safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/2312-7821-2022-10-2-96-109safetyrisk-256Research ArticleГЛАВНАЯ ТЕМА: АКТУАЛЬНЫЕ ПРОБЛЕМЫ БЕЗОПАСНОСТИ АНТИБАКТЕРИАЛЬНОЙ ТЕРАПИИMAIN TOPIC: RELEVANT SAFETY ISSUES OF ANTIMICROBIAL TREATMENTОценка влияния коморбидной патологии на эффективность и безопасность применения β-лактамных антибиотиков у пациентов с внебольничной пневмониейEvaluation of the Effect of Comorbidity on the Efficacy and Safety of β-Lactam Antibiotics in Patients with Community-Acquired Pneumoniahttps://orcid.org/0000-0003-1009-9609МуслимоваО. В.MuslimovaO. V.

Муслимова Ольга Валерьевна, кандидат медицинских наук.

Петровский б-р, д. 8, стр. 2, Москва, 127051

Olga V. Muslimova, Cand. Sci. (Med.).

8/2 Petrovsky Blvd, Moscow 127051

muslimova@expmed.ruhttps://orcid.org/0000-0002-6389-2099СоковаЕ. А.SokovaE. A.

Сокова Елена Андреевна, кандидат медицинских наук, доцент.

Петровский б-р, д. 8, стр. 2, Москва, 127051; Трубецкая ул., д. 8, стр. 2, Москва, 119991

Elena A. Sokova, Cand. Sci. (Med.), Associate Professor.

8/2 Petrovsky Blvd., Moscow 127051; 8/2 Trubetskaya St., Moscow 119991

sokova@expmed.ruhttps://orcid.org/0000-0001-7024-5546ПрокофьевА. Б.ProkofievA. B.

Прокофьев Алексей Борисович, доктор медицинских наук, профессор.

Петровский б-р, д. 8, стр. 2, Москва, 127051

Alexey B. Prokofiev, Dr. Sci. (Med.), Professor.

8/2 Petrovsky Blvd, Moscow 127051

prokofiev@expmed.ruhttps://orcid.org/0000-0002-9198-8661ЖуравлеваМ. В.ZhuravlevaM. V.

Журавлева Марина Владимировна, доктор медицинских наук, профессор.

Петровский б-р, д. 8, стр. 2, Москва, 127051; Трубецкая ул., д. 8, стр. 2, Москва, 119991

Marina V. Zhuravleva, Dr. Sci. (Med.), Professor.

8/2 Petrovsky Blvd, Moscow 127051; 8/2 Trubetskaya St., Moscow 119991

zhuravleva@expmed.ruhttps://orcid.org/0000-0003-4856-9346ШапченкоА. В.ShapchenkoA. V.

Шапченко Анна Валерьевна, кандидат медицинских наук, доцент.

Делегатская ул., д. 20, стр. 1, Москва, 127473

Anna V. Shapchenko, Cand. Sci. (Med.), Associate Professor.

20/1 Delegatskaya St., Moscow 127473

muslimova@expmed.ruhttps://orcid.org/0000-0003-3855-5899АлександроваТ. В.AlexandrovaT. V.

Александрова Татьяна Владимировна, кандидат медицинских наук.

Петровский б-р, д. 8, стр. 2, Москва, 127051

Tatiana V. Alexandrova, Cand. Sci. (Med.).

8/2 Petrovsky Blvd, Moscow 127051

aleksandrova@expmed.ruФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian FederationФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской Федерации; Федеральное государственное автономное образовательное учреждение высшего образования «Первый Московский государственный медицинский университет им. И.М. Сеченова» Министерства здравоохранения Российской Федерации (Сеченовский университет)РоссияScientific Centre for Expert Evaluation of Medicinal Products; I.M. Sechenov First Moscow State Medical University (Sechenov University)Russian FederationФедеральное государственное бюджетное учреждение высшего образования «Московский государственный медико-стоматологический университет им. А.И. Евдокимова» Министерства здравоохранения Российской ФедерацииРоссияA.I. Yevdokimov Moscow State University of Medicine and DentistryRussian Federation20220307202210296109Copyright © Муслимова О.В., Сокова Е.А., Прокофьев А.Б., Журавлева М.В., Шапченко А.В., Александрова Т.В., 20222022Муслимова О.В., Сокова Е.А., Прокофьев А.Б., Журавлева М.В., Шапченко А.В., Александрова Т.В.Muslimova O.V., Sokova E.A., Prokofiev A.B., Zhuravleva M.V., Shapchenko A.V., Alexandrova T.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/256

