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Pathogens (Basel, Switzerland) Mar 2024(1) Background: Despite being considered a non-pathogenic yeast, recently, a growing occurrence of infections has been noted. There is little knowledge about the drug...
(1) Background: Despite being considered a non-pathogenic yeast, recently, a growing occurrence of infections has been noted. There is little knowledge about the drug susceptibility of this species. Therefore, the objective of this research was to expand it and determine the drug susceptibility profile of a local collection of clinical isolates of this species. (2) Methods: This study contained 55 clinical isolates identified as using the MALDI-TOF method. The susceptibility of was tested to 10 antifungals (amphotericin B, flucytosine, fluconazole, voriconazole, posaconazole, micafungin, anidulafungin, caspofungin, and itraconazole) using MICRONAUT-AT tests and manogepix, a new drug, using the microdilution method according to EUCAST. (3) Results: Overall, most strains were classified as sensitive to amphotericin B and flucytosine (MIC ranges of ≤0.03-1 and ≤0.06-0.125, respectively) and also to echinocandins. However, five isolates expressed high MIC values for all of the tested azoles, indicating cross-resistance. The MIC range for manogepix was 0.001-0.125 mg/L, with an MIC of 0.03 mg/L and an MIC of 0.06 mg/L. (4) Conclusions: The occurrence of resistance to azoles may be a concerning problem and therefore should be investigated further. However, the new antifungal manogepix appears to be an interesting new therapeutic option for treating such infections.
PubMed: 38535591
DOI: 10.3390/pathogens13030248 -
Journal of Fungi (Basel, Switzerland) Mar 2024Commercial tests are often employed in clinical microbiology laboratories for antifungal susceptibility testing of filamentous fungi. Method-dependent epidemiological... (Review)
Review
Commercial tests are often employed in clinical microbiology laboratories for antifungal susceptibility testing of filamentous fungi. Method-dependent epidemiological cutoff values (ECVs) have been defined in order to detect non-wild-type (NWT) isolates harboring resistance mechanisms. We reviewed the literature in order to find studies where commercial methods were used to evaluate for in vitro susceptibility of filamentous fungi and assess their ability to detect NWT isolates according to the available ECVs. Data were found for the gradient concentration strips Etest and MIC Test Strips (MTS), broth microdilution Sensititre YeastOne (SYO), Micronaut-AM and the agar dilution VIPcheck assays. Applying itraconazole, voriconazole and posaconazole Etest ECVs for , Etest was able to detect 90.3% (84/93), 61.2% (90/147) and 86% (31/36) of isolates with known mutations, respectively. Moreover, Etest also was able to detect 3/3 mutants using caspofungin ECVs and 2/3 micafungin mutant isolates. Applying the voriconazole and posaconazole SYO ECVs, 57.7% (67/116) and 100% (47/47) of mutants with known substitutions were classified as NWT, respectively. VIPcheck detected 90.3% (159/176), 80.1% (141/176) and 66% (141/176)of mutants via itraconazole, voriconazole and posaconazole, respectively, whereas Micronaut-AM detected 88% (22/25). In conclusion, Etest posaconazole and itraconazole, as well as micafungin and caspofungin ECVs, detected mutants. On the other hand, while the posaconazole SYO ECV was able to detect mutants, similar data were not observed with the SYO voriconazole ECV.
PubMed: 38535222
DOI: 10.3390/jof10030214 -
Journal of Fungi (Basel, Switzerland) Mar 2024This study assessed the changes in species distribution and antifungal susceptibility patterns during the coronavirus disease 2019 (COVID-19) pandemic compared with a...
Changing Epidemiology of Clinical Isolates of Species during the Coronavirus Disease 2019 Pandemic: Data Analysis from a Korean Tertiary Care Hospital for 6 Years (2017-2022).
