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IDCases 2024Scedosporium, a widespread filamentous fungus found in diverse environments, has experienced a rise in cases due to escalating malignancies and chronic...
Scedosporium, a widespread filamentous fungus found in diverse environments, has experienced a rise in cases due to escalating malignancies and chronic immunosuppression. Clinical manifestations span mycetoma, airway involvement, and various infections, with osteomyelitis being a notable complication. We present a case of a 77-year-old female initially displaying cutaneous Scedosporium signs, which progressed to osteomyelitis. The patient, with a history of trauma, chronic low dose steroid use, and underlying conditions, presented with a foot injury caused by her dog. Despite initial management, worsening symptoms led to the identification of Scedosporium. A comprehensive approach involving debridement, antimicrobial therapy, and reduction of immunosuppression resulted in clinical improvement. The rarity of zoonotic transmission, diagnostic challenges, and antifungal efficacy are also discussed. The patient's positive trajectory emphasizes early diagnosis, targeted treatment, and vigilance in managing immunosuppression. An adaptable treatment protocol is proposed based on risk factors. Considering the rising opportunistic fungal infections and delayed culture results, initiating empirical antifungals based on clinical judgment and regional prevalence is vital for favorable outcomes.
PubMed: 38327878
DOI: 10.1016/j.idcr.2024.e01929 -
Life (Basel, Switzerland) Jan 2024There has been a substantial increase in the number of cases of invasive fungal infections worldwide, which is associated with a growing number of immunosuppressed... (Review)
Review
There has been a substantial increase in the number of cases of invasive fungal infections worldwide, which is associated with a growing number of immunosuppressed patients and a rise in antifungal resistance. Some fungi that were previously considered harmless to humans have become emerging pathogens. One of them is , a ubiquitous filamentous fungus commonly found in the environment, especially in the air and soil. belongs to a bigger group of hyaline fungi that cause hyalohyphomycosis, a fungal infection caused by fungi with colorless hyphae. Although this is a heterogeneous group of fungi, there are similarities regarding their ubiquity, ways of transmission, affected patients, and difficulties in diagnostics and treatment. In hyalohyphomycosis, the skin is one of the most affected organs, which is why the involvement of dermatologists is crucial for the initial assessment, since the timely recognition and early diagnosis of this condition can prevent life-threatening infections and death. In this review, we covered cutaneous hyalohyphomycosis caused by and other fungi in the same group, including , , , , , and genera.
PubMed: 38276283
DOI: 10.3390/life14010154 -
Therapeutic Advances in Infectious... 2024Invasive fungal infections are increasingly encountered with the expansion of iatrogenic immunosuppression, including not only solid organ and hematopoietic stem cell... (Review)
Review
Invasive fungal infections are increasingly encountered with the expansion of iatrogenic immunosuppression, including not only solid organ and hematopoietic stem cell transplant recipients but also patients with malignancies or autoimmune diseases receiving immunomodulatory therapies, such as Bruton Tyrosine Kinase (BTK) inhibitor. Their attributable mortality remains elevated, part of which is a contribution from globally emerging resistance in both molds and yeasts. Because antifungal susceptibility test results are often unavailable or delayed, empiric and tailored antifungal approaches including choice of agent(s) and use of combination therapy are heterogeneous and often based on clinician experience with knowledge of host's net state of immunosuppression, prior antifungal exposure, antifungal side effects and interaction profile, clinical severity of disease including site(s) of infection and local resistance data. In this review, we aim to summarize previous recommendations and most recent literature on treatment of invasive mold and yeast infections in adults to guide optimal evidence-based therapeutic approaches. We review the recent data that support use of available antifungal agents, including the different triazoles that have now been studied in comparison to previously preferred agents. We discuss management of complex infections with specific emerging fungi such as spp., spp., , and . We briefly explore newer antifungal agents or formulations that are now being investigated to overcome therapeutic pitfalls, including but not limited to olorofim, rezafungin, fosmanogepix, and encochleated Amphotericin B. We discuss the role of surgical resection or debridement, duration of treatment, follow-up modalities, and need for secondary prophylaxis, all of which remain challenging, especially in patients chronically immunocompromised or awaiting more immunosuppressive therapies.