Инфекции нижнего отдела респираторного тракта, к которым относится внебольничная пневмония (ВП), являются самой частой причиной смерти среди всех пациентов с инфекционными заболеваниями. Наличие у пациента с ВП коморбидной патологии предполагает возможность взаимного влияния и изменения течения как основного заболевания, так и коморбидных к нему заболеваний, а также изменение эффективности и безопасности проводимой лекарственной терапии. Цель работы: анализ данных литературы о структуре коморбидности при ВП и ее влиянии на эффективность и безопасность терапии β-лактамными антибиотиками. Установлено, что наиболее часто ВП возникает у пациентов с хронической обструктивной болезнью легких, сердечно-сосудистыми заболеваниями (ишемической болезнью сердца, артериальной гипертензией, хронической сердечной недостаточностью), цереброваскулярной болезнью, хронической болезнью почек, сахарным диабетом, бронхиальной астмой, лейкемией, анемией, деменцией, неврологическими нарушениями и онкопатологией. Самым частым возбудителем ВП независимо от возраста пациента и сопутствующей патологии является пневмококк (Streptococcus pneumoniae), далее — внутриклеточные патогены (микоплазмы, хламидии) и гемофильная палочка, а также возбудители респираторных вирусных инфекций. С учетом этого в качестве стартовой эмпирической терапии ВП назначают в основном β-лактамные антибиотики, эффективные в отношении пневмококка. При наличии у пациентов с ВП сопутствующих хронических заболеваний и состояний спектр возбудителей пневмонии может отличаться от такового в общей популяции и включать редкие возбудители и полирезистентные штаммы. Эффективность антибиотикотерапии у пациентов с коморбидной патологией снижается, что влечет за собой утяжеление течения как ВП, так и сопутствующих заболеваний. Такому контингенту пациентов может потребоваться более длительное лечение антибактериальными препаратами, в том числе β-лактамами, или использование антибиотиков в дозах, обеспечивающих более высокую минимальную подавляющую концентрацию, что сопряжено с высоким риском развития нежелательных реакций и со снижением безопасности антибактериальной терапии.

Lower respiratory tract infections, which include community-acquired pneumonia (CAP), are the most common cause of death among all infectious diseases. The presence of a comorbid pathology in a patient with CAP suggests a possibility of mutual influence and changes in the course of both the underlying disease and comorbidities, as well as changes in the effectiveness and safety of ongoing drug therapy. The aim of the study was to analyse literature data on the structure of comorbidity in CAP patients and its impact on the efficacy and safety of therapy with β-lactam antibiotics. It has been established that CAP most often occurs in patients with chronic obstructive pulmonary disease, cardiovascular diseases (ischemic heart disease, arterial hypertension, and chronic heart failure), cerebrovascular disease, chronic kidney disease, diabetes mellitus, bronchial asthma, leukemia, anemia, dementia, neurological disorders, and cancer. The most common causative agent of CAP, regardless of the patient’s age and comorbidity, is pneumococcus (Streptococcus pneumoniae), followed by intracellular pathogens (mycoplasmas, chlamydia) and Haemophilus influenzae, as well as respiratory viruses. With this in mind, the initial empiric therapy for CAP mainly includes β-lactam antibiotics, which are effective against pneumococcus. If patients with CAP have concomitant chronic diseases and conditions, the spectrum of pneumonia pathogens may differ from that in the general population and include rare pathogens and multidrug-resistant strains. The effectiveness of antibiotic therapy in such patients is reduced, which leads to a worsening of the course of both CAP and concomitant diseases. This patient population may require longer treatment with antibiotics, including β-lactams, or the use of antibiotics at doses that provide a higher minimum inhibitory concentration, which is associated with a high risk of adverse reactions and a decrease in the safety of antibiotic therapy.

