Journal of global antimicrobial resistance · 2022
Serotonin reuptake inhibitors effect on fluconazole activity against resistant Candida glabrata strains.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Alkhalifa Bashar A, Bulatova Nailya R, abuRokba Waed, Darwish Rula M
Аннотация
OBJECTIVES: The study aimed to evaluate four selective serotonin reuptake inhibitors (SSRIs) as modifiers of fluconazole activity against resistant strains of Candida glabrata.
METHODS: The effect of SSRIs on fluconazole activity was studied using the checkerboard method against C. glabrata strains (CBS 138, CBS 850821, DSY 562, DSY 565, ATCC 22553 and ATCC 90030); fractional inhibitory concentration index (FIC) was calculated and time-kill curve was used for the most prominent combination for further evaluation.
RESULTS: All used SSRIs have antifungal activity against the C. glabrata strains tested. A combination of fluconazole with fluoxetine or fluvoxamine showed indifferent effects (fractional inhibitory concentration index [FICI] in all strains >1 but <4), whereas a paroxetine-fluconazole combination showed an additive effect against DSY565 and CBS138, known to express efflux pumps as well as on ATCC strain (0.5 < FIC < 1) with indifferent effect on other strains used. The most promising combination was that of fluconazole with sertraline (FICI ≤0.5), where a synergistic effect was observed against all resistant and susceptible dose-dependent strains, including those known to express efflux pumps. This synergistic effect was confirmed by time-kill curve assay against all resistant C. glabrata and ATCC strains with a >2-log10 CFU/mL reduction caused by combination compared with a single active agent of fluconazole after 24 hours of incubation. A sertraline-fluconazole combination produced an additive effect on the reference ATCC strain.
CONCLUSION: Our data suggest that blocking active efflux pumps by sertraline may be considered the probable mechanism of synergism with fluconazole. The combination of sertraline with fluconazole could be a promising remedy for treatment of infections caused by resistant C. glabrata.
METHODS: The effect of SSRIs on fluconazole activity was studied using the checkerboard method against C. glabrata strains (CBS 138, CBS 850821, DSY 562, DSY 565, ATCC 22553 and ATCC 90030); fractional inhibitory concentration index (FIC) was calculated and time-kill curve was used for the most prominent combination for further evaluation.
RESULTS: All used SSRIs have antifungal activity against the C. glabrata strains tested. A combination of fluconazole with fluoxetine or fluvoxamine showed indifferent effects (fractional inhibitory concentration index [FICI] in all strains >1 but <4), whereas a paroxetine-fluconazole combination showed an additive effect against DSY565 and CBS138, known to express efflux pumps as well as on ATCC strain (0.5 < FIC < 1) with indifferent effect on other strains used. The most promising combination was that of fluconazole with sertraline (FICI ≤0.5), where a synergistic effect was observed against all resistant and susceptible dose-dependent strains, including those known to express efflux pumps. This synergistic effect was confirmed by time-kill curve assay against all resistant C. glabrata and ATCC strains with a >2-log10 CFU/mL reduction caused by combination compared with a single active agent of fluconazole after 24 hours of incubation. A sertraline-fluconazole combination produced an additive effect on the reference ATCC strain.
CONCLUSION: Our data suggest that blocking active efflux pumps by sertraline may be considered the probable mechanism of synergism with fluconazole. The combination of sertraline with fluconazole could be a promising remedy for treatment of infections caused by resistant C. glabrata.