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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">antibiotics</journal-id><journal-title-group><journal-title xml:lang="ru">Антибиотики и Химиотерапия</journal-title><trans-title-group xml:lang="en"><trans-title>Antibiot Khimioter = Antibiotics and Chemotherapy</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">0235-2990</issn><publisher><publisher-name>ООО «Издательство ОКИ»</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.37489/0235-2990-2024-69-3-4-42-50</article-id><article-id custom-type="edn" pub-id-type="custom">FSGBXG</article-id><article-id custom-type="elpub" pub-id-type="custom">antibiotics-1124</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>ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>EXPERIMENTAL STUDIES</subject></subj-group></article-categories><title-group><article-title>Прогнозирование эффективности азтреонама в отношении Klebsiella pneumoniae по результатам оценки чувствительности бактерии к антибиотику при увеличенном инокуляте</article-title><trans-title-group xml:lang="en"><trans-title>Prediction of Aztreonam Effectiveness Against Klebsiella pneumoniae Based on the Results of Antimicrobial Susceptibility Testing with Increased Inoculum</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2107-8259</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Алиева</surname><given-names>К. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Alieva</surname><given-names>K. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Алиева Камилла Натиговна — к. б. н., научный сотрудник лаборатории фармакокинетики и фармакодинамики</p><p>Москва</p><p>ResearcherID: AAG-68692019. Scopus Author ID: 57197836617</p></bio><bio xml:lang="en"><p>Kamilla N. Alieva — Ph. D. in Biology, Researcher at the Laboratory of Pharmacokinetics and Pharmacodynamics</p><p>Moscow</p><p>ResearcherID: AAG-6869-2019. Scopus Author ID: 57197836617</p></bio><email xlink:type="simple">qvimqwem@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7588-1733</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Голикова</surname><given-names>М. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Golikova</surname><given-names>M. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Голикова Мария Владимировна — к. б. н.</p><p>Москва</p><p>. ResearcherID: O-7873-2016. Scopus Author ID: 56497807500</p></bio><bio xml:lang="en"><p>Maria V. Golikova — Ph. D. in Biology</p><p>Moscow</p><p>ResearcherID: O-7873-2016. Scopus Author ID: 56497807500 </p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0008-9953-135X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кондратьева</surname><given-names>Д. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kondratieva</surname><given-names>D. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кондратьева Дарья Андреевна</p><p>Москва</p></bio><bio xml:lang="en"><p>Daria A. Kondratieva</p><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2092-5559</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кузнецова</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kuznetsova</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кузнецова Анастасия Алексеевна</p><p>Москва</p></bio><bio xml:lang="en"><p>Anastasiya A. Kuznetsova</p><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБНУ «Научно-исследовательский институт по изысканию новых антибиотиков им. Г. Ф. Гаузе» (ФГБНУ «НИИНА»)</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Gause Institute of New Antibiotics</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2024</year></pub-date><pub-date pub-type="epub"><day>21</day><month>06</month><year>2024</year></pub-date><volume>69</volume><issue>3-4</issue><fpage>42</fpage><lpage>50</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Алиева К.