внебольничная пневмонияβ-лактамыантибиотикикоморбидностьстартовая эмпирическая терапияантибиотикорезистентностьStreptococcus pneumoniaecommunity-acquired pneumoniaβ-lactamsantibioticscomorbidityinitial empirical therapyantibiotic resistanceStreptococcus pneumoniaeРабота выполнена в рамках государственного задания ФГБУ «НЦЭСМП» Минздрава России № 056-00001-22-00 на проведение прикладных научных исследований (номер государственного учета НИР 121022000154-2)The study reported in this publication was carried out as part of publicly funded research project No. 056-00001-22-00 and was supported by the Scientific Centre for Expert Evaluation of Medicinal Products (R&D public accounting No. 121022000154-2)ReferencesPiffer F, Tardini F, Cosentini R. The IDSA/ATS consensus guidelines on the management of CAP in adults. Breathe. 2007;4(2):110–5.Piffer F, Tardini F, Cosentini R. The IDSA/ATS consensus guidelines on the management of CAP in adults. Breathe. 2007;4(2):110–5.Lim WS, Baudouin SV, George RC, Hill AT, Jamieson C, Le Jeune I, et al. British Thoracic Society guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax. 2009;64(Suppl III):iii1–55. https://doi.org/10.1136/thx.2009.121434Lim WS, Baudouin SV, George RC, Hill AT, Jamieson C, Le Jeune I, et al. British Thoracic Society guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax. 2009;64(Suppl III):iii1–55. https://doi.org/10.1136/thx.2009.121434Оганов РГ, Денисов ИН, Симаненков ВИ, Бакулин ИГ, Бакулина НВ, Болдуева СА и др. Коморбидная патология в клинической практике. Клинические рекомендации. Кардиоваскулярная терапия и профилактика. 2017;16(6):5–56. [Oganov RG, Denisov IN, Simanenkov VI, Bakulin IG, Bakulina NV, Boldueva SA, et al. Comorbidities in practice. Clinical guidelines. Kardiovaskulyarnaya terapiya i profilaktika = Cardiovascular Therapy and Prevention. 2017;16(6):5–56 (In Russ.)] https://doi.org/10.15829/1728-8800-2017-6-5-56Oganov RG, Denisov IN, Simanenkov VI, Bakulin IG, Bakulina NV, Boldueva SA, et al. Comorbidities in practice. Clinical guidelines. Kardiovaskulyarnaya terapiya i profilaktika = Cardiovascular Therapy and Prevention. 2017;16(6):5–56 (In Russ.) https://doi.org/10.15829/1728-8800-2017-6-5-56Sharma R, Sandrock CE, Meehan J, Theriault N. Community-acquired bacterial pneumonia – changing epidemiology, resistance patterns, and newer antibiotics: spotlight on delafloxacin. Clin Drug Investig. 2020;40(10):947–60. https://doi.org/10.1007/s40261-020-00953-zSharma R, Sandrock CE, Meehan J, Theriault N. Community-acquired bacterial pneumonia — changing epidemiology, resistance patterns, and newer antibiotics: spotlight on delafloxacin. Clin Drug Investig. 2020;40(10):947–60. https://doi.org/10.1007/s40261-020-00953-zОганов РГ, Симаненков ВИ, Бакулин ИГ, Бакулина НВ, Барбараш ОЛ, Бойцов СА и др. Коморбидная патология в клинической практике. Алгоритмы диагностики и лечения. Кардиоваскулярная терапия и профилактика. 2019;18(1):5–66. [Oganov RG, Simanenkov VI, Bakulin IG, Bakulina NV, Barbarash OL, Boytsov SA, et al. Comorbidities in clinical practice. Algorithms for diagnostics and treatment. Kardiovaskulyarnaya terapiya i profilaktika = Cardiovascular Therapy and Prevention. 