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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">vestib</journal-id><journal-title-group><journal-title xml:lang="ru">Известия Национальной  академии наук Беларуси. Серия биологических наук</journal-title><trans-title-group xml:lang="en"><trans-title>Proceedings of the National Academy of Sciences of Belarus, Biological Series</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1029-8940</issn><issn pub-type="epub">2524-230X</issn><publisher><publisher-name>The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.29235/1029-8940-2022-67-3-332-342</article-id><article-id custom-type="elpub" pub-id-type="custom">vestib-826</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОБЗОРЫ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REVIEWS</subject></subj-group></article-categories><title-group><article-title>Изучение синергии антибактериальных препаратов с использованием метода  «шахматной доски» и анализа «времени уничтожения»</article-title><trans-title-group xml:lang="en"><trans-title>Studying synergy of antibacterial drugs using the “checkerboard” method and the “time-kill” analysis</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7368-0623</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Артюх</surname><given-names>Т. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Artyukh</surname><given-names>T. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Артюх Татьяна Валерьевна – магистр мед. наук, ассистент</p><p>ул. Горького, 80, 230009, г. Гродно</p></bio><bio xml:lang="en"><p>Tatiana V. Artyukh ‒ Master of Medical Sciences, Assistant</p><p>80, Gorky Str., 230009, Grodno</p></bio><email xlink:type="simple">taniaartsiukh@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Гродненский государственный медицинский университет</institution></aff><aff xml:lang="en"><institution>Grodno State Medical University</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2022</year></pub-date><pub-date pub-type="epub"><day>04</day><month>08</month><year>2022</year></pub-date><volume>67</volume><issue>3</issue><fpage>332</fpage><lpage>342</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Артюх Т.В., 2022</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="ru">Артюх Т.В.</copyright-holder><copyright-holder xml:lang="en">Artyukh T.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://vestibio.belnauka.by/jour/article/view/826">https://vestibio.belnauka.by/jour/article/view/826</self-uri><abstract><p>Использование комбинаций антибиотиков является перспективным направлением антибактериальной терапии инфекций, вызванных антибиотикоустойчивыми штаммами. Основной целью комбинированной антибиотикотерапии является достижение синергидного эффекта и расширение спектра антибактериальной активности в отношении мультирезистентных микроорганизмов. В связи с наличием у бактерий разнообразных механизмов резистентности даже к препаратам одной группы микробиологическая эффективность комбинаций антибиотиков трудно прогнозируема. Поэтому для подбора эффективных комбинаций антибиотиков требуется проводить микро- биологическое тестирование изолятов, выделенных от конкретного пациента.</p><p>В настоящее время в Республике Беларусь комбинированная антибиотикотерапия назначается эмпирически, а в случае ее клинической неэффективности проводится замена препаратов. Одной из причин ограниченного тестирования, несмотря на доступность питательных сред и диагностических материалов, является отсутствие адаптированных для локальных микробиологических лабораторий нормативно-технических методик выявления синергии.</p><p>Цель настоящей работы ‒ анализ современных методов исследования эффектов синергии антибактериальных препаратов и возможности их внедрения в практическую медицину.</p><p>В результате поиска публикаций в базе данных PubMed на тему повышения антибактериального эффекта антибиотиков по запросу «checkerboard method» and «time-kill» за период с 2016 по 2021 г. было найдено 947 результатов, при этом отмечалась тенденция к росту числа этих исследований.</p><p>Метод «шахматной доски» и анализ «time-kill» являются наиболее распространенными и надежными тестами in vitro, которые отражают эффекты, получаемые при комбинации антибиотиков как друг с другом, так и с другими соединениями.