Onychomycosis, defined as a fungal nail infection, affects 5.5% of the global population. Our objectives were to analyse prescription trends of onychomycosis medications using the Medicare Part D Prescribers database from 2016 to 2020, stratified by physician specialty. There was a 4% annual increase in the total cost of onychomycosis medications, with a notable decrease of 12.8% in 2020 during the COVID-19 pandemic. Physicians demonstrated a strong consideration for price when selecting treatments, with the least expensive medications (ciclopirox and terbinafine) accounting for nearly 99% of all prescriptions. In contrast, the more costly medications (efinaconazole and tavaborole) were rarely prescribed. In addition, physicians often opted for the less costly generic versions of ciclopirox and itraconazole, prescribing them 99% and 91% of the time, respectively. Notably, physician assistants and nurse practitioners had higher overall increases in prescription rates, at 15%, compared to 1%-6% for other specialties. There are no recent United States onychomycosis guidelines, and our study emphasizes cost considerations when prescribing onychomycosis treatments.

Methylene blue (MB) and flavin mononucleotide (FMN)-mediated photodynamic therapy (PDT) have demonstrated local antimicrobial effect, but no direct comparative study has been published so far for the treatment of toenail onychomycosis. To directly compare the short and medium-term efficacy of MB versus FMN as photosensitizers in PDT for toenail onychomycosis by applying them in a 40% w/w urea cream in two different dye concentrations. Forty toenails with distal and lateral subungual moderate onychomycosis due to dermatophyte fungi were randomised to receive 10 weekly sessions of PDT mediated by four topical formulations including MB or FMN at two different concentrations: Group I: 0.1% w/w MB; Group II: 2% w/w MB; Group III: 0.1% w/w FMN; and Group IV: 2% w/w FMN. Photographs were used for onychomycosis severity index (OSI) estimation allowing clinical assessment at any point of the study. Microscopic and microbiological evaluations were carried out at baseline, 27- and 35-week follow-ups. Side effects were recorded along with patient satisfaction. At week 27, mycological cure rates were 60%, 30%, 50% and 40% and complete cure rates were 0%, 20%, 10% and 20%, for Groups I, II, III and IV respectively. At week 35, mycological cure rates were 70%, 70%, 70% and 60% and complete cure rates were 30%, 50%, 70% and 30%, for Groups I, II, III and IV respectively. All cream formulations were safe and patients were fairly satisfied. Results of the present work confirm PDT as a therapeutic alternative for onychomycosis. Although all cream formulations were safe and effective, with a good degree of satisfaction, higher cure rates were obtained with 2% w/w MB cream and 0.1% w/w FMN cream.

Paracoccidioidomycosis is the most prevalent systemic mycosis in Latin America, with a high incidence in Brazil, Colombia and Venezuela, and constitutes a serious public health problem, a frequent cause of morbidity and disability for work. Some mechanisms of cell death are described as important tools in infectious processes. When apoptosis is blocked, RIPK (Receptor-interacting protein kinase) 3 dependent, a caspase-independent form of cell death, can limit the replication and spread of pathogens. Some molecules that mediate necroptosis include RIPK3 and have been extensively studied due to their signalling mechanism and pathological function. RIPK3 activates NLRP1 and NLRP3-mediated inflammasome formation. Caspase-1 has an important role in processing the cytokines ILβ and IL18 to their active form. Such molecules are part of the inflammasome characterization, whose caspase-1-dependent activation promotes the death of pyroptotic cells and the secretion of proinflammatory cytokines. Knowledge about the mechanisms of pathogen-mediated cell death can be useful for understanding of the pathogenesis of infections and inflammatory conditions. The objective of this work was to identify the mechanisms of programmed cell death and inflammasome components in human oral mucosal lesions of paracoccidioidomycosis through immunohistochemical methods and identification of RIPK-3, IL1β, IL18, NLRP-1 and caspase-1. Thirty specimens were included, and a histopathological analysis of the lesions was performed using haematoxylin-eosin staining. Our results on insitu expression of inflammasome elements and programmed cell death showed increased expression of IL-1β, NLRP-1, caspase-1 and RIPK-3. We suggest that inflammasome complex participate in the immunopathogenesis in paracoccidioidomycosis oral lesions in an interplay with RIPK3.

