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Journal of Medical Case Reports Mar 2022Scedosporium apiospermum, an opportunistic and filamentous fungus, is a rarely seen ocular entity that is difficult to identify and heal. We report a challenging case...
BACKGROUND
Scedosporium apiospermum, an opportunistic and filamentous fungus, is a rarely seen ocular entity that is difficult to identify and heal. We report a challenging case of S. apiospermium keratitis and discuss the treatment modalities in light of previous studies.
CASE PRESENTATION
A 30-year-old Turkish farmer with a history of contact lens misuse presented to our clinic with a painful corneal abscess and severe vision loss in his left eye. S. apiospermum was identified by spectrophotometric analysis. The patient was successfully treated with therapeutic penetrating keratoplasty, but was resistant to fluconazole and amphotericin B and susceptible but unresponsive to voriconazole.
CONCLUSION
S. apiospermum keratitis should be considered in the differential diagnosis of immunocompromised and immunocompetent patients with history of ocular trauma and contact lens use, especially those who do not respond to treatment.
Topics: Adult; Antifungal Agents; Eye Infections, Fungal; Humans; Keratitis; Scedosporium; Voriconazole
PubMed: 35241155
DOI: 10.1186/s13256-022-03315-9 -
Cureus Aug 2023sinusitis is an opportunistic fungal infection that is difficult to treat due to its inherent resistance to many antifungal agents. Infections may cause both localized...
sinusitis is an opportunistic fungal infection that is difficult to treat due to its inherent resistance to many antifungal agents. Infections may cause both localized or disseminated disease usually in skin and soft tissues. Immunocompetent persons are typically unaffected and disseminated disease occurs in immunocompromised hosts. is a common hyaline mold causing sinopulmonary disease in those with hematologic malignancies and neutropenia. A 38-year-old Caucasian male with a medical history significant for HIV with intermittent treatment compliance, high-grade diffuse large B cell lymphoma (DLBCL) on chemotherapy, and hemophagocytic lymphohistiocytosis (HLH) presented with right-sided facial pain and fever. Maxillofacial computed tomography (CT) showed thickening and opacification of the sphenoid and maxillary sinuses concerning for fungal sinusitis. Endoscopic transsphenoidal debridement showed fungal growth of and the patient's blood cultures were ultimately negative. The patient underwent debridement of fungal sinusitis as well as right medial maxillectomy and ethmoidectomy. A three-month course of voriconazole was started and completed with weekly liver enzyme tests to monitor medication side effects. He has since been observed well as an outpatient with his oncologist after three months loss to follow-up and his infection has resolved.
PubMed: 37711912
DOI: 10.7759/cureus.43475 -
The Canadian Journal of Infectious... Jan 1999Fungemia due to Scedosporium prolificans is described in a young woman with a relapse of acute lymphoblastic leukemia. Several days after starting reinduction...
Fungemia due to Scedosporium prolificans is described in a young woman with a relapse of acute lymphoblastic leukemia. Several days after starting reinduction chemotherapy, the patient presented with fever, neutropenia and blood cultures showing fungi on Gram stain. The patient died despite therapy with antifungal agents, including fluconazole and amphotericin B. Fungi grew from blood cultures, and was subsequently identified as Scedosporium prolificans.
PubMed: 22346375
DOI: 10.1155/1999/635193 -
Antimicrobial Agents and Chemotherapy Oct 2020is an opportunistic fungal pathogen with low susceptibility to current antifungal drugs. Here, we tested the susceptibility of 8 drugs against 42 clinical isolates....
is an opportunistic fungal pathogen with low susceptibility to current antifungal drugs. Here, we tested the susceptibility of 8 drugs against 42 clinical isolates. All isolates showed high MICs to voriconazole (MIC>16 μg/ml), itraconazole (MIC>16 μg/ml), posaconazole (MIC>16 μg/ml), isavuconazole (MIC>16 μg/ml), amphotericin B (MIC>16 μg/ml), and terbinafine (MIC>64 μg/ml) and high minimum effective concentrations (MECs) to micafungin (MEC>8 μg/ml), with the exception of miltefosine showing an MIC value of 4 μg/ml. We examined six different drug combinations and found that the combination of voriconazole and terbinafine achieved the most synergistic effort against We then annotated the whole genome and located its and genes. We completely sequenced the two genes to determine if any mutation would be related to azole and echinocandin resistance in We found no amino acid changes in Cyp51 protein and no tandem repeats in the 5' upstream region of the gene. However, we identified three intrinsic amino acid residues (G138S, M220I, and T289A) in the Cyp51 protein that were linked to azole resistance. Likewise, two intrinsic amino acid residues (F639Y, W695F) that have reported to confer echinocandin resistance were found in Fks1 hot spot regions. In addition, three new amino acid alterations (D440A, S634R, and H1245R) were found outside Fks1 hot spot regions, and their contributions to echinocandin resistance need future investigation. Overall, our findings support the notion that is intrinsically resistant to azoles and echinocandins.
