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Journal of Medical Microbiology Mar 2024The increasing prevalence and growing resistance of fungi present a significant peril to public health. There are only four classes of antifungal medicines available...
The increasing prevalence and growing resistance of fungi present a significant peril to public health. There are only four classes of antifungal medicines available today, and few candidates are in clinical trials. Rapid and sensitive diagnostic techniques are lacking for most fungal pathogens, and those that do exist are expensive or hard to obtain. This study aimed to evaluate the feasibility of a novel automated antifungal susceptibility testing system, Fungus AST, in comparison to the broth microdilution method (BMD) recommended by the Clinical and Laboratory Standards Institute (CLSI). A total of 101 clinical spp. isolates were collected from the Zengcheng Branch of Nanfang Hospital and subjected to antifungal susceptibility testing. Antifungal susceptibility was assessed using the Fungus AST method and the BMD. In this study, we introduce a novel automated antifungal susceptibility testing system, Fungus AST, which detects the turbidity and/or colour intensity of microdilution wells using a four-wavelength detection technology in real time and is designed to match the growth characteristics of strains over time. Based on our analysis, all reportable ranges of Fungus AST were suitable for clinical fungal isolates in PR China. Within ±twofold dilutions, reproducibility was 100 %. Considering the BMD as a referenced method, ten antifungal agents (anidulafungin, caspofungin, micafungin, fluconazole, voriconazole, posaconazole, itraconazole, amphotericin B, 5-flucytosine and nystatin) showed an essential agreement of >95 %. The category agreement of five antifungal agents (anidulafungin, caspofungin, micafungin, fluconazole and voriconazole) was excellent at >90 %. One isolate and voriconazole showed a major error (ME) (1.7 %), and no other ME or very ME agents were found. Given the above, it can be argued that the utilization of Fungus AST is a discretionary automated approach. More improvements are needed in Fungus AST compared to the BMD system for a wider range of clinical isolates, including different types of fungi.
Topics: Antifungal Agents; Voriconazole; Colorimetry; Fluconazole; Anidulafungin; Caspofungin; Micafungin; Reproducibility of Results; Nephelometry and Turbidimetry; Algorithms
PubMed: 38440953
DOI: 10.1099/jmm.0.001811 -
Mycoses Mar 2024Fluconazole-resistant Candida parapsilosis is a matter of concern.
Fluconazole-resistant Candida parapsilosis genotypes from hospitals located in five Spanish cities and one in Italy: Description of azole-resistance profiles associated with the Y132F ERG11p substitution.
BACKGROUND
Fluconazole-resistant Candida parapsilosis is a matter of concern.
OBJECTIVES
To describe fluconazole-resistant C. parapsilosis genotypes circulating across hospitals in Spain and Rome and to study their azole-resistance profile associated with ERG11p substitutions.
PATIENTS/METHODS
We selected fluconazole-resistant C. parapsilosis isolates (n = 528 from 2019 to 2023; MIC ≥8 mg/L according to EUCAST) from patients admitted to 13 hospitals located in five Spanish cities and Rome. Additionally, we tested voriconazole, posaconazole, isavuconazole, amphotericin B, micafungin, anidulafungin and ibrexafungerp susceptibility.
RESULTS
Of the 53 genotypes found, 49 harboured the Y132F substitution, five of which were dominating city-specific genotypes involving almost half the isolates. Another genotype involved isolates harbouring the G458S substitution. Finally, we found two genotypes with the wild-type ERG11 gene sequence and one with the R398I substitution. All isolates were fully susceptible/wild-type to amphotericin B, anidulafungin, micafungin and ibrexafungerp. The azole-resistance patterns found were: voriconazole-resistant (74.1%) or voriconazole-intermediate (25.2%), posaconazole-resistant (10%) and isavuconazole non-wild-type (47.5%). Fluconazole-resistant and voriconazole non-wild-type isolates were likely to harbour substitution Y132F if posaconazole was wild type; however, if posaconazole was non-wild type, substitution G458S was indicated if isavuconazole MIC was >0.125 mg/L or substitution Y132F if isavuconazole MIC was ≤0.125 mg/L.
CONCLUSIONS
We detected a recent clonal spread of fluconazole-resistant C. parapsilosis across some cities in Spain, mostly driven by dominating city-specific genotypes, which involved a large number of isolates harbouring the Y132F ERG11p substitution. Isolates harbouring substitution Y132F can be suspected because they are non-susceptible to voriconazole and rarely posaconazole-resistant.
