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Journal of Fungi (Basel, Switzerland) May 2024The efficacy of different echinocandins is assessed by evaluating the in vitro activity of a novel antifungal, rezafungin, against invasive fungal isolates in comparison...
The efficacy of different echinocandins is assessed by evaluating the in vitro activity of a novel antifungal, rezafungin, against invasive fungal isolates in comparison with anidulafungin and caspofungin. Using the broth microdilution (BMD) method, the susceptibility of 1000 clinical isolates (including 400 , 200 , 200 , 150 and 50 ) and 150 isolates (100 and 50 ) from the Eastern China Invasive Fungi Infection Group (ECIFIG) was tested for the antifungals including anidulafungin, rezafungin, caspofungin and fluconazole. The echinocandins showed strong activity against that was maintained against fluconazole-resistant isolates. The GM MIC (geometric mean minimum inhibitory concentration) value of rezafungin was found to be comparable to that of anidulafungin or caspofungin against the five tested common species. exhibited higher resistance rates (about 8.67-40.67% in different antifungals) than the other four species. Through the sequencing of genes, we searched for mutations in echinocandin-resistant isolates and found that all displayed alterations in S654P. The determined MEC (minimal effective concentration) values against and for rezafungin (0.116 μg/mL, 0.110 μg/mL) are comparable to those of caspofungin (0.122 μg/mL, 0.142 μg/mL) but higher than for anidulafungin (0.064 μg/mL, 0.059 μg/mL). Thus, the in vitro activity of rezafungin appears comparable to anidulafungin and caspofungin against most common and species. Rezafungin showed higher susceptibility rates against . Rezafungin indicates its potent activity for potential clinical application.
PubMed: 38921383
DOI: 10.3390/jof10060397 -
Journal of Fungi (Basel, Switzerland) May 2024The incidence of infections has increased in the last decade, posing a serious threat to public health. Appropriately facing this challenge requires precise...
The incidence of infections has increased in the last decade, posing a serious threat to public health. Appropriately facing this challenge requires precise epidemiological data on species and antimicrobial resistance incidence, but many countries lack appropriate surveillance programs. This study aims to bridge this gap for Morocco by identifying and phenotyping a year-long collection of clinical isolates (n = 93) from four clinics in Tetouan. We compared the current standard in species identification with molecular methods and assessed susceptibility to fluconazole and anidulafungin. Our results identified limitations in currently used diagnostics approaches, and revealed that ranks as the most prevalent species with 60 strains (64.52%), followed by with 14 (15.05%), with 6 (6.45%), and with 4 (4.30%). In addition, we report the first identification of in Morocco. Susceptibility results for fluconazole revealed that some isolates were approaching MICs resistance breakpoints in (2), and (1). Our study also identified anidulafungin resistant strains in (1), (1), and (2), rendering the two strains from the latter species multidrug-resistant due to their innate resistance to fluconazole. These results raise concerns about species identification and antifungal resistance in Morocco and highlight the urgent need for more accurate methods and preventive strategies to combat fungal infections in the country.
PubMed: 38921360
DOI: 10.3390/jof10060373 -
Access Microbiology 2024stands as the predominant fungal genus in the airways of cystic fibrosis (CF) patients, significantly contributing to their morbidity and mortality. represents the...
stands as the predominant fungal genus in the airways of cystic fibrosis (CF) patients, significantly contributing to their morbidity and mortality. represents the primary causative species for infections, though the emergence of rare species within the section has become noteworthy. Among these, is particularly significant due to its frequent misidentification and intrinsic resistance to azole antifungal agents. In the management of invasive aspergillosis and resistant infections, combination antifungal therapy has proven to be an effective approach. This report documents a case involving the death of a CF patient due to a pulmonary exacerbation linked to the colonization of multiple species, including , , and , and treated with Itraconazole (ITC) monotherapy. We delineated the procedures used to characterize the isolates in clinical settings and simulated the impact of the combination antifungal therapy on the isolates obtained from the patient. We evaluated three different combinations: Amphotericin B (AMB)+Voriconazole (VRC), AMB+Anidulafungin (AND), and VRC+AND. Notably, all strains isolated from the patient exhibited a significant decrease in their minimum inhibitory concentration (MIC) or minimum effective concentration (MEC) values when treated with all antifungal combinations. The VRC+AMB combination demonstrated the most synergistic effects. This case report emphasizes the critical importance of susceptibility testing and precise identification of species to enhance patient prognosis. It also underscores the potential benefits of combined antifungal treatment, which, in this case, could have led to a more favourable patient outcome.
