-
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 -
Archives of Microbiology Jun 2024Aspergillus fumigatus is a ubiquitous filamentous fungus commonly found in the environment. It is also an opportunistic human pathogen known to cause a range of... (Review)
Review
Aspergillus fumigatus is a ubiquitous filamentous fungus commonly found in the environment. It is also an opportunistic human pathogen known to cause a range of respiratory infections, such as invasive aspergillosis, particularly in immunocompromised individuals. Azole antifungal agents are widely used for the treatment and prophylaxis of Aspergillus infections due to their efficacy and tolerability. However, the emergence of azole resistance in A. fumigatus has become a major concern in recent years due to their association with increased treatment failures and mortality rates. The development of azole resistance in A. fumigatus can occur through both acquired and intrinsic mechanisms. Acquired resistance typically arises from mutations in the target enzyme, lanosterol 14-α-demethylase (Cyp51A), reduces the affinity of azole antifungal agents for the enzyme, rendering them less effective, while intrinsic resistance refers to a natural resistance of certain A. fumigatus isolates to azole antifungals due to inherent genetic characteristics. The current review aims to provide a comprehensive overview of azole antifungal resistance in A. fumigatus, discusses underlying resistance mechanisms, including alterations in the target enzyme, Cyp51A, and the involvement of efflux pumps in drug efflux. Impact of azole fungicide uses in the environment and the spread of resistant strains is also explored.
Topics: Aspergillus fumigatus; Azoles; Drug Resistance, Fungal; Antifungal Agents; Humans; Fungal Proteins; Aspergillosis; Microbial Sensitivity Tests; Cytochrome P-450 Enzyme System; Mutation
PubMed: 38878211
DOI: 10.1007/s00203-024-04026-z -
Journal of Zoo and Wildlife Medicine :... Jun 2024Aspergillosis is a major cause of morbidity and mortality in penguins, with triazole antifungal drugs being commonly used for prophylaxis and treatment. This report...
Aspergillosis is a major cause of morbidity and mortality in penguins, with triazole antifungal drugs being commonly used for prophylaxis and treatment. This report describes 15 cases of fatal hemolysis associated with liquid itraconazole and voriconazole formulations administered to African penguins () from four institutions. All penguins underwent stressful events (e.g. relocation, induced molt) and were administered commercial liquid itraconazole formulations or compounded voriconazole liquid suspension. Observed clinical signs in affected penguins prior to death included hyporexia, weight loss, lethargy, dyspnea, red-tinged droppings, and obtunded mentation. Intra- and extravascular hemolysis and hemoglobinuric nephrosis were the primary pathologic manifestations on postmortem examination. The concentration-dependent hemolytic potentials of itraconazole, voriconazole, and commercial and compounded vehicle suspensions were evaluated in vitro by exposing chicken whole blood as a surrogate for penguin blood. Hemoglobin content in blood plasma was then measured by spectrophotometry. Neither itraconazole nor voriconazole alone induced hemolysis in vitro. The vehicle ingredients sorbitol and hydromellose induced hemolysis, but not at predicted plasma levels in chicken erythrocytes, suggesting neither the azole antifungals nor their major vehicles alone were likely to contribute to hemolysis in vivo in these penguins. Potential mechanisms of toxicosis include generation of an unmeasured reactive metabolite causing hemolysis, preexisting erythrocyte fragility, or species-specific differences in hemolytic thresholds that were not assessed in the chicken erythrocyte model. More research is needed on the potential for toxicosis of azole antifungal drugs and carrier molecules in this and other avian species.