</p></abstract><trans-abstract xml:lang="en"><p>The use of combinations of antibiotics is a promising area of antibiotic therapy of bacterial infections caused by antibiotic-resistant strains. The main goal of combined antibiotic therapy is to achieve a synergistic effect and to expand a spectrum of antibacterial activity against multi-resistant microorganisms. Due to the presence of various mechanisms of resistance in bacteria, even to drugs of the same group, the microbiological efficacy of antibiotic combinations is difficult to predict. Therefore, to select effective combinations of antibiotics, it is required to conduct a microbiological testing of isolates isolated from a particular patient.</p><p>Currently, in the Republic of Belarus, the appointment of combined antibiotic therapy is carried out empirically, and in the event of its clinical ineffectiveness, the drugs are replaced. One of the reasons for a limited testing, with the availability of culture media and diagnostic materials, is the lack of regulatory and technical methods for identifying synergy adapted to local microbiological laboratories.</p><p>The purpose of this publication was to analyze the literature data illustrating the relevance of analyzing the methods for studying the effects of synergy of antibacterial drugs and the possibility of their introduction into practical medicine.</p><p>As a result of a search for publications in the PubMed database on the topic of increasing the antibacterial effect of antibiotics on the request the “checkerboard” method and the “time-kill” analysis for the period from 2016 to 2021, 947 results were found with an upward trend in research.</p><p>“Checkerboard” and “time-kill” assays are the most common, reliable in vitro tests that reflect the effects of antibiotic combinations and the effects of antibiotic combinations with other compounds.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>антибиотикорезистентность</kwd><kwd>комбинации антибиотиков</kwd><kwd>синергия</kwd><kwd>метод «шахматной доски»</kwd><kwd>анализ «time-kill»</kwd></kwd-group><kwd-group xml:lang="en"><kwd>antibiotic resistance</kwd><kwd>antibiotic combinations</kwd><kwd>synergy</kwd><kwd>“checkerboard method”</kwd><kwd>“time-kill” analysis</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Eliopoulos, G. M. Antibiotic combinations: Should they be tested? / G. M. Eliopoulos, S. T. Eliopoulos // Clin. Microbil. Rev. – 1988. – Vol. 1, N 2. – P. 139–156. https://doi.org/10.1128/CMR.1.2.139</mixed-citation><mixed-citation xml:lang="en">Eliopoulos G. M., Eliopoulos C. T. Antibiotic combinations: should they be tested? Clinical Microbiology Reviews, 1988, vol. 1, no. 2, pp. 139‒156. https://doi.org/10.1128/CMR.1.2.139</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Microbiological efficiency of the combinations of two carbapenems against antibiotic resistant Klebsiella pneumoniae strains / D. V. Tapalski [et al.] // Rus. Clin. Lab. Diagn. – 2021. – Vol. 66, N 5. – P. 304–309. https://doi.org/10.51620/0869-2084-2021-66-5-304-309</mixed-citation><mixed-citation xml:lang="en">Tapalski D. V., Timoshkova E. V., Petrovskaya T. A., Osipkina O. V., Karpov I. A. Microbiological efficiency of the combinations of two carbapenems against antibiotic resistant Klebsiella pneumoniae strains. Russian Clinical Laboratory Diagnostics, 2021, vol. 23, no. 5, pp. 304–309. https://doi:10.51620/0869-2084-2021-66-5-304-309</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">National estimates of healthcare costs associated with multidrug-resistant bacterial infections among hospitalized patients in the United States / R. E. Nelson [et al.] // Clin. Infect. Dis. – 2021. – Vol. 72, N 1. – P. 17–26. https://doi.org/10.1093/cid/ciaa1581</mixed-citation><mixed-citation xml:lang="en">Nelson R. E., Hatfield K. M., Wolford H., Samore M. H., Scott R. D., Reddy S. C., Olubajo B., Paul P., Jernigan J. A., Baggs J. National estimates of healthcare costs associated with multidrug-resistant bacterial infections among hospitalized patients in the United States. Clinical Infectious Diseases, 2021, vol. 29, no. 72, pp. 17–26. https://doi.10.1093/cid/ciaa1581</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">The future