2019;18(1):5–66 (In Russ.)] https://doi.org/10.15829/1728-8800-2019-1-5-66Oganov RG, Simanenkov VI, Bakulin IG, Bakulina NV, Barbarash OL, Boytsov SA, et al. Comorbidities in clinical practice. Algorithms for diagnostics and treatment. Kardiovaskulyarnaya terapiya i profilaktika = Cardiovascular Therapy and Prevention. 2019;18(1):5–66 (In Russ.) https://doi.org/10.15829/1728-8800-2019-1-5-66Тарловская ЕИ. Коморбидность и полиморбидность – современная трактовка и насущные задачи, стоящие перед терапевтическим сообществом. Кардиология. 2018;58(9S):29–38. [Tarlovskaya EI. Comorbidity and polymorbidity – a modern interpretation and urgent tasks facing the therapeutic community. Kardiologiya = Cardiology. 2018;58(9S):29–38 (In Russ.)] https://doi.org/10.18087/cardio.2562Tarlovskaya EI. Comorbidity and polymorbidity — a modern interpretation and urgent tasks facing the therapeutic community. Kardiologiya = Cardiology. 2018;58(9S):29–38 (In Russ.) https://doi.org/10.18087/cardio.2562Зырянов СК, Ченкуров МС, Ивжиц МА, Батечко ЮА, Иванова ЕБ, Якунина МА. Исследование структуры сопутствующих заболеваний и этиологии внебольничной пневмонии у пациентов пожилого и старческого возраста. Клиническая микробиология и антимикробная химиотерапия. 2020;(3):242–8. [Zyryanov SK, Chenkurov MS, Ivzhits MA, Batechko YuA, Ibanova EB, Yakunina MA. Etiology of community-acquired pneumonia and prevalence of comorbidities in elderly patient population. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya = Clinical Microbiology and Antimicrobial Chemotherapy. 2020;(3):242–8 (In Russ.)] https://doi.org/10.36488/cmac.2020.3.242-248Zyryanov SK, Chenkurov MS, Ivzhits MA, Batechko YuA, Ibanova EB, Yakunina MA. Etiology of community-acquired pneumonia and prevalence of comorbidities in elderly patient population. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya = Clinical Microbiology and An timicrobial Chemotherapy. 2020;(3):242–8 (In Russ.) https://doi.org/10.36488/cmac.2020.3.242-248Ramirez JA, Wiemken TL, Peyrani P, Arnold FW, Kelley R, Mattingly WA, et al. Adults hospitalized with pneumonia in the United States: incidence, epidemiology, and mortality. Clin Infect Dis. 2017;65(11):1806–12. https://doi.org/10.1093/cid/cix647Ramirez JA, Wiemken TL, Peyrani P, Arnold FW, Kelley R, Mattingly WA, et al. Adults hospitalized with pneumonia in the United States: incidence, epidemiology, and mortality. Clin Infect Dis. 2017;65(11):1806– 12. https://doi.org/10.1093/cid/cix647Андержанова АА, Мелешкина ЮА. Внебольничная пневмония. Диагностика, подходы к лечению. Клиницист. 2019;13(1–2):55–64. [Anderzhanova AA, Meleshkina YuA. Community-acquired pneumonia. Diagnosis, treatment approaches. Klinitsist = Clinician. 2019;13(1–2):55–64 (In Russ.)] https://doi.org/10.17650/1818-8338-2019-13-1-2-55-64Anderzhanova AA, Meleshkina YuA. Community-acquired pneumonia. Diagnosis, treatment approaches. Klinitsist = Clinician. 2019;13(1–2):55–64 (In Russ.) https://doi.org/10.17650/1818-8338-2019-13-1-2-55-64Carugati M, Aliberti S, Sotgiu G, Blasi F, Gori A, Menendez R, et al. Bacterial etiology of community-acquired pneumonia in immunocompetent hospitalized patients and appropriateness of empirical treatment recommendations: an international point-prevalence study. Eur J Clin Microbiol Infect Dis. 2020;39(8):1513–25. https://doi.org/10.1007/s10096-020-03870-3Carugati M, Aliberti S, Sotgiu G, Blasi F, Gori A, Menendez R, et al. Bacterial etiology of community-acquired pneumonia in immunocompetent