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Open Forum Infectious Diseases Jun 2024Treatments for emerging and rare invasive fungal diseases (IFDs) represent a critical unmet medical need. For IFDs that occur less frequently than invasive... (Review)
Review
Treatments for emerging and rare invasive fungal diseases (IFDs) represent a critical unmet medical need. For IFDs that occur less frequently than invasive aspergillosis, such as mucormycosis, hyalohyphomycosis, and phaeohyphomycosis, randomized controlled clinical trials are impractical and unlikely to meet urgent public health needs. Understanding regulatory approaches for approval of drugs for rare cancers and rare metabolic diseases could help meet the challenges of studying drugs for rare IFDs. A single-arm, controlled clinical trial with a high-quality external control(s), with confirmatory evidence from nonclinical studies, including pharmacokinetic/pharmacodynamic data in predictive animal models of the disease may support findings of effectiveness of new drugs and biologics. Control populations may include historical controls from published literature, patient registries, and/or contemporaneous external control groups. Continuous engagement among clinicians, industrial sponsors, and regulatory agencies to develop consensus on trial design and innovative development pathways for emergent and rare invasive fungal diseases is important.
PubMed: 38887484
DOI: 10.1093/ofid/ofae257 -
Open Forum Infectious Diseases Jun 2024Among solid organ transplant recipients taking belatacept, 15% developed invasive fungal diseases. The most common invasive fungal diseases were aspergillosis (56%) and...
An Unexpectedly High Incidence of Invasive Fungal Diseases in Solid Organ Transplant Recipients Taking Belatacept for Organ Rejection Prophylaxis: A Single-Center Retrospective Cohort Study.
Among solid organ transplant recipients taking belatacept, 15% developed invasive fungal diseases. The most common invasive fungal diseases were aspergillosis (56%) and candidiasis (22%). The infected cohort was more likely to receive basiliximab, undergo lung transplantation, or identify as White. Higher rates of aspergillosis were seen in this lung cohort than previously reported.
PubMed: 38887477
DOI: 10.1093/ofid/ofae158 -
Open Forum Infectious Diseases Jun 2024Prior reports have suggested a possible increase in the frequency of invasive fungal infections (IFIs) with use of a Bruton tyrosine kinase inhibitor (BTKi) for...
Risk of Invasive Fungal Infections in Patients With Chronic Lymphocytic Leukemia Treated With Bruton Tyrosine Kinase Inhibitors: A Case-Control Propensity Score-Matched Analysis.
BACKGROUND
Prior reports have suggested a possible increase in the frequency of invasive fungal infections (IFIs) with use of a Bruton tyrosine kinase inhibitor (BTKi) for treatment of chronic lymphoid malignancies such as chronic lymphocytic leukemia (CLL), but precise estimates are lacking. We aim to characterize the prevalence of IFIs among patients with CLL, for whom a BTKi is now the first-line recommended therapy.
METHODS
We queried TriNetX, a global research network database, to identify adult patients with CLL using the code (C91.1) and laboratory results. We performed a case-control propensity score-matched analysis to determine IFIs events by BTKi use. We adjusted for age, sex, ethnicity, and clinical risk factors associated with an increased risk of IFIs.
RESULTS
Among 5358 matched patients with CLL, we found an incidence of 4.6% of IFIs in patients on a BTKi versus 3.5% among patients not on a BTKi at 5 years. Approximately 1% of patients with CLL developed an IFI while on a BTKi within this period. Our adjusted IFI event analysis found an elevated rate of pneumonia (PJP) (0.5% vs 0.3%, = .02) and invasive candidiasis (3.5% vs 2.7%, = .012) with the use of a BTKi. The number needed to harm for patients taking a BTKi was 120 and 358 for invasive candidiasis and PJP, respectively.
CONCLUSIONS
We found an adjusted elevated rate of PJP and invasive candidiasis with BTKi use. The rates are, however, low with a high number needed to harm. Additional studies stratifying other IFIs with specific BTKis are required to identify at-risk patients and preventive, cost-effective interventions.
PubMed: 38887474
DOI: 10.1093/ofid/ofae115 -
The Clinical Respiratory Journal Jun 2024
Allergic Bronchopulmonary Aspergillosis (ABPA) With Colonized Aspergillus fumigatus Detected by Metagenomic Next-Generation Sequencing on Tissue Samples: A Distinct Subset of ABPA With a Higher Risk of Exacerbation.
