-
American Journal of Transplantation :... Feb 2018
Topics: Humans; Mycoses; Salvage Therapy; Scedosporium; Transplant Recipients; Triazoles
PubMed: 29206346
DOI: 10.1111/ajt.14616 -
Clinical Microbiology Reviews Jan 2008Scedosporium spp. are increasingly recognized as causes of resistant life-threatening infections in immunocompromised patients. Scedosporium spp. also cause a wide... (Review)
Review
Scedosporium spp. are increasingly recognized as causes of resistant life-threatening infections in immunocompromised patients. Scedosporium spp. also cause a wide spectrum of conditions, including mycetoma, saprobic involvement and colonization of the airways, sinopulmonary infections, extrapulmonary localized infections, and disseminated infections. Invasive scedosporium infections are also associated with central nervous infection following near-drowning accidents. The most common sites of infection are the lungs, sinuses, bones, joints, eyes, and brain. Scedosporium apiospermum and Scedosporium prolificans are the two principal medically important species of this genus. Pseudallescheria boydii, the teleomorph of S. apiospermum, is recognized by the presence of cleistothecia. Recent advances in molecular taxonomy have advanced the understanding of the genus Scedosporium and have demonstrated a wider range of species than heretofore recognized. Studies of the pathogenesis of and immune response to Scedosporium spp. underscore the importance of innate host defenses in protection against these organisms. Microbiological diagnosis of Scedosporium spp. currently depends upon culture and morphological characterization. Molecular tools for clinical microbiological detection of Scedosporium spp. are currently investigational. Infections caused by S. apiospermum and P. boydii in patients and animals may respond to antifungal triazoles. By comparison, infections caused by S. prolificans seldom respond to medical therapy alone. Surgery and reversal of immunosuppression may be the only effective therapeutic options for infections caused by S. prolificans.
Topics: Administration, Inhalation; Animals; Antifungal Agents; Arthritis; Biodiversity; Bone Diseases, Infectious; Central Nervous System Fungal Infections; Eye Infections, Fungal; Humans; Immunocompromised Host; Immunosuppressive Agents; Microbial Sensitivity Tests; Mycetoma; Phylogeny; Respiratory Tract Infections; Scedosporium
PubMed: 18202441
DOI: 10.1128/CMR.00039-07 -
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 -
Current Fungal Infection Reports 2016Posaconazole is a second-generation triazole agent with a potent and broad antifungal activity. In addition to the oral suspension, a delayed-release tablet and... (Review)
Review
Posaconazole is a second-generation triazole agent with a potent and broad antifungal activity. In addition to the oral suspension, a delayed-release tablet and intravenous formulation with improved pharmacokinetic properties have been introduced recently. Due to the large interindividual and intraindividual variation in bioavailability and drug-drug interactions, therapeutic drug monitoring (TDM) is advised to ensure adequate exposure and improve clinical response for posaconazole. Here, we highlight and discuss the most recent findings on pharmacokinetics and pharmacodynamics of posaconazole in the setting of prophylaxis and treatment of fungal infections and refer to the challenges associated with TDM of posaconazole.
PubMed: 27358662
DOI: 10.1007/s12281-016-0255-4 -
Emerging Infectious Diseases Jun 2024Scedosporium spp. and Lomentospora prolificans are emerging non-Aspergillus filamentous fungi. The Scedosporiosis/lomentosporiosis Observational Study we previously... (Observational Study)
Observational Study Review
Scedosporium spp. and Lomentospora prolificans are emerging non-Aspergillus filamentous fungi. The Scedosporiosis/lomentosporiosis Observational Study we previously conducted reported frequent fungal vascular involvement, including aortitis and peripheral arteritis. For this article, we reviewed 7 cases of Scedosporium spp. and L. prolificans arteritis from the Scedosporiosis/lomentosporiosis Observational Study and 13 cases from published literature. Underlying immunosuppression was reported in 70% (14/20) of case-patients, mainly those who had solid organ transplants (10/14). Osteoarticular localization of infection was observed in 50% (10/20) of cases; infections were frequently (7/10) contiguous with vascular infection sites. Scedosporium spp./Lomentospora prolificans infections were diagnosed in 9 of 20 patients ≈3 months after completing treatment for nonvascular scedosporiosis/lomentosporiosis. Aneurysms were found in 8/11 aortitis and 6/10 peripheral arteritis cases. Invasive fungal disease--related deaths were high (12/18 [67%]). The vascular tropism of Scedosporium spp. and L. prolificans indicates vascular imaging, such as computed tomography angiography, is needed to manage infections, especially for osteoarticular locations.
