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Frontiers in Cellular and Infection... 2023Mucormycosis (MCR) is an emerging and frequently lethal fungal infection caused by the Mucorales family, with , , and , accounting for > 90% of all cases. MCR is seen in... (Review)
Review
Mucormycosis (MCR) is an emerging and frequently lethal fungal infection caused by the Mucorales family, with , , and , accounting for > 90% of all cases. MCR is seen in patients with severe immunosuppression such as those with hematologic malignancy or transplantation, Diabetes Mellitus (DM) and diabetic ketoacidosis (DKA) and immunocompetent patients with severe wounds. The recent SARS COV2 epidemy in India has resulted in a tremendous increase in MCR cases, typically seen in the setting of uncontrolled DM and corticosteroid use. In addition to the diversity of affected hosts, MCR has pleiotropic clinical presentations, with rhino-orbital/rhino-cerebral, sino-pulmonary and necrotizing cutaneous forms being the predominant manifestations. Major insights in MCR pathogenesis have brought into focus the host receptors (GRP78) and signaling pathways (EGFR activation cascade) as well as the adhesins used by Mucorales for invasion. Furthermore, studies have expanded on the importance of iron availability and the complex regulation of iron homeostasis, as well as the pivotal role of mycotoxins as key factors for tissue invasion. The molecular toolbox to study Mucorales pathogenesis remains underdeveloped, but promise is brought by RNAi and CRISPR/Cas9 approaches. Important recent advancements have been made in early, culture-independent molecular diagnosis of MCR. However, development of new potent antifungals against Mucorales remains an unmet need. Therapy of MCR is multidisciplinary and requires a high index of suspicion for initiation of early Mucorales-active antifungals. Reversal of underlying immunosuppression, if feasible, rapid DKA correction and in selected patients, surgical debulking are crucial for improved outcomes.
Topics: Humans; Mucormycosis; Antifungal Agents; COVID-19; Mucorales; Diabetes Mellitus; Iron
PubMed: 37808914
DOI: 10.3389/fcimb.2023.1254919 -
Frontiers in Cellular and Infection... 2023
Topics: Humans; Mucormycosis
PubMed: 37743863
DOI: 10.3389/fcimb.2023.1280784 -
Transplant International : Official... 2023Solid organ transplant (SOT) recipients have a higher risk of developing invasive mould diseases (IMD). Isavuconazole is a novel broad-spectrum azole active against... (Review)
Review
Solid organ transplant (SOT) recipients have a higher risk of developing invasive mould diseases (IMD). Isavuconazole is a novel broad-spectrum azole active against spp. and Mucor, well tolerated, with an excellent bioavailability and predictable pharmacokinetics, that penetrates in most tissues rapidly, and has few serious adverse effects, including hepatic toxicity. Contrary to other broad-spectrum azoles, such as voriconazole and posaconazole, isavuconazole appears to show significant smaller drug-drug interactions with anticalcineurin drugs. We have performed an extensive literature review of the experience with the use of isavuconazole in SOT, which included the SOTIS and the ISASOT studies, and published case reports. More than 140 SOT recipients treated with isavuconazole for IMD were included. Most patients were lung and kidney recipients treated for an infection. Isavuconazole was well tolerated (less than 10% of patients required treatment discontinuation). The clinical responses appeared comparable to that found in other high-risk patient populations. Drug-drug interactions with immunosuppressive agents were manageable after the reduction of tacrolimus and the adjustment of mTOR inhibitors at the beginning of treatment. In conclusion, isavuconazole appears to be a reasonable option for the treatment of IMD in SOT. More clinical studies are warranted.
Topics: Humans; Antifungal Agents; Aspergillosis; Nitriles; Organ Transplantation; Transplant Recipients; Voriconazole
PubMed: 38161768
DOI: 10.3389/ti.2023.11845 -
Microorganisms Jul 2023Fungal osteomyelitis is considered a rare disease, and the published literature mainly comprises case reports, case series and narrative reviews. A systematic review was... (Review)
Review
Fungal osteomyelitis is considered a rare disease, and the published literature mainly comprises case reports, case series and narrative reviews. A systematic review was undertaken to provide a practice-based global perspective on this disease, focusing on epidemiology and treatment strategies. We searched MEDLINE, EMBASE and Cochrane Library between the 3rd and 8th of March 2023 using a predefined search string. We included studies with at least one patient with a diagnosis of fungal osteomyelitis published before the 1st of January 2023. We included all study designs except for reviews, and we excluded non-English languages and grey literature. After exclusion, 678 studies, mostly case reports, were included. Descriptive analysis was performed on 1072 patients. The most common aetiological agent was (26.5%), followed by (20.7%) and (16.8%), and the bones most frequently involved were the vertebrae. We described the characteristics of patients divided by site of infection, and we found that diabetes mellitus, disseminated fungal infection, surgery and local lesion were major risk factors. We also successfully associated duration of treatment with outcome. We provided a general overview of this rare disease, and we highlighted the need for high-quality investigations on the subject.
