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BACKGROUND: In recent years, the prevalence of respiratory fungal diseases has increased. Polyene antifungal drugs play a pivotal role in the treatment of these conditions, with amphotericin B (AmB) being the most representative drug. This study aimed to evaluate the efficacy and safety of topical administration of AmB in the treatment of respiratory fungal infections.
METHODS: We conducted a retrospective study on hospitalized patients treated with topical administered AmB for respiratory fungal infections from January 2014 to June 2023.
RESULTS: Data from 36 patients with invasive pulmonary fungal infections treated with topical administration of AmB were collected and analyzed. Nebulization was administered to 27 patients. After the treatment, 17 patients evidenced improved conditions, whereas 10 patients did not respond and died in the hospital. One patient experienced an irritating cough as an adverse reaction. Seven patients underwent tracheoscopic instillation, and two received intrapleural irrigation; they achieved good clinical therapeutic efficacy without adverse effects.
CONCLUSIONS: The combined application of systemic antifungal treatment and topical administration of AmB yielded good therapeutic efficacy and was well-tolerated by the patients. Close monitoring of routine blood tests, liver and kidney function, and levels of electrolytes, troponin, and B-type natriuretic peptide supported this conclusion.

Ibrexafungerp (formerly SCY-078) is the first member of the triterpenoid class that prevents the synthesis of the fungal cell wall polymer β-(1,3)-D-glucan by inhibiting the enzyme glucan synthase. We evaluated the in vivo efficacy of ibrexafungerp against pulmonary mucormycosis using an established murine model. Neutropenic mice were intratracheally infected with either Rhizopus delemar or Mucor circinelloides. Treatment with placebo (diluent control), ibrexafungerp (30 mg/kg, PO BID), liposomal amphotericin B (LAMB 10 mg/kg IV QD), posaconazole (PSC 30 mg/kg PO QD), or a combination of ibrexafungerp plus LAMB or ibrexafungerp plus PSC began 16 h post-infection and continued for 7 days for ibrexafungerp or PSC and through day 4 for LAMB. Ibrexafungerp was as effective as LAMB or PSC in prolonging median survival (range: 15 days to >21 days) and enhancing overall survival (30%-65%) vs placebo (9 days and 0%; P < 0.001) in mice infected with R. delemar. Furthermore, median survival and overall percent survival resulting from the combination of ibrexafungerp plus LAMB were significantly greater compared to all monotherapies (P ≤ 0.03). Similar survival results were observed in mice infected with M. circinelloides. Monotherapies also reduce the lung and brain fungal burden by ~0.5-1.0log10 conidial equivalents (CE)/g of tissue vs placebo in mice infected with R. delemar (P < 0.05), while a combination of ibrexafungerp plus LAMB lowered the fungal burden by ~0.5-1.5log10 CE/g compared to placebo or any of the monotherapy groups (P < 0.03). These results are promising and warrant continued investigation of ibrexafungerp as a novel treatment option against mucormycosis.

While rare, the likelihood of encountering a case of a pulmonary endemic mycosis (PEM) in the UK is increasing. Diagnosis may be challenging, often leading to considerable delay to appropriate treatment. Clinical suspicion must be present for respiratory disease, particularly in the immunocompromised or in those not responding to empiric treatment approaches, and an extended travel history should be obtained. This article summarises the epidemiology of PEM, key clinical features, diagnostic strategies and management.

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This study explored the utility of quantitative real-time panfungal PCR assay in diagnosing invasive pulmonary fungal diseases (IPFD) in non-neutropenic patients. Panfungal PCR assay was performed on respiratory tract specimens from patients whose clinical signs could not exclude fungal infection. At the same time, the samples were subjected to bacterial and fungal culture, microscopic examination and galactomannan antigen (GM) test in order to find the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the 4 diagnostic methods in proven and probable cases. 518 specimens were collected while 63 respiratory tract specimens tested by PCR had positive results. According to diagnostic criteria, 40 patients were diagnosed with IPFD, with 12 proven, 20 probable and 8 possible cases. Among these, 33 patients of PCR results were positive, most of which were from BALF samples (44.12%). 23 cases were caused by Aspergillus species, with Aspergillus fumigatus was the major cause. Other Aspergillus species, including Aspergillus flavus, Aspergillus terreus and Aspergillus nidulans were found in 1 sample respectively. Candida species were found in 5 samples, Pneumocystis jeroveci pneumonia (PJP) in 4 samples and Mucormycosis in 1 sample. An analysis of proven/probable diagnosis showed a sensitivity of 78.13%, specificity of 92.18%, PPV of 39.68% and NPV of 98.46% for PCR and 50%, 85.27%, 35.7%, 95.65% for GM test respectively. The Ct value difference between proven/probable and possible cases had no statistical significance (P = .824). Fungal culture showed a sensitivity of 17.5% while microscopic examination sensitivity of 32.5%. Through stratified analysis, no apparent correlation was found between the Ct value of the PCR assay and GM value (r: 0.223, P = .294). But a conjunction of the 2 tests raised the PPV of Aspergillus to 90%. As shown in this study, the panfungal RT-PCR assay has high sensitivity and consistency with serological test and culture. Its high PPV in the detection of Aspergillus and PJP were also evident.