PubMed: 38737802
DOI: 10.1099/acmi.0.000758.v3 -
IDCases 2024is an emerging opportunistic yeast in the Mediterranean region typically isolated from immunocompromised patients, usually affected by blood malignancies. We reported a...
is an emerging opportunistic yeast in the Mediterranean region typically isolated from immunocompromised patients, usually affected by blood malignancies. We reported a rare case of infection, isolated from a drainage fluid in a patient affected by lung cancer recovered in the University Hospital of Campania "Luigi Vanvitelli", Naples, Italy. The isolate was identified by phenotypic methods, i.e., Gram and Lactophenol cotton blue (LCB) staining, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis. We identified on the third day from Sabouraud Dextrose Agar supplemented with chloramphenicol and gentamicin. Antifungal susceptibility test revealed that 5-fluorocytosine was the most active drug against , followed by itraconazole and voriconazole, micafungin, amphotericin B and fluconazole, posaconazole, anidulafungin, and caspofungin. Our data showed the importance of an early cultural and fast microbiology diagnosis based on the characteristic morphologic features observed in Gram-stained smears of blood culture positive bottles, and the validation via MALDI-TOF MS. This dual approach has significant impact in the clinical management of infectious diseases and antibiotic stewardship, by integrating sample processing, fluid handling, and detection for rapid bacterial diagnosis.
PubMed: 38681078
DOI: 10.1016/j.idcr.2024.e01959 -
Antibiotics (Basel, Switzerland) Apr 2024Patients undergoing extracorporeal membrane oxygenation (ECMO) often require therapy with anti-infective drugs. The pharmacokinetics of these drugs may be altered during...
Patients undergoing extracorporeal membrane oxygenation (ECMO) often require therapy with anti-infective drugs. The pharmacokinetics of these drugs may be altered during ECMO treatment due to pathophysiological changes in the drug metabolism of the critically ill and/or the ECMO therapy itself. This study investigates the latter aspect for commonly used anti-infective drugs in an ex vivo setting. A fully functional ECMO device circulated an albumin-electrolyte solution through the ECMO tubes and oxygenator. The antibiotic agents cefazolin, cefuroxim, cefepime, cefiderocol, linezolid and daptomycin and the antifungal agent anidulafungin were added. Blood samples were taken over a period of four hours and drug concentrations were measured via high-pressure liquid chromatography (HPLC) with UV detection. Subsequently, the study analyzed the time course of anti-infective concentrations. The results showed no significant changes in the concentration of any tested anti-infectives throughout the study period. This ex vivo study demonstrates that the ECMO device itself has no impact on the concentration of commonly used anti-infectives. These findings suggest that ECMO therapy does not contribute to alterations in the concentrations of anti-infective medications in severely ill patients.
PubMed: 38667049
DOI: 10.3390/antibiotics13040373 -
Journal of Infection and Public Health Jun 2024Candidemia is the most common healthcare associated invasive fungal infection. Over the last few decades, candidemia caused by Candida species other than Candida...
BACKGROUND
Candidemia is the most common healthcare associated invasive fungal infection. Over the last few decades, candidemia caused by Candida species other than Candida albicans, particularly the Candida parapsilosis complex, has emerged worldwide. The aims of this study were: to analyze the genotypic and phenotypic characteristics of C. parapsilosis strains isolated from blood cultures and the environment in a hospital in southern Italy, to study the possible source of infection and to correlate the isolated strains.
METHODS
From April to October 2022, cases of candidemia due to C. parapsilosis in patients admitted to a hospital in the Apulia region were investigated. However, 119 environmental samples from the intensive care unit were collected for identification of the likely environmental reservoir of infection. Routine antifungal (amphotericin B, anidulafungin, fluconazole) susceptibility was performed on all isolates. Whole genome sequencing was performed to study the genotypic correlation of the isolates. Biofilm biomass and metabolic activity were also quantified for all isolates.
RESULTS
A total of 43 C. parapsilosis isolates were cultured from the bloodstream of each patient in different departments, and seven surface samples were positive for C. parapsilosis. Most of the isolated yeasts (41/50; 85 %) were resistant to fluconazole and were genetically related to each other, suggesting an ongoing clonal outbreak of this pathogen. The fluconazole-susceptible isolates produced significantly more biofilm than did the resistant isolates. Metabolic activity was also higher for fluconazole-susceptible than resistant isolates.
CONCLUSION
Cross-transmission of the microorganisms is suggested by the phenotypic similarity and genetic correlation between clinical and environmental strains observed in our study.
Topics: Humans; Italy; Candidemia; Antifungal Agents; Candida parapsilosis; Genotype; Cross Infection; Hospitals, Teaching; Microbial Sensitivity Tests; Phenotype; Biofilms; Drug Resistance, Fungal; Whole Genome Sequencing; Female; Fluconazole; Male
PubMed: 38631066
DOI: 10.1016/j.jiph.2024.04.009 -
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 -
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 -
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