PubMed: 37513000
DOI: 10.3390/microorganisms11071828 -
Gastroenterology Research Oct 2023Mucormycosis is a devastating fungal infection that is usually seen in immunocompromised hosts. It is caused by fungi of the subphylum , order , with most cases caused... (Review)
Review
Mucormycosis is a devastating fungal infection that is usually seen in immunocompromised hosts. It is caused by fungi of the subphylum , order , with most cases caused by , , or species. It can involve any organ system and can disseminate in severe cases. Lately, there has been an increased number of reports for mucormycosis infection in immunocompetent patients. Gastrointestinal system involvement is rare compared to other organ systems but has been increasingly reported in the literature. Mucormycosis can affect any part of the gastrointestinal tract and lead to different presentations depending on the area of involvement. Due to the paucity of the condition, there has been no specific guidelines on how to treat gastrointestinal mucormycosis. In this review, we discuss the risk factors of gastrointestinal mucormycosis, clinical presentation, approach to diagnosis, and most recent treatment modalities for gastrointestinal mucormycosis.
PubMed: 37937225
DOI: 10.14740/gr1662 -
3 Biotech Jul 2023The COVID-19 survivors and long-term steroid administered patients exhibit a variety of fungal co-infections. The lives of COVID-19 patients and survivors are hampered... (Review)
Review
The COVID-19 survivors and long-term steroid administered patients exhibit a variety of fungal co-infections. The lives of COVID-19 patients and survivors are hampered by fungal species of the genera , , and . There have been cases of mucormycosis, aspergillosis, and candidiasis in COVID-19 patients. The treatments given to these opportunistic fungal infections include polyene like amphotericin B, azoles including imidazoles like ketoconazole, miconazole, and triazoles like fluconazole, voriconazole, itraconazole, Echinocandin derivatives like- caspofungin, micafungin, immunomodulatory therapy, granulocyte transfusion, etc. A successful recovery and the reduction of fatalities depend on prompt diagnosis and treatment. To reduce mortality, advanced techniques to identify such uncommon infections at a very early stage are necessary. This review's goal is to provide a summary of the systemic and superficial opportunistic fungal infections that the COVID-19 survivors were dealing with, including information on illness incidence, pathogenicity, and treatment.
PubMed: 37309405
DOI: 10.1007/s13205-023-03648-2 -
Microbial Ecology Oct 2023Fungi can colonize organic matter present in subterranean sites and have a significant role as dwellers in different microniches of cave habitats. In order to analyze...
Fungi can colonize organic matter present in subterranean sites and have a significant role as dwellers in different microniches of cave habitats. In order to analyze the content of airborne fungal propagules in different parts of "Stopića Cave," a touristic site in Serbia, air sampling was carried out in three seasons during 2020, prior to and during the onset of COVID-19 pandemic. Culturable mycobiota was identified using both microscopic techniques and ITS region/BenA gene barcoding, while multivariate analyses were employed to establish the link between fungal taxa and different environmental factors. The maximal measured fungal propagule concentrations were recorded during spring sampling which were based on fungal propagule concentration categories; the cave environment matches the category V. A total of 29 fungal isolates were identified, while Aspergillus, Cladosporium, Fusarium, Lecanicillium, Mucor, and Penicillium were the most diverse genera. According to the trophic mode, most of the isolated fungal species were pathotrophs (75.86%), but when regarding ecological guilds, the most dominant were undefined saprobes and animal pathogens (41.38% for each). Show caves are especially vulnerable to human impacts, and the fungal propagules' concentration within the caves could be good indices for the level of ecological disturbance.
Topics: Animals; Humans; Fungi; Caves; Serbia; Pandemics; COVID-19; Seasons; Air Microbiology; Environmental Monitoring
PubMed: 37000232
DOI: 10.1007/s00248-023-02214-w -
Frontiers in Cellular and Infection... 2023The identification of by metagenomic next-generation sequencing (mNGS) remains a challenging task due to the difficulty of nucleic acid extraction. The objective of...
PURPOSE
The identification of by metagenomic next-generation sequencing (mNGS) remains a challenging task due to the difficulty of nucleic acid extraction. The objective of this study was to determine whether mNGS could provide an accurate and efficient method for detecting invasive pulmonary (IPA) in immunocompromised patients (ICP).
METHODS
A total of 133 ICP admitted to the ICU between January 2020 and September 2022 were enrolled in the study, of which 46 were diagnosed with IPA and 87 were non-IPA cases. The bronchoalveolar lavage fluid (BALF) was analyzed for the presence of and other co-pathogens using mNGS, and its diagnostic performance was compared to conventional microbial tests (CMTs) that included smear, cultures, serum and BALF galactomannan (GM) test. Clinical composite diagnosis was used as the reference standard.
