Activity of a Long-Acting Echinocandin, Rezafungin, and Comparator Antifungal Agents Tested against Contemporary Invasive Fungal Isolates (SENTRY Program, 2016 to 2018)

Pfaller, Michael A.; Carvalhaes, Cecília G; Messer, S. A.; Rhomberg, Paul R.; Castanheira, Mariana

doi:10.1128/aac.00099-20

Cited by 53 publications

(30 citation statements)

References 44 publications

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“…is comparable to other members of the echinocandin class. Data based on Candida, Aspergillus and C. neoformans isolates collected worldwide in 2014 and 2015 confirm preliminary observations about rezafungin susceptibility [39,104,105]. According to the collected data, it appears that the upper limit of WT MIC distributions for Candida spp.…”

Section: Next-generation Echinocandinssupporting

confidence: 69%

“…was ≤0.12 mg/L, but for C. parapsilosis and C. orthopsilosis was ≤4 mg/L, and the MEC was ≤0.03 mg/L for Aspergillus spp. [39,105]. Rezafungin also exhibited activity against biofilm, through reductions in biofilm thicknesses in mature and early phases and also through inhibition of the formation of biofilm during adhesion [108].…”

Section: Next-generation Echinocandinsmentioning

confidence: 98%

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Review on Current Status of Echinocandins Use

Mroczyńska

Brillowska-Dąbrowska

2020

Antibiotics

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Fungal infections are rising all over the world every year. There are only five medical compound classes for treatment: triazoles, echinocandins, polyenes, flucytosine and allylamine. Currently, echinocandins are the most important compounds, because of their wide activity spectrum and much lower sides effects that may occur during therapy with other drugs. Echinocandins are secondary metabolites of fungi, which can inhibit the biosynthesis of β-(1,3)-D-glucan. These compounds have fungicidal and fungistatic activity depending on different genera of fungi, against which they are used. Echinocandin resistance is rare—the major cause of resistance is mutations in the gene encoding the β-(1,3)-D-glucan synthase enzyme. In this review of the literature we have summarized the characteristics of echinocandins, the mechanism of their antifungal activity with pharmacokinetics and pharmacodynamics, and the resistance issue.

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Section: Next-generation Echinocandinssupporting

confidence: 69%

Section: Next-generation Echinocandinsmentioning

confidence: 98%

Review on Current Status of Echinocandins Use

Mroczyńska

Brillowska-Dąbrowska

2020

Antibiotics

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“…An initial dose of 400 mg rezafungin produces 22.7 mg/L C max and 1160 mg·h/L AUC values in the first week, pharmacokinetic parameters, which are 2.95- to 3.24-fold and 1.4- to 1.9-fold higher, respectively, compared to C max and AUC values produced by standard daily doses of anidulafungin, caspofungin, and micafungin [ 10 , 12 ]. In vitro, rezafungin activity is comparable to that of the three approved echinocandins against common and uncommon Candida species, including C. auris [ 14 , 15 ]. However, data on killing kinetics against different C. auris clades are absent.…”

Section: Introductionmentioning

confidence: 99%

Comparison of In Vitro Killing Activity of Rezafungin, Anidulafungin, Caspofungin, and Micafungin against Four Candida auris Clades in RPMI-1640 in the Absence and Presence of Human Serum

et al. 2021

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Candida auris is an emerging and frequently multidrug-resistant pathogen against which the echinocandins are the preferred therapeutic option. We compared killing activities of anidulafungin, caspofungin, micafungin, and rezafungin against 13 isolates representing four C. auris clades (South Asian n = 3; East Asian n = 3; South African n = 3; South American n = 4, of which two were of environmental origin). Minimum inhibitory concentration MICs and killing kinetics in RPMI-1640 and RPMI-1640 plus 50% serum (50% serum) were determined. The four echinocandins were never fungicidal and induced large aggregates in RPMI-1640 and, less markedly, in 50% serum. Colony forming unit CFU decreases were found more consistently in 50% serum than in RPMI-1640. Isolates from the East Asian clade were killed at ≥1–≥ 4 mg/L with all echinocandins regardless of media. Anidulafungin and micafungin produced killing at peak drug serum concentration (8 mg/L) against environmental but not clinical isolates from the South American and the South African clades. Micafungin at ≥8 mg/L but not anidulafungin produced CFU decreases against the South Asian clade as well. In 50% serum, rezafungin at ≥1–≥ 8 mg/L produced killing against all four clades. The next generation echinocandin, rezafungin, showed the same or better activity at clinically attainable trough concentration regardless of media, compared with anidulafungin, caspofungin, and micafungin against all four tested C. auris clades.

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“…The increased number of biofilm-associated infections is exacerbated by a paucity of antifungal agents or therapeutic strategies in development that have unique mechanisms of action or possess alternative approaches, respectively [ 11 ]. Currently, the most promising antifungal agents are already in Phase 3 including ibrexafungerp [ 12 ], rezafungin [ 13 ], super bioavailable itraconazole [ 14 ], and VT-1161 [ 15 ]. Recently investigated alternative therapeutic approaches involve high-dose therapy with available antifungal agents [ 16 , 17 , 18 ], antifungal lock therapy [ 19 ], and combination-based therapies [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Fungal Quorum-Sensing Molecules: A Review of Their Antifungal Effect against Candida Biofilms

Kovács

Majoros

2020

JoF

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The number of effective therapeutic strategies against biofilms is limited; development of novel therapies is urgently needed to treat a variety of biofilm-associated infections. Quorum sensing is a special form of microbial cell-to-cell communication that is responsible for the release of numerous extracellular molecules, whose concentration is proportional with cell density. Candida-secreted quorum-sensing molecules (i.e., farnesol and tyrosol) have a pivotal role in morphogenesis, biofilm formation, and virulence. Farnesol can mediate the hyphae-to-yeast transition, while tyrosol has the opposite effect of inducing transition from the yeast to hyphal form. A number of questions regarding Candida quorum sensing remain to be addressed; nevertheless, the literature shows that farnesol and tyrosol possess remarkable antifungal and anti-biofilm effect at supraphysiological concentration. Furthermore, previous in vitro and in vivo data suggest that they may have a potent adjuvant effect in combination with certain traditional antifungal agents. This review discusses the most promising farnesol- and tyrosol-based in vitro and in vivo results, which may be a foundation for future development of novel therapeutic strategies to combat Candida biofilms.

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Activity of a Long-Acting Echinocandin, Rezafungin, and Comparator Antifungal Agents Tested against Contemporary Invasive Fungal Isolates (SENTRY Program, 2016 to 2018)

Cited by 53 publications

References 44 publications

Review on Current Status of Echinocandins Use

Review on Current Status of Echinocandins Use

Comparison of In Vitro Killing Activity of Rezafungin, Anidulafungin, Caspofungin, and Micafungin against Four Candida auris Clades in RPMI-1640 in the Absence and Presence of Human Serum

Fungal Quorum-Sensing Molecules: A Review of Their Antifungal Effect against Candida Biofilms

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