Ассоциированная с мутациями генов FKS резистентность Candida glabrata к эхинокандинам: насколько актуальна проблема?

Клиническая Микробиология и Антимикробная Химиотерапия. 2016; 18(2):130-145

​ Веселов А.В.
Сandida glabrata кандидоз эхинокандины FKS резистентность
Раздел
Антибиотикорезистентность
Тип
Журнальная статья
Публикация
Клиническая Микробиология и Антимикробная Химиотерапия. 2016; 18(2):130-145

Аннотация

Резистентность возбудителей системных Candida-инфекций является краеугольным камнем подбора эффективной терапии. Но если раньше проблема ограничивалась только устойчивостью к азоловым антимикотикам, то к настоящему времени накоплен определённый объём данных о случаях неэффективности терапии эхинокандинами — препаратами выбора при большинстве клинических форм инвазивного кандидоза. Наибольшее число сообщений касается такого проблемного вида как C. glabrata, частота выделения которого имеет неуклонную тенденцию к росту, и который обладает рядом уникальных структурно-функциональных особенностей. Основополагающим механизмом формирования резистентности к эхинокандинам грибов рода Candida вообще, и C. glabrata в частности, являются приобретённые, в большинстве случаев на фоне длительной терапии, мутации генов FKS1/FKS2, отвечающих за активность мишени действия эхинокандинов — фермента β-1,3-D-глюкансинтетазы. Проблемы, связанные с детекцией таких штаммов обычными методиками определения чувствительности, привели, в частности, к пересмотру интерпретационных критериев для существующих протоколов. Информация о типах мутаций потенциально может помочь в разработке методов детекции определённых изменений на уровне генов, которые смогут с большой вероятностью прогнозировать неэффективность терапии эхинокандинами. Выявление штаммов C. glabrata, устойчивых к эхинокандинам, является важной клинической проблемой в плане выбора и новых подходов в терапии, включая поиск новых мишеней действия препаратов. В отсутствие таковых политика применения антимикотиков в стационаре должна помочь в снижении необоснованного использования эхинокандинов — основного промоутера появления резистентных штаммов Candida.

Веселов Александр Валерьевич

НИИ антимикробной химиотерапии ГБОУ ВПО СГМУ Минздрава России, Смоленск, Россия

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