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Frontiers in Cellular and Infection... 2024Mucormycosis is an uncommon invasive fungal infection that has a high mortality rate in patients with severe underlying diseases, which leads to immunosuppression. Due...
BACKGROUND
Mucormycosis is an uncommon invasive fungal infection that has a high mortality rate in patients with severe underlying diseases, which leads to immunosuppression. Due to its rarity, determining the incidence and optimal treatment methods for mucormycosis in children is challenging. Metagenomic next-generation sequencing (mNGS) is a rapid, precise and sensitive method for pathogen detection, which helps in the early diagnosis and intervention of mucormycosis in children. In order to increase pediatricians' understanding of this disease, we conducted a study on the clinical features of mucormycosis in children and assessed the role of mNGS in its diagnosis.
METHODS
We retrospectively summarized the clinical data of 14 children with mucormycosis treated at the First Affiliated Hospital of Zhengzhou University from January 2020 to September 2023.
RESULTS
Of the 14 cases, 11 case of mucormycosis were classified as probable, and 3 cases were proven as mucormycosis. Most children (85.71%) had high-risk factors for mucormycosis. All 14 children had lung involvement, with 5 cases of extrapulmonary dissemination. Among the 14 cases, 4 cases underwent histopathological examination of mediastinum, lung tissue or kidney tissue, in which fungal pathogens were identified in 3 patients. Fungal hyphae was identified in 3 cases of mucormycosis, but only 1 case yielded a positive culture result. All patients underwent mNGS testing with samples from blood (8/14), bronchoalveolar lavage fluid (6/14), and tissue (1/14). mNGS detected fungi in all cases: 7 cases had , 4 cases had , 3 cases had , 1 case had , and 1 case had . Coinfections were found with in 3 cases, bacteria in 3 cases, and viruses in 5 cases.
CONCLUSION
Children with mucormycosis commonly exhibit non-specific symptoms like fever and cough during the initial stages. Early diagnosis based on clinical symptoms and imaging is crucial in children suspected of having mucormycosis. mNGS, as a supplementary diagnostic method, offers greater sensitivity and shorter detection time compared to traditional mucormycosis culture or histopathological testing. Additionally, mNGS enables simultaneous detection of bacteria and viruses, facilitating timely and appropriate administration of antibiotics and thereby enhancing patient outcomes.
Topics: Humans; Mucormycosis; High-Throughput Nucleotide Sequencing; Male; Female; Child; Child, Preschool; Metagenomics; Retrospective Studies; Infant; Adolescent; Invasive Fungal Infections; China
PubMed: 38915923
DOI: 10.3389/fcimb.2024.1368165 -
Scientific Reports Jun 2024Azole antifungal drugs are commonly used to treat vulvovaginal candidiasis (VVC). The nephrotoxicity and developmental toxicity of azole drugs have not been...
Azole antifungal drugs are commonly used to treat vulvovaginal candidiasis (VVC). The nephrotoxicity and developmental toxicity of azole drugs have not been systematically analyzed in the real world. We used the FDA Adverse Event Reporting System (FAERS) to investigate the adverse events (AEs) associated with imidazole therapy for VVC. FAERS data (from quarter 1 2004 to quarter 3 2022) were retrieved using OpenVigil 2.1, and AEs were retrieved and standardized according to the Medical Dictionary for Regulatory Activities (MedDRA). In the top 10 System Organ Class (SOC), all four drugs have been found to have kidney and urinary system diseases and pregnancy. We found significant signals, including clotrimazole [bladder transitional cell carcinoma, (report odds ratio, ROR = 291.66)], [fetal death, (ROR = 10.28)], ketoconazole[nephrogenic anemia (ROR = 22.1)], [premature rupture of membranes (ROR = 22.91 46.45, 11, 3)], Miconazole[hematuria (ROR = 19.03)], [neonatal sepsis (ROR = 123.71)], [spontaneous abortion (ROR = 5.98)], Econazole [acute kidney injury (ROR = 4.41)], [spontaneous abortion (ROR = 19.62)]. We also discovered new adverse reactions that were not reported. Therefore, when using imidazole drugs for treatment, it is necessary to closely monitor the patient's renal function, pay attention to the developmental toxicity of the fetus during pregnancy, and be aware of potential adverse reactions that may occur.
