Invasive Fungal Diseases in Adult Patients in Intensive Care Unit (FUNDICU): 2024 consensus definitions from ESGCIP, EFISG, ESICM, ECMM, MSGERC, ISAC, and ISHAM.

PURPOSE: The aim of this document was to develop standardized research definitions of invasive fungal diseases (IFD) in non-neutropenic, adult patients without classical host factors for IFD, admitted to intensive care units (ICUs). METHODS: After a systematic assessment of the diagnostic performance for IFD in the target population of already existing definitions and laboratory tests, consensus definitions were developed by a panel of experts using the RAND/UCLA appropriateness method. RESULTS: Standardized research definitions were developed for proven invasive candidiasis, probable deep-seated candidiasis, proven invasive aspergillosis, probable invasive pulmonary aspergillosis, and probable tracheobronchial aspergillosis. The limited evidence on the performance of existing definitions and laboratory tests for the diagnosis of IFD other than candidiasis and aspergillosis precluded the development of dedicated definitions, at least pending further data. The standardized definitions provided in the present document are aimed to speed-up the design, and increase the feasibility, of future comparative research studies.

Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial.

BACKGROUND: The trans-membrane protease serine 2 (TMPRSS2) is essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and infection. Efficacy and safety of TMPRSS2 inhibitors in patients with coronavirus disease 2019 (Covid-19) have not been evaluated in randomized trials. METHODS: We conducted an investigator-initiated, double-blind, randomized, placebo-controlled multicenter trial in patients hospitalized with confirmed SARS-CoV-2 infection from April 4, to December 31, 2020. Within 48 h of admission, participants were randomly assigned in a 2:1 ratio to receive the TMPRSS2 inhibitor camostat mesilate 200 mg three times daily for 5 days or placebo. The primary outcome was time to discharge or clinical improvement measured as ≥2 points improvement on a 7-point ordinal scale. Other outcomes included 30-day mortality, safety and change in oropharyngeal viral load. FINDINGS: 137 patients were assigned to receive camostat mesilate and 68 to placebo. Median time to clinical improvement was 5 days (interquartile range [IQR], 3 to 7) in the camostat group and 5 days (IQR, 2 to 10) in the placebo group (P = 0·31). The hazard ratio for 30-day mortality in the camostat compared with the placebo group was 0·82 (95% confidence interval [CI], 0·24 to 2·79; P = 0·75). The frequency of adverse events was similar in the two groups. Median change in viral load from baseline to day 5 in the camostat group was -0·22 log10 copies/mL (p <0·05) and -0·82 log10 in the placebo group (P <0·05). INTERPRETATION: Under this protocol, camostat mesilate treatment was not associated with increased adverse events during hospitalization for Covid-19 and did not affect time to clinical improvement, progression to ICU admission or mortality. ClinicalTrials.gov Identifier: NCT04321096. EudraCT Number: 2020-001200-42.

The burden of fungal disease in Denmark.

The aim of this study is to calculate the burden of fungal disease in Denmark. We identified all published epidemiology papers reporting fungal infection rates in Denmark. Where no data existed, we used numbers of specific populations at risk and fungal infection frequencies in those populations to estimate national incidence or prevalence. Approximately, one in six Danes will suffer from a fungal infection each year, most of which are skin or mucosal diseases causing disability but no deaths. Good data exist on candidaemia where a national voluntary reporting system is in place and have shown a high rate (9.6 per 100,000 inhabitants) compared other European countries. We present estimates of invasive aspergillosis and chronic pulmonary aspergillosis with rates of 4.4 per 100,000 and 3.1 per 100,000 inhabitants, respectively. Further studies are needed in order to better ascertain high-burden fungal infections such as recurrent vulvovaginal candidiasis (~1350 cases in 100,000 women) as well as allergic bronchopulmonary aspergillosis (~131 cases in 100,000 inhabitants) and severe asthma with fungal sensitisation (cases in 100,000 inhabitants). In conclusion, more than 93,000 Danes or about 2% of Denmark's population will have a non-trivial fungal infection during 1 year, which underscores the magnitude of the fungal burden.

Vertebral infection with Candida albicans failing caspofungin and fluconazole combination therapy but successfully treated with high dose liposomal amphotericin B and flucytosine.

A patient with Candida spondylitis failed two weeks of fluconazole combined with caspofungin, and the infection relapsed despite six weeks of liposomal amphotericin B followed by two months of fluconazole. Six months therapy with high dose liposomal amphotericin B combined with flucytosine effectively cured the patient.

Successful management of invasive aspergillosis presenting as pericarditis in an adult patient with chronic granulomatous disease.

Invasive aspergillosis (IA) is a major cause of death among patients with chronic granulomatous disease (CGD). Few cases of cardiac aspergillosis have been published on CGD patients. Diagnosis of IA in CGD patients can be hampered by lack of characteristic symptoms and clinical signs and the serum galactomannan assay is often negative. We report the first CGD patient with IA presenting as pericarditis where combined antifungal therapy resulted in a successful outcome.