Literature on emollient use in the management of chronic and recurrent dermatophytosis is limited. To assess the efficacy of emollient in the remission maintenance of chronic and recurrent dermatophytosis. In this randomized open-label study with the intention to treat, 80 patients with chronic recurrent dermatophytosis were randomized into two groups, where both groups were treated adequately for 6 weeks, followed by continuation of topical azole in group A and topical emollient in group B for 6 weeks. Clinical remission was determined by disappearance signs and symptoms of tinea lesions with or without hyperpigmentation. Physician and patient global assessment scores were evaluated every 2 weeks for 6 weeks to assess remission maintenance. A total of 80 patients of chronic and recurrent dermatophytosis were assessed for remission maintenance. The recurrence of disease occurred in 20 patients overall, wherein 7 patients (17.5%) in group A and 13 patients (32.5%) in group B at the end of the study (18 weeks); however, the difference between the two groups was not statistically significant (p = .121). The mean physician global assessment scores of group A and group B at 12 weeks were 4.45 ± 0.74 and 4.15 ± 0.92, 4.43 ± 0.90 and 4.10 ± 0.98 at 14 weeks, 4.0 ± 1.32 and 3.98 ± 1.23 at 16 weeks, 3.85 ± 1.44 and 3.90 ± 1.35 at 18 weeks, respectively. The mean patient global assessment scores of group A and group B were 4.65 ± 0.62 and 4.25 ± 0.87 at 12 weeks, 4.40 ± 0.87 and 4.17 ± 0.98 at 14 weeks, 4.18 ± 1.15 and 4.12 ± 1.30 at 16 weeks and 3.97 ± 1.33 and 3.90 ± 1.51 at 18 weeks. The present study concludes that the efficacy of emollient was not inferior to topical luliconazole for maintaining remission in chronic and recurrent dermatophytosis.

Cryptococcal meningitis (CM) is an invasive fungal infection with a poor prognosis that often occurs in both healthy individuals and compromised hosts, such as patients infected with human immunodeficiency virus (HIV). Unlike CM in HIV patients, evidence regarding CM in non-HIV patients is limited to small retrospective studies. To identify the pretreatment prognostic factors for CM in non-HIV patients. We conducted a large retrospective analysis of CM in non-HIV patients using data from a nationwide Japanese database. The study included hospitalized patients diagnosed with CM between 1 April 2010 and 31 March 2017. All-cause mortality was compared between patients with CM with and without HIV infection. Poor diagnostic factors were analysed in the non-HIV CM group. Overall, 533 (64 HIV and 469 non-HIV) patients met the criteria. The mortality rate at 90 days was significantly lower in the HIV group (6.3% vs. 25.4% p = .0002). In a logistic regression analysis of the non-HIV group, age ≥ 65 y (odds ratio [OR] 2.37, 95% CI 1.17-4.78), impaired consciousness (Japan Coma Scale ≥1) (OR 2.25, 95% CI 1.29-3.93), haemodialysis (OR 3.53, 95% CI 1.12-11.20) and previous corticosteroid usage (OR 2.40, 95% CI 1.37-4.19) were associated with poor prognosis at 30 days after diagnosis. More caution is suggested when treating non-HIV with CM in older patients with impaired consciousness, previous corticosteroid usage and haemodialysis.

Invasive fungal diseases (IFDs) play an important role in the supportive care of paediatric patients with acute leukaemia and those undergoing allogeneic haematopoietic cell transplantation, and they are associated with significantly decreased overall survival rates in affected individuals. Relative to adults, children and adolescents are distinct in terms of host biology, predisposing conditions, presentation and epidemiology of fungal diseases, and in the pharmacology of antifungal agents. The paediatric development of antifungal agents has moved forward in a coordinated manner, and major advances have been made regarding concepts and recommendations for the prevention and treatment of IFDs. However, antifungal therapy is increasingly complex, and a solid knowledge of the available options is needed more than ever for successful management. This narrative review provides a summary of the paediatric development of agents that have been recently approved (anidulafungin, posaconazole) or are in advanced stages of development (isavuconazole). It also reviews the emerging evidence for the efficacy of echinocandins for prophylaxis of invasive aspergillosis, presents new data on alternative dosing regimens of echinocandins and voriconazole, and provides a brief overview of new antifungal agents in clinical development that are expected to be developed for paediatric patients.

