Summary
Background
Currently, the biological diagnosis of Pneumocystis jirovecii pneumonia (PjP infection) usually relies on microbiological investigations in bronchial‐alveolar lavage fluid (BALF) by conventional staining methods and/or molecular biology. However, bronchial‐alveolar lavage is sometimes complicated to manage, especially in weakened patients. Therefore, alternative clinical samples—easier to collect—are warranted in such specific contexts.
Objective
Over a four‐year period, diagnostic performance of an original method based on combination of quantitative real‐time polymerase chain reaction (qPCR) in nasopharyngeal aspirate (NPA) with measurement of β‐(1, 3)‐D‐glucan antigen (BDG) in serum was prospectively assessed in a single centre.
Patients/methods
Results were compared with those obtained in BALF through direct staining methods and qPCR. True positives were defined by an independent committee based on clinical, radiological and biological data. Overall, 48 individuals with a definitive diagnosis of PjP infection were included, and 48 controls were selected upon matching for age, sex and underlying disease(s).
Results
qPCR results were strongly correlated between BALF and NPA (P < .0001). Altogether, greater diagnostic performance was achieved when establishing the positive cut‐off of BDG antigen at 143 pg/mL. In such conditions, sensitivity of the testing based on either positive BDG measurement or positive qPCR in NPA was then calculated at 93.75%, 95%CI [82.37%‐98.40%], and specificity at 97.87%, 95%CI [87.66%‐100.00%].
Conclusions
Further validation through multicentre studies is now required, especially for establishing clear cut‐offs. However, one could already state that combination of qPCR in the NPA with BDG measurement in serum may be a valuable substitute for BALF examination.
Aspergillus fumigatus
is an airborne opportunistic fungal pathogen responsible for severe infections. Among them, invasive pulmonary aspergillosis has become a major concern as mortality rates exceed 50% in immunocompromised hosts. In parallel, allergic bronchopulmonary aspergillosis frequently encountered in cystic fibrosis patients, is also a comorbidity factor. Current treatments suffer from high toxicity which prevents their use in weakened subjects, resulting in impaired prognostic. Because of their low toxicity and high specificity, anti-infectious therapeutic antibodies could be a new alternative to conventional therapeutics. In this study, we investigated the potential of
Chitin Ring Formation
cell wall transglycosylases of
A. fumigatus
to be therapeutic targets for therapeutic antibodies. We demonstrated that the Crf target was highly conserved, regardless of the pathophysiological context; whereas the
CRF1
gene was found to be 100% conserved in 92% of the isolates studied, Crf proteins were expressed in 98% of the strains. In addition, we highlighted the role of Crf proteins in fungal growth, using a deletion mutant for
CRF1
gene, for which a growth decrease of 23.6% was observed after 48 h. It was demonstrated that anti-Crf antibodies neutralized the enzymatic activity of recombinant Crf protein, and delayed fungal growth by 12.3%
in vitro
when added to spores. In a neutropenic rat model of invasive pulmonary aspergillosis, anti-Crf antibodies elicited a significant recruitment of neutrophils, macrophages and T CD4 lymphocytes but it was not correlated with a decrease of fungal burden in lungs and improvement in survival. Overall, our study highlighted the potential relevance of targeting Crf cell wall protein (CWP) with therapeutic antibodies.
The epidemiology of invasive fungal diseases (IFDs) is hard to delineate given the difficulties in ascertaining the diagnosis that is often based on the confrontation of clinical and microbiological criteria. The present report underlines the interest of active surveillance involving mycologists and clinicians to describe the global incidence and that of the main IFDs.
Aspergillosis is pervasive in bird populations, especially those under human care. Its management can be critically impacted by exposure to high levels of conidia and by resistance to azole drugs.
The fungal contamination in the environment of a Humboldt penguin (Spheniscus humboldti) group, housed in a French zoological park next to numerous large crop fields, was assessed through three serial sessions of surface sampling in nests, in 2018-20: all isolates were counted and characterized by sequencing. When identified as A. fumigatus, they were systematically screened for resistance mutations in the cyp51A gene and tested for MICs determination. In the same time, the clinical incidence of aspergillosis was evaluated in the penguin population by the means of systematic necropsy and mycological investigations. A microsatellite-based analysis tracked the circulation of A. fumigatus strains.
Environmental investigations highlighted substantial increase of the fungal load during the summer season (>12-fold vs. the other timepoints) and large overrepresentation of species belonging to the Aspergillus section Fumigati, ranging from 22.7 to 94.6% relative prevalence. Only one cryptic species was detected (A. nishimurae), and one isolate exhibited G138S resistance mutation with elevated MICs. The overall incidence of aspergillosis was measured at ∼3.4% case-years, and mostly in juveniles. The analysis of microsatellite polymorphism revealed a high level of genetic diversity among A. fumigatus clinical isolates. In contrast, one environmental strain appeared largely overrepresented during the summer sampling session. In all, the rural location of the zoo did not influence the emergence of resistant strains.
Our objective was to compare the ertapenem minimal inhibitory concentrations (MICs) for Enterobacter cloacae isolates categorized intermediate or resistant to ertapenem when measured with the Vitek 2 system, with the MICs for these isolates when measured by two methods performed in agar medium: the Etest and agar plate dilution method (APDM). Overall, 50 E. cloacae isolates were included in the study. The mean MIC of ertapenem was 2.92±1.77μg/ml according to the Vitek 2 system, 0.94±0.84μg/ml according to the Etest strips, and 0.93±0.62μg/ml according to the APDM. Furthermore, the MICs determined by the Vitek 2 system were higher than the MICs determined by the two other methods for 96% of strains. Lastly, according to the Etest strips and APDM, 42% of E. cloacae were susceptible to ertapenem. No carbapenemase was identified by the screening method used. Using the Vitek 2 system to determine ertapenem MICs for E. cloacae can have potential consequences in terms of additional carbapenemase-detecting tests and antimicrobial therapy. It would be interesting to determine if the Vitek 2 system is more effective for the detection of carbapenemase producers with low-level carbapenem resistance than the two methods performed in agar medium.
Introduction:Microsporidiosis is an emerging opportunistic infection in renal transplantation (RT) recipients. We aimed to describe its clinical presentation and treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.