PubMed: 38249542
DOI: 10.1177/20499361231224980 -
Journal of Fungi (Basel, Switzerland) Jan 2024Most reported members of that have been reported originate from the terrestrial environment, where they act as saprobes or plant pathogens. However, our understanding...
Most reported members of that have been reported originate from the terrestrial environment, where they act as saprobes or plant pathogens. However, our understanding of their species diversity and distribution in the marine environment remains vastly limited, with only 22 species in nine genera having been reported so far. A survey of the fungal diversity in intertidal areas of China's mainland has revealed the discovery of several strains from 14 marine algae and 15 sediment samples. Based on morphological characteristics and LSU-ITS-- multilocus phylogeny using Bayesian inference and maximum likelihood methods, 48 strains were identified as 18 species belonging to six genera. Among these, six new species were discovered: , , , , and . Additionally, the worldwide distribution of the species within this family across various marine habitats was briefly reviewed and discussed. Our study expands the knowledge of species diversity and distribution of in the marine environment.
PubMed: 38248952
DOI: 10.3390/jof10010045 -
Medical Mycology Jan 2024Infections with Scedosporium spp. are emerging in the past two decades and are associated with a high mortality rate. Microbiological detection can be associated with...
Infections with Scedosporium spp. are emerging in the past two decades and are associated with a high mortality rate. Microbiological detection can be associated with either colonization or infection. Evolution from colonization into infection is difficult to predict and clinical management upon microbiological detection is complex. Microbiological samples from 2015 to 2021 were retrospectively analyzed in a single tertiary care center. Classification into colonization or infection was performed upon first microbiological detection. Clinical evolution was observed until July 2023. Further diagnostic procedures after initial detection were analyzed. Among 38 patients with microbiological detection of Scedosporium spp., 10 were diagnosed with an infection at the initial detection and two progressed from colonization to infection during the observation time. The main sites of infection were lung (5/12; 41.6%) followed by ocular sites (4/12; 33.3%). Imaging, bronchoscopy or biopsies upon detection were performed in a minority of patients. Overall mortality rate was similar in both groups initially classified as colonization or infection [30.7% and 33.3%, respectively (P = 1.0)]. In all patients where surgical debridement of site of infection was performed (5/12; 42%); no death was observed. Although death occurred more often in the group without eradication (3/4; 75%) compared with the group with successful eradication (1/8; 12.5%), statistical significance could not be reached (P = 0.053). As therapeutic management directly impacts patients' outcome, a multidisciplinary approach upon microbiological detection of Scedosporium spp. should be encouraged. Data from larger cohorts are warranted in order to analyze contributing factors favoring the evolution from colonization into infection.
Topics: Humans; Retrospective Studies; Scedosporium; Antifungal Agents; Clinical Relevance; Risk Factors
PubMed: 38242842
DOI: 10.1093/mmy/myae002 -
Antimicrobial Agents and Chemotherapy Feb 2024Manogepix is a potent new antifungal agent targeting the fungal Gwt1 enzyme. Manogepix has previously demonstrated potent activity against clinical isolates of both...