of antibiotics begins with discovering new combinations / M. Zhu [et al.] // Ann. N. Y. Acad. Sci. – 2021. – Vol. 1496, N 1. – P. 82–96. https://doi.org/10.1111/nyas.14649</mixed-citation><mixed-citation xml:lang="en">Zhu M., Tse M. W., Weller J., Chen J., Blainey P. C. The future of antibiotics begins with discovering new combinations. Annals of the New York Academy of Sciences, 2021, vol. 1496, no. 1, pp. 82–96. https://doi.10.1111/nyas.14649</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Ma, J. Current methods for quantifying drug synergism / J. Ma, A. Motsinger-Reif // Protein Bioinform. – 2019. – Vol. 1, N 2. – P. 43–48.</mixed-citation><mixed-citation xml:lang="en">Ma J., Motsinger-Reif A. Current methods for quantifying drug synergism. Protein Bioinformatics, 2019, vol. 1, no. 2, pp. 43–48.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Вагнер, Х. Исследование синергии: создание нового поколения фитопрепаратов / Х. Вагнер, Г. УльрихМерцених // Рус. мед. журн. Мед. обозрение. – 2016. – Т. 24, № 3. – С. 183‒189.</mixed-citation><mixed-citation xml:lang="en">Vagner Kh., Ul’rikh-Mertsenikh G. Synergy research: creating a new generation of herbal medicines. Russkii meditsinskii zhurnal. Meditsinskoe obozrenie [Russian medical journal. Medical review], 2016, vol. 24, no. 3, pp. 183–189 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Duarte, F. Gastric-resistant isoniazid pellets reduced degradation of rifampicin in acidic medium [Electronic resource] / F. Duarte [et al.] // Braz. J. Pharm. Sci. – 2014. – Vol. 50, N 4. – P. 749–755. https://doi.org/10.1590/S1984-82502014000400010</mixed-citation><mixed-citation xml:lang="en">Frejre F. D., Kamara M. B., Dantas M. G., Soares Aragao S. F., de Lima i Moura T. F. A., Rafin F. N. Gastric-resistant isoniazid pellets reduced degradation of rifampicin in acidic medium. Brazilian Journal of Pharmaceutical Sciences, 2014, vol. 50, no. 4, pp. 749–755. https://doi.org/10.1590/S1984-82502014000400010</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Король, Л. А. Иберогаст ‒ эффективная фитотерапия функциональных заболеваний желудочнокишечного тракта / Л. А. Король, С. А. Скатков // Терапия. – 2016. – № 5. – С. 88–95.</mixed-citation><mixed-citation xml:lang="en">Korol’ L. A., Skatkov S. A. Iberogast ‒ effective herbal medicine for functional diseases of the gastrointestinal tract. Terapiya [Therapy], 2016, no. 5, pp. 88–95 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Gut-brain-microbiota axis: antibiotics and functional gastrointestinal disorders / T. Karakan [et al.] // Nutrients. – 2021. – Vol. 13, N 2. – Art. 389. https://doi.org/10.3390/nu13020389</mixed-citation><mixed-citation xml:lang="en">Karakan T., Ozkul C., Küpeli Akkol E., Bilici S., Sobarzo-Sánchez E., Capasso R. Gut-brain-microbiota axis: antibiotics and functional gastrointestinal disorders. Nutrients, 2021, vol. 13, no. 2, art. 389. https://doi.10.3390/nu13020389</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">In vitro сombined inhibitory activities of β-Lactam antibiotics and clavulanic acid against blaKPC-2-positive Klebsiella pneumoniae / M. Peng [et al.] // Infect. Drug Resist. – 2021. – Vol. 14. – P. 361–368. https://doi.org/10.2147/IDR.S292612</mixed-citation><mixed-citation xml:lang="en">Peng M., Han R., Guo Y., Zheng Y., Yang F., Xu X., Hu F. In vitro combined inhibitory activities of β-lactam antibiotics and clavulanic acid against blaKPC-2-positive Klebsiella pneumoniae. Infection and Drug Resistance, 2021, vol. 2, no. 14, pp. 361–368. https://doi.org/10.2147/IDR.S292612</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Антимикробная и противогрибковая активность экстрактов лишайников, распространенных на территории Беларуси / Д. В. Тапальский [и др.] // Журн. микробиол., эпидемиол. и иммунобиол. – 2017. – № 2. – С. 60–65.</mixed-citation><mixed-citation xml:lang="en">Tapal’skii D. V., Petrenev D. R., Khramchenkova O. M., Doroshkevich A. S. Antimicrobial and antifungal activity of lichen extracts common in Belarus. Zhurnal mikrobiologii, epidemiologii i immunobiologii [Journal of microbiology, epidemiology and immunobiology], 2017, no. 2, pp. 60–65 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Синергидное действие катионного пептида хоминина и нового дезинфектанта на основе изохинолина на образование биоплeнок полирезистентных стафилококков / Л. И. Кононова [и др.] // Антибиотики и химиотерапия. – 2020. – Т. 65. – № 5‒6. – С. 11‒18.