Background: Candida auris is an emerging MDR pathogen. It shows reduced susceptibility to azole drugs and, in some strains, high amphotericin B MICs have been described. For these reasons, echinocandins were proposed as first-line treatment for C. auris infections. However, information on how echinocandins and amphotericin B act against this species is lacking.
Objectives: Our aim was to establish the killing kinetics of anidulafungin, caspofungin and amphotericin B against C. auris by time-kill methodology and to determine if these antifungals behave as fungicidal or fungistatic agents against this species.
Methods: The susceptibility of 50 C. auris strains was studied. Nine strains were selected (based on echinocandin MICs) to be further studied. Minimal fungicidal concentrations, in vitro dose-response and time-kill patterns were determined.
Results: Echinocandins showed lower MIC values than amphotericin B (geometric mean of 0.12 and 0.94 mg/L, respectively). Anidulafungin and caspofungin showed no fungicidal activity at any concentration (maximum log decreases in cfu/mL between 1.34 and 2.22). On the other hand, amphotericin B showed fungicidal activity, but at high concentrations (≥2.00 mg/L). In addition, the tested polyene was faster than echinocandins at killing 50% of the initial inoculum (0.92 versus >8.00 h, respectively).
Conclusions: Amphotericin B was the only agent regarded as fungicidal against C. auris. Moreover, C. auris should be considered tolerant to caspofungin and anidulafungin considering that their MFC:MIC ratios were mostly ≥32 and that after 6 h of incubation the starting inoculum was not reduced in >90%.
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http://dx.doi.org/10.1093/jac/dkz178 | DOI Listing |
J Clin Microbiol
January 2025
Element Iowa City (JMI Laboratories), North Liberty, Iowa, USA.
This study addresses the use of other echinocandins as surrogate markers to predict the susceptibility of rezafungin against the six most common spp. The Clinical Laboratory Standards Institute (CLSI) reference broth microdilution method was performed to test 5,720 clinical isolates of six different species. Species-specific interpretative criteria by CLSI breakpoints or epidemiological cutoff values were applied.
View Article and Find Full Text PDFAntibiotics (Basel)
December 2024
Neonatal Intensive Care Unit, School of Medicine, University of Ioannina, 45500 Ioannina, Greece.
The neonatal intensive care unit (NICU) population, especially low birth weight and critically ill neonates, is at risk of invasive infections, which are associated with high mortality rates and unfavorable long-term outcomes. The timely initiation of an appropriate antifungal treatment has been demonstrated to enhance the prognosis. Factors that should be considered in the choice of an antifungal agent include the causative strain, the presence and location of deep tissue infection, any previous use of antifungal prophylaxis, and the presence of implanted devices.
View Article and Find Full Text PDFClin Chem
January 2025
Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, United States.
Background: Candida auris is an emerging multidrug-resistant pathogen. Interpretation of susceptibility testing can be difficult since minimum inhibitory concentration (MIC) breakpoints have not been fully established.
Methods: All C.
Front Pharmacol
December 2024
Department of Pharmacy Practice, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia.
Clin Pharmacokinet
January 2025
Pharmacy Service, Division of Medicines, Hospital Clinic of Barcelona, Universitat de Barcelona, Barcelona, Spain.
In recent years, many population pharmacokinetic (popPK) models have been developed for echinocandins to better understand the pharmacokinetics (PK) of these antifungals. This comprehensive review aimed to summarize popPK models of echinocandins (micafungin, caspofungin, anidulafungin, and rezafungin), by focusing on dosage optimization to maximize the probability of attaining the PK/PD target proposed in special populations. A search in PubMed, Embase, Web of Science, and Scopus, supplemented by the bibliography of relevant articles, was conducted from inception to March 2024, including both observational and prospective trials.
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