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Background. Invasive fungal infections are found most frequently in immunosuppressed and critically ill hospitalized patients. Antifungal therapy is often required for long periods. Safety data from the clinical development program of the triazole antifungal agent, posaconazole, were analyzed. Methods. A total of 428 patients with refractory invasive fungal infections (n = 362) or febrile neutropenia (n = 66) received posaconazole in 2 phase II/III open-label clinical trials. Also, 109 of these patients received posaconazole therapy for ⩾6 months. Incidences of treatment-emergent, treatment-related, and serious adverse events and abnormal laboratory parameters were recorded during these studies. Results. Treatment-emergent, treatment-related adverse events were reported in 38% of the overall patient population. The most common treatment-related adverse events were nausea (8%) and vomiting (6%). Treatment-related serious adverse events occurred in 8% of patients. Low rates of treatment-related corrected QT interval and/or QT interval prolongation (1%) and elevation of hepatic enzymes (2%) were reported as adverse events. Treatment-emergent, treatment-related adverse events occurred at similar rates in patients who received posaconazole therapy for <6 months and ⩾6 months. Conclusions. Prolonged posaconazole treatment was associated with a generally favorable safety profile in seriously ill patients with refractory invasive fungal infections. Long-term therapy did not increase the risk of any individual adverse event, and no unique adverse event was observed with longer exposure to posaconazole.

In preventing invasive fungal disease (IFD) in patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), clinical trials demonstrated efficacy of posaconazole over fluconazole and itraconazole. However, effectiveness of posaconazole has not been investigated in the United States in real‐world setting outside the environment of controlled clinical trial. We performed a single‐center, retrospective cohort study of 130 evaluable patients ≥18 years of age admitted to Duke University Hospital between 2004 and 2010 who received either posaconazole or fluconazole as prophylaxis during first induction or first reinduction chemotherapy for AML or MDS. The primary endpoint was possible, probable, or definite breakthrough IFD. Baseline characteristics were well balanced between groups, except that posaconazole recipients received reinduction chemotherapy and cytarabine more frequently. IFD occurred in 17/65 (27.0%) in the fluconazole group and in 6/65 (9.2%) in the posaconazole group (P = 0.012). Definite/probable IFDs occurred in 7 (10.8%) and 0 patients (0%), respectively (P = 0.0013). In multivariate analysis, fluconazole prophylaxis and duration of neutropenia were predictors of IFD. Mortality was similar between groups. This study demonstrates superior effectiveness of posaconazole over fluconazole as prophylaxis of IFD in AML and MDS patients. Such superiority did not translate to reductions in 100‐day all‐cause mortality. In adults receiving first induction or first reinduction chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), posaconazole prophylaxis was associated with significantly fewer invasive fungal infections than fluconazole prophylaxis. This study demonstrates superior effectiveness of posaconazole over fluconazole as prophylaxis of invasive fungal disease in AML and MDS patients.

Patients with allergic fungal rhinosinusitis (AFRS) are typically atopic and immunocompetent. Despite combined modality treatment based on surgery and immunomodulation, the potential for recidivism is well recognized. A study was conducted in a military hospital in India to identify the factors responsible for recidivism in AFRS and to suggest measures to overcome it. Sixty patients with AFRS (42 new cases and 18 cases that required revision surgery) were managed between January 2009 and July 2013. Patients underwent endoscopic, radiologic, and laboratory evaluation for AFRS followed by functional endoscopic sinus surgery. Each patient received oral prednisolone, 1 mg/kg/day, for 1 week preoperatively and 0.5 mg/kg/day for 4 weeks postoperatively. A randomly selected group of 30 patients (group A) received oral prednisolone 0.4 mg/kg/day for the next 4 weeks, tapered to 0.2 mg/kg/day for the next 2 months and to 0.1 mg/kg/day for the last 2 months. The drug was stopped after 6 months. In the remaining 30 patients (group B), oral prednisolone was tapered within 2 months. Topical steroid sprays were advised in all patients. Recidivism was observed in 12 of 42 (28.6%) patients presenting for the first time with AFRS: 9 patients from group B (30%) and 3 patients from group A (10%). Besides inadequate postoperative oral steroid therapy, suboptimal functional endoscopic sinus surgery, noncompliance with intranasal sprays, nonadherence to Kupferberg staging, inadequate follow-up, failure of surgeons to impart health education to patients, and unavailability of ENT consultation in rural belts were found to be factors causing recidivism.

