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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 -
Antimicrobial Agents and Chemotherapy Oct 2021and Fusarium species are emerging opportunistic pathogens, causing invasive fungal diseases in humans, particularly in immunocompromised patients. Biofilm-related...
and Fusarium species are emerging opportunistic pathogens, causing invasive fungal diseases in humans, particularly in immunocompromised patients. Biofilm-related infections are associated with increased morbidity and mortality. Here, we assessed the ability of Scedosporium apiospermum and Fusarium solani species complex (FSSC) isolates to form biofilms and evaluated the efficacy of deoxycholate amphotericin B (D-AMB), liposomal amphotericin B (L-AMB), and voriconazole (VRC), alone or in combination, against mature biofilms. Biofilm formation was assessed by safranin staining and spectrophotometric measurement of optical density. Planktonic and biofilm damage was assessed by XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt] reduction assay. Planktonic cell and biofilm MICs were determined as the minimum concentrations that caused ≥50% fungal damage compared to untreated controls. The combined activity of L-AMB (0.5 to 32 mg/liter) and VRC (0.125 to 64 mg/liter) against biofilms was determined by the checkerboard microdilution method and analyzed by the Bliss independence model. Biofilm MICs of D-AMB and L-AMB against S. apiospermum isolates were 1 and 2 mg/liter and against FSSC isolates were 0.5 and 1 mg/liter, respectively. Biofilm MICs of VRC against S. apiospermum and FSSC were 32 mg/liter and >256 mg/liter, respectively. Synergistic effects were observed at 2 to 4 mg/liter of L-AMB combined with 4 to 16 mg/liter of VRC against S. apiospermum biofilms (mean Δ ± standard error, 17% ± 3.7%). Antagonistic interactions were found at 0.5 to 4 mg/liter of L-AMB combined with 0.125 to 16 mg/liter of VRC against FSSC isolates, at -28% ± 2%. D-AMB and L-AMB were more efficacious against S. apiospermum and FSSC biofilms than VRC.
Topics: Amphotericin B; Antifungal Agents; Biofilms; Fusarium; Humans; Microbial Sensitivity Tests; Scedosporium; Voriconazole
PubMed: 34370583
DOI: 10.1128/AAC.00638-21 -
Internal Medicine (Tokyo, Japan) 2017Scedosporium prolificans is a fungus that has demonstrated resistance against most currently available antifungal agents and which causes a rapidly disseminating and...
Scedosporium prolificans is a fungus that has demonstrated resistance against most currently available antifungal agents and which causes a rapidly disseminating and potentially fatal infection. A 68-year-old woman presented with a fever and consolidation in the lung field. Her symptoms and inflammatory reaction did not improve despite treatment with tazobactam/piperacillin, meropenem, and micafungin. Scedosporium prolificans was detected from the patient's bronchial lavage fluid, and we initiated treatment with voriconazole. Voriconazole was effective in shrinking the consolidation and suppressing the inflammatory reaction. The residual lesion was surgically resected because of the risk of systemic dissemination. The patient is currently alive without relapse or dissemination.
Topics: Aged; Antifungal Agents; Female; Humans; Lung Diseases, Fungal; Scedosporium; Treatment Outcome; Voriconazole
PubMed: 28420849
DOI: 10.2169/internalmedicine.56.7447 -
Case Reports in Orthopedics 2017, also known as , is a fungus widespread in soil, sewage, and manure. This species is highly virulent and is an emerging opportunistic pathogen found in penetrating...
, also known as , is a fungus widespread in soil, sewage, and manure. This species is highly virulent and is an emerging opportunistic pathogen found in penetrating injuries in immunocompromised patients. Here we report on an immunocompetent patient with bilateral hip -associated osteomyelitis and septic arthritis caused by intentional penetrating trauma. The condition was refractory to initial antimicrobial suppression and surgical irrigation and debridement. Successful outcome was achieved after incorporating a bilateral two-stage total-hip-arthroplasty with Voriconazole-loaded cement and spacer.
PubMed: 28163947
DOI: 10.1155/2017/3809732 -
Journal of Fungi (Basel, Switzerland) Aug 2019Central nervous system infections due to spp and other hyaline molds such as and spp are rare but fatal conditions. Invasion of the central nervous system (CNS) tends... (Review)
Review
Central nervous system infections due to spp and other hyaline molds such as and spp are rare but fatal conditions. Invasion of the central nervous system (CNS) tends to occur as a result of hematogenous dissemination among immunocompromised patients, and by local extension or direct inoculation secondary to trauma in immunocompetent hosts. Efforts should be directed to confirm the diagnosis by image-guided stereotactic brain biopsy when feasible. Non-culture methods could be useful to support the diagnosis, but they have not been validated to be performed in cerebral spinal fluid. Treatment of these infections is challenging given the variable susceptibility profile of these pathogens and the penetration of antifungal agents into the brain.
