAIS) scores. Safety was assessed by monitoring adverse events (AEs) and local tolerability. Results In laboratory investigations, CAP time‐dependently inhibited the growth of Malassezia yeasts in both planktonic and biofilm forms. Forty‐nine patients completed the clinical study. At week 2, success was achieved by 40.0% of subjects in the CAP group versus 58.3% in the itraconazole group (p = 0.199). The negative direct microscopy rates of follicular samples were 56.0% in the CAP group versus 66.7% in the itraconazole group (p = 0.444). No significant differences were found in the proportion of subjects achieving DLQI scores of 0/1 (p = 0.456) or in the GAIS responder rates (p = 0.588) between the two groups. Three patients in the CAP group and one patient in the itraconazole group reported mild AEs. Conclusion CAP demonstrated significant antifungal activity against Malassezia yeasts in vitro and exhibited comparable efficacy to itraconazole in treating MF patients. Without the associated adverse effects of oral antifungal drugs, CAP can be considered a promising and safe treatment modality for MF.

OBJECTIVES: Dermatophytic infections are the common fungal infections aggravated by hot and humid climate. Terbinafine and itraconazole are commonly used oral antifungal agents for the same. However, resistance to these drugs is being seen increasingly when used in the conventional doses and duration. Therefore, this study was designed to compare the efficacy of terbinafine and itraconazole in increased dosages and duration in the treatment of tinea corporis and tinea cruris. MATERIALS AND METHODS: In this randomized comparative study, patients of tinea cruris and tinea corporis were randomly divided into two groups of 160 each and were given oral terbinafine (Group I) and oral itraconazole (Group II) for 4 weeks. The scores and percentage change in scores of pruritus, scaling, and erythema were evaluated at 2 and 4 weeks. RESULTS: At the end of week 4, mycological cure was seen in 91.8% after 4 weeks in the itraconazole group as compared to 74.3% of patients in the terbinafine group. There was a significant improvement in percentage change in pruritus, scaling, and erythema in both the groups from 0 to 4 weeks. On comparing groups, the percentage change was significantly different in scaling from 0 to 2 weeks (5.4 vs. −4.8) and 2-4 weeks (16.7 vs. 29.6) between Group I and Group II, respectively. Clinical global improvement was better with itraconazole. Mild adverse effects such as gastrointestinal upset, headache, and taste disturbances were observed which were comparable in both the groups. CONCLUSIONS: Itraconazole and terbinafine seem to be equally effective and safe in the treatment of tinea cruris and tinea corporis.

Background. Reported sensitivity of the galactomannan enzyme immunoassay as an early diagnostic test for invasive aspergillosis (IA) has been widely variable, ranging from 29% to 100% in earlier clinical studies. Methods. Studies performed to data have analyzed performance using per-patient calculations, limiting their ability to measure the impact of clinical variables that change over time, such as receipt of preventive antifungal therapy. In our study, performance of the test was calculated in per-patient and per-test analyses in a large cohort of patients at high risk for IA from 2 North American centers. A total of 272 serum samples obtained from 46 patients with IA and 3005 serum samples obtained from 269 control patients were analyzed using multiple index cutoff values to define positivity. Results. Per-patient calculations yielded sensitivities of 43% and 70% using index cutoff values of 1.5 and 0.5, respectively; specificity decreased from 93% with use of the 1.5 index cutoff to 70% with use of the 0.5 index cutoff. Per-test calculations yielded sensitivities of 31% and 59% and specificities of 99% and 92% using index cutoff values of 1.5 and 0.5, respectively. Receipt of mold-active antifungal drugs on the day of testing decreased sensitivity; samples obtained from patients not receiving prophylactic or empirical antifungal drugs yielded a sensitivity of 89% and a specificity of 92% (with use of an index cutoff value of 0.5). Conclusions. These findings have direct implications for preventive strategies, because the diagnostic utility of the antigen assay is compromised during receipt of prophylactic or empirical antifungal therapies.

In chronic granulomatous disease of childhood, killing of microorganisms is impaired because of defects in the production of hydrogen peroxide. In this controlled study, 39 patients were treated in alternate years with either itraconazole or placebo, once per day. There were seven serious infections during treatment with placebo, and only one during treatment with itraconazole. Chronic granulomatous disease of childhood is a rare group of inherited disorders of phagocytic cells characterized clinically by recurrent life-threatening infections and excessive granuloma formation. 1 Phagocyte migration and phagocytosis are normal, but killing of microorganisms is impaired because of defective production of hydrogen peroxide and related products of oxygen metabolism. A variety of biochemical defects lead to the disorder. The current mortality rate is 2 to 5 percent per year. 2 In the absence of prophylaxis with antibiotics or interferon gamma, patients with chronic granulomatous disease have severe infections due to catalase-positive bacteria and fungi about once a year. Prophylaxis with . . .