Аннотация
РоссияВ настоящее время общепринятого определения гетерорезистентности нет, и чаще всего этот термин используют для описания неоднородности в уровне чувствительности отдельных клеток бактериальной суспензии, полученной из единичной колонии. При этом выделяют поликлональную и моноклональную гетерорезистентность. Под поликлональной гетерорезистентностью стоит понимать смешанную популяцию разных генетических линий одного вида с разной чувствительностью к антибиотикам. Моноклональная популяция всегда представлена одной генетической линией, в которой малая часть клеток проявляет устойчивость к антибиотику. Настоящий обзор посвящен только моноклональной гетерорезистентности. С точки зрения лабораторной диагностики, смешанная популяция в рамках одной колонии одного вида микроорганизма по признаку чувствительности к антибиотикам, является сложно дифференцируемым фенотипом. Гетерорезистентность в отношении разных антибиотиков встречается среди многих клинически значимых патогенов, в том числе и прихотливых. Использование методов диффузии в агар, серийных разведений, градиентных тестов, молекулярной детекции для оценки чувствительности к антибиотикам малоэффективны для выявления гете-рорезистентности. Клиническая значимость гетерорезистентности очевидна, определение ложной чувствительности ведет за собой назначение неадекватной антибактериальной терапии. В обзоре представлена сравнительная характеристика различных подходов для лабораторного определения фенотипа гетерорезистентности к разным антибактериальным препаратам. Приведено описание популяционного анализа и его различных модификаций как золотого стандарта выявления гетерорезистентности. Приведен сравнительный анализ подходов для выявления гетерорезистентности к ванкомицину у Staphylococcus aureus. Дана оценка роли классических методов определения чувствительности к антибиотикам для выявления гетерорезистентных фенотипов. В обзоре рассмотрены возможности использования методов молекулярного типирования и полногеномного секвенирования для выявления смешанных популяций. Гетерорезистентность является достаточно распространенным явлением, однако ее клиническое значение остается до конца не из-ученным. В настоящее время необходимы четкие определения и унификация методов выявления гетерорезистентности, особенно среди грамотрицательных патогенов. Очевидна необходимость разработки экспресс-методов для скрининга и выявления таких фенотипов в рутинной лабораторной практике.
Annotation
FederationSince there is currently no agreed upon definition of heteroresistance, this term is most frequently used to refer to the variation in the degree of susceptibility of individual bacteria in a bacterial suspension isolated from a single colony. There is a difference between polyclonal and monoclonal heteroresistance. It is necessary to understand that polyclonal heteroresistance is a mixed population of various lineages of the same species with varying antibiotic susceptibility. A monoclonal population is always rep-resented by a single lineage in which a small part of the cells is resistant to the antibiotic. Monoclonal heteroresistance is the only focus of this review. A mixed population within a colony of a single species of microorganism based on antibiotic susceptibility is a difficult-to-detect phenotype from the perspective of laboratory diagnostics. Many clinically significant pathogens, including fas-tidious ones, exhibit heteroresistance to different antibiotics. Heteroresistance cannot be identified using methods for determining antibiotic susceptibility such as agar diffusion, serial dilutions, gradient diffusion tests, or molecular detection. Heteroresistance has clear clinical implications and the definition of false sensitivity results in the prescription of ineffective antibiotic therapy. The review provides a comparison of various methods for laboratory determining the heteroresistance phenotype to various antibacte-rial drugs. The population analysis profile and all of its modifications are referred to as the gold standard for heteroresistance detection. It is presented a comparative analysis of methods for identifying vancomycin heteroresistance in Staphylococcus aureus. For the purpose of detecting heteroresistant phenotypes, the value of classical antibiotic susceptibility tests is discussed. The review examines the viability of identifying mixed populations using whole genome sequencing and molecular typing techniques. The clinical significance of heteroresistance, through a fairly common phenomenon, is still not fully understood. Currently, especially for gram-negative pathogens, clear definitions and a unified approach to heteroresistance detection are required. Developing express methods for screening and detecting such phenotypes in standard laboratory practice is obviously necessary.
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