<i>In Vitro</i>
            Activities of Ravuconazole and Isavuconazole against Dematiaceous Fungi

Zheng, Hailin; Song, Nana; Mei, Huan; Dong, Jiacheng; Li, Dongmei; Li, Xiaofang; Liu, Weida

doi:10.1128/aac.00643-20

Cited by 9 publications

(11 citation statements)

References 28 publications

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“…Like other azoles, ravuconazole targets the CYP51 enzyme leading to the destabilization of the fungal cell wall. Although it shows good in vitro activity against several fungal species [19, [28][29][30][31][32][33][34], clinical studies on ravuconazole have been discontinued in 2007 due to bioavailability issues [35]. Fosravuconazole, a prodrug to ravuconazole has since been acquired by Eisai Ltd (Japan) and is currently being investigated in a randomised, double-blinded DNDi sponsored clinical trial for mycetoma [36].…”

Section: Discussionmentioning

confidence: 99%

Screening the pandemic response box identified benzimidazole carbamates, Olorofim and ravuconazole as promising drug candidates for the treatment of eumycetoma

et al. 2022

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Eumycetoma is a chronic subcutaneous neglected tropical disease that can be caused by more than 40 different fungal causative agents. The most common causative agents produce black grains and belong to the fungal orders Sordariales and Pleosporales. The current antifungal agents used to treat eumycetoma are itraconazole or terbinafine, however, their cure rates are low. To find novel drugs for eumycetoma, we screened 400 diverse drug-like molecules from the Pandemic Response Box against common eumycetoma causative agents as part of the Open Source Mycetoma initiative (MycetOS). 26 compounds were able to inhibit the growth of Madurella mycetomatis, Madurella pseudomycetomatis and Madurella tropicana, 26 compounds inhibited Falciformispora senegalensis and seven inhibited growth of Medicopsis romeroi in vitro. Four compounds were able to inhibit the growth of all five species of fungi tested. They are the benzimidazole carbamates fenbendazole and carbendazim, the 8-aminoquinolone derivative tafenoquine and MMV1578570. Minimal inhibitory concentrations were then determined for the compounds active against M. mycetomatis. Compounds showing potent activity in vitro were further tested in vivo. Fenbendazole, MMV1782387, ravuconazole and olorofim were able to significantly prolong Galleria mellonella larvae survival and are promising candidates to explore in mycetoma treatment and to also serve as scaffolds for medicinal chemistry optimisation in the search for novel antifungals to treat eumycetoma.

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Section: Discussionmentioning

confidence: 99%

Screening the pandemic response box identified benzimidazole carbamates, Olorofim and ravuconazole as promising drug candidates for the treatment of eumycetoma

et al. 2022

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“…The heterogeneity of dematiaceous fungi makes susceptibility profiles valuable in determining the appropriate antifungal therapy for a given isolate. Given the lack of robust in‐vitro , pharmacokinetic, and pharmacodynamic data, as well as clinical outcomes data, there are no established MIC breakpoints for determining susceptibility; however, several genera have lower in‐vitro MICs for voriconazole, itraconazole, and posaconazole relative to fluconazole 193,194 . Ravuconazole and isavuconazole have also been found to have low MICs in certain species 194 .…”

Section: Discussionmentioning

confidence: 99%

“…193,194 Ravuconazole and isavuconazole have also been found to have low MICs in certain species. 194 We summarized reports that used BMD methods or of disseminated infections receiving combination therapy. 170 Disseminated infections in the present review received ≥ 2 antifungal agents more frequently (73%).…”

Section: F I G U R Ementioning

confidence: 99%

Dematiaceous fungal infections in solid organ transplantation: Systematic review and Bayesian meta‐analysis