This study assessed the changes in species distribution and antifungal susceptibility patterns during the coronavirus disease 2019 (COVID-19) pandemic compared with a pre-pandemic period in Korea. We retrospectively investigated the specimen, species type, and antifungal susceptibility of isolates obtained between 2016 and 2022. Data between two periods were compared: 2016-2019 (pre-pandemic) and 2020-2022 (pandemic). We included 11,396 clinical isolates of species (5137 isolates in the pre-pandemic and 6259 isolates in the pandemic). The most prevalent species was (50.4%), followed by (22.7%), (12.5%), and complex (12.5%). Their ranks were unchanged; however, their relative isolation ratios varied during the pandemic, exhibiting differences ranging from 0.4 to 2.5 across species. The incidence of candidemia increased during the pandemic (average 1.79 episodes per 10,000 patient days) compared with pre-pandemic levels (average 1.45 episodes per 10,000 patient days) in both intensive-care-unit (ICU) and non-ICU patients. Additionally, complex candidemia increased by 1.6-fold during the pandemic. During the pandemic, and candidemia significantly increased by 1.5- and 1.4-fold in ICU patients. In contrast, complex candidemia surged 2.1-fold in non-ICU patients. These species exhibited reduced resistance to fluconazole, voriconazole, caspofungin, and micafungin in the pandemic compared with the pre-pandemic. This study underscores the heightened incidence of -related infections during the COVID-19 pandemic and emphasizes the importance of ongoing surveillance of species epidemiology beyond the pandemic's scope.
PubMed: 38535202
DOI: 10.3390/jof10030193 -
Diagnostic Microbiology and Infectious... Jun 2024This study aimed to develop and validate a rapid method for identification by MALDI-TOF system and determination of the susceptibility to Fluconazole and Micafungin by...
This study aimed to develop and validate a rapid method for identification by MALDI-TOF system and determination of the susceptibility to Fluconazole and Micafungin by broth microdilution among Candidaspecies causing bloodstream infections. Subcultures from blood culture bottles were incubated for 5 hours (+/- 1h) and used to perform the tests, so that the turnaround time of rapid identification and susceptibility profile was about 5 and 24 hours, respectively. The rapid identification showed agreement of 92.05 %. Regarding the rapid broth microdilution for Fluconazole and Micafungin, the agreement was 97.06 % (p<0.001) and 100 % (p<0.001), and the Kappa coefficient was 0.91 (p<0.001) and 1.0 (p<0.001), respectively. To conclude, both rapid methods showed to be reproducible, inexpensive, easy to perform and time-saving. Thus, these methodologies could be useful to guide and adjust empirical antifungal therapy.
Topics: Micafungin; Humans; Microbial Sensitivity Tests; Candida; Antifungal Agents; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Blood Culture; Lipopeptides; Echinocandins; Fluconazole; Candidemia; Time Factors; Reproducibility of Results
PubMed: 38522370
DOI: 10.1016/j.diagmicrobio.2024.116271 -
Frontiers in Cellular and Infection... 2024is a genus of budding yeast that is mainly isolated from environmental samples, and 40 species have been detected. The yeast isolated from human clinical samples...
is a genus of budding yeast that is mainly isolated from environmental samples, and 40 species have been detected. The yeast isolated from human clinical samples usually only contain three species: , and . In this study, we isolated from a blood sample of a six-year-old female with a history of B-cell precursor lymphoblastic leukemia in Japan in 2022. Though the strain was morphologically identified as species by routine microbiological examinations, it was subsequently identified as by sequencing the internal transcribed spacer (ITS) of ribosomal DNA (rDNA). The isolate had amino acid substitutions in ERG11 and FKS1 associated with azole and echinocandin resistance, respectively, in species and showed intermediate-resistant to fluconazole and micafungin. The patient was successfully treated with micafungin. Furthermore, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) detected three novel peaks that are specific for , indicating that MALDI-MS analysis is useful for rapid detection of species in routine microbiological examinations.
Topics: Female; Humans; Child; Antifungal Agents; Blood Culture; Micafungin; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Microbial Sensitivity Tests; Candida; Saccharomycetales
PubMed: 38510957
DOI: 10.3389/fcimb.2024.1361432 -
MBio Apr 2024Recent epidemiological studies documented an alarming increase in the prevalence of echinocandin-resistant (ECR) blood isolates. ECR isolates are known to arise from a...
UNLABELLED
Recent epidemiological studies documented an alarming increase in the prevalence of echinocandin-resistant (ECR) blood isolates. ECR isolates are known to arise from a minor subpopulation of a clonal population, termed echinocandin persisters. Although it is believed that isolates with a higher echinocandin persistence (ECP) are more likely to develop ECR, the implication of ECP needs to be better understood. Moreover, replacing laborious and time-consuming traditional approaches to determine ECP levels with rapid, convenient, and reliable tools is imperative to advance our understanding of this emerging concept in clinical practice. Herein, using extensive and systemic infection models, we showed that high ECP isolates are less effectively cleared by micafungin treatment and exclusively give rise to ECR colonies. Additionally, we developed a flow cytometry-based tool that takes advantage of a SYTOX-based assay for the stratification of ECP levels. Once challenged with various collections of echinocandin-susceptible blood isolates, our assay reliably differentiated ECP levels and predicted ECP levels in real time under and conditions when compared to traditional methods relying on colony-forming unit counting. Given the high and low ECP predictive values of 92.3% and 82.3%, respectively, our assay showed a high agreement with traditional approach. Collectively, our study supports the concept of ECP level determination in clinical settings and provides a robust tool scalable for high-throughput settings. Application of this tool facilitates the interrogation of mutant and drug libraries to further our understanding of persister biology and designing anti-persister therapeutics.