Topics: Female; Humans; Candidiasis, Vulvovaginal; Antifungal Agents; Imidazoles; United States; United States Food and Drug Administration; Adverse Drug Reaction Reporting Systems; Pregnancy; Adult; Drug-Related Side Effects and Adverse Reactions; Miconazole; Clotrimazole
PubMed: 38914572
DOI: 10.1038/s41598-024-63315-1 -
Frontiers in Cellular and Infection... 2024Invasive mold diseases of the central nervous (CNS IMD) system are exceedingly rare disorders, characterized by nonspecific clinical symptoms. This results in...
BACKGROUND
Invasive mold diseases of the central nervous (CNS IMD) system are exceedingly rare disorders, characterized by nonspecific clinical symptoms. This results in significant diagnostic challenges, often leading to delayed diagnosis and the risk of misdiagnosis for patients. Metagenomic Next-Generation Sequencing (mNGS) holds significant importance for the diagnosis of infectious diseases, especially in the rapid and accurate identification of rare and difficult-to-culture pathogens. Therefore, this study aims to explore the clinical characteristics of invasive mold disease of CNS IMD in children and assess the effectiveness of mNGS technology in diagnosing CNS IMD.
METHODS
Three pediatric patients diagnosed with Invasive mold disease brain abscess and treated in the Pediatric Intensive Care Unit (PICU) of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2023 were selected for this study.
RESULTS
Case 1, a 6-year-old girl, was admitted to the hospital with "acute liver failure." During her hospital stay, she developed fever, irritability, and seizures. CSF mNGS testing resulted in a negative outcome. Multiple brain abscesses were drained, and was detected in pus culture and mNGS. The condition gradually improved after treatment with voriconazole combined with caspofungin. Case 2, a 3-year-old girl, was admitted with "acute B-lymphoblastic leukemia." During induction chemotherapy, she developed fever and seizures. was detected in the intracranial abscess fluid by mNGS, and the condition gradually improved after treatment with voriconazole combined with caspofungin, followed by "right-sided brain abscess drainage surgery." Case 3, a 7-year-old girl, showed lethargy, fever, and right-sided limb weakness during the pending chemotherapy period for acute B-lymphoblastic leukemia. and was detected in the cerebrospinal fluid by mNGS. The condition gradually improved after treatment with amphotericin B combined with posaconazole. After a six-month follow-up post-discharge, the three patients improved without residual neurological sequelae, and the primary diseases were in complete remission.
CONCLUSION
The clinical manifestations of CNS IMD lack specificity. Early mNGS can assist in identifying the pathogen, providing a basis for definitive diagnosis. Combined surgical treatment when necessary can help improve prognosis.
Topics: Humans; Female; High-Throughput Nucleotide Sequencing; Child; Metagenomics; Brain Abscess; Antifungal Agents; Invasive Fungal Infections; Male; Central Nervous System Fungal Infections; Child, Preschool; Aspergillus fumigatus; Caspofungin
PubMed: 38912204
DOI: 10.3389/fcimb.2024.1393242 -
Clinics in Dermatology Jun 2024Artificial Intelligence (AI) has evolved to become a significant force in various domains, including medicine. We explore the role of AI in pathology, with a specific...
Artificial Intelligence (AI) has evolved to become a significant force in various domains, including medicine. We explore the role of AI in pathology, with a specific focus on dermatopathology and neoplastic dermatopathology. AI, encompassing Machine Learning (ML) and Deep Learning (DL), has demonstrated its potential in tasks ranging from diagnostic applications on Whole Slide Imaging (WSI) to predictive and prognostic functions in skin pathology. In dermatopathology, studies have assessed AI's ability to identify skin lesions, classify melanomas, and improve diagnostic accuracy. Results indicate that AI, particularly Convolutional Neural Networks (CNNs), can outperform human pathologists in terms of sensitivity and specificity. Moreover, AI aids in predicting disease outcomes, identifying aggressive tumors, and differentiating between various skin conditions. Neoplastic dermatopathology showcases AI's prowess in classifying melanocytic lesions, discriminating between melanomas and nevi, and aiding dermatopathologists in making accurate diagnoses. Studies emphasize the reproducibility and diagnostic aid that AI provides, especially in challenging cases. In inflammatory and lymphoproliferative dermatopathology, limited research exists, but studies show attempts to use AI to differentiate conditions like Mycosis Fungoides and eczema. While some results are promising, further exploration is needed in these areas. We highlight the extraordinary interest AI has garnered in the scientific community and its potential to assist clinicians and pathologists. Despite the advancements, we have stress edthe importance of collaboration between medical professionals, computer scientists, bioinformaticians, and engineers to harness AI's benefits while acknowledging its limitations and risks. The integration of AI into dermatopathology holds great promise, positioning it as a valuable tool rather than as a replacement for human expertise.