Radcliffe

Azar

et al. 2022

Transplant Infectious Dis

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Background: Dematiaceous fungi cause a number of infectious syndromes referred to as phaeohyphomycosis among both immunocompetent and immunocompromised hosts. We performed a systematic review to characterize these infections in solid organ transplant recipients (SOTR). Methods:We searched PubMed database (last searched 1/6/2022) for Englishlanguage reports on dematiaceous fungal infections in SOTR. Included reports needed individualized demographic, treatment, and outcome data; pediatric reports were excluded. A universally applicable bias assessment was performed on reports. Models for infection type and outcome were created using the Bayesian paradigm. Results:We included 149 reports on 201 cases of dematiaceous fungal infections in SOTR. The mean age was 54 years, 72% were men, and kidney recipients accounted for 61% of cases. Skin and soft tissue infection (SSTI) was the most common infectious syndrome (73%). Death from infection occurred in 7% of cases (14/201), with disseminated (32%) cases having the highest mortality. Our model for infection type predicted the relative probability of central nervous system infection to be highest in liver recipients. Across all transplant types, higher relative probabilities of disseminated and pulmonary infections occur in the early post-transplant period, and the predicted probabilities for these infection types decreased after 100 months post-transplantation.Discussion: We identified SSTI as the most common dematiaceous fungal infections in SOTR. Disseminated infections carried the worst prognosis. The evidence in this review is limited by the heterogeneity of included cases. No funding source was used, and this review's protocol was not registered.

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“… 14 Clinical case reports also showed that fungal melanonychia caused by different Candida spp. was successfully treated with oral fosravuconazole 15‐17 . It is, therefore, reasonable to expect that ravuconazole will become a new oral treatment option against other manifestations of candidiasis.…”

Section: Introductionmentioning

confidence: 99%

“…was successfully treated with oral fosravuconazole. [15][16][17] It is, therefore, reasonable to expect that ravuconazole will become a new oral treatment option against other manifestations of candidiasis.…”

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confidence: 99%

In Vitro activity of ravuconazole against Candida auris and vaginal candida isolates

Dong

Liang

Zheng

et al. 2021

Mycoses

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Background Ravuconazole is an extended‐spectrum triazole agent that is efficient in vitro against Candida spp. and has been approved to work as an oral formulae for onychomycosis in Japan in 2018. However, nobody had determined the MIC of ravuconazole against the Candida auris, which is known as an emerging multidrug‐resistant yeast. Meanwhile, rare is known of the in vitro activity of ravuconazole against vaginal Candida isolates. Objectives To investigate the activity of ravuconazole against C. auris and vaginal Candida isolates of China and assess the feasibility of ravuconazole in the treatment of candidiasis caused by C. auris and other Candida spp. Methods We determined the in vitro activity of ravuconazole and 9 comparators against 15 C. auris isolates and determined the MIC of ravuconazole on 525 vaginal Candida isolates (Candida albicans, Candida tropicalis, Candida glabrata and Candida parapsilosis) from 9 provinces of China by Clinical and Laboratory Standards Institute (CLSI) methodology. Results The MICs of fluconazole and amphotericin B on C. auris were much higher than second‐generation azoles and echinocandins. Ravuconazole was active against all the C. auris isolates and as effective as isavuconazole, posaconazole and echinocandins while showed a better antifungal activity than itraconazole, voriconazole to C. auris. For vaginal Candida isolates, the proportion of ravuconazole‐resistant isolates is 0.19% (1/525). Conclusions Ravuconazole was in good active against C. auris and vaginal Candida isolates, which suggested ravuconazole could be used in the treatment of drug‐resistant candidiasis.

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In Vitro Activities of Ravuconazole and Isavuconazole against Dematiaceous Fungi

Cited by 9 publications

References 28 publications

Screening the pandemic response box identified benzimidazole carbamates, Olorofim and ravuconazole as promising drug candidates for the treatment of eumycetoma

Screening the pandemic response box identified benzimidazole carbamates, Olorofim and ravuconazole as promising drug candidates for the treatment of eumycetoma

Dematiaceous fungal infections in solid organ transplantation: Systematic review and Bayesian meta‐analysis

In Vitro activity of ravuconazole against Candida auris and vaginal candida isolates

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