hospitalized patients and appropriateness of empirical treatment recommendations: an international point-prevalence study. Eur J Clin Microbiol Infect Dis. 2020;39(8):1513–25. https://doi.org/10.1007/s10096-020-03870-3Carugati M, Aliberti S, Reyes LF, Sadud RF, Irfan M, Prat C, et al. Microbiological testing of adults hospitalised with community-acquired pneumonia: an international study. ERJ Open Res. 2018;4(4):00096-2018. https://doi.org/10.1183/23120541.00096-2018Carugati M, Aliberti S, Reyes LF, Sadud RF, Irfan M, Prat C, et al. Microbiological testing of adults hospitalised with community-acquired pneumonia: an international study. ERJ Open Res. 2018;4(4):00096-2018. https://doi.org/10.1183/23120541.00096-2018Цыганко ДВ, Бердникова НГ, Красных ЛМ, Меньшов ВА, Политкина СН, Антоновский ЮА. Некоторые клинико-фармакологические аспекты терапии внебольничной пневмонии. Эффективная фармакотерапия. 2019;15(27):28–36. [Tsyganko DV, Berdnikova NG, Krasnykh LM, Men’shov VA, Politkina SN, Antonovsky YuA. Some clinical and pharmacological aspects of community pneumonia therapy. Effektivnaya farmakoterapiya = Effective Pharmacotherapy. 2019;15(27):28–36 (In Russ.)] https://doi.org/10.33978/2307-3586-2019-15-27-28-36Tsyganko DV, Berdnikova NG, Krasnykh LM, Men’shov VA, Politkina SN, Antonovsky YuA. Some clinical and pharmacological aspects of community pneumonia therapy. Effektivnaya farmakoterapiya = Effective Pharmacotherapy. 2019;15(27):28–36 (In Russ.) https://doi.org/10.33978/2307-3586-2019-15-27-28-36Бобылев АА, Рачина СА, Авдеев СН, Козлов РС, Дехнич НН. Внебольничная пневмония у пациентов пожилого и старческого возраста. Пульмонология. 2015;25(3):261–76. [Bobylev AA, Rachina SA, Avdeev SN, Kozlov RS, Dehnich NN. Community-acquired pneumonia in elderly and very elderly patients. Pulmonologiya = Pulmonology. 2015;25(3):261–76 (In Russ.)] https://doi.org/10.18093/0869-0189-2015-25-3-261-276Bobylev AA, Rachina SA, Avdeev SN, Kozlov RS, Dehnich NN. Community-acquired pneumonia in elderly and very elderly patients. Pulmonologiya = Pulmonology. 2015;25(3):261–76 (In Russ.) https://doi.org/10.18093/0869-0189-201525-3-261-276Corral JM, Pascual-Guardia S, Amati F, Aliberti S, Masclans JR, Soni N, et al. Aspiration risk factors, microbiology, and empiric antibiotics for patients hospitalized with community-acquired pneumonia. Chest. 2021;159(1):58–72. https://doi.org/10.1016/j.chest.2020.06.079Corral JM, Pascual-Guardia S, Amati F, Aliberti S, Masclans JR, Soni N, et al. Aspiration risk factors, microbiology, and empiric antibi otics for patients hospitalized with community-acquired pneumonia. Chest. 2021;159(1):58–72. https://doi.org/10.1016/j.chest.2020.06.079Viasus D, Garcia-Vidal C, Castellote J, Adamuz J, Verdaguer R, Dorca J. Community-acquired pneumonia in patients with liver cirrhosis: clinical features, outcomes, and usefulness of severity scores. Medicine (Baltimore). 2011;90(2):110–8. https://doi.org/10.1097/MD.0b013e318210504cViasus D, Garcia-Vidal C, Castellote J, Adamuz J, Verdaguer R, Dorca J. Community-acquired pneumonia in patients with liver cirrhosis: clinical features, outcomes, and usefulness of severity scores. Medicine (Baltimore). 2011;90(2):110–8. https://doi.org/10.1097/MD.0b013e318210504cФомин ИВ. Хроническая сердечная недостаточность в Российской Федерации: что сегодня мы знаем и что должны делать. Российский кардиологический журнал. 