Н., Голикова М.В., Кондратьева Д.А., Кузнецова А.А., 2024</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="ru">Алиева К.Н., Голикова М.В., Кондратьева Д.А., Кузнецова А.А.</copyright-holder><copyright-holder xml:lang="en">Alieva K.N., Golikova M.V., Kondratieva D.A., Kuznetsova A.A.</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://www.antibiotics-chemotherapy.ru/jour/article/view/1124">https://www.antibiotics-chemotherapy.ru/jour/article/view/1124</self-uri><abstract><sec><title>Актуальность</title><p>Актуальность. Минимальная подавляющая концентрация (МПК) антибиотика не позволяет прогнозировать риск развития устойчивости бактерий под воздействием антибиотика из-за малой выборки бактерий. Минимальная подавляющая концентрация антибиотика при увеличенном инокуляте (МПКВИ) может стать подходящим для такой цели параметром за счёт увеличенной выборки и простоты определения.</p></sec><sec><title>Цель</title><p>Цель. Исследование направлено на оценку потенциала использования МПКВИ как параметра для прогнозирования развития устойчивости Klebsiella pneumoniae к азтреонаму.</p></sec><sec><title>Методы</title><p>Методы. Оценили значения МПК и МПКВИ азтреонама в отношении двух штаммов K. pneumoniae методом микроразведений (объём 0,2 мл; инокулят 5×105 и 5×107 КОЕ/мл, соответственно) и сопоставили результаты с эффектом азтреонама в динамической системе in vitro, где моделировали режим применения азтреонама 2 г каждые 8 ч в виде 2-часовой инфузии в течение 5 сут.</p></sec><sec><title>Результаты</title><p>Результаты. Эффективность азтреонама в отношении K. pneumoniae, наблюдаемая в динамической системе, согласовывалась со значениями МПКВИ после уточнения результатов по оценке жизнеспособности бактерий. При визуальной оценке значения МПКВИ были сильно завышены из-за избыточной мутности вследствие образования филаментных форм бактерии под действием азтреонама.</p></sec><sec><title>Заключение</title><p>Заключение. Параметр МПКВИ можно использовать для прогнозирования развития устойчивости K. pneumoniae к азтреонаму при оценке значений данного параметра по численности жизнеспособных клеток, но не по визуальной границе роста. </p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Background</title><p>Background. The minimum inhibitory concentration (MIC) does not predict the risk of antibacterial resistance development due to a small sample of tested bacteria. Minimum inhibitory concentration at an increased inoculum (MICHI) may become a suitable parameter for this purpose as a sample of tested bacteria is larger while the method of determination remains easy.</p><p>The aim of the study was to evaluate the potential of using MICHI as a parameter for predicting the resistance development in Klebsiella pneumoniae to aztreonam.</p></sec><sec><title>Methods</title><p>Methods. Aztreonam MIC and MICHI values were assessed against two strains of K. pneumoniae using the microdilution method (0.2 ml volume; inoculum of 5×105 and 5×107 CFU/ml, respectively) and compared the results with the effect of aztreonam in a dynamic in vitro model, in which  aztreonam regimen of 2 grams every 8 hours as a 2-hour infusion for 5 days was simulated.</p></sec><sec><title>Results</title><p>Results. The efficacy of aztreonam against K. pneumoniae observed in the dynamic model was consistent with the MICHIs values assessed based on bacterial viability. During the visual assessment, the MICHIs values were greatly overestimated due to excessive turbidity caused by the formation of filamentous forms of bacteria exposed to aztreonam.