PubMed: 31480311
DOI: 10.3390/jof5030079 -
Radiology Case Reports May 2022Voriconazole is a broad-spectrum triazole antifungal used to treat invasive fungal infections. It is commonly used prophylactically in immunocompromized patient cohorts,...
Voriconazole is a broad-spectrum triazole antifungal used to treat invasive fungal infections. It is commonly used prophylactically in immunocompromized patient cohorts, including transplant recipients. Diffuse periostitis is a very rare complication of chronic voriconazole use. It is associated with diffuse bone pain, elevated serum alkaline phosphatase and fluorine levels. Characteristic imaging findings include periosteal thickening with a dense, nodular, irregular and often bilateral pattern. We describe the case of a 71-year-old female who presented with multifocal bone pain six years following double lung transplantation. Her post transplantation course had been complicated by a life threatening episode of sepsis secondary to Scedosporium apiospermum, a rare invasive fungal infection following which lifelong prophylaxis with oral Voriconazole was commenced. We discuss the characteristic clinical and imaging manifestations of this rare condition.
PubMed: 35309380
DOI: 10.1016/j.radcr.2022.01.078 -
BMC Infectious Diseases Jan 2016Lomentospora prolificans (formally Scedosporium prolificans) is an environmental mould with a global distribution. Endocarditis caused by L. prolificans is a rare but... (Review)
Review
BACKGROUND
Lomentospora prolificans (formally Scedosporium prolificans) is an environmental mould with a global distribution. Endocarditis caused by L. prolificans is a rare but serious emerging disease in immunocompromised patients. Prior to this case there have only been eight cases reported in the literature. Diagnosis can be challenging and there are no evidence-based guidelines for treatment.
CASE PRESENTATION
We report a 75-year-old woman with ovarian carcinoma who presented with fever after chemotherapy. Repeated sterile site cultures remained negative until day 22 of admission, when Lomentospora prolificans was isolated from blood cultures. Following extensive investigations, including Fluoro-D-glucose positron emission tomography (FDG-PET) and transoephageal echocardiography (TOE), the patient was diagnosed with endocarditis complicated by cerebral emboli. The patient was considered unsuitable for surgical intervention and passed away five days after the fungus was isolated.
CONCLUSION
Endocarditis caused by Lomentospora prolificans is a rare but emerging condition, with limited treatment options and a high mortality. Awareness of the increasing incidence of Lomentospora prolificans infection, diagnosed often at an advanced stage, with potential for endocarditis may prompt earlier echocardiography or FDG-PET imaging. Further studies are needed to determine the optimal combination and duration of anti-fungal agents, used in conjunction with aggressive surgical excision where feasible.
Topics: Aged; Antineoplastic Agents; Brain; Carboplatin; Echocardiography; Endocarditis; Female; Humans; Magnetic Resonance Imaging; Ovarian Neoplasms; Positron-Emission Tomography; Radiography; Scedosporium
PubMed: 26822980
DOI: 10.1186/s12879-016-1372-y -
Journal of the American Veterinary... Jun 2001Scedosporium prolificans was associated with arthritis and degenerative osteomyelitis in a 6-year-old Thoroughbred racehorse. The horse was suspected to have an...
Scedosporium prolificans was associated with arthritis and degenerative osteomyelitis in a 6-year-old Thoroughbred racehorse. The horse was suspected to have an inflammatory lesion of the interosseous tendon, but treatment had resulted in only a minimal response. Shortly after diagnostic arthrocentesis of the left metacarpophalangeal joint was performed, the joint became severely swollen, and radiography of the area revealed lysis of the distal end of the third metacarpal bone, the proximal sesamoid bones, and the proximal end of the proximal phalanx. The horse did not respond to treatment and was euthanatized. At necropsy, severe erosive arthritis and degenerative osteomyelitis of the left metacarpophalangeal joint were seen. Swab specimens of the ulcerated lesions of the articular cartilage were submitted for microbial culture, and Scedosporium prolificans was isolated. Scedosporium prolificans is a newly recognized opportunistic fungal pathogen of humans and animals. In humans, S prolificans typically causes focal locally invasive infections that primarily involve musculoskeletal tissues; most often, infection is a result of penetrating trauma or surgical incision. In immunocompromised patients, fatal disseminated infection can occur. The fungus is resistant to almost all currently available antimycotic agents.