Topics: Humans; Scedosporium; France; Male; Middle Aged; Aged; Female; Mycoses; Adult; Antifungal Agents; Aged, 80 and over; Invasive Fungal Infections
PubMed: 38781681
DOI: 10.3201/eid3006.231409 -
Antimicrobial Agents and Chemotherapy Nov 2019While spp. remain the major cause of invasive mold infections in hematologic cancer patients and transplant recipients, other opportunistic molds, such as , , and spp.... (Review)
Review
While spp. remain the major cause of invasive mold infections in hematologic cancer patients and transplant recipients, other opportunistic molds, such as , , and spp. are increasingly encountered in an expanding population of patients with severe and prolonged immunosuppression. High potential for tissue invasion and dissemination, resistance to multiple antifungals and high mortality rates are hallmarks of these non- invasive mold infections (NAIMIs). Assessment of drug efficacy is particularly difficult in the complex treatment scenarios of NAIMIs. Specifically, correlation between susceptibility and responses to antifungals is hard to assess, in view of the multiple, frequently interrelated factors influencing outcomes, such as pharmacokinetic/pharmacodynamic parameters determining drug availability at the site of infection, the net state of immune suppression, delay in diagnosis, or surgical debulking of infectious foci. Our current therapeutic approach of NAIMIs should evolve toward a better integration of the dynamic interactions between the pathogen, the drug and the host. Innovative concepts of experimental research may consist in manipulating the host immune system to induce a specific antifungal response or targeted drug delivery. In this review, we discuss the challenges in the management of NAIMIs and provide an update about the latest advances in diagnostic and therapeutic approaches.
Topics: Antifungal Agents; Drug Resistance, Fungal; Humans; Immunocompromised Host; Invasive Fungal Infections
PubMed: 31481441
DOI: 10.1128/AAC.01244-19 -
Antimicrobial Agents and Chemotherapy Sep 2022Previous studies show high agreement between MIC spectrophotometric readings and visual inspection of azoles and amphotericin B against Aspergillus fumigatus isolates....
EUCAST-Obtained Olorofim MICs against Aspergillus and Scedosporium Species and Lomentospora prolificans Showed High Agreements between Visual Inspection and Spectrophotometric Readings.
Previous studies show high agreement between MIC spectrophotometric readings and visual inspection of azoles and amphotericin B against Aspergillus fumigatus isolates. Here, we tested and compared the activity of a novel antifungal, olorofim, against Aspergillus spp., spp., and Lomentospora prolificans by visual inspection and spectrophotometric readings. Clinical isolates of Aspergillus ( = 686) and ( = 36) spp. and ( = 13) were tested. Olorofim MICs were evaluated-following the EUCAST E.Def 9.4 procedure-by visual inspection or spectrophotometric readings (combinations of either ≥90% or ≥95% fungal growth inhibition endpoints compared to drug-free control endpoints and different wavelengths [405 nm, 450 nm, 492 nm, 540 nm, and 620 nm]). We observed high activity of olorofim against all tested Aspergillus spp. (MICs up to 0.06 mg/L), except for A. calidoustus, and against and spp. (MICs up to 0.125 mg/L). The combination of ≥90% fungal growth inhibition endpoints at wavelengths of ≥492 nm resulted in high essential agreements with A. fumigatus and lesser agreement with non- Aspergillus, spp., and , although the number of isolates studied was low. This single-center study shows high agreement among olorofim MICs against A. fumigatus by visual inspection and spectrophotometric readings (≥90% fungal growth inhibition endpoints and wavelengths of ≥492 nm) and encouraging results against non- Aspergillus spp., spp., and .
Topics: Acetamides; Amphotericin B; Antifungal Agents; Aspergillus; Piperazines; Pyrimidines; Pyrroles; Scedosporium
PubMed: 35924916
DOI: 10.1128/aac.00849-22 -
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 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 -
Brazilian Journal of Microbiology :... Mar 2021Cystic fibrosis (CF) causes a variety of symptoms in different organs, but the majority of the morbidity and mortality of CF is related with pulmonary conditions....
Cystic fibrosis (CF) causes a variety of symptoms in different organs, but the majority of the morbidity and mortality of CF is related with pulmonary conditions. Primary infections are usually bacterial, and when treated with antibiotics, yeast infections appear or become more evident. Studies show that different microorganisms can co-inhabit the same environment and the interactions could be synergistic or antagonistic. Using techniques including viable and non-viable cell-to-cell interactions, mixed culture in liquid, and solid media sharing or not the supernatant, this study has evaluated interactions between the fungal species Scedosporium apiospermum and Scedosporium boydii with the bacterial species Staphylococcus aureus, Pseudomonas aeruginosa, and Burkholderia cepacia. Cell-to-cell interactions in liquid medium showed that P. aeruginosa and B. cepacia were able to reduce fungal viability but only in the presence of alive bacteria. Interactions without cell contact using a semi-permeable membrane showed that all bacteria were able to inhibit both fungal growths/viabilities. Cell-free supernatants from bacterial growth reduced fungal viability in planktonic fungal cells as well as in some conditions for preformed fungal biomass. According to the chemical analysis of the bacterial supernatants, the predominant component is protein. In this work, we verified that bacterial cells and their metabolites, present in the supernatants, can play anti-S. apiospermum and anti-S. boydii roles on fungal growth and viability.
Topics: Cystic Fibrosis; Humans; Microbial Viability; Mycoses; Pseudomonas aeruginosa; Scedosporium; Staphylococcus aureus
PubMed: 33442865
DOI: 10.1007/s42770-020-00415-w