</p></sec><sec><title>Conclusions</title><p>Conclusions. The MICHI parameter can be used to predict the development of resistance in K. pneumoniae to aztreonam when assessing the values of this parameter by the number of viable cells, but not by the visual boundary of bacterial growth.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>азтреонам</kwd><kwd>Klebsiella pneumoniae</kwd><kwd>динамическая система in vitro</kwd><kwd>оценка чувствительности бактерий к антибиотикам</kwd></kwd-group><kwd-group xml:lang="en"><kwd>aztreonam</kwd><kwd>Klebsiella pneumoniae</kwd><kwd>in vitrodynamic model</kwd><kwd>antimicrobial susceptibility testing</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Исследование выполнено за счёт гранта Российского научного фонда (№ 22-75-00066).</funding-statement><funding-statement xml:lang="en">The study was supported by a grant from the Russian Science Foundation  (No. 22-75-00066).</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Национальный стандарт Российской Федерации ГОСТ Р ИСО 207761-2022. Исследование чувствительности инфекционных агентов и оценка функциональных характеристик изделий для исследования чувствительности к антимикробным средствам. Часть 1. Референтный метод микроразведений в бульоне для лабораторного исследования активности антимикробных агентов по отношению к быстрорастущим аэробным бактериям, вызывающим инфекционные заболевания.</mixed-citation><mixed-citation xml:lang="en">Natsional'nyj standart Rossijskoj Federatsii GOST R ISO 20776-1-2022. Issledovanie chuvstvitel'nosti infektsionnykh agentov i otsenka funktsional'nykh kharakteristik izdelij dlya issledovaniya chuvstvitel'nosti k antimikrobnym sredstvam. Chast' 1. Referentnyj metod mikrorazvedenij v bul'one dlya laboratornogo issledovaniya aktivnosti antimikrobnykh agentov po otnoshenijyu k bystrorastushchim aerobnym bakteriyam, vyzyvajyushchim infektsionnye zabolevaniya. (in Russian)]</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Baquero M., Galán J.C., del Carmen Turrientes M., Cantón R., Coque T.M., Martínez J.L., et al. Increased mutation frequencies in Escherichia coli isolates harboring extended-spectrum β-lactamases. Antimicrob Agents Chemother. 2005; 49 (11): 4754–4756. doi: 10.1128/AAC.49.11.47544756.2005.</mixed-citation><mixed-citation xml:lang="en">Baquero M., Galán J.C., del Carmen Turrientes M., Cantón R., Coque T.M., Martínez J.L., et al. Increased mutation frequencies in Escherichia coli isolates harboring extended-spectrum β-lactamases. Antimicrob Agents Chemother. 2005; 49 (11): 4754–4756. doi: 10.1128/AAC.49.11.47544756.2005.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Woodford N., Ellington M.J. The emergence of antibiotic resistance by mutation. Clin Microbiol Infect. 2007; 13 (1): 5–18. doi: 10.1111/j.14690691.2006.01492.x.</mixed-citation><mixed-citation xml:lang="en">Woodford N., Ellington M.J. The emergence of antibiotic resistance by mutation. Clin Microbiol Infect. 2007; 13 (1): 5–18. doi: 10.1111/j.14690691.2006.01492.x.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Mushtaq S., Vickers A., Ellaby N., Woodford N., Livermore D.M. Selection and characterization of mutational resistance to aztreonam/avibactam in β-lactamase-producing Enterobacterales. J Antimicrob Chemother. 2022; 77: 98–111. doi: 10.1093/jac/dkab346.</mixed-citation><mixed-citation xml:lang="en">Mushtaq S., Vickers A., Ellaby N., Woodford N., Livermore D.M. Selection and characterization of mutational resistance to aztreonam/avibactam in β-lactamase-producing Enterobacterales. J Antimicrob Chemother. 