“The end of the era of antibiotics” — myth or reality: what the past COVID-19 pandemic has shown

Abstract

BACKGROUND: During the coronavirus disease 2019 pandemic, the sale of antimicrobials (AMPs) in the pharmacy network and their purchases by healthcare facilities of the Russian Federation have significantly increased. Microbiological monitoring conducted at the City Clinical Hospital No. 67 named after L.A. Vorokhobov of the Moscow Health Department in 2020–2021 revealed an urgent problem: gram-negative bacteria, which are dominated by multidrug-resistant (MDR) strains, are now mainly isolated from patients with healthcare-associated infections (HAIs). Pharmacoeconomic studies have shown that the cost of one course of targeted antibiotic therapy for HAIs can increase by 6–12 times compared with a similar course of therapy in the absence of nosocomial MDR and extensively drug-resistant (XDR) pathogens.

AIM: To increase the effectiveness of preventive measures aimed at preventing the spread of hospital-acquired pathogen strains in the intensive care unit (ICU) using effective bacteriophages against MDR strains of Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Acinetobacter baumannii, which were selected in accordance with an individualized algorithm.

MATERIALS AND METHODS: The study included two groups, totaling 20 patients, who were on prolonged mechanical ventilation in the ICU of City Clinical Hospital No. 67 named after L.A. Vorokhobov of the Moscow Health Department in 2022. The second group received 20 mL of bacteriophages via an intragastric tube for five consecutive days. The concept of a personalized approach to phage therapy for various forms of HAIs caused by nosocomial MDR pathogens in patients of a multidisciplinary hospital has been proposed and tested.

RESULTS: With this medical technology, the effectiveness of phage therapy for various nosological forms of HAIs caused by nosocomial MDR and XDR strains increased by 30%, and the effectiveness of the initial antibiotic therapy regimen was ≥70%. The economic effect of the combination of antibiotic therapy and phage therapy (booster therapy) amounted to more than 3 million rubles compared with the use of AMP alone for treating patients with HAIs caused by nosocomial MDR/XDR strains.

CONCLUSIONS: Booster therapy as a variant of IIB therapy reduces the cost of treatment of AMPs of various forms of HAIs by ≥2.5 times compared with AMPs alone.

Keywords

HAIs / hospital strains / MDRs / personalized phage therapy / combined antibiotic/phage therapy for HAIs

References

[1] Nikiforov VV, Suranova TG, Mironov AYu, Zabozlaev FG. New coronavirus infection (COVID-19): etiology, epidemiology, clinic, diagnosis, treatment and prevention. Moscow: Academy of Postgraduate Education of the Federal State Budgetary Institution “FNCC FMBA of Russia”; 2020. 48 p. (In Russ).

[2] Никифоров В.В., Суранова Т.Г., Миронов А.Ю., Забозлаев Ф.Г. Новая коронавирусная инфекция (COVID-19): этиология, эпидемиология, клиника, диагностика, лечение и профилактика. Москва : Академия постдипломного образования ФГБУ «ФНКЦ ФМБА России», 2020. 48 с.

[3] Petrova LV, Mironov AY, Gusarov VG, et al. Etiological structure of infectious complications and microbial colonization in patients of COVID-19 hospital of a multidisciplinary federal medical institution. Epidemiology and Infectious Diseases. 2021;26(6):270–282. (In Russ). doi: 10.17816/EID109205

[4] Петрова Л.В., Миронов А.Ю., Гусаров В.Г., и др. Видовой спектр микроорганизмов, выделенных у пациентов госпиталя COVID-19 многопрофильного федерального медицинского учреждения // Эпидемиология и инфекционные болезни. 2021. Т. 26, № 6. С. 270–282. doi: 10.17816/EID109205

[5] Mironov AYu, Savitskaya KI, Vorobyev AA. Conditionally pathogenic microorganisms in respiratory tract diseases in patients of the Moscow region. Journal of Microbiology, Epidemiology and Immunobiology. 2000;1:81–84. (In Russ).

[6] Миронов А.Ю., Савицкая К.И., Воробьёв А.А. Условно-патогенные микроорганизмы при заболеваниях дыхательных путей у больных региона Московской области // Журнал микробиологии, эпидемиологии и иммунобиологии. 2000. Т. 1. С. 81–84.