Topics: Humans; Azoles; Fluconazole; Candida parapsilosis; Cities; Voriconazole; Amphotericin B; Anidulafungin; Micafungin; Italy; Hospitals; Genotype; Triazoles; Nitriles; Triterpenes; Glycosides; Pyridines
PubMed: 38438313
DOI: 10.1111/myc.13706 -
Medical Mycology Mar 2024Hyphal pellet formation by Aspergillus species in liquid cultures is one of the main obstacles to high-throughput anti-Aspergillus reagent screening. We previously...
Hyphal pellet formation by Aspergillus species in liquid cultures is one of the main obstacles to high-throughput anti-Aspergillus reagent screening. We previously constructed a hyphal dispersion mutant of Aspergillus fumigatus by disrupting the genes encoding the primary cell wall α-1,3-glucan synthase Ags1 and putative galactosaminogalactan synthase Gtb3 (Δags1Δgtb3). Mycelial growth of the mutant in liquid cultures monitored by optical density was reproducible, and the dose-response of hyphal growth to antifungal agents has been quantified by optical density. However, Δags1Δgtb3 still forms hyphal pellets in some rich growth media. Here, we constructed a disruptant lacking all three α-1,3-glucan synthases and galactosaminogalactan synthase (Δags1Δags2Δags3Δgtb3), and confirmed that its hyphae were dispersed in all the media tested. We established an automatic method to monitor hyphal growth of the mutant in a 24-well plate shaken with a real-time plate reader. Dose-dependent growth suppression and unique growth responses to antifungal agents (voriconazole, amphotericin B, and micafungin) were clearly observed. A 96-well plate was also found to be useful for the evaluation of mycelial growth by optical density. Our method is potentially applicable to high-throughput screening for anti-Aspergillus agents.
Topics: Animals; Aspergillus fumigatus; Antifungal Agents; Hyphae; Mycelium; Amphotericin B
PubMed: 38429972
DOI: 10.1093/mmy/myae011 -
Medical Mycology Journal 2024Disseminated trichosporonosis is a rare fungal infection whose risk factors are hematological malignancies and neutropenia. Recently, breakthrough Trichosporon... (Review)
Review
Disseminated trichosporonosis is a rare fungal infection whose risk factors are hematological malignancies and neutropenia. Recently, breakthrough Trichosporon infections after administration of micafungin, the first-line systemic antifungal agent in compromised hosts, have been widely recognized. A man in his seventies about 1 month into chemotherapy for acute megakaryoblastic leukemia presented with a worsening fever and dyspnea. The patient was being administered with empirical micafungin therapy for suspected candidiasis. As the symptoms progressed, scattered erythema appeared on the trunk, some with a dark red vesicle at the center. Blood cultures identified Trichosporon asahii, as did the specimen of the skin biopsy. On the basis also of the presence of pneumonia on chest computed tomography, we confirmed the diagnosis of disseminated trichosporonosis and changed the antifungal agent from micafungin to voriconazole. Blood culture turned out to be negative 1 month after administrating voriconazole. However, the patient died of the leukemia. Our review of previous reports on cutaneous manifestations of disseminated trichosporonosis revealed that despite their morphological diversity, erythema with a red papule or vesicle at the center, implying necrosis, was also observed in previous cases. Our case report suggests that dermatologists should be aware of skin manifestations of disseminated trichosporonosis after micafungin administration, especially in cases of hematological malignancies.
Topics: Male; Humans; Micafungin; Antifungal Agents; Voriconazole; Trichosporonosis; Leukemia, Megakaryoblastic, Acute; Trichosporon; Hematologic Neoplasms; Erythema
PubMed: 38417883
DOI: 10.3314/mmj.23-00009 -
Journal of Global Antimicrobial... Jun 2024This study aimed to identify the resistance mechanisms to micafungin and fluconazole in a clinical isolate of Candida glabrata.
OBJECTIVES
This study aimed to identify the resistance mechanisms to micafungin and fluconazole in a clinical isolate of Candida glabrata.
METHODS
The isolate was whole-genome sequenced to identify amino acid changes in key proteins involved in antifungal resistance, and the isolate was further characterised by pathogenicity-related phenotypic assays that supported the sequencing results.
RESULTS
Amino acid substitutions were detected in 8 of 17 protein candidates. Many of these substitutions were novel, including in CHS3, CHS3B, and KRE5, which are involved in the development of micafungin resistance. Regarding fluconazole resistance, overexpression of efflux pumps was observed. Our isolate did not exhibit an increased virulence potential compared with the control strain; however, a significant increase in chitin content and potential to resist the cell surface disruptant sodium dodecyl sulphate was observed.