Topics: Animals; Spheniscidae; Bird Diseases; Hemolysis; Antifungal Agents; Voriconazole; Itraconazole; Triazoles; Male; Female; Animals, Zoo
PubMed: 38875206
DOI: 10.1638/2023-0073 -
Annals of Intensive Care Jun 2024
PubMed: 38874854
DOI: 10.1186/s13613-024-01318-x -
Current Research in Microbial Sciences 2024Ibrexafungerp (IBX) is a new antifungal drug that recently entered the antifungal landscape. It disrupts fungal cell wall synthesis by non-competitive inhibition of the... (Review)
Review
Ibrexafungerp (IBX) is a new antifungal drug that recently entered the antifungal landscape. It disrupts fungal cell wall synthesis by non-competitive inhibition of the β-(1,3)-D-glucan (BDG) synthase enzyme. It has demonstrated activity against a range of pathogens including and spp., as well as retaining its activity against azole-resistant and echinocandin-resistant strains. It also exhibits anti-biofilm properties. Pharmacokinetic (PK) studies revealed favorable bioavailability, high protein binding, and extensive tissue distribution with a low potential for CYP-mediated drug interactions. It is characterized by the same mechanism of action of echinocandins with limited cross-resistance with other antifungal agents. Resistance to this drug can arise from mutations in the genes, primarily mutations in . In vivo, IBX was found to be effective in murine models of invasive candidiasis (IC) and invasive pulmonary aspergillosis (IPA). It also showed promising results in preventing and treating infections. Clinical trials showed that IBX was effective and non-inferior to fluconazole in treating vulvovaginal candidiasis (VVC), including complicated cases, as well as in preventing its recurrence. These trials positioned it as a Food and Drug Administration (FDA)-approved option for the treatment and prophylaxis of VVC. Trials showed comparable responses to standard-of-care in IC, with favorable preliminary results in infections in terms of efficacy and tolerability as well as in refractory cases of IC. Mild adverse reactions have been reported including gastrointestinal symptoms. Overall, IBX represents a significant addition to the antifungal armamentarium, with its unique action, spectrum of activity, and encouraging clinical trial results warranting further investigation.
PubMed: 38873590
DOI: 10.1016/j.crmicr.2024.100245 -
Transplantation and Cellular Therapy Jun 2024Invasive fungal infections (IFI) pose a significant complication after hematopoietic stem cell transplantation (HSCT). Isavuconazole (ISV) is a new generation azole with...
BACKGROUND
Invasive fungal infections (IFI) pose a significant complication after hematopoietic stem cell transplantation (HSCT). Isavuconazole (ISV) is a new generation azole with a favourable adverse effect and interaction profile approved for the treatment of invasive aspergillosis and mucormycosis.
OBJECTIVES
We analysed the indications, effectiveness, adverse event profile and drug interaction management of ISV in the real-world setting in adults who received allogeneic-HSCT (allo-HSCT) within the Spanish Group of HSCT and Cell Therapy (GETH-TC).
MATERIAL AND METHODS
We conducted a multicenter retrospective study of all consecutive adult allo-HSCT recipients (≥18 years) who received ISV either for IFI treatment or prophylaxis, from December 2017 to August 2021, in 20 centers within the Spanish Group of Hematopoietic Stem Cell Transplantation and Cell Therapy (GETH-TC).
RESULTS
166 adult allografted patients who received ISV from 2017 to 2021 were included. Median age was 48 years with 43% females. In 81 (49%) patients, ISV was used for treatment of IFI, and in 85 (51%) for prophylaxis. Median duration of ISV administration for IFI treatment was 57 days (range 31-126) and 86 days (range 33-196) for prophylaxis. Most frequent indication for treatment was invasive aspergillosis (78%), followed by mucormycosis (6%). Therapeutic success (45%) was the most frequent reason for ISV withdrawal. In the prophylaxis group, the resolution of IFI risk factors was the most frequent reason for withdrawal (62%). Six (7%) breakthrough IFI were reported. The majority of patients (80%) presented pharmacological interactions. Twenty one patients (13%) reported adverse events related to ISV, mainly liver biochemistry abnormalities, that lead to ISV withdrawal in 7 patients (4%).
CONCLUSIONS
ISV was effective and well tolerated for IFI treatment and prophylaxis, with a manageable interaction profile.
PubMed: 38871055
DOI: 10.1016/j.jtct.2024.06.009