2022; 77: 98–111. doi: 10.1093/jac/dkab346.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Zaccard C.R., Schell R.F., Spiegel C.A. Efficacy of bilateral bronchoalveolar lavage for diagnosis of ventilator-associated pneumonia. J Clin Microbiol. 2009; 47 (9): 2918–2924. doi: 10.1128/JCM.00747-09.</mixed-citation><mixed-citation xml:lang="en">Zaccard C.R., Schell R.F., Spiegel C.A. Efficacy of bilateral bronchoalveolar lavage for diagnosis of ventilator-associated pneumonia. J Clin Microbiol. 2009; 47 (9): 2918–2924. doi: 10.1128/JCM.00747-09.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Gadsby N.J., McHugh M.P., Russell C.D., Mark H., Conway Morris A., Laurenson I.F., et al. Development of two real-time multiplex PCR assays for the detection and quantification of eight key bacterial pathogens in lower respiratory tract infections. Clin Microbiol Inf. 2015; 21 (8): 788.e1788.e13. doi: 10.1016/j.cmi.2015.05.004.</mixed-citation><mixed-citation xml:lang="en">Gadsby N.J., McHugh M.P., Russell C.D., Mark H., Conway Morris A., Laurenson I.F., et al. Development of two real-time multiplex PCR assays for the detection and quantification of eight key bacterial pathogens in lower respiratory tract infections. Clin Microbiol Inf. 2015; 21 (8): 788.e1788.e13. doi: 10.1016/j.cmi.2015.05.004.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Wang H., Gu X., Weng Y., Xu T., Fu Z., Peng W., et al. Quantitative analysis of pathogens in the lower respiratory tract of patients with chronic obstructive pulmonary disease. BMC Pulmonary Medicine. 2015; 15: 94. doi: 10.1186/s12890-015-0094-z.</mixed-citation><mixed-citation xml:lang="en">Wang H., Gu X., Weng Y., Xu T., Fu Z., Peng W., et al. Quantitative analysis of pathogens in the lower respiratory tract of patients with chronic obstructive pulmonary disease. BMC Pulmonary Medicine. 2015; 15: 94. doi: 10.1186/s12890-015-0094-z.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Homma T., Hori T., Sugimori G., Yamano Y. Pharmacodynamic assessment based on mutant prevention concentrations of fluoroquinolones to prevent the emergence of resistant mutants of Streptococcus pneumoniae. Antimicrob Agents Chemother. 2007; 51 (11): 3810–3815. doi: 10.1128/AAC.01372-06.</mixed-citation><mixed-citation xml:lang="en">Homma T., Hori T., Sugimori G., Yamano Y. Pharmacodynamic assessment based on mutant prevention concentrations of fluoroquinolones to prevent the emergence of resistant mutants of Streptococcus pneumoniae. Antimicrob Agents Chemother. 2007; 51 (11): 3810–3815. doi: 10.1128/AAC.01372-06.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Firsov A.A., Smirnova M.V., Strukova E.N., Vostrov S.N., Portnoy Y.A., Zinner S.H. Enrichment of resistant Staphylococcus aureus at ciprofloxacin concentrations simulated within the mutant selection window: bolus versus continuous infusion. Int J Antimicrob Agents. 2008; 32: 488–493. doi: 10.1016/j.ijantimicag.2008.06.031.</mixed-citation><mixed-citation xml:lang="en">Firsov A.A., Smirnova M.V., Strukova E.N., Vostrov S.N., Portnoy Y.A., Zinner S.H. Enrichment of resistant Staphylococcus aureus at ciprofloxacin concentrations simulated within the mutant selection window: bolus versus continuous infusion. Int J Antimicrob Agents. 2008; 32: 488–493. doi: 10.1016/j.ijantimicag.2008.06.031.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Liang B., Bai N., Cai Y., Wang R., Drlica K., Zhao X. Mutant prevention concentration-based pharmacokinetic/pharmacodynamic indices as dosing targets for suppressing the enrichment of levofloxacin-resistant subpopulations of Staphylococcus aureus. Antimicrob Agents Chemother. 