暂无摘要。

BACKGROUND: Histoplasmosis is mainly described as a disseminated disease in people living with HIV (PLHIV). Compared to historical descriptions in immunocompetent individuals, knowledge is lacking on the detailed clinical and radiological findings and outcomes of pulmonary histoplasmosis (PH). Overlooked or misdiagnosed with other AIDS-defining condition, prognostic of PLHIV may be at risk because of inappropriate care.
METHODS: A retrospective multicentric study was conducted in PLHIV from French Guiana between January 1988 and October 2019. Proven PH were documented through mycological direct examination, culture, or histology. Patients with concomitant respiratory infections were excluded.
RESULTS: Among 65 patients, sex ratio M:F was 2.4 with a median age of 39 years [IQR 25-75%: 34-44]. Median CD4 count was 24 cells/mm3 [11-71], with histoplasmosis as the AIDS-defining condition in 88% and concomitant AIDS-defining conditions in 29%. Clinical findings were fever (89%), cough (58%), dyspnea (35%), expectoration (14%), and hemoptysis (5%). Sixty-one X-rays and 24 CT-scans were performed. On X-rays, an interstitial lung disease was mainly found (77%). On CT-scans, a nodular pattern was predominant (83%): mostly miliary disease (63%), but also excavated nodules (35%). Consolidations were present in 46%, associated with miliary disease in 21%. Thoracic lymphadenopathies were found in 58%, mainly hilar and symmetric (33%). Despite antifungal treatment, case-fatality rate at one month was 22%.
CONCLUSIONS: When faced with an interstitial lung disease on X-rays or a miliary pattern on CT-scans in advanced PLHIV, physicians in endemic areas, apart from tuberculosis or pneumocystosis, should include histoplasmosis as part of their differential diagnoses.

A novel coronavirus (CoV) known as severe acute respiratory syndrome CoV type 2 is the causative agent for the development of CoV disease 2019 (Covid-19). Covid-19 may increase the risk of developing pulmonary histoplasmosis due to immune dysregulation. In addition, Covid-19 may enhance the propagation of acute pulmonary histoplasmosis due to lung injury and inflammation, and using corticosteroids in severely affected Covid-19 patients may reactivate latent pulmonary histoplasmosis. Likewise, activation of inflammatory signaling pathways during H. capsulatum infection may increase the severity of Covid-19 and vice versa. Furthermore, lymphopenia in Covid-19 may increase the risk for the progress of pulmonary histoplasmosis besides activation of inflammatory signaling pathways during H. capsulatum infection may increase the severity of Covid-19 and vice versa. Therefore, this critical review aimed to find the potential link between Covid-19 pneumonia and pulmonary histoplasmosis concerning the immunological response.

Secretory phospholipase B1 (PLB1) and biofilms act as microbial virulence factors and play an important role in pulmonary cryptococcosis. This study aims to formulate the ethanolic extract of propolis-loaded niosomes (Nio-EEP) and evaluate the biological activities occurring during PLB1 production and biofilm formation of Cryptococcus neoformans. Some physicochemical characterizations of niosomes include a mean diameter of 270 nm in a spherical shape, a zeta-potential of -10.54 ± 1.37 mV, and 88.13 ± 0.01% entrapment efficiency. Nio-EEP can release EEP in a sustained manner and retains consistent physicochemical properties for a month. Nio-EEP has the capability to permeate the cellular membranes of C. neoformans, causing a significant decrease in the mRNA expression level of PLB1. Interestingly, biofilm formation, biofilm thickness, and the expression level of biofilm-related genes (UGD1 and UXS1) were also significantly reduced. Pre-treating with Nio-EEP prior to yeast infection reduced the intracellular replication of C. neoformans in alveolar macrophages by 47%. In conclusion, Nio-EEP mediates as an anti-virulence agent to inhibit PLB1 and biofilm production for preventing fungal colonization on lung epithelial cells and also decreases the intracellular replication of phagocytosed cryptococci. This nano-based EEP delivery might be a potential therapeutic strategy in the prophylaxis and treatment of pulmonary cryptococcosis in the future.