Time-Kill Kinetics of Rezafungin (CD101) in Vagina-Simulative Medium for Fluconazole-Susceptible and Fluconazole-ResistantCandida albicansand Non-albicans CandidaSpecies

Abstract

Background While echinocandins demonstrate excellent efficacy against Candida species in disseminated infections and demonstrate potent minimal inhibitory concentration (MIC) values under standard susceptibility testing conditions, investigation under conditions relevant to the vaginal environment was needed. We assessed the antifungal activity and time-kill kinetics of the novel echinocandin rezafungin (formerly CD101) under such conditions, against Candida species relevant to vulvovaginal candidiasis (VVC). Methods Susceptibility testing of fluconazole-susceptible and fluconazole-resistant C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, and C. krusei was performed in RPMI at pH 7.0 and in vagina-simulative medium (VSM) at pH 4.2 for topical rezafungin, terconazole, fluconazole, and amphotericin B. Time-kill kinetics were evaluated for rezafungin and terconazole at 2, 8, 32, and 128 μg/ml over 72 hours. ResultsRezafungin MIC values were the same or 2-fold higher in VSM/pH 4.2 versus RPMI/pH 7.0. Some C. albicans terconazole MIC values were lower, but most were significantly higher in VSM than in RPMI. Rezafungin was fungicidal against 11/14 strains and near-fungicidal against the others. Terconazole (128 μg/ml) was fungicidal against C. krusei and near-fungicidal against susceptible C. parapsilosis but fungistatic versus all other strains evaluated. ConclusionRezafungin retained anti-Candida activity and fungicidal activity under in vitro conditions relevant to VVC.

K21 Compound, a Potent Antifungal Agent: Implications for the Treatment of Fluconazole-Resistant HIV-Associated Candida Species

“…K21 was considered to have fungicidal activity when there was a reduction in microbial growth of ≥3log 10 decrease in colony count after 24 h, resulting in about 99.9% reduction in CFU/ml relative to the initial inoculum. Fungistatic activity was considered as a reduction in growth lower than 99.9% or < 3log 10 in CFU/ml from the initial inoculum after 24 h (Locke et al, 2018).…”

Incorporation of Inclusion Complexes in the Dissolvable Microneedle Ocular Patch System for the Efficiency of Fluconazole in the Therapy of Fungal Keratitis

“…The average number of colonies (log cfu/mL) versus time (h) was constructed. 36,37 Parameters of fungicide activity were characterized by a decrease in microbial growth of ≥3 logs cfu/mL or a 99.99% reduction in microbial growth against the initial inoculum after 24 h. Conversely, fungistatic activity was characterized by a decrease in microbial growth <3 logs cfu/mL or a decrease in microbial growth of less than 99.99% after 24 h. 38 2.9. Preparation of DMN.…”

<p>Current Aspects in the Biology, Pathogeny, and Treatment of <em>Candida krusei</em>, a Neglected Fungal Pathogen</p>

“…[168][169][170] Although C. krusei is a rare etiological agent of vaginitis, the use of local clotrimazole, ciclopirox olamine, terconazole, and boric acid is recommended. 171,172 In veterinary infections though, isolates resistant to fluorocytosine, itraconazole, ketoconazole, and amphotericin B have been reported. 141 The pharmacological alternatives to treat candidiasis caused by C. krusei in animals include sulphamethoxypyridazine in cases of bovine mastitis.…”