Systemic sporotrichosis occurs when organs, other than subcutaneous tissues and lymph nodes, are infected. Interestingly, systemic sporotrichosis in apparently immunocompetent individuals is increasing in Brazil, but data on clinical manifestations and risk factors are scarce. Most of the existing data on such condition relate to people living with HIV. We aimed to study the risk factors associated with systemic sporotrichosis among HIV-negative and HIV-positive patients. We performed a retrospective cross-sectional study with 80 patients from Brazil, diagnosed between 2014 and 2021. The association between disease classification, clinical presentation and risk factors were analysed by logistic regression. Of the 80 patients, 29 (36.3%) presented with systemic sporotrichosis. All HIV-positive patients developed the systemic form, with increased mortality (p = .002). Alcohol ingestion (p = .009) and diabetes (p = .010) were associated with systemic disease. Alcohol ingestion seemed to favour pulmonary infection (p = .013) and, diabetes favoured osteoarticular (p = .009) and ocular involvement (p = .033). The occurrence of fever (p = .001) and weight loss (p = .006) were significantly associated with systemic sporotrichosis, while meningeal involvement (p = .001) increased mortality risk. Nine (11.3%) patients died from sporotrichosis. The presence of fungal structures in the mycological examination of the patients' lesions were associated with the systemic form (p = .017) and death (p = .002). Our study points to the factors that drive systemic sporotrichosis other than HIV, such as alcohol ingestion and diabetes. Considering the high number of patients presenting severe sporotrichosis, the recognising these factors may contribute to timely diagnosis and proper treatment.

Tinea capitis (TC), a fungal infection that occurs in children, is primarily caused by dermatophytes such as Trichophyton and Microsporum species. For Trichophyton species, treatment with terbinafine is considered more effective than griseofulvin treatment. Specific populations, such as refugee children, are more susceptible to TC. This study aimed to describe and compare the response to treatment among Israeli and refugee children with TC. We retrospectively reviewed data collected on refugee and Israeli children with TC between January 2004 and January 2020. Overall, 3358 children with TC (refugees: 1497; Israelis: 1861) were identified. Among these, 86% of the refugee children had TC caused by Trichophyton violaceum, 65% of the Israeli children had TC caused by Microsporum canis and 83% of all children were treated with griseofulvin. Overall, 14% of the refugees showed a partial response to a griseofulvin dose of ≤25 mg/kg/day; however, they showed a complete response upon increasing the dose to ≥30 mg/kg/day. No significant adverse effects were observed. The over-crowded day care centres and dense living make refugee children more susceptible to TC than the general population, and griseofulvin dosage adjustment is necessary. TC, due to Trichophyton species, could benefit from receiving an increased dose of griseofulvin in a suspension form, which is cheaper than terbinafine.

Fusarium species are an emerging cause of onychomycosis, and the number of cases has dramatically increased in recent decades worldwide. This review presents an overview of the onychomycosis cases caused by Fusarium species and diagnosis and treatment that have been reported in the literature. The most common causative agent of onychomycosis is F. solani species complex, which accounts for 11.68% of the cases of Fusarium onychomycosis, followed by the F. oxysporum species complex (164 out of 1669), which is accounted for 9.83% of the total. F. fujikuroi species complex (42 out of 1669) and F. dimerum species complex (7 out of 1669) are responsible for 2.52% and 0.42 cases, respectively. Fusarium nail infections were reported in patients aged range 1-98, accounting for 5.55% (1669 out of 30082) of all cases. Asia has the highest species diversity of Fusarium onychomycosis (31.51%). South America accounts for 21.09%, and the most common causative agent is F. solani (19.32%), followed by F. oxysporum species complex (15.63%). Europe accounts for 4.90% of cases caused by F. oxysporum, followed by F. solani. Africa accounts for 23.87% of the cases due to the F. solani species complex, followed by F. oxysporum and F. fujikuroi. Distal and lateral subungual onychomycosis was the most common clinical symptom accounting for 58.7% (135 out of 230) of the cases. Data analysis relieved that terbinafine and itraconazole are active treatments for Fusarium onychomycosis. For a definitive diagnosis, combining of direct examination, culture and sequencing of the elongation factor of translation 1α are recommended. Accurate identification of the causative agents of onychomycosis due to Fusarium species and antifungal susceptibility testing is essential in patient management.