Topics: Humans; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Male; High-Throughput Nucleotide Sequencing; Female; Middle Aged; Metagenomics; Adult; Disease Progression; Aged
PubMed: 38886877
DOI: 10.1111/crj.13794 -
Mycoses Jun 2024Serum galactomannan (GM) testing is essential for diagnosing invasive aspergillosis (IA), particularly in immunocompromised individuals. The global lack of on-site GM... (Comparative Study)
Comparative Study
BACKGROUND
Serum galactomannan (GM) testing is essential for diagnosing invasive aspergillosis (IA), particularly in immunocompromised individuals. The global lack of on-site GM testing capacities necessitates cost-effective alternatives, such as .the clarus Aspergillus GM enzyme immunoassay prototype (clarus AGM prototype).
METHODS
This single-centre, cross-sectional study compared the diagnostic performance of the clarus AGM prototype (IMMY, Norman, Oklahoma) with the serological gold standard (=Platelia AGM assay; Bio-Rad, Marnes-la-Cocquette, France). IA was classified according to modified 2020 EORTC/MSG consensus and 2024 FUNDICU criteria. In total, 300 prospectively (May-Dec 2023) and retrospectively (2012-2015) collected samples were included.
RESULTS
Among 300 samples from 232 patients, 49 (16%) were classified as proven (n = 1) or probable IA (n = 48). In non-IA cases (n = 250), one patient was classified as possible IA. With the manufacturer recommended cut-off of ≥0.2, sensitivity and specificity of the clarus AGM prototype were 27% (13/49; 95% confidence interval [CI]: 15%-41%) and 99% (248/250; 95% CI: 97%-100%), respectively, while sensitivity and specificity were 78% and 79% when using the optimised Youden's cut-off of 0.0045 ODI. ROC curve analysis demonstrated an area under the curve (AUC) of 0.829 (95% CI: 0.760-0.898) for the clarus AGM prototype in distinguishing between proven/probable IA and non-IA. The AUC for the Platelia AGM was 0.951 (95% CI: 0.909-994). Spearman's correlation analysis showed a weak correlation between the two assays (0.382; p < .001).
CONCLUSIONS
The weak correlation between the clarus AGM prototype and Platelia AGM highlights the need for further investigation into the clinical performance of the clarus AGM prototype, giving the different antigen epitopes addressed.
Topics: Humans; Mannans; Galactose; Invasive Pulmonary Aspergillosis; Immunoenzyme Techniques; Cross-Sectional Studies; Male; Middle Aged; Female; Sensitivity and Specificity; Aged; Retrospective Studies; Aspergillus; Adult; Prospective Studies; Antigens, Fungal; Aged, 80 and over; Young Adult; ROC Curve
PubMed: 38886163
DOI: 10.1111/myc.13756 -
Lung Jun 2024Bronchiectasis is predominantly marked by neutrophilic inflammation. The relevance of type 2 biomarkers in disease severity and exacerbation risk is poorly understood....
PURPOSE
Bronchiectasis is predominantly marked by neutrophilic inflammation. The relevance of type 2 biomarkers in disease severity and exacerbation risk is poorly understood. This study explores the clinical significance of these biomarkers in bronchiectasis patients.
METHODS
In a cross-sectional cohort study, bronchiectasis patients, excluding those with asthma or allergic bronchopulmonary aspergillosis, underwent clinical and radiological evaluations. Bronchoalveolar lavage samples were analyzed for cytokines and microbiology. Blood eosinophil count (BEC), serum total immunoglobulin E (IgE), and fractional exhaled nitric oxide (FeNO) were measured during stable disease states. Positive type 2 biomarkers were defined by established thresholds for BEC, total IgE, and FeNO.
RESULTS
Among 130 patients, 15.3% demonstrated BEC ≥ 300 cells/μL, 26.1% showed elevated FeNO ≥ 25 ppb, and 36.9% had high serum total IgE ≥ 75 kU/L. Approximately 60% had at least one positive type 2 biomarker. The impact on clinical characteristics and disease severity was variable, highlighting BEC and FeNO as reflective of different facets of disease severity and exacerbation risk. The combination of low BEC with high FeNO appeared to indicate a lower risk of exacerbation. However, Pseudomonas aeruginosa colonization and a high neutrophil-to-lymphocyte ratio (NLR ≥ 3.0) were identified as more significant predictors of exacerbation frequency, independent of type 2 biomarker presence.
CONCLUSIONS
Our study underscores the distinct roles of type 2 biomarkers, highlighting BEC and FeNO, in bronchiectasis for assessing disease severity and predicting exacerbation risk. It advocates for a multi-biomarker strategy, incorporating these with microbiological and clinical assessments, for comprehensive patient management.
PubMed: 38884647
DOI: 10.1007/s00408-024-00707-0 -
Indian Journal of Otolaryngology and... Jun 2024Invasive fungal infections are uncommon in an immunocompetent host and pose a real diagnostic dilemma. As they have a propensity for locoregional destruction,...
