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PLoS Pathogens Jun 2024
Review
Topics: Humans; Dermatomycoses; Arthrodermataceae; Antifungal Agents
PubMed: 38870096
DOI: 10.1371/journal.ppat.1012258 -
Mycopathologia Jun 2024The incidence of breakthrough mold infections (bIMI) has been increasing, due to routine administration of broad-spectrum antifungal prophylaxis and an increasing pool... (Review)
Review
The incidence of breakthrough mold infections (bIMI) has been increasing, due to routine administration of broad-spectrum antifungal prophylaxis and an increasing pool of high-risk patient populations, with fungi more challenging to treat, resulting in a sustained high mortality, despite progress in diagnostic and therapeutic options. Pharmacokinetics of antifungal drugs, fungal, and host, including genetic, factors play a role in the emergence of bIMI. Suggested therapeutic approaches have included change of antifungal class treatment, with amphotericin-B products predominating as first-line empirical treatment and switching from one broad-spectrum azole to another remaining the most frequently used treatment modalities. Future perspectives include determining individual susceptibility to IMI to tailor prophylaxis and treatment strategies, improved diagnostic tests, and the introduction of new antifungal agents that may reduce morbidity and mortality caused by bIMI.
Topics: Humans; Invasive Fungal Infections; Antifungal Agents; Fungi; Incidence; Drug Resistance, Fungal
PubMed: 38869662
DOI: 10.1007/s11046-024-00864-z -
BMC Infectious Diseases Jun 2024Several antifungal agents are available for primary therapy in patients with invasive aspergillosis (IA). Although a few studies have compared the effectiveness of... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
Several antifungal agents are available for primary therapy in patients with invasive aspergillosis (IA). Although a few studies have compared the effectiveness of different antifungal agents in treating IA, there has yet to be a definitive agreement on the best choice. Herein, we perform a network meta-analysis comparing the efficacy of different antifungal agents in IA.
METHODS
We searched PubMed, Embase, and the Cochrane Central Register of Controlled Clinical Trials databases to find studies (both randomized controlled trials [RCTs] and observational) that reported on treatment outcomes with antifungal agents for patients with IA. The study quality was assessed using the revised tool for risk of bias and the Newcastle Ottawa scale, respectively. We performed a network meta-analysis (NMA) to summarize the evidence on antifungal agents' efficacy (favourable response and mortality).
RESULTS
We found 12 studies (2428 patients) investigating 11 antifungal agents in the primary therapy of IA. There were 5 RCTs and 7 observational studies. When treated with monotherapy, isavuconazole was associated with the best probability of favourable response (SUCRA, 77.9%; mean rank, 3.2) and the best reduction mortality against IA (SUCRA, 69.1%; mean rank, 4.1), followed by voriconazole and posaconazole. When treated with combination therapy, Liposomal amphotericin B plus caspofungin was the therapy associated with the best probability of favourable response (SUCRA, 84.1%; mean rank, 2.6) and the best reduction mortality (SUCRA, 88.2%; mean rank, 2.2) against IA.
CONCLUSION
These findings suggest that isavuconazole, voriconazole, and posaconazole may be the best antifungal agents as the primary therapy for IA. Liposomal amphotericin B plus caspofungin could be an alternative option.
Topics: Antifungal Agents; Humans; Network Meta-Analysis; Aspergillosis; Treatment Outcome; Caspofungin; Randomized Controlled Trials as Topic; Invasive Fungal Infections; Triazoles; Amphotericin B; Voriconazole; Nitriles; Pyridines
PubMed: 38867163
DOI: 10.1186/s12879-024-09477-9 -
Revista Do Instituto de Medicina... 2024Hyalohyphomycosis and phaeohyphomycosis are groups of mycoses caused by several agents and show different clinical manifestations. We report a case of an...
Hyalohyphomycosis and phaeohyphomycosis are groups of mycoses caused by several agents and show different clinical manifestations. We report a case of an immunocompromised patient who presented rare manifestations of opportunistic mycoses: mycetoma-like hyalohyphomycosis on his right foot caused by Colletotrichum gloeosporioides, followed by cutaneous phaeohyphomycosis on his right forearm caused by Exophiala oligosperma. Further to the rarity of this case, the patient's lesion on the foot shows that the clinical aspects of mycetomas could falsely appear in other fungal infections similar to hyalohyphomycosis. We also show that the muriform cells that were seen in the direct and anatomopathological examination of the skin are not pathognomonic of chromoblastomycosis, as observed in the lesion of the patient's forearm.
Topics: Humans; Male; Chromoblastomycosis; Mycetoma; Diagnosis, Differential; Immunocompromised Host; Hyalohyphomycosis; Exophiala; Middle Aged
PubMed: 38865572
DOI: 10.1590/S1678-9946202466034 -
Mycopathologia Jun 2024Aspergillus fumigatus is a saprophytic fungal pathogen that causes opportunistic infections in animals and humans. Azole resistance has been reported globally in human...