Topics: Antifungal Agents; Aspergillus fumigatus; Azoles; Drug Resistance, Fungal; Echinocandins; Fungal Proteins; Microbial Sensitivity Tests; Scedosporium
PubMed: 32816726
DOI: 10.1128/AAC.00318-20 -
Infection and Drug Resistance 2021Cystic fibrosis (CF) is an inherited multisystem disease characterised by bronchiectasis and chronic respiratory infections which eventually cause end stage lung... (Review)
Review
Cystic fibrosis (CF) is an inherited multisystem disease characterised by bronchiectasis and chronic respiratory infections which eventually cause end stage lung disease. Lung transplantation (LTx) is a well-established treatment option for patients with CF-associated lung disease, improving survival and quality of life. Navigating recurrent infections in the setting of LTx is often difficult, where immune suppression must be balanced against the constant threat of infection. Sepsis/infections are one of the major contributors to post-LTx mortality and multiresistant organisms (eg, complex, complex, spp. and spp.) pose a significant threat to survival. This review will summarize current and novel therapies to assist with the management of multiresistant bacterial, mycobacterial, viral and fungal infections which threaten the CF LTx cohort.
PubMed: 34916813
DOI: 10.2147/IDR.S301153 -
BMC Microbiology Jan 2022This study was aimed to determine the potency of Minocycline (MIN) and azoles, including itraconazole (ITR), voriconazole (VOR) and posaconazole (POS) against...
BACKGROUND
This study was aimed to determine the potency of Minocycline (MIN) and azoles, including itraconazole (ITR), voriconazole (VOR) and posaconazole (POS) against Scedosporium and Lomentospora species.
RESULTS
This study revealed that MIN exhibited no significant antifungal activity against any of the tested strains, whereas in vitro combination of MIN with ITR, VOR or POS showed satisfactory synergistic effects against 8 (80%), 1 (10%), and 9 (90%) strains, respectively. Moreover, combined use of MIN with azoles decreased the minimum inhibitory concentration (MIC) range from 5.33-16 μg/ml to 1-16 μg/ml for ITR, from 0.42-16 μg/ml to 0.21-16 μg/ml for VOR, and from 1.33-16 μg/ml to 0.33-16 μg/ml for POS. Meanwhile, no antagonistic interactions were observed between the above combinations. The G. mellonella infection model demonstrated the in vivo synergistic antifungal effect of MIN and azoles.
CONCLUSIONS
The present study demonstrated that combinations between MIN and azoles lead to synergistic antimicrobial effects on Scedosporium and Lomentospora species, while showing a potential for overcoming and preventing azole resistance.
Topics: Animals; Antifungal Agents; Ascomycota; Azoles; Drug Resistance, Fungal; Drug Synergism; Humans; Larva; Microbial Sensitivity Tests; Minocycline; Moths; Scedosporium
PubMed: 35016611
DOI: 10.1186/s12866-021-02433-6 -
Antimicrobial Agents and Chemotherapy Sep 2021Clinically relevant members of the / species complex and Lomentospora prolificans are generally resistant against currently available systemic antifungal agents , and...
Clinically relevant members of the / species complex and Lomentospora prolificans are generally resistant against currently available systemic antifungal agents , and infection due to these species is difficult to treat. We studied the efficacy of a new fungicidal agent, olorofim (formerly F901318), against scedosporiosis and lomentosporiosis in neutropenic animals. Cyclophosphamide-immunosuppressed CD-1 mice infected by Scedosporium apiospermum, Pseudallescheria boydii (Scedosporium boydii), and Lomentospora prolificans were treated by intraperitoneal administration of olorofim (15 mg/kg of body weight every 8 h for 9 days). The efficacy of olorofim treatment was assessed by the survival rate at 10 days postinfection, levels of serum (1-3)-β-d-glucan (BG), histopathology, and fungal burdens of kidneys 3 days postinfection. Olorofim therapy significantly improved survival compared to that of the untreated controls; 80%, 100%, and 100% of treated mice survived infection by Scedosporium apiospermum, Pseudallescheria boydii, and Lomentospora prolificans, respectively, while less than 20% of the control mice (phosphate-buffered saline [PBS] treated) survived at 10 days postinfection. In the olorofim-treated neutropenic CD-1 mice infected with any of the three species, serum BG levels were significantly suppressed and fungal DNA detected in the target organs was significantly lower than in controls. Furthermore, histopathology of kidneys revealed no or only a few lesions with hyphal elements in the olorofim-treated mice, while numerous fungal hyphae were present in control mice. These results indicate olorofim to be a promising therapeutic agent for systemic scedosporiosis/lomentosporiosis, devastating emerging fungal infections that are difficult to treat with currently available antifungals.