2011; 55 (5): 2409–2412. doi: 10.1128/AAC.00975-10.</mixed-citation><mixed-citation xml:lang="en">Liang B., Bai N., Cai Y., Wang R., Drlica K., Zhao X. Mutant prevention concentration-based pharmacokinetic/pharmacodynamic indices as dosing targets for suppressing the enrichment of levofloxacin-resistant subpopulations of Staphylococcus aureus. Antimicrob Agents Chemother. 2011; 55 (5): 2409–2412. doi: 10.1128/AAC.00975-10.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Zhao X., Drlica K. Restricting the selection of antibiotic-resistant mutants: a general strategy derived from fluoroquinolone studies. Clin Infect Dis. 2001; 33 (Suppl 3): S147–S156. doi: 10.1086/321841.</mixed-citation><mixed-citation xml:lang="en">Zhao X., Drlica K. Restricting the selection of antibiotic-resistant mutants: a general strategy derived from fluoroquinolone studies. Clin Infect Dis. 2001; 33 (Suppl 3): S147–S156. doi: 10.1086/321841.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Lenhard J.R., Bulman Z.P. Inoculum effect of b-lactam antibiotics. J Antimicrob Chemother. 2019; 74: 2825–2843. doi: 10.1093/jac/dkz226.</mixed-citation><mixed-citation xml:lang="en">Lenhard J.R., Bulman Z.P. Inoculum effect of b-lactam antibiotics. J Antimicrob Chemother. 2019; 74: 2825–2843. doi: 10.1093/jac/dkz226.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Golikova M.V., Strukova E.N., Alieva K.N., Ageevets V.A., Avdeeva A.A., Sulian O.S., et al. Meropenem MICs at standard and high inocula and mutant prevention concentration inter-relations: comparative study with non-carbapenemase-producing and OXA-48-, KPC- and NDMProducing Klebsiella pneumoniae. Antibiotics. 2023; 12: 872. doi: 10.3390/antibiotics12050872.</mixed-citation><mixed-citation xml:lang="en">Golikova M.V., Strukova E.N., Alieva K.N., Ageevets V.A., Avdeeva A.A., Sulian O.S., et al. Meropenem MICs at standard and high inocula and mutant prevention concentration inter-relations: comparative study with non-carbapenemase-producing and OXA-48-, KPC- and NDMProducing Klebsiella pneumoniae. Antibiotics. 2023; 12: 872. doi: 10.3390/antibiotics12050872.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">The European Committee on Antimicrobial Susceptibility Testing. Breakpoint Tables for Interpretation of MICs and Zone Diameters. Version 13.0, 2023. Доступно по: http://www.eucast.org. Ссылка активна на 16.11.2023.</mixed-citation><mixed-citation xml:lang="en">The European Committee on Antimicrobial Susceptibility Testing. Breakpoint Tables for Interpretation of MICs and Zone Diameters. Version 13.0, 2023. Доступно по: http://www.eucast.org. Ссылка активна на 16.11.2023.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Blaser J., Stone B.B., Zinner S.H. Two compartment kinetic model with multiple artificial capillary units. J Antimicrob Chemother. 1985; 15 (Suppl A): 131–137. DOI: 10.1093/jac/15.suppl_A.131.</mixed-citation><mixed-citation xml:lang="en">Blaser J., Stone B.B., Zinner S.H. Two compartment kinetic model with multiple artificial capillary units. J Antimicrob Chemother. 1985; 15 (Suppl A): 131–137. DOI: 10.1093/jac/15.suppl_A.131.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Alieva K.N., Golikova M.V., Dovzhenko S.A., Kobrin M.B., Strukova E.N., Ageevets V.A., et al. Testing the mutant selection window hypothesis with meropenem: In vitro model study with OXA-48-producing Klebsiella pneumoniae. PLoS ONE. 2023; 18 (8): e0288660. doi: 10.1371/journal.pone.0288660.