Real-life epidemiology and current outcomes of hospitalized adults with invasive fungal infections.

We aimed to describe the current epidemiology of both hosts with invasive fungal infections (IFIs) and causative fungi. And, detail outcomes of these infections at 12 weeks in a real-life cohort of hospitalized patients. The study was retrospective and observational to describe IFI diagnosed in a tertiary hospital (February 2017-December 2021). We included all consecutive patients meeting criteria for proven or probable IFI according to EORTC-MSG and other criteria. A total of 367 IFIs were diagnosed. 11.7% were breakthrough infections, and 56.4% were diagnosed in the intensive care unit. Corticosteroid use (41.4%) and prior viral infection (31.3%) were the most common risk factors for IFI. Lymphoma and pneumocystis pneumonia were the most common baseline and fungal diseases. Only 12% of IFI occurred in patients with neutropenia. Fungal cultures were the most important diagnostic tests (85.8%). The most frequent IFIs were candidemia (42.2%) and invasive aspergillosis (26.7%). Azole-resistant Candida strains and non-fumigatus Aspergillus infections represented 36.1% and 44.5% of the cases, respectively. Pneumocystosis (16.9%), cryptococcosis (4.6%), and mucormycosis (2.7%) were also frequent, as well as mixed infections (3.4%). Rare fungi accounted for 9.5% of infections. Overall, IFI mortality at 12 weeks was 32.2%; higher rates were observed for Mucorales (55.6%), Fusarium (50%), and mixed infections (60%). We documented emerging changes in both hosts and real-life IFI epidemiology. Physicians should be aware of these changes to suspect infections and be aggressive in diagnoses and treatments. Currently, outcomes for such clinical scenarios remain extremely poor.

Current epidemiology of the host and fungi and IFI treatments are changing. Real-life data on this subject are scarce. We present our most recent evidence to highlight the importance of the ongoing challenges that require further investigation and clinical adjustments.

Case report: Challenges in immune reconstitution following hematopoietic stem cell transplantation for CTLA-4 insufficiency-like primary immune regulatory disorders.

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) haploinsufficiency is a T-cell hyperactivation disorder that can manifest with both immunodeficiency and immune dysregulation. Approximately one-third of patients may present mild symptoms and remain stable under supportive care. The remaining patients may develop severe multiorgan autoimmunity requiring lifelong immunosuppressive treatment. Hematopoietic stem cell transplantation (HSCT) is potentially curable for patients with treatment-resistant immune dysregulation. Nevertheless, little experience is reported regarding the management of complications post-HSCT. We present case 1 (CTLA-4 haploinsufficiency) and case 2 (CTLA-4 insufficiency-like phenotype) manifesting with severe autoimmunity including cytopenia and involvement of the central nervous system (CNS), lung, and gut and variable impairment of humoral responses. Both patients underwent HSCT for which the main complications were persistent mixed chimerism, infections, and immune-mediated complications [graft-versus-host disease (GVHD) and nodular lung disease]. Detailed management and outcomes of therapeutic interventions post-HSCT are discussed. Concretely, post-HSCT abatacept and human leukocyte antigen (HLA)-matched sibling donor lymphocyte infusions may be used to increase T-cell donor chimerism with the aim of correcting the immune phenotype of CTLA-4 haploinsufficiency.

Rapid molecular syndromic testing for aetiological diagnosis of gastrointestinal infections and targeted antimicrobial prescription: experience from a reference paediatric hospital in Spain.

Aetiological diagnosis of gastrointestinal infections is challenging since a wide range of bacteria, parasites and viruses can be causal agents and derived clinical manifestations appear quite similar. Our aim was to evaluate contribution of the novel QIAstat-DxGastrointestinal Panel (GIP) to aetiological diagnosis of gastrointestinal infections and rational antimicrobial prescription in a reference paediatric hospital. Evaluation included comparison of diagnostic yield and agreement of results of QIAstat-Dx GIP and conventional microbiological methods. Parallel testing was performed on stool samples collected prospectively from children admitted to Sant Joan de Deu Barcelona Hospital (Spain) during the period February-March 2019. Influence of the panel test use on antimicrobial prescription was assessed using a pre-post study design. Eighty-six (68.8%) out of 125 specimens were positive by QIAstat-Dx GIP versus 44 (35.2%) positive by a composite of conventional methods (p<0.001). Global agreement of panel test results with rotavirus-adenovirus antigen detection (92.8%) and a two-step antigen/toxin and PCR-based algorithm for toxigenic Clostridioides difficile detection (87.5%) was greater than that with bacterial culture (76.0%) and parasite microscopic identification (64.3%). Panel test results orientated antimicrobial prescription changes in 18 (14.4%) patients, including antimicrobial start in 11 cases initially untreated, targeted antimicrobial prescription in 5 and discontinuation in 2 cases empirically treated. Results showed that QIAstat-Dx GIP significantly expanded aetiological diagnosis of gastrointestinal infections compared to conventional microbiological methods while orientating a more judicious use of antimicrobial drugs in hospitalised children.

Performance Comparison of a Novel Rapid Stand-alone Molecular Test and a 2-Step Diagnostic Algorithm for Clostridioides difficile Detection in Children.

BACKGROUND: We aimed to evaluate diagnostic performance of the cobas® Liat® Cdiff test, a novel single-step automated polymerase chain reaction (PCR) assay for rapid diagnosis of toxigenic Clostridioides difficile infection (CDI) in stool samples from children with clinical symptoms of CDI. METHODS: Assessment of cobas Liat Cdiff diagnostic yield, time of analytical process and agreement of results with those of a 2-step diagnostic algorithm. The sequential algorithm combined an enzyme immunoassay (EIA) targeting antigen glutamate dehydrogenase (GDH), enterotoxin-A and cytotoxin-B, and a confirmatory PCR in EIA GDH-positive and toxin-negative samples. Fresh stool samples were collected prospectively from patients 2-18 years of age that were attended in Hospital Sant Joan de Deu (Barcelona, Spain) during December 2018-August 2019. RESULTS: A total of 122 specimens were collected from 91 children (mean age, 8 years; 69.7% male). cobas Liat Cdiff identified 24 (19.7%) positive samples. EIA yielded 97 (79.5%) GDH- and toxin-negative results, 11 (9.0%) GDH- and toxin-positive results, and 14 (11.5%) GDH-positive and toxin-negative results, of which 11 (9.0%) were positive for the toxin by the confirmatory PCR. Overall, GDH- and toxin-positive samples detected by the sequential algorithm were 22 (18.0%). Comparatively, the new test reduced time of the analytical process significantly (20 vs. 35.4 minutes, P < 0.001). CONCLUSION: Use of cobas Liat Cdiff showed similar detection yield compared with a 2-step diagnostic algorithm that combined an EIA and a confirmatory PCR while decreasing the time of the analytical process markedly in stool samples from children suspected of CDI.