PubMed: 38909860
DOI: 10.1016/j.clindermatol.2024.06.010 -
Journal de Mycologie Medicale Jun 2024Histoplasma capsulatum is the etiological agent of histoplasmosis, the most common endemic pulmonary mycosis. Itraconazole (ITZ) is the choice for mild disease and a...
INTRODUCTION
Histoplasma capsulatum is the etiological agent of histoplasmosis, the most common endemic pulmonary mycosis. Itraconazole (ITZ) is the choice for mild disease and a step-down therapy in severe and disseminated clinical presentations. Drug encapsulation into nanoparticles (NPs) is an alternative to improve drug solubility and bioavailability, reducing undesirable interactions and drug degradation and reaching the specific therapeutic target with lower doses.
OBJECTIVE
evaluate the antifungal and immunomodulatory effect of ITZ encapsulated into poly(lactic-co-glycolic acid) (PLGA) NPs, administrated orally and intraperitoneally in an in vivo histoplasmosis model.
RESULTS
After intranasal infection and treatment of animals with encapsulated ITZ by intraperitoneal and oral route, fungal burden control, biodistribution, immune response, and histopathology were evaluated. The results showed that the intraperitoneal administered and encapsulated ITZ has an effective antifungal effect, significantly reducing the Colony-Forming-Units (CFU) after the first doses and controlling the infection dissemination, with a higher concentration in the liver, spleen, and lung compared to the oral treatment. In addition, it produced a substantial immunomodulatory effect on pro- and anti-inflammatory cytokines and immune cell infiltrates confirmed by histopathology.
CONCLUSIONS
Overall, results suggest a synergistic effect of the encapsulated drug and the immunomodulatory effect contributing to infection control, preventing their dissemination.
PubMed: 38908332
DOI: 10.1016/j.mycmed.2024.101494 -
Medicina 2024
Topics: Humans; Bronchitis; Tracheitis; Aspergillosis; Male; Aspergillus; Middle Aged; Female
PubMed: 38907982
DOI: No ID Found -
Frontiers in Cellular and Infection... 2024species comprise a ubiquitous pathogenic fungal genus responsible for causing candidiasis. They are one of the primary causatives of several mucosal and systemic...
species comprise a ubiquitous pathogenic fungal genus responsible for causing candidiasis. They are one of the primary causatives of several mucosal and systemic infections in humans and can survive in various environments. In this study, we investigated the antifungal, anti-biofilm, and anti-hyphal effects of six -substituted phthalimides against three species. Of the derivatives, -butylphthalimide (NBP) was the most potent, with a minimum inhibitory concentration (MIC) of 100 µg/ml and which dose-dependently inhibited biofilm at sub-inhibitory concentrations (10-50 µg/ml) in both the fluconazole-resistant and fluconazole-sensitive and . NBP also effectively inhibited biofilm formation in other pathogens including uropathogenic , , , and , along with the polymicrobial biofilms of and . NBP markedly inhibited the hyphal formation and cell aggregation of and altered its colony morphology in a dose-dependent manner. Gene expression analysis showed that NBP significantly downregulated the expression of important hyphal- and biofilm-associated genes, i.e., , , and , upon treatment. NBP also exhibited mild toxicity at concentrations ranging from 2 to 20 µg/ml in a nematode model. Therefore, this study suggests that NBP has anti-biofilm and antifungal potential against various strains.
Topics: Biofilms; Antifungal Agents; Phthalimides; Microbial Sensitivity Tests; Candida albicans; Hyphae; Candida; Candidiasis; Animals; Humans; Candida parapsilosis; Fungal Proteins; Fluconazole
PubMed: 38903941
DOI: 10.3389/fcimb.2024.1414618 -
Frontiers in Veterinary Science 2024Fungal diseases are frequently associated with elevated mortality rates in elasmobranchs. Currently, there is a notable absence of scientifically validated therapeutic...
Updates on antifungal pharmacotherapy in elasmobranchs: pharmacokinetics of 4 mg/kg voriconazole after IM and IV administration in undulate skates () maintained under human care.
INTRODUCTION
Fungal diseases are frequently associated with elevated mortality rates in elasmobranchs. Currently, there is a notable absence of scientifically validated therapeutic medications that can ensure both effectiveness and safety when administered to this group of animals. The empirical prescription of azole antifungal agents, particularly voriconazole, has been posited as a potentially efficacious treatment approach for addressing most common mycoses in sharks and rays. However, there are still no published pharmacokinetic studies supporting its use in elasmobranchs and there is a lack of scientific base for its utilization in elasmobranchs.