Objectives Severe or critical COVID-19 is associated with intensive care unit admission, increased secondary infection rate, and would lead to significant worsened prognosis. Risks and characteristics relating to secondary infections in severe COVID-19 have not been described. Methods Severe and critical COVID-19 patients from Shanghai were included. We collected lower respiratory, urine, catheters, and blood samples according to clinical necessity and culture and mNGS were performed. Clinical and laboratory data were archived. Results We found 57.89% (22/38) patients developed secondary infections. The patient receiving invasive mechanical ventilation or in critical state has a higher chance of secondary infections (P<0.0001). The most common infections were respiratory, blood-stream and urinary infections, and in respiratory infections, the most detected pathogens were gram-negative bacteria (26, 50.00%), following by gram-positive bacteria (14, 26.92%), virus (6, 11.54%), fungi (4, 7.69%), and others (2, 3.85%). Respiratory Infection rate post high flow, tracheal intubation, and tracheotomy were 12.90% (4/31), 30.43% (7/23), and 92.31% (12/13) respectively. Secondary infections would lead to lower discharge rate and higher mortality rate. Conclusion Our study originally illustrated secondary infection proportion in severe and critical COVID-19 patients. Culture accompanied with metagenomics sequencing increased pathogen diagnostic rate. Secondary infections risks increased after receiving invasive respiratory ventilations and intravascular devices, and would lead to a lower discharge rate and a higher mortality rate.

Melanins provide fungi protection from environmental stressors, support their ecological roles, and can confer virulence in pathogens. While the function, structure, and synthesis of melanins in fungi are not fully understood, they have been shown to have varied roles. Recent research has revealed a wide range of functions, from radiation resistance to increasing virulence, shedding light on fungal diversity. Understanding fungal melanins can provide useful information, from harnessing the properties of these various melanins to targeting fungal infections.Key Points• Melanotic fungi are widespread in nature.• Melanin functions to protect fungi in the environment from a range of stresses.• Melanin contributes to pathogenesis and drug resistance of pathogenic fungi.

The generally accepted definition of ecthyma gangrenosum (EG) states that this condition is pathognomonic of Pseudomonas septicemia ( Pseudomonas aeruginosa ) and that it should usually be seen in immunocompromised patients, particularly those with underlying malignant disease. The cases described in the literature present a somewhat different picture. Our objective was to analyze this controversy. The review analyzes 167 cases of EG that were described in the literature from 1975 to 2014. All articles on EG cases with EG-specific tissue defect that had signs of general and/or local infection and skin necrosis were included and analyzed, whatever the etiology detected. Necrotic lesions of the skin diagnosed as EG have various microbiological etiology, can occur in immunocompetent or even healthy persons, and are not necessarily connected with septicemia. In published cases, P. aeruginosa was detected in 123 cases (73.65 %); of them, there were only 72 cases (58.5 %) with sepsis. Other bacterial etiology was detected in 29 cases (17.35 %) and fungi were detected in 15 cases (9 %). While the clinical picture of the disease and the treatment strategy remain the same, there is no need to invent two separate definitions for Pseudomonas and non- Pseudomonas cases. We suggest accepting a broader definition of EG.

A biopsy of skin tissue demonstrated small budding yeasts, resembling those of Histoplasma capsulatum, in addition to larger pleomorphic cells. [...]the fungus that grew in culture had a dissimilar microscopic appearance [1, 2]. [...]occurring infections of animals have not been demonstrated [22]. Schwartz and colleagues found that intraperitoneal inoculations with Es. africanus were fatal to wild-type mice at doses of 106 conidia, whereas lower doses did not cause disease (although the organism could still be cultured from their livers and spleens with inoculae as low as 102 conidia) [20]. [...]C57BL/6 mice were more susceptible to disease than BALB/c mice [20]. First report of urease activity in the novel systemic fungal pathogen Emergomyces africanus: A comparison with the neurotrope Cryptococcus neoformans.