IMPORTANCE
is a prevalent fungal pathogen able to replicate inside macrophages and rapidly develop resistance against frontline antifungal echinocandins. Multiple studies have shown that echinocandin resistance is fueled by the survival of a small subpopulation of susceptible cells surviving lethal concentrations of echinocandins. Importantly, bacterial pathogens that exhibit high antibiotic persistence also impose a high burden and generate more antibiotic-resistant colonies. Nonetheless, the implications of echinocandin persistence (ECP) among the clinical isolates of have not been defined. Additionally, ECP level determination relies on a laborious and time-consuming method, which is prone to high variation. By exploiting systemic infection and models, we showed that isolates with a higher ECP are associated with a higher burden and more likely develop echinocandin resistance upon micafungin treatment. Additionally, we developed an assay that reliably determines ECP levels in real time. Therefore, our study identified isolates displaying high ECP levels as important entities and provided a reliable and convenient tool for measuring echinocandin persistence, which is extendable to other fungal and bacterial pathogens.
Topics: Echinocandins; Candida glabrata; Micafungin; Drug Resistance, Fungal; Microbial Sensitivity Tests; Antifungal Agents; Anti-Bacterial Agents
PubMed: 38501869
DOI: 10.1128/mbio.00072-24 -
Journal of Clinical Microbiology Apr 2024Although the Vitek 2 system is broadly used for antifungal susceptibility testing of spp., its performance against has been assessed using limited number of isolates...
Evaluation of the Vitek 2 system for antifungal susceptibility testing of using a representative international panel of clinical isolates: overestimation of amphotericin B resistance and underestimation of fluconazole resistance.
Although the Vitek 2 system is broadly used for antifungal susceptibility testing of spp., its performance against has been assessed using limited number of isolates recovered from restricted geographic areas. We therefore compared Vitek 2 system with the reference Clinical and Laboratory Standards Institute (CLSI) broth microdilution method using an international collection of 100 . isolates belonging to different clades. The agreement ±1 twofold dilution between the two methods and the categorical agreement (CA) based on the Centers for Disease Control and Prevention's (CDC's) tentative resistance breakpoints and Vitek 2-specific wild-type upper limit values (WT-ULVs) were determined. The CLSI-Vitek 2 agreement was poor for 5-flucytosine (0%), fluconazole (16%), and amphotericin B (29%), and moderate for voriconazole (61%), micafungin (67%), and caspofungin (81%). Significant interpretation errors were recorded using the CDC breakpoints for amphotericin B (31% CA, 69% major errors; MaEs) and fluconazole (69% CA, 31% very major errors; VmEs), but not for echinocandins (99% CA, 1% MaEs for both micafungin and caspofungin) for which the Vitek 2 allowed correct categorization of echinocandin-resistant mutant isolates. Discrepancies were reduced when the Vitek 2 WT-ULV of 16 mg/L for amphotericin B (98% CA, 2% MaEs) and of 4 mg/L for fluconazole (96% CA, 1% MaEs, 3% VmEs) were used. In conclusion, the Vitek 2 system performed well for echinocandin susceptibility testing of . Resistance to fluconazole was underestimated whereas resistance to amphotericin B was overestimated using the CDC breakpoints of ≥32 and ≥2 mg/L, respectively. Vitek 2 minimun inhibitory concentrations (MICs) >4 mg/L indicated resistance to fluconazole and Vitek 2 MICs ≤16 mg/L indicated non-resistance to amphotericin B.
Topics: Humans; Fluconazole; Amphotericin B; Antifungal Agents; Candida auris; Micafungin; Caspofungin; Microbial Sensitivity Tests; Echinocandins
PubMed: 38501836
DOI: 10.1128/jcm.01528-23 -
European Journal of Clinical... May 2024This study investigates how surfactants affect the in-vitro anti-infective efficacy of micafungin, caspofungin, anidulafungin, and amphotericin B in treating pulmonary...