Manogepix is a potent new antifungal agent targeting the fungal Gwt1 enzyme. Manogepix has previously demonstrated potent activity against clinical isolates of both (except ) and species. This study determined the activity of manogepix and comparators against a large collection of infrequently encountered yeast and molds. Manogepix demonstrated potent activity against infrequently encountered yeasts exhibiting elevated MIC values to other drug classes, including spp. (MIC, 0.008/0.12 mg/L), () (MIC, 0.03/0.06 mg/L), (MIC, 0.016-0.06 mg/L), (MIC, 0.016 mg/L), and (MIC, 0.03/0.12 mg/L). Similarly, manogepix was active against infrequently encountered mold isolates and strains exhibiting elevated MIC/MEC values to echinocandins, azoles, and amphotericin B, including (MEC, 0.004 mg/L), spp. (MEC, 0.016/0.06 mg/L), () species complex (MEC, 0.016/0.03 mg/L), (MEC, 0.03/0.06 mg/L), (MEC, 0.008 mg/L), spp. (MEC, ≤0.008/0.016 mg/L), (MEC, 0.06 mg/L), (MEC range, 0.016-0.12 mg/L), and spp. (MEC, 0.03/0.06 mg/L). Manogepix demonstrated potent activity against a majority of the infrequently encountered yeast and mold isolates tested including strains with elevated MIC/MEC values to other drug classes. Additional clinical development of manogepix (fosmanogepix) in difficult-to-treat, resistant fungal infections is warranted.
Topics: Triazoles; Antifungal Agents; Fungi; Aminopyridines; Yeasts; Candida; Microbial Sensitivity Tests; Isoxazoles
PubMed: 38205999
DOI: 10.1128/aac.01132-23 -
Frontiers in Cellular and Infection... 2023Mucoromycosis is a highly aggressive angio-invasive disease of humans caused by fungi in the zygomycete order, Mucorales. While is the principal agent of mucoromycosis,...
Mucoromycosis is a highly aggressive angio-invasive disease of humans caused by fungi in the zygomycete order, Mucorales. While is the principal agent of mucoromycosis, other Mucorales fungi including , , , , and are able to cause life-threatening rhino-orbital-cerebral, pulmonary, gastro-intestinal and necrotising cutaneous infections in humans. Diagnosis of the disease currently relies on non-specific CT, lengthy and insensitive culture from invasive biopsy, and time-consuming histopathology of tissue samples. At present, there are no rapid antigen tests that detect Mucorales-specific biomarkers of infection, and which allow point-of-care diagnosis of mucoromycosis. Here, we report the development of an IgG2b monoclonal antibody (mAb), TG11, which binds to extracellular polysaccharide (EPS) antigens of between 20 kDa and 250 kDa secreted during hyphal growth of Mucorales fungi. The mAb is Mucorales-specific and does not cross-react with other yeasts and molds of clinical importance including , , , , and species. Using the mAb, we have developed a Competitive lateral-flow device that allows rapid (30 min) detection of the EPS biomarker in human serum and bronchoalveolar lavage (BAL), with a limit of detection (LOD) in human serum of ~100 ng/mL serum (~224.7 pmol/L serum). The LFD therefore provides a potential novel opportunity for detection of mucoromycosis caused by different Mucorales species.
Topics: Humans; Mucorales; Antibodies, Monoclonal; Aspergillus; Fusarium; Biomarkers
PubMed: 38145040
DOI: 10.3389/fcimb.2023.1305662 -
Heliyon Dec 2023To investigate the efficiency of amniotic membrane transplantation (AMT) combined with conjunctival flap covering surgery (CFCS) for patients with corneal perforations...
PURPOSE
To investigate the efficiency of amniotic membrane transplantation (AMT) combined with conjunctival flap covering surgery (CFCS) for patients with corneal perforations in fungal keratitis (FK).
METHODS
In this non-comparative, retrospective case series, 16 participants of corneal perforation in FK were successfully treated by a combination of multilayer AMT and bipedicle conjunctival flap with partial tenon's capsule. Corneal healing, recurrence of FK, visual acuity, and relevant complications were reported as outcome measures.
RESULTS
Sixteen patients (13 male, 3 female) had a mean age of 58.8 ± 10.3 (range 29-72) years. The mean diameter of corneal perforation was 1.9 ± 0.7 (range 0.5-2.8) mm. Corneal perforations healed and all the patients preserved their eyeballs. During the 11.0 ± 4.4 (range 6-18) months of follow-up, there was no recurrence of FK in any of these cases. Visual acuity improved in 15 eyes (93.8 %) and remained unchanged in 1 patient (6.3 %) who had no light perception when first admitted. All 6 patients who accepted secondary keratoplasty showed improved best corrected visual acuity of more than 4 lines. The most frequently found fungi were (6 of 16, 37.5 %) and (4 of 16, 25.0 %), followed by 1 (1 of 16, 6.3 %).