CONCLUSIONS
This clinical Candida glabrata isolate experienced a change in cell wall architecture, which correlates with the development of micafungin resistance.
Topics: Candida glabrata; Antifungal Agents; Humans; Micafungin; Chitin; Drug Resistance, Fungal; Microbial Sensitivity Tests; Fluconazole; Whole Genome Sequencing; Candidiasis; Fungal Proteins; Amino Acid Substitution; Cell Wall
PubMed: 38408565
DOI: 10.1016/j.jgar.2024.02.012 -
Journal de Mycologie Medicale Mar 2024Antifungal susceptibility testing (AFST) is essential to ensure appropriate antifungal therapy in candidaemia. This study compared two commercial colorimetric broth...
PURPOSE
Antifungal susceptibility testing (AFST) is essential to ensure appropriate antifungal therapy in candidaemia. This study compared two commercial colorimetric broth microdilution tests: Sensititre YeastOne (SYO; Thermo Scientific) and Micronaut-AM EUCAST AFST (M-AM; Bruker) for the AFST of Candida spp.
MATERIAL AND METHODS
A total of 74 yeast strains, including C. albicans (n = 40) and non-albicans Candida species (NACS) (n = 34), were obtained from blood cultures of patients admitted to a tertiary care hospital in Belgium from 2017 to 2022. AFST by SYO and by M-AM were performed according to the manufacturers' protocols and interpreted using CLSI and EUCAST guidelines, respectively. Essential and categorical agreements (EA and CA), very major, major and minor discrepancies were calculated for amphotericin B, echinocandins and azoles considering SYO as the reference method.
RESULTS
In total, 441 and 392 isolate-antifungal results were evaluable for EA and CA, respectively. SYO and M-AM, showed a high level of concordance for C. albicans strains, with an EA and CA ≥90 % for all tested antifungals. However, we noted significant discordances for NACS, the lowest EA were observed with micafungin (50 %) and voriconazole (58.8 %). These discrepancies were likely due to differences in the raw MIC values obtained by the two methods and the different interpretation breakpoints used by CLSI and EUCAST.
CONCLUSION
Our study showed excellent agreement between SYO and M-AM for AFST of C. albicans, while the equivalency was lower for NACS. AFST method should be carefully selected, considering the results might impact the choice of antifungals for non-albicans candidaemia.
Topics: Humans; Antifungal Agents; Microbial Sensitivity Tests; Echinocandins; Candidemia; Candida; Candida albicans
PubMed: 38401236
DOI: 10.1016/j.mycmed.2024.101465 -
Journal of Infection and Chemotherapy :... Feb 2024The fungus Wickerhamiella pararugosa (Candida pararugosa) has been detected in various human organs but has rarely caused bloodstream infections. This report presents a...
The fungus Wickerhamiella pararugosa (Candida pararugosa) has been detected in various human organs but has rarely caused bloodstream infections. This report presents a case of central venous catheter-related bloodstream infection (CRBSI) of W. pararugosa in an adult. A female patient in her 80s was admitted to our facility for intestinal obstruction caused by colorectal cancer. The patient's ability to consume food was hindered, necessitating the insertion of a central venous catheter (CVC) into the internal jugular vein. On day 3 after admission, the patient developed a fever, prompting blood and CVC tip cultures to be performed. On day 5, yeast-like fungi were discovered in the blood cultures, and fosfluconazole (fluconazole [FLCZ] pro-drug) treatment was initiated. On day 8, yeast-like fungi were identified in both the blood and CVC tip cultures, leading to a diagnosis of CRBSI. The fungus was identified as W. pararugosa through biochemical and genetic characterization. This finding justified the use of micafungin (MCFG) for combination therapy. On day 17, the minimum inhibitory concentrations (MIC) for FLCZ and MCFG were 4-8 and 0.06 μg/mL, respectively. Accordingly, the treatment was changed to monotherapy with MCFG. After a 21-day treatment regimen, the patient was discharged on day 31. We present a case of CRBSI caused by W. pararugosa in an adult with intestinal obstruction. The notable increase in the MIC of FLCZ necessitated monotherapy with MCFG, which resulted in successful recovery of the patient.
PubMed: 38369124
DOI: 10.1016/j.jiac.2024.02.014 -
Journal of Infection and Chemotherapy :... Feb 2024Phaeohyphomycosis is caused by dematiaceous (pigmented) fungi. Most phaeohyphomycosis is non-invasive infections, however, they can lead to invasive infections,...