PURPOSE
This study investigates how surfactants affect the in-vitro anti-infective efficacy of micafungin, caspofungin, anidulafungin, and amphotericin B in treating pulmonary mycoses.
METHODS
MIC values for antifungal agents were determined against Candida krusei (now Pichia kudriavzevii) ATCC 6258, Candida albicans ATCC 90028, and 18 clinical isolates using the broth microdilution method in RPMI medium, following EUCAST recommendations. MIC assays included testing with and without Curosurf® surfactant at 1 mg/mL for C. krusei ATCC 6258 and all C. krusei isolates. Subsequent Time-kill studies in Sabouraud broth involved testing both C. albicans ATCC 90028 and C. krusei ATCC 6258 strains at concentrations equal their respective MIC values, with and without surfactant, using all four antifungals. CFU/mL were assessed at multiple time points up to 24 h. TKCs with different surfactant concentrations for C. krusei ATCC 6258 and mini-TKCs at various concentrations relative to the MIC of C. krusei isolates and the reference strain were conducted with micafungin, anidulafungin, and caspofungin.
RESULTS
MIC results showed that 1 µg/mL surfactant reduced killing of micafungin and anidulafungin against C. krusei, while caspofungin was unaffected. Amphotericin B's MIC decreased by half. TKCs demonstrated significant effects of surfactant on micafungin and anidulafungin against C. krusei, with complete abolition of anidulafungin's activity against C. albicans.
CONCLUSION
This in-vitro study highlights the concentration-dependent inhibitory effect of surfactant on antifungal activity against C. krusei and, to some extent, C. albicans, necessitating further clinical validation for invasive lung mycoses treatment.
Topics: Antifungal Agents; Microbial Sensitivity Tests; Humans; Pulmonary Surfactants; Candida albicans; Candida; Micafungin; Candidiasis; Amphotericin B; Echinocandins; Caspofungin
PubMed: 38483681
DOI: 10.1007/s10096-024-04799-7 -
BMC Infectious Diseases Mar 2024Chronic disseminated candidiasis (CDC) is a severe but rarely seen fungal infection presenting in patients with hematologic malignancies after a prolonged duration of... (Review)
Review
Chronic disseminated candidiasis (CDC) is a severe but rarely seen fungal infection presenting in patients with hematologic malignancies after a prolonged duration of neutropenia. A high index of suspicion is required to diagnose CDC as standard culture workup is often negative. While tissue biopsy is the gold standard of diagnosis, it is frequently avoided in patients with profound cytopenias and increased bleeding risks. A presumptive diagnosis can be made in patients with recent neutropenia, persistent fevers unresponsive to antibiotics, imaging findings of hypoechoic, non-rim enhancing target-like lesions in the spleen and liver, and mycologic evidence. Here, we describe the case of an 18-year-old woman with relapsed B-cell acute lymphoblastic leukemia treated with re-induction chemotherapy who subsequently developed CDC with multi-organ involvement. The diagnosis was made based on clinical and radiologic features with positive tissue culture from a skin nodule and hepatic lesion. The patient was treated for a total course of 11 months with anti-fungal therapy, most notably amphotericin B and micafungin, and splenectomy. After initial diagnosis, the patient was monitored with monthly CT abdomen imaging that showed disease control after 5 months of anti-fungal therapy and splenectomy. The diagnosis, treatment, and common challenges of CDC are outlined here to assist with better understanding, diagnosis, and treatment of this rare condition.
Topics: Female; Humans; Adolescent; Leukemia, Myeloid, Acute; Candidiasis; Hematologic Neoplasms; Neutropenia
PubMed: 38448809
DOI: 10.1186/s12879-024-09172-9 -
Medical Mycology Case Reports Mar 2024is emerging as a highly resistant species of the complex causing invasive and mucocutaneous infections. In this study, three cases of vulvovaginal candidiasis caused...
is emerging as a highly resistant species of the complex causing invasive and mucocutaneous infections. In this study, three cases of vulvovaginal candidiasis caused by are described and identified by Internal Transcribed Spacer 1-2 sequencing. All isolates were susceptible in vitro to anidulafungin, micafungin, caspofungin, 5-flucytosine, posaconazole, voriconazole, itraconazole, amphotericin B, and showed dose-dependent susceptibility to fluconazole. In two patients, three doses of oral fluconazole were effective, while one patient developed clinical fluconazole resistance with a new relapse after 6 months. Increasing the weekly dose of fluconazole showed to be effective in this patient.
PubMed: 38444800
DOI: 10.1016/j.mmcr.2024.100640