2016;(8):7–13. [Fomin IV. Chronic heart failure in Russian Federation: what do we know and what to do. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2016;(8):7–13 (In Russ.)] https://doi.org/10.15829/1560-4071-2016-8-7-13Fomin IV. Chronic heart failure in Russian Federation: what do we know and what to do. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2016;(8):7–13 (In Russ.) https://doi.org/10.15829/1560-4071-2016-8-7-13Maggioni AP, Dahlstrom U, Filippatos G, Chioncel O, Leiro MC, Drozdz J, et al. EURObservational Research Programme: regional differences and 1-year follow-up results of the Heart Failure Pilot Survey (ESC-HF Pilot). Eur J Heart Fail. 2013;15(7):808–17. https://doi.org/10.1093/eurjhf/hft050Maggioni AP, Dahlstrom U, Filippatos G, Chioncel O, Leiro MC, Drozdz J, et al. EURObservational Research Programme: regional differences and 1-year follow-up results of the Heart Failure Pilot Survey (ESC-HF Pilot). Eur J Heart Fail. 2013;15(7):808–17. https://doi.org/10.1093/eurjhf/hft050Виноградова НГ, Поляков ДС, Фомин ИВ. Риски повторной госпитализации пациентов с ХСН при длительном наблюдении в специализированном центре лечения ХСН и в реальной клинической практике. Кардиология. 2020;60(3):59–69. [Vinogradova NG, Polyakov DS, Fomin IV. The risks of re-hospitalization of patients with heart failure with prolonged follow-up in a specialized center for the treatment of heart failure and in real clinical practice. Kardiologiya = Cardiology. 2020;60(3):59–69 (In Russ.)]. https://doi.org/10.18087/cardio.2020.3.n1002Vinogradova NG, Polyakov DS, Fomin IV. The risks of re-hospitalization of patients with heart failure with prolonged follow-up in a specialized center for the treatment of heart failure and in real clinical practice. Kardiologiya = Cardiology. 2020;60(3):59–69 (In Russ.) https://doi.org/10.18087/cardio.2020.3.n1002Joffe E, Justo D, Mashav N, Swartzon M, Gur H, Berliner S, Paran Y. C-reactive protein to distinguish pneumonia from acute decompensated heart failure. Clin Biochem. 2009;42(16–17):1628–34. https://doi.org/10.1016/j.clinbiochem.2009.08.007Joffe E, Justo D, Mashav N, Swartzon M, Gur H, Berliner S, Paran Y. C-reactive protein to distinguish pneumonia from acute decompensated heart failure. Clin Biochem. 2009;42(16–17):1628–34. https://doi.org/10.1016/j.clinbiochem.2009.08.007Muñoz-Rivas N, Jiménez-García R, Méndez-Bailón M, Hernandez-Barrera V, de Miguel-Diez J, Lorenzo-Villalba N, et al. Type 2 diabetes increases the risk of hospital admission for heart failure and reduces the risk of in hospital mortality in Spain (2001–2015). Eur J Intern Med. 2019;59:53–9. https://doi.org/10.1016/j.ejim.2018.08.011Muñoz-Rivas N, Jiménez-García R, Méndez-Bailón M, Hernandez-Barrera V, de Miguel-Diez J, Lorenzo-Villalba N, et al. Type 2 diabetes increases the risk of hospital admission for heart failure and reduces the risk of in hospital mortality in Spain (2001–2015). Eur J Intern Med. 2019;59:53–9. https://doi.org/10.1016/j.ejim.2018.08.011Бирюкова ЕВ, Гуров АВ, Юшкина МА. Сахарный диабет и гнойно-воспалительные заболевания ЛОР-органов. Сахарный диабет. 2012;15(2):54–9. [Biryukova EV, Gurov AV, Yushkina MA. Diabetes mellitus and pyoinflammatory diseases of ENT organs. Sakharny diabet = Diabetes Mellitus. 