</mixed-citation><mixed-citation xml:lang="en">Kononova L. I., P’yankov I. A., Smolyak A. A., Shklyaev Yu. V., Korobov V. P. Synergistic effect of the cationic peptide hominin and a new disinfectant based on isoquinoline on formation of biofilms in multidrug-resistant Staphylococci. Antibiotiki i khimioterapiya [Antibiotics and сhemotherapy], 2020, vol. 65, no. 6, pp. 11–18 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Odds, F. C. Synergy, antagonism, and what the chequerboard puts between them / F. C. Odds // J. Antimicrob. Chemother. – 2003. – Vol. 52, N 1. – P. 1. https://doi.org/10.1093/jac/dkg301</mixed-citation><mixed-citation xml:lang="en">Odds F. C. Synergy, antagonism, and what the chequerboard puts between them. Journal of Antimicrobial Chemotherapy, 2003, vol. 52, no. 1. https://doi.org/10.1093/jac/dkg301</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Тапальский, Д. В. Методы определения чувствительности к комбинациям антибиотиков грамотрицательных бактерий с экстремальной и полной антибиотикорезистентностью : инструкция по применению / Д. В. Тапальский, Л. В. Лагун. – Гомель : Гомел. гос. мед. ун-т, 2017. – 27 с.</mixed-citation><mixed-citation xml:lang="en">Tapal’skii D. V., Lagun L. V. Methods for determining sensitivity to a combination of antibiotics, gram-negative bacteria with hypersensitivity and complete antibiotic resistance: indications for use. Gomel, Gomel State Medical University, 2017. 27 p. (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Multiple combination bactericidal antibiotic testing for patients with cystic fibrosis infected with Burkholderia cepacia / S. D. Aaron [et al.] // Am. J. Respir. Crit. Care Med. – 2000. – Vol. 4, N 1. – P. 1206–1212. https://doi.org/10.1164/ajrccm.161.4.9907147</mixed-citation><mixed-citation xml:lang="en">Aaron S., Ferris W., Henry D., Speert D., Macdonald N. Multiple combination bactericidal antibiotic testing for patients with cystic fibrosis infected with Burkholderia cepacia. American Journal of Respiratory and Critical Care Medicine, 2000, vol. 161, no. 4, pp. 1206–1212. https://doi.org/10.1164/ajrccm.161.4.9907147</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Multiple combination bactericidal antibiotic testing for patients with cystic fibrosis infected with multiresistant strains of Pseudomonas aeruginosa / B. J. Lang [et al.] // Am. J. Respir. Crit. Care Med. – 2000. – Vol. 162, N 6. – P. 2241–2245. https://doi.org/10.1164/ajrccm.162.6.2005018</mixed-citation><mixed-citation xml:lang="en">Lang B., Aaron S., Ferris W., Hebert P., MacDonald N. Multiple combination bactericidal antibiotic testing for patients with cystic fibrosis infected with multiresistant strains of Pseudomonas aeruginosa. American Journal of Respiratory and Critical Care Medicine, 2000, vol. 162, no. 6. pp. 2241–2245. https://doi.org/10.1164/ajrccm.162.6.2005018</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Antimicrobial synergy testing: comparing the tobramycin and ceftazidime gradient diffusion methodology used in assessing synergy in cystic fibrosis-derived multidrug-resistant Pseudomonas aeruginosa / I. N. Okoliegbe [et al.] // Antibiotics. – 2021. – Vol. 10, N 8. – Art. 967. https://doi.org/10.3390/antibiotics10080967</mixed-citation><mixed-citation xml:lang="en">Okoliegbe I. N., Hijazi K., Cooper K., Ironside C., Gould I. M. Antimicrobial synergy testing: comparing the tobramycin and ceftazidime gradient diffusion methodology used in assessing synergy in cystic fibrosis-derived multidrug-resistant Pseudomonas aeruginosa. Antibiotics (Basel), 2021, vol. 10, no. 8, art. 967. https://doi.org/10.3390/antibiotics10080967</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">CombiANT: Antibiotic interaction testing made easy / N. Fatsis-Kavalopoulos [et al.] // PLoS Biol. – 2020. – Vol. 18, N 9. – P. e3000856. https://doi.org/10.1371/journal.pbio.3000856</mixed-citation><mixed-citation xml:lang="en">Fatsis-Kavalopoulos N., Roemhild R., Tang P-C., Kreuger J., Andersson D. I. CombiANT: Antibiotic interaction testing made easy. PLoS Biology, 2020, vol. 18, no. 9, p. e3000856. https://doi.org/10.1371/journal.pbio.3000856</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Activity of cefepime in combination with the novel β-lactamase inhibitor taniborbactam (VNRX-5133) against extended-spectrum-β-lactamase-producing isolates in in vitro checkerboard assays / W. Kloezen [et al.] // Antimicrob. Agents Chemother. – 2021. – Vol. 65, N 4. – P. e02338-20. https://doi.org/10.1128/AAC.02338-20</mixed-citation><mixed-citation xml:lang="en">Kloezen W., Melchers R. J., Georgiou P.