Invasive fungal infections are uncommon in an immunocompetent host and pose a real diagnostic dilemma. As they have a propensity for locoregional destruction, clinic-radiological findings can mislead to a faulty diagnosis of a malignancy. Here we present a case of Primary Aspergillus dacryocystitis in an immunocompetent individual initially thought to be an orbital malignancy until the histopathological examination.
PubMed: 38883535
DOI: 10.1007/s12070-023-04346-4 -
Indian Journal of Otolaryngology and... Jun 2024Multidrug resistant strains and fungi add to treatment conundrums in skull base osteomyelitis (SBO). Deep tissue culture in these patients is challenging due to their...
Multidrug resistant strains and fungi add to treatment conundrums in skull base osteomyelitis (SBO). Deep tissue culture in these patients is challenging due to their advanced age and co-morbidities. Besides, fungal culture positivity is seen only in 60% of invasive aspergillosis. To determine the efficacy of a minimally invasive test-Serum Galactomannan (sGM)-for diagnosing fungal SBO. Prospective observational study. Thirty- three patients, clinically diagnosed with SBO were included in this study. Baseline ESR (Erythrocyte Sedimentation Rate), CRP (C- Reactive Protein), pain score, and sGM were noted for all patients. Antifungal Voriconazole was initiated on patients if the sGM values were more than 0.8. At the 12th week of treatment, all parameters were repeated and compared with the baseline values. A significant reduction was noted in ESR, CRP, and pain scores at the 12th week of treatment compared to the baseline values in patients with raised sGM values who were started on Voriconazole. For a culture-proven fungal skull base osteomyelitis with a cut-off value of sGM > / = 0.8, the obtained sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 81.82, 36.36, 39.13, 80 and 51.52% respectively. At a cut-off value of sGM > / = 01.6, the values of sensitivity/specificity, PPV, NPV and accuracy were 81.82/72.73%, 60%, 88.89% and 75.76%. Culture-negative patients in SBO with sGM value > 0.8 were more likely to be fungal SBO. An sGM cut-off of 1.6 was observed to give maximum accuracy for diagnosing fungal SBO.
PubMed: 38883534
DOI: 10.1007/s12070-024-04563-5 -
Indian Journal of Otolaryngology and... Jun 2024Isolated sphenoid sinus disease is a rare paranasal sinus (PNS) problem, comprising only 2-3% of cases of sinonasal diseases. It is caused mainly by inflammation, and...
Isolated sphenoid sinus disease is a rare paranasal sinus (PNS) problem, comprising only 2-3% of cases of sinonasal diseases. It is caused mainly by inflammation, and neoplastic causes are exceedingly rare. Due to the nonspecific nature of the symptoms and possible complications, the proper diagnosis and treatment has paramount importance. A 53-year-old woman with a history of diabetes experienced sudden paralysis of the right side of her body and face. A diagnostic workup revealed an acute infarction in her left medial pons and the left midbrain. However, an abnormal finding in her sphenoid sinus caught the neurologist's attention, which led to a consultation with the otorhinolaryngology service. During the sinonasal endoscopy, the surgeon detected the presence of secretions and fungal debris in the nasopharynx and sphenoid sinus. Following the surgery, antifungal treatment began. The pathology report revealed that the fungal ball was most likely caused by aspergillosis. According to the neurologist's opinion and the imaging results, the inflammation and infectious activity in the patient's sphenoid sinus may have damaged the basilar artery and caused the observed symptoms. This finding underlines the vital significance of the accurate diagnosis and treatment of sphenoid sinus disease, as it can prevent further complications.
PubMed: 38883483
DOI: 10.1007/s12070-024-04562-6 -
Mycopathologia Jun 2024A 67 year-old male was admitted in the ICU because of multi-organ failure due to sepsis secondary to Fournier's gangrene. He had sustained radical prostatectomy in the...
A 67 year-old male was admitted in the ICU because of multi-organ failure due to sepsis secondary to Fournier's gangrene. He had sustained radical prostatectomy in the last 48 hours. Peritoneal fluid and fatty tissue biopsies grew Aspergillus Fumigatus without concomitant pulmonary involvement. Postoperative acquisition via exogenous and endogenous routes is discussed, as this nosocomial entity is very rarely reported apart from peritoneal dialysis, especially in non-immunosuppressed patients.
Topics: Humans; Male; Aspergillus fumigatus; Aged; Peritonitis; Aspergillosis; Postoperative Complications; Prostatectomy
PubMed: 38878212
DOI: 10.1007/s11046-024-00858-x