[7] Mitrokhin SD, Orlova OE, Yankovskaya OS, et al. Real-life antimicrobial therapy in hospitalized patients with COVID-19 (preliminary results and recommendations). Clinical Microbiology and Antimicrobial Chemotherapy. 2022;24(2):181–192. (In Russ). doi: 10.36488/cmac.2022.2.181-192

[8] Митрохин С.Д., Орлова О.Е., Янковская О.С., и др. Опыт применения антибактериальной терапии у пациентов с новой коронавирусной инфекцией COVID-19 на госпитальном этапе лечения (предварительные итоги и рекомендации) // Клиническая микробиология и антимикробная химиотерапия. 2022. Т. 24, № 2. С. 181–192. doi: 10.36488/cmac.2022.2.181-192

[9] Vorobyev AA, Bykov AS, Boychenko MN, et al. Medical microbiology, virology and immunology. Moscow: Meditsinskoe informatsionnoe agentstvo; 2015. 704 p. (In Russ).

[10] Воробьев А.А., Быков А.С., Бойченко М.Н., и др. Медицинская микробиология, вирусология и иммунология. Москва : Медицинское информационное агентство, 2015. 704 с.

[11] Yakovleva SV, Zhuravleva MV, Protsenko DN, Beloborodova VB, editors. The SCAT program (Antimicrobial Therapy Control Strategy) in the provision of inpatient medical care: methodological recommendations. Moscow: s.n.; 2016. (In Russ).

[12] Программа СКАТ (Стратегия Контроля Антимикробной Терапии) при оказании стационарной медицинской помощи : методические рекомендации / под ред. С.В. Яковлева, М.В. Журавлевой, Д.Н. Проценко, В.Б. Белобородова. Москва : [б. и.], 2016.

[13] Mitrokhin SD, Orlova OE, Gosteva IV, Shkoda AS. Appointment of Antimicrobial Medications in a Hospital Depending on the Results of Microbiological Monitoring of HAI. Antibiotics and Chemotherapy. 2020;65(9-10):21–27. (In Russ). doi: 10.37489/0235-2990-2020-65-9-10-21-27

[14] Митрохин С.Д., Орлова О.Е., Гостева И.В., Шкода А.С. Потребление антимикробных лекарственных средств в стационаре в зависимости от результатов микробиологического мониторинга ИСМП // Антибиотики и химиотерапия. 2020. Т. 65, № 9-10. С. 21–27. doi: 10.37489/0235-2990-2020-65-9-10-21-27

[15] Mitrokhin SD. Biotherapy — the answer to the global problem of resistance of bacteria to antibiotics in the twenty-first century. Vestnik Meditsinskogo tsentra Upravdelami Prezidenta Respubliki Kazakhstan. 2018;(4(73)):109–115. (In Russ).

[16] Митрохин С.Д. Биотерапия — ответ на проблему глобальной резистентности бактерий к антибиотикам в ХХI веке // Вестник Медицинского центра Управделами Президента Республики Казахстан. 2018. № 4 (73). С. 109–115.

[17] Mitrokhin SD, Sternin YuI. The significance of immunobiological drugs in the prevention of infections in the field of surgical intervention in cancer patients. Effektivnaya farmakoterapiya. 2011;25:46–52. (In Russ).

[18] Митрохин С.Д., Стернин Ю.И. Значимость иммунобиологических препаратов в профилактике инфекций области хирургического вмешательства у онкологических больных // Эффективная фармакотерапия. 2011. Т. 25. С. 46–52.

[19] Mitrokhin SD. The concept of prevention of infections in the field of surgical intervention in cancer patients using immunobiological drugs. Russian Medical Journal. 2011;19(32):2032–2037. (In Russ). EDN: QZJBLH

[20] Митрохин С.Д. Концепция профилактики инфекций области хирургического вмешательства у онкологических больных с использованием иммунобиологических препаратов // Русский медицинский журнал. 2011. Т. 19, № 32. С. 2032–2037. EDN: QZJBLH

[21] Aleshkin AV, Selkova EP, Ershova ON, et al. The concept of personalized phage therapy for patients of the intensive care unit and intensive care suffering from infections related to the provision of medical care. Fundamental and Clinical Medicine. 2018;3(2):66–74. (In Russ).

[22] Алёшкин А.В., Селькова Е.П., Ершова О.Н., и др. Концепция персонализированной фаготерапии пациентов отделения реанимации и интенсивной терапии, страдающих инфекциями, связанными с оказанием медицинской помощи // Фундаментальная и клиническая медицина. 2018. Т. 3, № 2. С. 66–74.

[23] Patent RUS №2664681 C1/ 06.09.2017. Byul. №24 Aleshkin VA, Aleshkin AV, Ershova ON, et al. Method of treatment of infection associated with provision of medical care caused by a pathogen or pathogens with multiple drug resistance. (In Russ).

[24] Патент РФ № 2664681 С1/ 06.09.2017. Бюл. № 24. Алёшкин В.А., Алёшкин А.В., Ершова О.Н., и др. Способ лечения инфекции, связанной с оказанием медицинской помощи, вызванной возбудителем или возбудителями с множественной лекарственной устойчивостью.

RIGHTS & PERMISSIONS

Eco-vector