Aspergillus fumigatus is a saprophytic fungal pathogen that causes opportunistic infections in animals and humans. Azole resistance has been reported globally in human A. fumigatus isolates, but the prevalence of resistance in isolates from animals is largely unknown. A retrospective resistance surveillance study was performed using a collection of clinical A. fumigatus isolates from various animal species collected between 2015 and 2020. Agar-based azole resistance screening of all isolates was followed by in vitro antifungal susceptibility testing and cyp51A gene sequencing of the azole-resistant isolates. Over the 5 year period 16 (11.3%) of 142 A. fumigatus culture-positive animals harbored an azole-resistant isolate. Resistant isolates were found in birds (15%; 2/13), cats (21%; 6/28), dogs (8%; 6/75) and free-ranging harbor porpoise (33%; 2/6). Azole-resistance was cyp51A mediated in all isolates: 81.3% (T-67G/)TR/L98H, 12.5% TR/Y121F/T289A. In one azole-resistant A. fumigatus isolate a combination of C(-70)T/F46Y/C(intron7)T/C(intron66)T/M172V/E427K single-nucleotide polymorphisms in the cyp51A gene was found. Of the animals with an azole-resistant isolate and known azole exposure status 71.4% (10/14) were azole naive. Azole resistance in A. fumigatus isolates from animals in the Netherlands is present and predominantly cyp51A TR-mediated, supporting an environmental route of resistance selection. Our data supports the need to include veterinary isolates in resistance surveillance programs. Veterinarians should consider azole resistance as a reason for therapy failure when treating aspergillosis and consider resistance testing of relevant isolates.
Topics: Aspergillus fumigatus; Animals; Azoles; Drug Resistance, Fungal; Aspergillosis; Antifungal Agents; Netherlands; Microbial Sensitivity Tests; Retrospective Studies; Fungal Proteins; Birds; Cats; Dogs; Cytochrome P-450 Enzyme System
PubMed: 38864903
DOI: 10.1007/s11046-024-00850-5 -
Journal of Clinical Microbiology Jun 2024
Topics: Humans; Male; Antifungal Agents; Hyphae; Mucormycosis; Spores, Fungal; Aged
PubMed: 38864632
DOI: 10.1128/jcm.01638-23 -
The American Journal of Case Reports Jun 2024BACKGROUND Histoplasma capsulatum is prevalent in the mid-eastern United States and is an environmental fungus that causes human infection by the inhalation of its...
BACKGROUND Histoplasma capsulatum is prevalent in the mid-eastern United States and is an environmental fungus that causes human infection by the inhalation of its spores. It is commonly associated with areas containing large amounts of bird excrement and can survive for years in the soil. Only 1% of infected individuals develop disseminated histoplasmosis or Histoplasma endocarditis. CASE REPORT A 61-year-old man with atrial fibrillation had 8 months of fatigue, low-grade fevers, night sweats, and unexplained weight loss presented to the Emergency Department. He worked and lived in Central Florida and although he raised cattle, he denied exposure to birds or bats with regularity. A transesophageal echocardiogram confirmed a sessile echo density on the atrial surface of the mitral valve. His microbial Karius cell-free DNA test from his blood sample was positive for Histoplasma capsulatum, and he was immediately given intravenous liposomal amphotericin for 2 weeks. A tissue valve was used to successfully replace his mitral valve along with a coronary artery bypass and a maze procedure for his persistent atrial fibrillation and atrial flutter. The diagnosis of mitral valve endocarditis from disseminated histoplasmosis was confirmed by pathological analysis, and he was sent home on long-term itraconazole maintenance treatment. CONCLUSIONS Surgical intervention in combination with anti-fungal medication can be a lifesaving intervention for disseminated histoplasmosis. A thorough history is particularly important when evaluating a patient with an unknown infectious source, especially assessing for risk factors, including exposure to environmental factors, workplace, and animals.
Topics: Humans; Histoplasmosis; Male; Middle Aged; Mitral Valve; Endocarditis; Florida; Antifungal Agents; Echocardiography, Transesophageal; Heart Valve Diseases; Histoplasma
PubMed: 38863182
DOI: 10.12659/AJCR.943306 -
Nature Communications Jun 2024More than 10 million people suffer from lung diseases caused by the pathogenic fungus Aspergillus fumigatus. Azole antifungals represent first-line therapeutics for most...