RESULTS
mNGS had a sensitivity, specificity, and accuracy of 82.6%, 97.7%, and 92.5%, respectively, in diagnosing IPA. These findings were comparable to those of the combination of multiple CMTs. Interestingly, the sensitivity of mNGS was superior to that of any single CMT method, as demonstrated by comparisons with smears (8.7%, < 0.001), culture (39.1%, < 0.001), serum GM (23.9%, < 0.001) and BALF GM (69.6%, = 0.031). mNGS was capable of accurately distinguish strains of genus, with a consistency of 77.8% with culture. Furthermore, mNGS also identified , , , and spp. in culture-negative cases. The sequencing reads of by mNGS exhibited extensive variation, ranging from 11 to1702. A positive correlation was observed between the optical density index of BALF GM and unique reads by mNGS (r = 0.607, = 0.001) in BALF-GM positive patients. Notably, mNGS was able to diagnose 35 out of 37 cases with mixed infection, with and being the most common co-pathogens.
CONCLUSIONS
mNGS presents a feasible and remarkably sensitive approach for detecting in ICP, thereby serving as a valuable adjunctive tool to CMT. Furthermore, mNGS's ability to accurately identify fungal species and co-pathogens can assist in guiding appropriate antimicrobial therapy.
Topics: Humans; Retrospective Studies; Aspergillosis; Invasive Pulmonary Aspergillosis; High-Throughput Nucleotide Sequencing; Immunocompromised Host
PubMed: 38188627
DOI: 10.3389/fcimb.2023.1209724 -
Gut Microbes 2024The fungal microbiota plays an important role in the pathogenesis of alcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD). In this study,...
The fungal microbiota plays an important role in the pathogenesis of alcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD). In this study, we aimed to compare changes of the fecal fungal microbiota between patients with ALD and NAFLD and to elucidate patterns in different disease stages between the two conditions. We analyzed fungal internal transcribed spacer 2 (ITS2) sequencing using fecal samples from a cohort of 48 patients with ALD, 78 patients with NAFLD, and 34 controls. The fungal microbiota differed significantly between ALD and NAFLD. The genera , , , and the species (), (), () were significantly increased in patients with ALD, whereas the genera and were significantly increased in the NAFLD cohort. We identified the fungal signature consisting of , , , and to have the highest discriminative ability to detect ALD vs NAFLD with an area under the curve (AUC) of 0.93. When stratifying the ALD and NAFLD cohorts by fibrosis severity, the fungal signature with the highest AUC of 0.92 to distinguish ALD F0-F1 vs NAFLD F0-F1 comprised , , , , and . For more advanced fibrosis stages (F2-F4), the fungal signature composed of , , , and achieved the highest AUC of 0.99 to differentiate ALD from NAFLD. This is the first study to identify a fungal signature to differentiate two metabolic fatty liver diseases from each other, specifically ALD from NAFLD. This might have clinical utility in unclear cases and might hence help shape treatment approaches. However, larger studies are required to validate this fungal signature in other populations of ALD and NAFLD.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; Liver Diseases, Alcoholic; Fibrosis; Mycobiome; Liver; Liver Cirrhosis
PubMed: 38298161
DOI: 10.1080/19490976.2024.2307586 -
Frontiers in Microbiology 2023Medicinal and recreational uses of , commonly known as cannabis or hemp, has increased following its legalization in certain regions of the world. Cannabis and hemp... (Review)
Review
Medicinal and recreational uses of , commonly known as cannabis or hemp, has increased following its legalization in certain regions of the world. Cannabis and hemp plants interact with a community of microbes (i.e., the phytobiome), which can influence various aspects of the host plant. The fungal composition of the phytobiome (i.e., mycobiome) currently consists of over 100 species of fungi, which includes phytopathogens, epiphytes, and endophytes, This mycobiome has often been understudied in research aimed at evaluating the safety of cannabis products for humans. Medical research has historically focused instead on substance use and medicinal uses of the plant. Because several components of the mycobiome are reported to produce toxic secondary metabolites (i.e., mycotoxins) that can potentially affect the health of humans and animals and initiate opportunistic infections in immunocompromised patients, there is a need to determine the potential health risks that these contaminants could pose for consumers. This review discusses the mycobiome of cannabis and hemp flowers with a focus on plant-infecting and toxigenic fungi that are most commonly found and are of potential concern (e.g., and spp.). We review current regulations for molds and mycotoxins worldwide and review assessment methods including culture-based assays, liquid chromatography, immuno-based technologies, and emerging technologies for these contaminants. We also discuss approaches to reduce fungal contaminants on cannabis and hemp and identify future research needs for contaminant detection, data dissemination, and management approaches. These approaches are designed to yield safer products for all consumers.
PubMed: 37928692
DOI: 10.3389/fmicb.2023.1278189