2012;15(2):54–9 (In Russ.)] https://doi.org/10.14341/2072-0351-5519Biryukova EV, Gurov AV, Yushkina MA. Diabetes mellitus and pyoinflammatory diseases of ENT organs. Sakharny diabet = Diabetes Mellitus. 2012;15(2):54–9 (In Russ.) https://doi.org/10.14341/2072-0351-5519Klekotka RB, Mizgała E, Król W. The etiology of lower respiratory tract infections in people with diabetes. Pneumonol Alergol Pol. 2015;83(5):401–8. https://doi.org/10.5603/PiAP.2015.0065Klekotka RB, Mizgała E, Król W. The etiology of lower respiratory tract infections in people with diabetes. Pneumonol Alergol Pol. 2015;83(5):401–8. https://doi.org/10.5603/PiAP.2015.0065Christou L, Pappas G, Falagas ME. Bacterial infection-related morbidity and mortality in cirrhosis. Am J Gastroenterol. 2007;102(7):1510–7. https://doi.org/10.1111/j.1572-0241.2007.01286.xChristou L, Pappas G, Falagas ME. Bacterial infection-related morbidity and mortality in cirrhosis. Am J Gastroenterol. 2007;102(7):1510–7. https://doi.org/10.1111/j.1572-0241.2007.01286.xTandon P, Garcia-Tsao G. Bacterial infections, sepsis, and multiorgan failure in cirrhosis. Semin Liver Dis. 2008;28(1):26–42. https://doi.org/10.1055/s-2008-1040319Tandon P, Garcia-Tsao G. Bacterial infections, sepsis, and multiorgan failure in cirrhosis. Semin Liver Dis. 2008;28(1):26–42. https://doi.org/10.1055/s-2008-1040319Borzio M, Salerno F, Piantoni L, Cazzaniga M, Angeli P, Bissoli F, et al. Bacterial infection in patients with advanced cirrhosis: a multicentre prospective study. Dig Liver Dis. 2001;33(1):41–8. https://doi.org/10.1016/s1590-8658(01)80134-1Borzio M, Salerno F, Piantoni L, Cazzaniga M, Angeli P, Bissoli F, et al. Bacterial infection in patients with advanced cirrhosis: a multicentre prospective study. Dig Liver Dis. 2001;33(1):41–8. https://doi.org/10.1016/s1590-8658(01)80134-1Cuomo G, Brancacci G, Stornaiuolo G, Manno D, Gaeta GL, Mussini C, et al. Bacterial pneumonia in patients with liver cirrhosis, with or without HIV co-infection: a possible definition of antibiotic prophylaxis associated pneumonia (APAP). Infect Dis (Lond). 2018;50(2):125–32. https://doi.org/10.1080/23744235.2017.1367414Cuomo G, Brancacci G, Stornaiuolo G, Manno D, Gaeta GL, Mussini C, et al. Bacterial pneumonia in patients with liver cirrhosis, with or without HIV co-infection: a possible definition of antibiotic prophylaxis associated pneumonia (APAP). Infect Dis (Lond). 2018;50(2):125–32. https://doi.org/10.1080/23744235.2017.1367414Sahuquillo-Arce JM, Menéndez R, Méndez R, Amara-Elori I, Zalacain R, Capelastegui A, et al. Age-related risk factors for bacterial aetiology in community-acquired pneumonia. Respirology. 2016;21(8):1472–9. https://doi.org/10.1111/resp.12851Sahuquillo-Arce JM, Menéndez R, Méndez R, Ama raElori I, Zalacain R, Capelastegui A, et al. Age-related risk factors for bacterial aetiology in community-acquired pneumonia. Respirology. 2016;21(8):1472–9. https://doi.org/10.1111/resp.12851Kollef KE, Schramm GE, Wills AR, Reichley RM, Micek ST, Kollef MH. Predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia attributed to potentially antibiotic-resistant gram-negative bacteria. Chest. 2008;134(2):281–7. https://doi.org/10.1378/chest.08-1116Kollef KE, Schramm GE, Wills AR, Reichley RM, Micek ST, Kollef MH. Predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia attributed to potentially antibiotic-resistant gram-negative bacteria. Chest. 