Topics: Acetamides; Animals; Antifungal Agents; Invasive Fungal Infections; Mice; Piperazines; Pyrimidines; Pyrroles; Scedosporium
PubMed: 34252298
DOI: 10.1128/AAC.00434-21 -
Journal of Fungi (Basel, Switzerland) Feb 2023and are a group of filamentous fungi with some clinically relevant species causing either localized, invasive, or disseminated infections. Understanding how the host...
and are a group of filamentous fungi with some clinically relevant species causing either localized, invasive, or disseminated infections. Understanding how the host immune response is activated and how fungi interact with the host is crucial for a better management of the infection. In this context, an α-glucan has already been described in , which plays a role in the inflammatory response. In the present study, an α-glucan has been characterized in and was shown to be exposed on the fungal surface. The α-glucan is recognized by peritoneal macrophages and induces oxidative burst in activated phagocytes. Its recognition by macrophages is mediated by receptors that include Dectin-1 and Mincle, but not TLR2 and TLR4. These results contribute to the understanding of how 's and 's physiopathologies are developed in patients suffering with scedosporiosis and lomentosporiosis.
PubMed: 36983458
DOI: 10.3390/jof9030291 -
Journal of Fungi (Basel, Switzerland) Feb 2023The incidence of invasive sino-pulmonary diseases due to non- hyaline molds is increasing due to an enlarging and evolving population of immunosuppressed hosts as well... (Review)
Review
The incidence of invasive sino-pulmonary diseases due to non- hyaline molds is increasing due to an enlarging and evolving population of immunosuppressed hosts as well as improvements in the capabilities of molecular-based diagnostics. Herein, we review the following opportunistic pathogens known to cause sinopulmonary disease, the most common manifestation of hyalohyphomycosis: spp., spp., , spp., spp., spp., , , species complex, , and species. To facilitate an understanding of the epidemiology and clinical features of sino-pulmonary hyalohyphomycoses in the context of host immune impairment, we utilized a host-based approach encompassing the following underlying conditions: neutropenia, hematologic malignancy, hematopoietic and solid organ transplantation, chronic granulomatous disease, acquired immunodeficiency syndrome, cystic fibrosis, and healthy individuals who sustain burns, trauma, or iatrogenic exposures. We further summarize the pre-clinical and clinical data informing antifungal management for each pathogen and consider the role of adjunctive surgery and/or immunomodulatory treatments to optimize patient outcome.
PubMed: 36836326
DOI: 10.3390/jof9020212 -
Frontiers in Cellular and Infection... 2022and infections in humans are generally chronic and stubborn. The use of azoles alone cannot usually inhibit the growth of these fungi. To further explore the combined...
and infections in humans are generally chronic and stubborn. The use of azoles alone cannot usually inhibit the growth of these fungi. To further explore the combined effect of multiple drugs and potential mechanisms of action, we tested the antifungal effects of tacrolimus (FK506) and everolimus in combination with azoles and on 15 clinical strains of / species and detected the level of Rhodamine 6G, ROS activity, and apoptosis. The results showed that the combinations of tacrolimus with itraconazole, voriconazole, and posaconazole showed synergistic effects on 9 strains (60%), 10 strains (73%), and 7 strains (47%), respectively, and the combinations of everolimus with itraconazole, voriconazole, and posaconazole showed synergistic effects on 8 strains (53%), 8 strains (53%), and 7 strains (47%), respectively. The synergistic effects might correspond to the elevated ROS activity (the tacrolimus + itraconazole group compared to the itraconazole group, ( < 0.05)), early apoptosis (itraconazole ( < 0.05) and voriconazole ( < 0.05) combined with everolimus), and late apoptosis (the tacrolimus + itraconazole group compared to the itraconazole group, ( < 0.01); the tacrolimus + posaconazole group compared to the posaconazole group, ( < 0.05)), but not inhibition of efflux pump activity. Our results suggested that a combination of tacrolimus or everolimus and azoles have a synergistic effect against . The synergistic mechanisms of action might be triggering excessive ROS activity and apoptosis, the survival rate of (sixth instar larvae) was significantly improved by tacrolimus alone, everolimus alone, azoles alone, and tacrolimus and everolimus combined with azoles separately ( < 0.05 for the tacrolimus group; < 0.01 for the everolimus group and the itraconazole group; = 0.0001 for the tacrolimus and posaconazole group; < 0.0001 for other groups except the everolimus and itraconazole group, everolimus and posaconazole group, and tacrolimus and itraconazole group). From the results, we infer that the combination of tacrolimus or everolimus with azoles has obvious synergistic effect on , and might enhance the level of apoptosis and necrosis. However, the synergistic effects were not related to the efflux pump. In conclusion, from our and study, tacrolimus and everolimus combined with azoles may have a synergistic effect in the treatment against , improving the drug activity of azoles and promoting a better prognosis for patients.
Topics: Ascomycota; Azoles; Everolimus; Humans; Itraconazole; Microbial Sensitivity Tests; Reactive Oxygen Species; Scedosporium; Tacrolimus; Voriconazole
PubMed: 35493742
DOI: 10.3389/fcimb.2022.864912