More than 10 million people suffer from lung diseases caused by the pathogenic fungus Aspergillus fumigatus. Azole antifungals represent first-line therapeutics for most of these infections but resistance is rising, therefore the identification of antifungal targets whose inhibition synergises with the azoles could improve therapeutic outcomes. Here, we generate a library of 111 genetically barcoded null mutants of Aspergillus fumigatus in genes encoding protein kinases, and show that loss of function of kinase YakA results in hypersensitivity to the azoles and reduced pathogenicity. YakA is an orthologue of Candida albicans Yak1, a TOR signalling pathway kinase involved in modulation of stress responsive transcriptional regulators. We show that YakA has been repurposed in A. fumigatus to regulate blocking of the septal pore upon exposure to stress. Loss of YakA function reduces the ability of A. fumigatus to penetrate solid media and to grow in mouse lung tissue. We also show that 1-ethoxycarbonyl-beta-carboline (1-ECBC), a compound previously shown to inhibit C. albicans Yak1, prevents stress-mediated septal spore blocking and synergises with the azoles to inhibit A. fumigatus growth.
Topics: Aspergillus fumigatus; Animals; Antifungal Agents; Protein Serine-Threonine Kinases; Fungal Proteins; Mice; Protein-Tyrosine Kinases; Dyrk Kinases; Azoles; Aspergillosis; Lung; Spores, Fungal; Female
PubMed: 38862481
DOI: 10.1038/s41467-024-48592-8 -
Turkish Journal of Ophthalmology Jun 2024A 78-year-old man with a history of lung cancer, chemotherapy, radiotherapy, and coronavirus disease 2019 infection experienced visual deterioration of two-weeks’...
A 78-year-old man with a history of lung cancer, chemotherapy, radiotherapy, and coronavirus disease 2019 infection experienced visual deterioration of two-weeks’ duration in his right eye. There was multifocal, yellowish-white retinitis foci, vascular engorgement, and scattered intraretinal hemorrhages extending from posterior pole to retinal periphery in the right eye, whereas the left eye was normal. Intravitreal vancomycin, ceftazidime, clindamycin, and dexamethasone were given for endogenous endophthalmitis initially. Vitreous culture confirmed the presence of Aspergillus lentulus, and he was treated with intravitreal amphotericin-B and voriconazole injections together with systemic amphotericin-B, voriconazole, posaconazole, and micafungin therapy. During follow-up, vitreoretinal surgery was performed because of rhegmatogenous retinal detachment, and he received one additional cycle of chemotherapy due to recurrence of the cancer. Although the retina was attached, enucleation was eventually required due to painful red eye. Atypical squamous cells beneath the neurosensory retina suggesting metastasis were noted on histopathological examination. Timely ocular examination is crucial for any immunocompromised patient having ocular symptoms. High level of suspicion for a fungal etiology is a must in these patients.
Topics: Humans; Endophthalmitis; Male; Aged; Eye Infections, Fungal; Immunocompromised Host; Lung Neoplasms; Aspergillosis; Aspergillus; Antifungal Agents; COVID-19; Vitreous Body; Intravitreal Injections; SARS-CoV-2
PubMed: 38860516
DOI: 10.4274/tjo.galenos.2024.44045 -
BMC Complementary Medicine and Therapies Jun 2024In the past few decades, there has been a notable rise in the occurrence of several types of candidiasis. Candida albicans is the most common cause of superficial fungal...
In the past few decades, there has been a notable rise in the occurrence of several types of candidiasis. Candida albicans is the most common cause of superficial fungal infections in humans. In this study, plumieride, one of the major iridoids from Plumeria obtusa L. leaves, was isolated and investigated for its potential against Candida albicans (CA)-induced dermatitis in mice. qRT-PCR was done to assess the impact of plumieride on the expression of the major virulence genes of CA. Five groups (n = 7) of adult male BALB/c mice were categorized into: group I: non-infected mice; group II: mice infected intradermally with 10-10 CFU/mL of CA; group III: CA-infected mice treated with standard fluconazole (50 mg/kg bwt.); group IV and V: CA-infected mice treated with plumieride (25- and 50 mg/kg. bwt., respectively). All the treatments were subcutaneously injected once a day for 3 days. Skin samples were collected on the 4th day post-inoculation to perform pathological, microbial, and molecular studies. The results of the in vitro study proved that plumieride has better antifungal activity than fluconazole, manifested by a wider zone of inhibition and a lower MIC. Plumieride also downregulated the expression of CA virulence genes (ALS1, Plb1, and Hyr1). CA-infected mice showed extensive dermatitis, confirmed by strong iNOS, TNF-α, IL-1β, and NF-κB genes or immune expressions. Whereas the treatment of CA-infected mice with plumieride significantly reduced the microscopic skin lesions and modulated the expression of all measured proinflammatory cytokines and inflammatory markers in a dose-dependent manner. Plumieride interfered with the expression of C. albicans virulence factors and modulated the inflammatory response in the skin of mice infected with CA.
Topics: Animals; Mice; Mice, Inbred BALB C; Male; Candida albicans; Antifungal Agents; Iridoids; Anti-Inflammatory Agents; Candidiasis; Disease Models, Animal
PubMed: 38858704
DOI: 10.1186/s12906-024-04508-z