</mixed-citation><mixed-citation xml:lang="en">Alieva K.N., Golikova M.V., Dovzhenko S.A., Kobrin M.B., Strukova E.N., Ageevets V.A., et al. Testing the mutant selection window hypothesis with meropenem: In vitro model study with OXA-48-producing Klebsiella pneumoniae. PLoS ONE. 2023; 18 (8): e0288660. doi: 10.1371/journal.pone.0288660.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Lodise T.P., Smith N.M., O’Donnell N., Eakin A.E., Holden P.N., Boissonneault K.R., et al. Determining the optimal dosing of a novel combination regimen of ceftazidime/avibactam with aztreonam against NDM-1producing Enterobacteriaceae using a hollow-fibre infection model. J Antimicrob Chemother. 2020; 75: 2622–2632. DOI: 10.1093/jac/dkaa197</mixed-citation><mixed-citation xml:lang="en">Lodise T.P., Smith N.M., O’Donnell N., Eakin A.E., Holden P.N., Boissonneault K.R., et al. Determining the optimal dosing of a novel combination regimen of ceftazidime/avibactam with aztreonam against NDM-1producing Enterobacteriaceae using a hollow-fibre infection model. J Antimicrob Chemother. 2020; 75: 2622–2632. DOI: 10.1093/jac/dkaa197</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Xu H. Zhou W., Zhou D., et al. Evaluation of aztreonam dosing regimens in patients with normal and impaired renal function: a population pharmacokinetic modeling and Monte Carlo simulation analysis. J Clin Pharmacol. 2017; 57: 336–344. doi: 10.1002/jcph.810.</mixed-citation><mixed-citation xml:lang="en">Xu H. Zhou W., Zhou D., et al. Evaluation of aztreonam dosing regimens in patients with normal and impaired renal function: a population pharmacokinetic modeling and Monte Carlo simulation analysis. J Clin Pharmacol. 2017; 57: 336–344. doi: 10.1002/jcph.810.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Cies J.J., LaCoursiere R.J., Moore II W.S., Chopra A. Therapeutic drug monitoring of prolonged infusion aztreonam for multi-drug resistant Pseudomonas aeruginosa: A Case Report. J Pediatr Pharmacol Ther. 2017; 22 (6): 467–470. doi: 10.5863/1551-6776-22.6.467.</mixed-citation><mixed-citation xml:lang="en">Cies J.J., LaCoursiere R.J., Moore II W.S., Chopra A. Therapeutic drug monitoring of prolonged infusion aztreonam for multi-drug resistant Pseudomonas aeruginosa: A Case Report. J Pediatr Pharmacol Ther. 2017; 22 (6): 467–470. doi: 10.5863/1551-6776-22.6.467.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Feng K., Jia N., Zhu P., Sy S., Liu Y., Dong D., et al. Aztreonam/avibactam effect on pharmacodynamic indices for mutant selection of Escherichia coli and Klebsiella pneumoniae harbouring serine- and New Delhi metallo-β-lactamases. J Antimicrob Chemother. 2021; 76: 2875–2883. DOI: 10.1093/jac/dkab292.</mixed-citation><mixed-citation xml:lang="en">Feng K., Jia N., Zhu P., Sy S., Liu Y., Dong D., et al. Aztreonam/avibactam effect on pharmacodynamic indices for mutant selection of Escherichia coli and Klebsiella pneumoniae harbouring serine- and New Delhi metallo-β-lactamases. J Antimicrob Chemother. 2021; 76: 2875–2883. DOI: 10.1093/jac/dkab292.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang J., Wu M., Diao S., Zhu S., Song C., Yue J., et al. Pharmacokinetic/pharmacodynamic evaluation of aztreonam/amoxicillin/clavulanate combination against New Delhi metallo-β-lactamase and serine-β-lactamase co-producing Escherichia coli and Klebsiella pneumoniae. Pharmaceutics. 2023; 15: 251. doi: 10.3390/pharmaceutics15010251.</mixed-citation><mixed-citation xml:lang="en">Zhang J., Wu M., Diao S., Zhu S., Song C., Yue J., et al. Pharmacokinetic/pharmacodynamic evaluation of aztreonam/amoxicillin/clavulanate combination against New Delhi metallo-β-lactamase and serine-β-lactamase co-producing Escherichia coli and Klebsiella pneumoniae. Pharmaceutics. 