-C., Mouton J. W., Meletiadis J. Activity of cefepime in combination with the novel β-lactamase inhibitor taniborbactam (VNRX-5133) against extended-spectrum-β-lactamase-producing isolates in in vitro checkerboard assays. Antimicrobial Agents and Chemotherapy, 2021, vol. 65, no. 4, p. e02338-20. https://doi.org/10.1128/AAC.02338-20</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Тапальский, Д. В. Чувствительность к комбинациям антибиотиков, продуцирующих карбапенемазы нозокомиальных штаммов грамотрицательных бактерий, выделенных в Беларуси / Д. В. Тапальский // Клин. микробиология и антимикроб. химиотерапия. – 2018. – Т. 20, № 3. – С. 182–191.</mixed-citation><mixed-citation xml:lang="en">Tapal’skii D. V. Susceptibility to combinations of antibiotics of carbapenemase-producing nosocomial strains of gram-negative bacteria isolated in Belarus. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya [Clinical microbiology and antimicrobial chemotherapy], 2018, vol. 20, no. 3, pp. 182–191 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Артюх, Т. В. Особенности резистентности клинических изолятов E. coli и C. albicans, образующих биопленку / Т. В. Артюх, Т. Н. Соколова, О. Б. Островская // Вестн. ВГМУ. – 2021. – Т. 20, № 1. – С. 46–54.</mixed-citation><mixed-citation xml:lang="en">Artyukh T. V., Sokolova T. N., Ostrovskaya O. B. Features of the resistance of clinical isolates of E. coli and C. albicans forming a biofilm. Vestnik Vitebskogo gosudarstvennogo meditsinskogo universiteta [Bulletin of Vitebsk State Medical University], 2021, vol. 20, no. 1, pp. 46–54 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Адамович, Т. Г. Методы изучения антимикробной активности антибиотиков и антисептиков in vitro / Т. Г. Адамович, И. А. Гаврилова, Е. Ю. Кирильчик // Современные технологии в медицинском образовании : материалы междунар. науч.-практ. конф., посвящ. 100-летию Белорус. гос. мед. ун-та, Минск, 1‒5 нояб. 2021 г. / Белорус. гос. мед. ун-т ; редкол. : С. П. Рубникович [и др.]. – Минск, 2021. – С. 1540–1543.</mixed-citation><mixed-citation xml:lang="en">Adamovich T. G., Gavrilova I. A., Kiril’chik E. Yu. Methods for studying the antimicrobial activity of antibiotics and antiseptics in vitro. Sovremennye tekhnologii v meditsinskom obrazovanii: materialy mezhdunarodnoi nauchno-prakticheskoi konferentsii, posvyashchennoi 100-letiyu Belorusskogo gosudarstvennogo meditsinskogo universiteta (Minsk, 01–05 noyabrya 2021 goda) [Modern technologies in medical education: materials of the international scientific and practical conference dedicated to the 100th anniversary of the Belarusian State Medical University (Minsk, November 01–05, 2021)]. Minsk, 2021, pp. 1540–1543 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Time-kill curve analysis and pharmacodynamic modelling for in vitro evaluation of antimicrobials against Neisseria gonorrhoeae / S. Foerster [et al.] // BMC Microbiol. – 2016. – Vol. 16. – Art. 216. https://doi.org/10.1186/s12866-016-0838-9</mixed-citation><mixed-citation xml:lang="en">Foerster S., Unemo M., Hathaway L. J., Low N., Althaus C. L. Time-kill curve analysis and pharmacodynamic modelling for in vitro evaluation of antimicrobials against Neisseria gonorrhoeae. BMC Microbiology, 2016, vol. 16, art. 216. https://doi.org/10.1186/s12866-016-0838-9</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Predicting the effects of Carbapenem/Carbapenemase inhibitor combinations against KPC-producing Klebsiella pneumoniae in time-kill experiments: alternative versus traditional approaches to MIC determination / A. V. Filimonova [et al.] // Antibiotics. – 2021. – Vol. 10, N 12. – Art. 1520. https://doi.org/10.3390/antibiotics10121520</mixed-citation><mixed-citation