Topics: Animals; Arthritis, Infectious; Drug Resistance, Fungal; Forelimb; Horse Diseases; Horses; Lameness, Animal; Male; Mycoses; Osteomyelitis; Radiography; Scedosporium
PubMed: 11394834
DOI: 10.2460/javma.2001.218.1800 -
Medical Mycology Apr 2018Cystic fibrosis (CF) is the major genetic inherited disease in Caucasian populations. The respiratory tract of CF patients displays a sticky viscous mucus, which allows... (Review)
Review
Cystic fibrosis (CF) is the major genetic inherited disease in Caucasian populations. The respiratory tract of CF patients displays a sticky viscous mucus, which allows for the entrapment of airborne bacteria and fungal spores and provides a suitable environment for growth of microorganisms, including numerous yeast and filamentous fungal species. As a consequence, respiratory infections are the major cause of morbidity and mortality in this clinical context. Although bacteria remain the most common agents of these infections, fungal respiratory infections have emerged as an important cause of disease. Therefore, the International Society for Human and Animal Mycology (ISHAM) has launched a working group on Fungal respiratory infections in Cystic Fibrosis (Fri-CF) in October 2006, which was subsequently approved by the European Confederation of Medical Mycology (ECMM). Meetings of this working group, comprising both clinicians and mycologists involved in the follow-up of CF patients, as well as basic scientists interested in the fungal species involved, provided the opportunity to initiate collaborative works aimed to improve our knowledge on these infections to assist clinicians in patient management. The current review highlights the outcomes of some of these collaborative works in clinical surveillance, pathogenesis and treatment, giving special emphasis to standardization of culture procedures, improvement of species identification methods including the development of nonculture-based diagnostic methods, microbiome studies and identification of new biological markers, and the description of genotyping studies aiming to differentiate transient carriage and chronic colonization of the airways. The review also reports on the breakthrough in sequencing the genomes of the main Scedosporium species as basis for a better understanding of the pathogenic mechanisms of these fungi, and discusses treatment options of infections caused by multidrug resistant microorganisms, such as Scedosporium and Lomentospora species and members of the Rasamsonia argillacea species complex.
Topics: Antifungal Agents; Cystic Fibrosis; Drug Resistance, Multiple, Fungal; Fungi; Genomics; Humans; Microbiological Techniques; Mycoses; Respiratory Tract Infections; Scedosporium
PubMed: 29538733
DOI: 10.1093/mmy/myx106 -
Medical Hypothesis, Discovery &... 2021(SA) is commonly present in temperate climates. It can induce cutaneous and subcutaneous tissue infections as well as disseminated infections in immunocompromised or... (Review)
Review
BACKGROUND
(SA) is commonly present in temperate climates. It can induce cutaneous and subcutaneous tissue infections as well as disseminated infections in immunocompromised or immunocompetent hosts. The eye is rarely involved. Keratomycosis is usually caused by plant-related injuries. Here, we describe a patient with a severe and sight-threatening corneal abscess caused by SA, which was associated with contact lens wear and was successfully treated with a combination of surgical and medical therapies.
CASE PRESENTATION
An otherwise healthy 22-year-old woman, with history of contact lens wearing, was referred to the Ophthalmic Department of Bari University, Bari, Italy for evaluation of a corneal abscess and hypopyon in her left eye. Intensive topical and systemic antibiotic therapy was initiated after obtaining con- junctival swabs. Within 2 days, her ophthalmic condition had worsened, and her best-corrected visual acuity (BCVA) dropped to counting fingers. She underwent penetrating keratoplasty, after which her ophthalmic condition improved. Microbiological culture, obtained from the explanted cornea, revealed SA infection. This was addressed with specific topical and systemic therapy using voriconazole. Two weeks later, the con- dition of her left eye was stable, with mild corneal edema and no sign of acute graft rejection. Her BCVA improved to 20/25, and all medications were discontinued, except for the steroid eye drop. The patient was scheduled for a 1-month follow-up.
CONCLUSIONS
Prompt identification of the etiological agent is mandatory to perform appropriate therapy in cases of keratomycosis. Surgery to remove the infected cornea is helpful in patients with deteriorating condition, in whom the initial medical therapy has failed. Topical and systemic antimycotic therapy, based on microbiological culture, is recommended as an adjunctive therapy for the surgical management of severe corneal mycotic abscesses.
PubMed: 37641616
DOI: 10.51329/mehdiophthal1425