METHODS
For this study, voriconazole was administered intravenously (IV) and intramuscularly (IM), at a single dose of 4 mg/kg to six adult undulate skates (). A washout period of 8 weeks was left between each route of administration. Blood samples were collected both before and at ten predetermined intervals after each dosing (0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, and 36 h after drug administration). Plasma concentrations were quantified using a validated high-performance liquid chromatography method, and pharmacokinetic (PK) data was analyzed through non-compartmental methods.
RESULTS
The mean extrapolated concentration at 0 h (C) after IV administration was 27.19 ± 7.15 μg/mL and the mean peak plasma concentrations (C) ± SEM after IM administration resulted 2.98 ± 0.28 μg/mL at a mean time to maximum concentration (T ) of 1.33 ± 0.17 h. Terminal half-lives were calculated and resulted 11.18 ± 1.32 h for IV injections and 9.59 ± 1.38 h for IM injections. The area under the curve extrapolated to infinity was determined as 58.14 ± 2.79 h·μg/ml following IV injections and 37.60 ± 6.67 h·μg/ml following IM injections. The IM-administered voriconazole exhibited a mean absolute bioavailability of 64.67 ± 11.47%.
DISCUSSION
These discoveries provide backing for the possible application of voriconazole through the intramuscular route in undulate skates and support using lower dosage regimens compared to those required for oral administration, emphasizing the importance of conducting further pharmacokinetic studies with antifungals in elasmobranchs.
PubMed: 38903684
DOI: 10.3389/fvets.2024.1376851 -
Annals of Clinical Microbiology and... Jun 2024Chromoblastomycosis (CBM), a chronic fungal infection affecting the skin and subcutaneous tissues, is predominantly caused by dematiaceous fungi in tropical and...
Chromoblastomycosis (CBM), a chronic fungal infection affecting the skin and subcutaneous tissues, is predominantly caused by dematiaceous fungi in tropical and subtropical areas. Characteristically, CBM presents as plaques and nodules, often leading to scarring post-healing. Besides traditional diagnostic methods such as fungal microscopy, culture, and histopathology, dermatoscopy and reflectance confocal microscopy can aid in diagnosis. The treatment of CBM is an extended and protracted process. Imiquimod, acting as an immune response modifier, boosts the host's immune response against CBM, and controls scar hyperplasia, thereby reducing the treatment duration. We present a case of CBM in Guangdong with characteristic reflectance confocal microscopy manifestations, effectively managed through a combination of itraconazole, terbinafine, and imiquimod, shedding light on novel strategies for managing this challenging condition.
Topics: Chromoblastomycosis; Imiquimod; Humans; Antifungal Agents; Itraconazole; Terbinafine; Male; Treatment Outcome; Microscopy, Confocal; Skin; Middle Aged
PubMed: 38902740
DOI: 10.1186/s12941-024-00718-y -
Nature Communications Jun 2024During pulmonary mucormycosis, inhaled sporangiospores adhere to, germinate, and invade airway epithelial cells to establish infection. We provide evidence that HIF1α...
During pulmonary mucormycosis, inhaled sporangiospores adhere to, germinate, and invade airway epithelial cells to establish infection. We provide evidence that HIF1α plays dual roles in airway epithelial cells during Mucorales infection. We observed an increase in HIF1α protein accumulation and increased expression of many known HIF1α-responsive genes during in vitro infection, indicating that HIF1α signaling is activated by Mucorales infection. Inhibition of HIF1α signaling led to a substantial decrease in the ability of R. delemar to invade cultured airway epithelial cells. Transcriptome analysis revealed that R. delemar infection induces the expression of many pro-inflammatory genes whose expression was significantly reduced by HIF1α inhibition. Importantly, pharmacological inhibition of HIF1α increased survival in a mouse model of pulmonary mucormycosis without reducing fungal burden. These results suggest that HIF1α plays two opposing roles during mucormycosis: one that facilitates the ability of Mucorales to invade the host cells and one that facilitates the ability of the host to mount an innate immune response.
Topics: Mucormycosis; Animals; Hypoxia-Inducible Factor 1, alpha Subunit; Mucorales; Humans; Epithelial Cells; Mice; Signal Transduction; Mice, Inbred C57BL; Disease Models, Animal; Lung; Female; Gene Expression Profiling
PubMed: 38902255
DOI: 10.1038/s41467-024-49637-8