-
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 -
The New England Journal of Medicine Jul 2014The recent outbreak of meningitis linked to epidural injections of methylprednisolone acetate has brought renewed attention to mold infections of the central nervous... (Review)
Review
The recent outbreak of meningitis linked to epidural injections of methylprednisolone acetate has brought renewed attention to mold infections of the central nervous system (CNS). Although uncommon, these infections are often devastating and difficult to treat. This focused review of the epidemiologic aspects, clinical characteristics, and treatment of mold infections of the CNS covers a group of common pathogens: aspergillus, fusarium, and scedosporium species, molds in the order Mucorales, and dematiaceous molds. Infections caused by these pathogen groups have distinctive epidemiologic profiles, clinical manifestations, microbiologic characteristics, and therapeutic implications, all of which clinicians should understand.
Topics: Antifungal Agents; Central Nervous System Fungal Infections; Early Diagnosis; Fungi; Humans
PubMed: 25006721
DOI: 10.1056/NEJMra1216008 -
Interdisciplinary Perspectives on... 2018and are important fungal species isolated from immunocompromised patients. Previous studies have demonstrated that these filamentous fungi exist as saprophytes in the...
and are important fungal species isolated from immunocompromised patients. Previous studies have demonstrated that these filamentous fungi exist as saprophytes in the soil and showed the highest minimum inhibitory concentration to several drugs. We aimed to examine how UVC affects the and by investigating the role of UVC on growth, induction of apoptosis by ethidium bromide (EB)/acridine orange (AO) staining, and transcriptomic study of caspase recruitment domain family, member 9 (CARD-9) gene. Our studies showed that 15 minutes of exposure to UVC light effectively increased reduction in both organisms and caused changes in colony morphology, color, and hyphal growth pattern. After 15 min of UVC irradiation, apoptotic cells were quantitated by EB/AO staining, and the percentage of apoptosis was 96.06% in and 28.30% in . CARD-9 gene expression results confirmed that apoptosis was induced in and after UVC treatment and that showed a higher expression of apoptosis signaling than . Our study explored the effects of UVC in the inactivation of and . We hope that our data is useful to other researchers in future studies.
PubMed: 30631350
DOI: 10.1155/2018/3748594 -
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 -
Brazilian Journal of Microbiology :... Jun 2020Scedosporium spp. and Lomentospora prolificans are filamentous fungi that emerged as human pathogens; however, their mechanisms of virulence/pathogenesis are still...
Scedosporium spp. and Lomentospora prolificans are filamentous fungi that emerged as human pathogens; however, their mechanisms of virulence/pathogenesis are still largely unknown. In the present work, we have evaluated the interaction of S. apiospermum, S. minutisporum, S. aurantiacum, and L. prolificans with lung epithelial cells (A549 line). The results showed that conidia were able to interact with A549 cells, displaying association indexes of 73.20, 117.98, 188.01, and 241.63 regarding S. apiospermum, L. prolificans, S. minutisporum, and S. aurantiacum, respectively. Light microscopy images evidenced morphological changes in epithelial cells, including rounding and detachment, especially during the interaction with L. prolificans. Plasma membrane injuries were detected in A549 cells after 1 h of co-culturing with S. aurantiacum and S. minutisporum and after 4 h with S. apiospermum and L. prolificans, as judged by the passive incorporation of propidium iodide. After 24 h of fungi-epithelial cells interaction, only mycelia were observed covering the A549 monolayer. Interestingly, the mycelial trap induced severe damage in the A549 cells, culminating in epithelial cell death. Our results demonstrate some relevant events that occur during the contact between lung epithelial cells and Scedosporium/Lomentospora species, including conidial adhesion and hyphal growth with consequent irreversible injury on A549 cells, adding light to the infection process caused by these opportunistic and multidrug-resistant fungi.
Topics: A549 Cells; Epithelial Cells; Host-Pathogen Interactions; Humans; Lung; Scedosporium; Spores, Fungal; Virulence
PubMed: 31736016
DOI: 10.1007/s42770-019-00183-2 -
Medical Mycology Jul 2023The (1→3)-β-D-glucan (BDG) is a component of the fungal cell wall that can be detected in serum and used as an adjunctive tool for the diagnosis of invasive mold... (Meta-Analysis)
Meta-Analysis
The (1→3)-β-D-glucan (BDG) is a component of the fungal cell wall that can be detected in serum and used as an adjunctive tool for the diagnosis of invasive mold infections (IMI) in patients with hematologic cancer or other immunosuppressive conditions. However, its use is limited by modest sensitivity/specificity, inability to differentiate between fungal pathogens, and lack of detection of mucormycosis. Data about BDG performance for other relevant IMI, such as invasive fusariosis (IF) and invasive scedosporiosis/lomentosporiosis (IS) are scarce. The objective of this study was to assess the sensitivity of BDG for the diagnosis of IF and IS through systematic literature review and meta-analysis. Immunosuppressed patients diagnosed with proven or probable IF and IS, with interpretable BDG data were eligible. A total of 73 IF and 27 IS cases were included. The sensitivity of BDG for IF and IS diagnosis was 76.7% and 81.5%, respectively. In comparison, the sensitivity of serum galactomannan for IF was 27%. Importantly, BDG positivity preceded the diagnosis by conventional methods (culture or histopathology) in 73% and 94% of IF and IS cases, respectively. Specificity was not assessed because of lacking data. In conclusion, BDG testing may be useful in patients with suspected IF or IS. Combining BDG and galactomannan testing may also help differentiating between the different types of IMI.
Topics: Animals; Fusariosis; beta-Glucans; Invasive Fungal Infections; Sensitivity and Specificity
PubMed: 37381179
DOI: 10.1093/mmy/myad061 -
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 -
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