Micafungin-breakthrough Coniochaeta hoffmannii (Lecythophora hoffmannii) fungemia following cord blood transplant in a patient with acute myeloid leukemia successfully treated with voriconazole.
Phaeohyphomycosis is caused by dematiaceous (pigmented) fungi. Most phaeohyphomycosis is non-invasive infections, however, they can lead to invasive infections, including fungemia and disseminated disease, particularly in severely immunocompromised patients. Invasive phaeohyphomycosis has recently emerged, however, the treatment strategy was not determined because of the intrinsic resistance to antifungals and the lack of clinical experience. Here, we describe a novel case of echinocandin-breakthrough Coniochaeta hoffmannii (Lecythophora hoffmannii) fungemia after hematopoietic stem cell transplantation, which was identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and ribosomal RNA sequencing. The patient was a female in her 40s who had acute myeloid leukemia refractory to chemotherapy before progressing to cord blood transplantation. Before developing fungemia, the patient was administered multiple broad-spectrum antibiotics and micafungin for recurrent infections and prophylaxis. Clinical and microbiological responses to liposomal amphotericin B were poor but improved after replacement to voriconazole and engraftment. A literature review of the previously reported cases with C. hoffmannii human infections imply that disruption of the cutaneous/mucosal barrier and the use of antimicrobial agents, both antibiotics and antifungals, could incite C. hoffmannii invasive infections.
PubMed: 38369121
DOI: 10.1016/j.jiac.2024.02.011 -
The Journal of Infectious Diseases Feb 2024Invasive fungal pathogen Candida auris has become a public health threat causing outbreaks of high mortality infections. Drug resistance often limits treatment options....
Invasive fungal pathogen Candida auris has become a public health threat causing outbreaks of high mortality infections. Drug resistance often limits treatment options. For Candida albicans, subinhibitory concentrations of echinocandins unmask immunostimulatory β-glucan, augmenting immunity. Here we analyze the impact of echinocandin treatment of C. auris on β-glucan exposure and human neutrophil interactions. We show subinhibitory concentrations lead to minimal glucan unmasking and only subtle influences on neutrophil functions for the isolates belonging to circulating clades. The data suggest that echinocandin treatment will not largely alter phagocytic responses. Glucan masking pathways appear to differ between C. auris and C. albicans.
PubMed: 38330449
DOI: 10.1093/infdis/jiae043 -
Transplantation Proceedings Apr 2024Pediatric living-donor liver transplantation (LDLT) candidates often receive long-term antibiotic treatment. Micafungin has been used as an antifungal agent after LDLT,...
BACKGROUND
Pediatric living-donor liver transplantation (LDLT) candidates often receive long-term antibiotic treatment. Micafungin has been used as an antifungal agent after LDLT, but the adequate dose after pediatric LDLT was unknown. Here, we report micafungin blood concentrations after pediatric LDLT and discuss its safety and adequate dosing.
METHODS
Pediatric patients with data on micafungin concentrations after LDLT were identified. Those with surgical complications were excluded. All patients received standard tacrolimus-based immunosuppression. A micafungin dose of 1 mg/kg was administered once daily for 10 days starting on postoperative day (POD) 1. The trough and peak micafungin blood concentrations were evaluated on PODs 1, 4, 7, and 10. Beta D glucan levels and liver function tests were assessed to determine micafungin effectiveness and safety.
RESULTS
Ten patients were enrolled, with a median age of 1.2 years. The median graft vs body weight ratio was 2.7%. The primary diseases were biliary atresia (n = 7), Alagille syndrome (n = 2), and progressive familial intrahepatic cholestasis type 2 (n = 1). Mean peak micafungin levels were 4.47, 6.27, 5.47, and 5.47 µg/mL on PODs 1, 4, 7, and 10, respectively. Mean trough levels were 2.03, 1.88, and 2.66 µg/mL on PODs 4, 7, and 10, respectively. The micafungin half-lives were 13.7, 14.7, and 14.0 hours on PODs 4, 7, and 10, respectively. Beta D glucan levels were 4.4 pg/mL and 3.7 pg/mL before and after transplantation, respectively, indicating no significant difference (P = .3). No clinical fungal infections were observed.
CONCLUSION
Micafungin administration is safe and effective after pediatric LDLT.
Topics: Humans; Micafungin; Liver Transplantation; Antifungal Agents; Living Donors; Male; Female; Infant; Child, Preschool; Child; Immunosuppressive Agents; Lipopeptides
PubMed: 38326203
DOI: 10.1016/j.transproceed.2024.01.020