xml:lang="en">Filimonova A. V., Golikova M. V., Strukova E. N., Portnoy Y. A., Kuznetsova A. A., Zinner S. H. Predicting the effects of carbapenem/carbapenemase inhibitor combinations against KPC-producing Klebsiella pneumoniae in time-kill experiments: alternative versus traditional approaches to MIC determination. Antibiotics (Basel), 2021, vol. 10, no. 12, art. 1520. https://doi.org/10.3390/antibiotics10121520</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Chan, E. L. Determination of synergy by two methods with eight antimicrobial combinations against tobramycinsusceptible and tobramycin-resistant strains of Pseudomonas / T. L. Chen, R. J. Zabransky // Microb. Drug Resist. – 1987. – Vol. 6, N 2. – P. 157–164. https://doi.org/10.1016/0732-8893(87)90101-5</mixed-citation><mixed-citation xml:lang="en">Chan E. L., Zabransky R. J. Determination of synergy by two methods with eight antimicrobial combinations against tobramycin-susceptible and tobramycin-resistant strains of Pseudomonas. Microbial Drug Resistance, 1987, vol. 6, no. 2, pp. 157–164. https://doi.org/10.1016/0732-8893(87)90101-5</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Эпиднадзор за устойчивостью к противомикробным препаратам в Центральной Азии и Европе – 2019 г. [Электронный ресурс] // Ежегодный доклад Европейского Регионального бюро ВОЗ. – Режим доступа: https://www.euro.who.int/__data/assets/pdf_file/0011/473267/CAESAR-annual-report-2019-rus.pdf. – Дата доступа: 13.01.2022.</mixed-citation><mixed-citation xml:lang="en">Antimicrobial resistance surveillance in Central Asia and Europe, Annual report of the WHO Regional Office for Europe (2019). Available at: https://www.euro.who.int/__data/assets/pdf_file/0011/473267/CAESAR-annual-report-2019-rus. pdf (accessed 12.11.2021).</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Co-infections in people with COVID-19: a systematic review and meta-analysis / L. Lansbury [et al.] // J. Infect. – 2020. – Vol. 81, N 2. – P. 266–275. https://doi.org/10.1016/j.jinf.2020.05.046</mixed-citation><mixed-citation xml:lang="en">Lansbury L., Lim B., Baskaran V., Lim W. S. Co-infections in people with COVID-19: a systematic review and metaanalysis. Journal of Infection, 2020, vol. 81, no. 2, pp. 266–275. https://doi.org/10.1016/j.jinf.2020.05</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Синопальников, А. И. Пандемия COVID-19 – «пандемия» антибактериальной терапии / А. П. Синопальников // Клин. микробиология и антимикроб. химиотерапия. – 2021. – Т. 23, № 1. – С. 5–15.</mixed-citation><mixed-citation xml:lang="en">Sinopal’nikov A. I. COVID19 pandemic is a «pandemic» of antimicrobial therapy. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya [Clinical Microbiology and Antimicrobial Chemotherapy], 2021, vol. 23, no. 1, pp. 5–15 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Антибиотикорезистентность Klebsiella pneumoniae на фоне пандемии COVID-19: опыт многопрофильного стационара / Д. В. Тапальский [и др.] // Инфекц. болезни: новости, мнения, обучение. – 2021. – Т. 10, № 3. – С. 15‒22.</mixed-citation><mixed-citation xml:lang="en">Tapal’skii D. V., Karpova E. V., Akulenok O. M., Okulich V. K., Generalov I. I., Leskova N. Yu. [et al.]. Antibiotic resistance of Klebsiella pneumoniae against the backdrop of the COVID-19 pandemic: experience of a multidisciplinary hospital. Infektsionnye bolezni: novosti, mneniya, obuchenie [Infectious diseases: news, opinion, education], 2021, vol. 10, no. 3, pp. 15–22 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Evaluation of the therapeutic outcomes of antibiotic regimen against carbapenemase-producing Klebsiella pneumoniae: a systematic review and meta-analysis / C. Y. Effah [et al.] // Front Pharmacol. – 2021. – Vol. 12. – Art. 597907. https://doi.org/10.3389/fphar.2021.597907</mixed-citation><mixed-citation xml:lang="en">Effah C. Y., Drokow E. K., Agboyibor C., Liu S., Nuamah E., Sun T. [et al.]. Evaluation of the therapeutic outcomes of antibiotic regimen against carbapenemase-producing Klebsiella pneumoniae: a systematic review and meta-analysis. Frontiers in Pharmacology, 2021, vol. 12, art. 597907. https://doi.org/10.3389/fphar.2021.597907</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
