Частота бактериальных коинфекций среди пациентов с COVID-19 невелика, поэтому избыточное назначение антибиотиков может способствовать селекции резистентных штаммов энтеробактерий и грамотрицательных неферментирующих бактерий.Цель исследования -оценка локальных особенностей и генетических механизмов антибиотикорезистентности K. pneumoniae на фоне пандемии инфекции COVID-19.Материал и методы. Отобрано 37 устойчивых к карбапенемам штаммов K. pneumoniae, выделенных в 2016, 2017 и 2020 гг. от госпитализированных пациентов, в том числе 15 штаммов, выделенных от пациентов с COVID-19. Методом микроразведений в бульоне определены минимальные подавляющие концентрации (МПК) меропенема и колистина. Определение МПК эравациклина, цефидерокола, цефтазидима/авибактама, меропенема/ваборбактама, имипенема/релебактама выполнено с использованием диагностической системы Sensititre на планшетах EUMDROXF. Чувствительность к 11 комбинациям из 2 разных антибиотиков определена модифицированным методом тестирования бактерицидности различных комбинаций. Для 4 штаммов K. pneumoniae выполнено высокопроизводительное секвенирование с последующим поиском детерминант антибиотикорезистентности и вирулентности, а также с оценкой плазмидных профилей.Результаты. Все штаммы были устойчивы к меропенему (МПК 50 32 мг/л, МПК 90 128 мг/л) и продуцировали карбапенемазы KPC и OXA-48. Штаммы, выделенные в 2016-2017 гг., были чувствительны к колистину (МПК 2 мг/л), в 2020 г. сохраняли чувствительность только 26,7% штаммов (МПК 50 64 мг/л, МПК 90 256 мг/л). Чувствительность к комбинациям из 2 антибиотиков с включением колистина сократилась с 84,6-100% в 2016-2017 гг. до 26,7-66,7% в 2020 г. Выделенные в 2020 г. штаммы сохраняли чувствительность к цефтазидиму/авибактаму (МПК 1 мг/л). Выявлено 5 штаммов, устойчивых к цефидероколу c МПК 8 мг/л. Штаммы 2564 и 3125, выделенные в 2020 г. из мокроты пациентов с инфекцией COVID-19, относились к различным сиквенс-типам (ST512 и ST23) и содержали ген карбапенемазы bla OXA-48, штамм 2564 дополнительно содержал ген карбапенемазы bla KPC-27. Устойчивость к колистину была вызвана инактивацией генов mgrB за счет инсерций IS1-и IS5-подобных транспозонов.Заключение. Выполненные генетические исследования демонстрируют многообразие механизмов антибиотикорезистентности у K. pneumoniae, приводящих к формированию устойчивости в том числе к антибиотикам, до настоящего времени не использовавшимся в Республике Беларусь.
Identification of numerous mechanisms of resistance to colistin and other antibiotics is possible using whole genome sequencing. Objectives. To assess the molecular-genetic mechanisms of resistance to polymyxins and antibiotics of other groups in nosocomial Klebsiella pneumoniae strains. Material and methods. For 13 multidrug- and extensively drug-resistant K.pneumoniae strains semiconductor sequencing was performed in the Ion PGM System genomic sequencer (Thermo Fisher Scientific, USA). The assembly of genomic sequences and their annotation were carried out. The PROVEAN software tool was used to predict the influence of nucleotide replacements on the structure of amino acid sequences and functional activity of proteins. The identification of antibiotic resistance genes and the search for efflux mechanisms were performed by the ResFinder v.4.1 and CARD web resources. Results. Several types of β-lactamase genes were detected simultaneously in all strains, as well as genes of resistance to fosfomycin. Genes of resistance to aminoglycosides were identified in 11 strains, to chloramphenicol - in 10, to rifampicin - in 5, to macrolides - in 4. The mcr phosphoethanolamine transferase genes were absent in all strains. Functionally significant substitutions were revealed in the pmrB gene (D150Y, T157P, G207S) comparing the studied samples with the reference K. pneumoniae strain ATCC 700603. Changes in the mgrB gene were also found in colistin-resistant strains (W20R replacement, insertional inactivation of the gene by transposons of the IS1, IS4 and IS5 families). Conclusions. The results of whole genome sequencing represent the significant resistance of nosocomial Klebsiella pneumoniae strains to the majority of antibiotics including β-lactams, aminoglycosides, fluoroquinolones, fosfomycin, chloramphenicol, polymyxins. Genetic determinants of colistin resistance were revealed (insertional inactivation and deletion of the mgrB gene; D150Y, T157P and G207S substitutions in the pmrB gene) in strains with colistin MIC 64-128 mg/l and their absence in colistin-susceptible strains.
Objective. To assess the susceptibility of K.pneumoniae and A.baumanii strains isolated from hospitalized COVID-19 patients to antibiotics and their combinations.Materials and methods. The minimum inhibitory concentrations (MICs) of meropenem and colistin were determined for 47 A.baumannii and 51K.pneumoniaestrains isolated from the hospitalized COVID-19 patients by the broth microdilution method. The susceptibility to 11 antibiotic combinations was assessed using the method of multiple combination bactericidal testing.Results. Colistin resistance was detected in 31.9 % of A.baumannii strains (MIC50 — 0.5 mg/l, MIC90 — 16 mg/l) and in 80.4 % of K.pneumoniaestrains (MIC50 — 16 mg/l, MIC90 — 256 mg/l). It has been shown that double antibiotic combinations with the inclusion of colistin exhibit bactericidal or bacteriostatic activity against 76.6–87.2 % of A.baumannii strains. Combinations with the addition of meropenem, colistin and macrolides exhibited bactericidal activity against 78.4–80.4 % of K.pneumoniae strains. Combinations of two carbapenems were not active, the combination of meropenem-colistin had a bactericidal effect only in 13.7 % of K.pneumoniae strains.Conclusion. Widespread colistin resistance was found in carbapenem-resistant K.pneumoniae and A.baumannii strains isolated from the hospitalized COVID-19 patients. The combinations of antibiotics that have a synergistic antibacterial effect in their pharmacokinetic/pharmacodynamic concentrations have been determined.
Poliomyelitis is a typical anthroponosis, in natural conditions it infects only humans. The only effective strategy for combating the infection is preventive vaccination. The polio vaccine induces long-lasting humoral and local immunity. The article presents a brief history of polio vaccine development, and compares live and inactivated vaccines currently licensed and used in Russia. It also dwells upon the benefits and shortcomings of each of these vaccines. The results of analysis demonstrated that all foreign-made and domestically-produced polio vaccines currently used in Russia meet international requirements in terms of main quality characteristics and comply with the WHO recommendations. The article looks into some issues arising from the use of live polio vaccine, in particular the development of vaccine-associated paralytic polio, and the appearance of vaccine-derived polioviruses. It reviews the main approaches of the current WHO polio eradication initiative, and summarises the outcomes of the 30-year period since the adoption of the Global Polio Eradication Initiative. The article describes the transition from live attenuated oral polio vaccine (types 1, 2 and 3) to bivalent vaccine (live attenuated oral polio vaccine, types 1 and 3). It discusses the necessity of using polio vaccines (both live and inactivated) at the final stage of polio eradication. The article presents the new National Immunisation Schedule.
The article investigates the epistemological grounds of differentiation of sociocultural perception of space in philosophical-legal presentations.
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