2023; 15: 251. doi: 10.3390/pharmaceutics15010251.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Alieva K.N., Golikova M.V., Kuznetsova A.A., Zinner S.H. Fluorescence microscopy: determination of meropenem activity against Klebsiella pneumoniae. Antibiotics. 2023; 12: 1170. doi: 10.3390/antibiotics12071170.</mixed-citation><mixed-citation xml:lang="en">Alieva K.N., Golikova M.V., Kuznetsova A.A., Zinner S.H. Fluorescence microscopy: determination of meropenem activity against Klebsiella pneumoniae. Antibiotics. 2023; 12: 1170. doi: 10.3390/antibiotics12071170.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Eng R.H.K., Cherubin C., Smith S.M., Buccini F. Inoculum effect of β-lactam antibiotics on Enterobacteriaceae. Antimicrob Agents Chemother. 1985; 28 (2): 601–606. doi: 10.1128/aac.28.5.601.</mixed-citation><mixed-citation xml:lang="en">Eng R.H.K., Cherubin C., Smith S.M., Buccini F. Inoculum effect of β-lactam antibiotics on Enterobacteriaceae. Antimicrob Agents Chemother. 1985; 28 (2): 601–606. doi: 10.1128/aac.28.5.601.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Cushnie TPT, O’Driscoll NH, Lamb AJ. Morphological and ultrastructural changes in bacterial cells as an indicator of antibacterial mechanism of action. Cell Mol Life Sci. 2016; 73: 4471–4492. doi: 10.1007/s00018-0162302-2.</mixed-citation><mixed-citation xml:lang="en">Cushnie TPT, O’Driscoll NH, Lamb AJ. Morphological and ultrastructural changes in bacterial cells as an indicator of antibacterial mechanism of action. Cell Mol Life Sci. 2016; 73: 4471–4492. doi: 10.1007/s00018-0162302-2.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Maglio D., Ong C., Banevicius M.A., Geng Q., Nightingale C.H., Nicolau D.P. Determination of the in vivo pharmacodynamic profile of cefepime against extended-spectrum-beta-lactamase-producing Escherichia coli at various inocula. Antimicrob Agents Chemother. 2004; 48 (6): 1941–1947. doi: 10.1128/AAC.48.6.1941–1947.2004.</mixed-citation><mixed-citation xml:lang="en">Maglio D., Ong C., Banevicius M.A., Geng Q., Nightingale C.H., Nicolau D.P. Determination of the in vivo pharmacodynamic profile of cefepime against extended-spectrum-beta-lactamase-producing Escherichia coli at various inocula. Antimicrob Agents Chemother. 2004; 48 (6): 1941–1947. doi: 10.1128/AAC.48.6.1941–1947.2004.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Szabó D., Máthe ́ A., Filetóth Z., Anderlik P., Rókusz L., Rozgonyi F. In vitro and in vivo activities of amikacin, cefepime, amikacin plus cefepime, and imipenem against an SHV-5 extended-spectrum β-lactamase-producing Klebsiella pneumoniae strain. Antimicrob Agents Chemother. 2001; 45 (4): 1287–1291. doi: 10.1128/aac.45.4.1287-1291.2001.</mixed-citation><mixed-citation xml:lang="en">Szabó D., Máthe ́ A., Filetóth Z., Anderlik P., Rókusz L., Rozgonyi F. In vitro and in vivo activities of amikacin, cefepime, amikacin plus cefepime, and imipenem against an SHV-5 extended-spectrum β-lactamase-producing Klebsiella pneumoniae strain. Antimicrob Agents Chemother. 2001; 45 (4): 1287–1291. doi: 10.1128/aac.45.4.1287-1291.2001.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Mizunaga S., Kamiyama T., Fukuda Y., Takahata M., Mitsuyama J. Influence of inoculum size of Staphylococcus aureus and Pseudomonas aeruginosa on in vitro activities and in vivo efficacy of fluoroquinolones and carbapenems. J Antimicrob Chemother. 2005; 56: 91–96. doi: 10.1093/jac/dki163.</mixed-citation><mixed-citation xml:lang="en">Mizunaga S., Kamiyama T., Fukuda Y., Takahata M., Mitsuyama J. Influence of inoculum size of Staphylococcus aureus and Pseudomonas aeruginosa on in vitro activities and in vivo efficacy of fluoroquinolones and carbapenems. J Antimicrob Chemother. 