Fungal diseases of the central nervous system (CNS) are associated with severe neurological damage and death in immunocompromised hosts, yet they remain neglected in research and policy. Neuroinflammation, a common clinical feature of fungal infection, has been implicated as a key driver of brain injury, but the mechanisms underlying its contribution to pathology are not well understood. The aim of this Review is to discuss the double-edged role of neuroinflammation in the pathogenesis of fungal infections. We provide an overview of the immune barriers that protect the CNS from fungal infection, the fungal strategies that enable immune evasion and neuroinvasion, and the complex mechanisms underlying the development of neuroinflammation during fungal infection. Finally, we explore how both insufficient and excessive neuroinflammatory responses drive neuropathology, and we conclude by outlining current challenges as well as potential directions for advancing future research in this overlooked field.

Snake fungal disease (SFD) is a clinical syndrome associated with dermatitis, myositis, osteomyelitis, and pneumonia in several species of free-ranging snakes in the US. The causative agent has been suggested as Ophidiomyces ophiodiicola, but other agents may contribute to the syndrome and the pathogenesis is not understood. To understand the role of O. ophiodiicola in SFD, a cottonmouth snake model of SFD was designed. Five cottonmouths (Agkistrodon piscivorous) were experimentally challenged by nasolabial pit inoculation with a pure culture of O. ophiodiicola. Development of skin lesions or facial swelling at the site of inoculation was observed in all snakes. Twice weekly swabs of the inoculation site revealed variable presence of O. ophiodiicola DNA by qPCR in all five inoculated snakes for 3 to 58 days post-inoculation; nasolabial flushes were not a useful sampling method for detection. Inoculated snakes had a 40% mortality rate. All inoculated snakes had microscopic lesions unilaterally on the side of the swabbed nasolabial pit, including erosions to ulcerations and heterophilic dermatitis. All signs were consistent with SFD; however, the severity of lesions varied in individual snakes, and fungal hyphae were only observed in 3 of 5 inoculated snakes. These three snakes correlated with post-mortem tissue qPCR evidence of O. ophiodiicola. The findings of this study conclude that O. ophiodiicola inoculation in a cottonmouth snake model leads to disease similar to SFD, although lesion severity and the fungal load are quite variable within the model. Future studies may utilize this model to further understand the pathogenesis of this disease and develop management strategies that mitigate disease effects, but investigation of other models with less variability may be warranted.

Penicillium marneffei is an emerging pathogenic fungus that can cause a life-threatening systemic mycosis in immunocompromised hosts, especially in patients with AIDS. This infection is endemic in Southeast Asia. With the prevalence of AIDS in this area, the number of patients with systemic penicilliosis marneffei is found to be increasing rapidly in mainland China in recent years. We recently reviewed 668 cases of penicilliosis marneffei in mainland China from January 1984 to December 2009 in cnki, cqvip, CBMdisc and PubMed. We analyzed epidemiological and clinical features, laboratory findings, reaction to therapy and prognosis of the disease. We found that 99.4 % of the cases were reported in the southern part of China; among these cases, 42.8 % were from Guangxi (286 cases) and 40.6 % were from Guangdong province (271 cases). Five hundred and eighty-six cases (87.7 %) of penicilliosis marneffei were reported with infection by the human immunodeficiency virus, 25 cases (3.8 %) with other immunocompromised diseases, and 57 cases (8.5 %) without any documented underlying diseases. Fever, weight loss, anemia, lymphadenopathy, hepatosplenomegaly, respiratory signs and skin lesions were the common clinical manifestations of P. marneffei infections. The 569 cases received antifungal therapy with a mortality of 24.3 % (138 cases), 99 cases who had not received antifungal therapy had a mortality of 50.6 %. P. marneffei was an emerging pathogenic fungus and become a medical and public health importance in mainland China. The immunocompromised patients should pay more attention to P. marneffei infection in the endemic areas.