CONCLUSIONS
Combination AMT with CFCS is a safe and effective surgery for patients with corneal perforations in FK, particularly where eye banks and fresh corneas are not available. This surgery could preserve the integrity of the eyeball and avoid the recurrence of FK. Besides, it provides a greater opportunity for further optical keratoplasty.
PubMed: 38107269
DOI: 10.1016/j.heliyon.2023.e22693 -
IMA Fungus Dec 2023Emerging fungal pathogens are a global challenge for humankind. Many efforts have been made to understand the mechanisms underlying pathogenicity in bacteria, and OMICs...
Emerging fungal pathogens are a global challenge for humankind. Many efforts have been made to understand the mechanisms underlying pathogenicity in bacteria, and OMICs techniques are largely responsible for those advancements. By contrast, our limited understanding of opportunism and antifungal resistance is preventing us from identifying, limiting and interpreting the emergence of fungal pathogens. The genus Scedosporium (Microascaceae) includes fungi with high tolerance to environmental pollution, whilst some species can be considered major human pathogens, such as Scedosporium apiospermum and Scedosporium boydii. However, unlike other fungal pathogens, little is known about the genome evolution of these organisms. We sequenced two novel genomes of Scedosporium aurantiacum and Scedosporium minutisporum isolated from extreme, strongly anthropized environments. We compared all the available Scedosporium and Microascaceae genomes, that we systematically annotated and characterized ex novo in most cases. The genomes in this family were integrated in a Phylum-level comparison to infer the presence of putative, shared genomic traits in filamentous ascomycetes with pathogenic potential. The analysis included the genomes of 100 environmental and clinical fungi, revealing poor evolutionary convergence of putative pathogenicity traits. By contrast, several features in Microascaceae and Scedosporium were detected that might have a dual role in responding to environmental challenges and allowing colonization of the human body, including chitin, melanin and other cell wall related genes, proteases, glutaredoxins and magnesium transporters. We found these gene families to be impacted by expansions, orthologous transposon insertions, and point mutations. With RNA-seq, we demonstrated that most of these anciently impacted genomic features responded to the stress imposed by an antifungal compound (voriconazole) in the two environmental strains S. aurantiacum MUT6114 and S. minutisporum MUT6113. Therefore, the present genomics and transcriptomics investigation stands on the edge between stress resistance and pathogenic potential, to elucidate whether fungi were pre-adapted to infect humans. We highlight the strengths and limitations of genomics applied to opportunistic human pathogens, the multifactoriality of pathogenicity and resistance to drugs, and suggest a scenario where pressures other than anthropic contributed to forge filamentous human pathogens.
PubMed: 38049914
DOI: 10.1186/s43008-023-00128-3 -
IScience Nov 2023Although severe cases of invasive mycoses of different hypoxic and anoxic body parts have been reported, growth and drug susceptibility of fungal pathogens under...
Although severe cases of invasive mycoses of different hypoxic and anoxic body parts have been reported, growth and drug susceptibility of fungal pathogens under anaerobic conditions remains understudied. The current study evaluated anaerobic growth potential and drug susceptibility of environmental isolates under aerobic and anaerobic conditions. All tested strains showed equivalent growth and higher sensitivity to tested antifungal drugs under anaerobic conditions with lower minimum inhibitory concentration (MIC) as compared to aerobic conditions. Antifungal azoles were effective against isolates under both aerobic and anaerobic conditions. Most strains were resistant to antifungal echinocandins and polyenes under aerobic conditions but exhibited sensitivity under anaerobic conditions. This study provides evidence that resistance of to antifungal drugs varies with oxygen concentration and availability and suggests re-evaluating clinical breakpoints for antifungal compounds to treat invasive fungal infections more effectively.
PubMed: 37965151
DOI: 10.1016/j.isci.2023.108304