2005; 56: 91–96. doi: 10.1093/jac/dki163.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Lee D.-G., Murakami Y., Andes D.R., Craig W.A. Inoculum effects of ceftobiprole, daptomycin, linezolid, and vancomycin with Staphylococcus aureus and Streptococcus pneumoniae at inocula of 105 and 107 CFU injected into opposite thighs of neutropenic mice. Antimicrob Agents Chemother. 2013; 57 (3): 1434–1441. DOI: 10.1128/aac.00362-12.</mixed-citation><mixed-citation xml:lang="en">Lee D.-G., Murakami Y., Andes D.R., Craig W.A. Inoculum effects of ceftobiprole, daptomycin, linezolid, and vancomycin with Staphylococcus aureus and Streptococcus pneumoniae at inocula of 105 and 107 CFU injected into opposite thighs of neutropenic mice. Antimicrob Agents Chemother. 2013; 57 (3): 1434–1441. DOI: 10.1128/aac.00362-12.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Harada Y., Morinaga Y., Kaku N., Nakamura S., Uno N., Hasegawa H., et al. In vitro and in vivo activities of piperacillin-tazobactam and meropenem at different inoculum sizes of ESBL-producing Klebsiella pneumoniae. Clin Microbiol Infect. 2014; 20: O831–O839. doi: 10.1111/1469-0691.12677.</mixed-citation><mixed-citation xml:lang="en">Harada Y., Morinaga Y., Kaku N., Nakamura S., Uno N., Hasegawa H., et al. In vitro and in vivo activities of piperacillin-tazobactam and meropenem at different inoculum sizes of ESBL-producing Klebsiella pneumoniae. Clin Microbiol Infect. 2014; 20: O831–O839. doi: 10.1111/1469-0691.12677.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Saeki M., Shinaqawa M., Yakuwa Y., Nirasawa S., Sato Y., Yanagihara N., et al. Inoculum effect of high concentrations of methicillin-susceptible Staphylococcus aureus on the efficacy of cefazolin and other betalactams. J Infect Chemother. 2018; 24 (3): 212–215. doi: 10.1016/j.jiac.2017.10.021.</mixed-citation><mixed-citation xml:lang="en">Saeki M., Shinaqawa M., Yakuwa Y., Nirasawa S., Sato Y., Yanagihara N., et al. Inoculum effect of high concentrations of methicillin-susceptible Staphylococcus aureus on the efficacy of cefazolin and other betalactams. J Infect Chemother. 2018; 24 (3): 212–215. doi: 10.1016/j.jiac.2017.10.021.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Fantin B., Poujade J., Grégoire N., Chau F., Roujansky A., Kieffer N., et al. The inoculum effect of Escherichia coli expressing mcr-1 or not on colistin activity in a murine model of peritonitis. Clin Microbiol Inf. 2019; 25 (12): 1563.e5–1563.e8. doi: 10.1016/j.cmi.2019.08.021.</mixed-citation><mixed-citation xml:lang="en">Fantin B., Poujade J., Grégoire N., Chau F., Roujansky A., Kieffer N., et al. The inoculum effect of Escherichia coli expressing mcr-1 or not on colistin activity in a murine model of peritonitis. Clin Microbiol Inf. 2019; 25 (12): 1563.e5–1563.e8. doi: 10.1016/j.cmi.2019.08.021.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">McNeil J.C., Sommer L.M., Boyle M., Hogan P., Vallejo J.G., Hultén K.G., et al. Cefazolin inoculum effect and methicillin-susceptible Staphylococcus aureus osteoarticular infections in children. Antimicrob Agents Chemother. 2020; 64 (9): e00703-20. doi: 10.1128/AAC.00703-20.</mixed-citation><mixed-citation xml:lang="en">McNeil J.C., Sommer L.M., Boyle M., Hogan P., Vallejo J.G., Hultén K.G., et al. Cefazolin inoculum effect and methicillin-susceptible Staphylococcus aureus osteoarticular infections in children. Antimicrob Agents Chemother. 2020; 64 (9): e00703-20. doi: 10.1128/AAC.00703-20.</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>