2008;134(2):281–7. https://doi.org/10.1378/chest.08-1116Zilberberg MD, Shorr AF, Micek ST, Vazquez-Gillamet C, Kollef MH. Multi-drug resistance, inappropriate initial antibiotic therapy and mortality in Gram-negative severe sepsis and septic shock: a retrospective cohort study. Crit Care. 2014;18(6):596. https://doi.org/10.1186/s13054-014-0596-8Zilberberg MD, Shorr AF, Micek ST, Vazquez-Gillamet C, Kollef MH. Multi-drug resistance, inappropriate initial antibiotic therapy and mortality in Gram-negative severe sepsis and septic shock: a retrospective cohort study. Crit Care. 2014;18(6):596. https://doi.org/10.1186/s13054-014-0596-8Aliberti S, Di Pasquale M, Zanaboni AM, Cosentini R, Brambilla AM, Seghezzi S, et al. Stratifying risk factors for multidrug-resistant pathogens in hospitalized patients coming from the community with pneumonia. Clin Infect Dis. 2012;54(4):470–8. https://doi.org/10.1093/cid/cir840Aliberti S, Di Pasquale M, Zanaboni AM, Cosentini R, Brambilla AM, Seghezzi S, et al. Stratifying risk factors for multidrug-resistant pathogens in hospitalized patients coming from the community with pneumonia. Clin Infect Dis. 2012;54(4):470–8. https://doi.org/10.1093/cid/cir840Aliberti S, Cilloniz C, Chalmers JD, Zanaboni AM, Cosentini R, Tarsia P, et al. Multidrug-resistant pathogens in hospitalised patients coming from the community with pneumonia: a European perspective. Thorax. 2013;68(11):997–9. https://doi.org/10.1136/thoraxjnl-2013-203384Aliberti S, Cilloniz C, Chalmers JD, Zanaboni AM, Cosentini R, Tarsia P, et al. Multidrug-resistant pathogens in hospitalised patients coming from the community with pneumonia: a European perspective. Thorax. 2013;68(11):997–9. https://doi.org/10.1136/thoraxjnl-2013-203384Sparham S, Charles PGP. Controversies in diagnosis and management of community-acquired pneumonia. Med J Aust. 2017;206(7):316–9. https://doi.org/10.5694/mja16.01463Sparham S, Charles PGP. Controversies in diagnosis and management of community-acquired pneumonia. Med J Aust. 2017;206(7):316–9. https://doi.org/10.5694/mja16.01463Garin N, Felix G, Chuard C, Genne D, Carballo S, Hugli O, et al. Predictors and implications of early clinical stability in patients hospitalized for moderately severe community-acquired pneumonia. PLoS ONE. 2016;11(6):е0157350. https://doi.org/10.1371/journal.pone.0157350Garin N, Felix G, Chuard C, Genne D, Carballo S, Hugli O, et al. Predictors and implications of early clinical stability in patients hospitalized for moderately severe community-acquired pneumonia. PLoS ONE. 2016;11(6):е0157350. https://doi.org/10.1371/journal.pone.0157350Bauer K, West J, O'Brien J, Goff D. Extended-infusion cefepime reduces mortality in patients with Pseudomonas aeruginosa infections. Antimicrob Agents Chemother. 2013;57(7):2907–12. https://doi.org/10.1128/AAC.02365-12Bauer K, West J, O‘Brien J, Goff D. Extended-infusion cefepime reduces mortality in patients with Pseudomonas aeruginosa infections. Antimicrob Agents Chemother. 2013;57(7):2907–12. https://doi.org/10.1128/AAC.02365-12Lagace-Wiens P, Rubinstein E. Adverse reactions to beta–lactam antimicrobials. Expert Opin Drug Saf. 2012;11(3):381–99. https://doi.org/10.1517/14740338.2012.643866Lagace-Wiens P, Rubinstein E. Adverse reactions to beta–lactam antimicrobials. Expert Opin Drug Saf. 2012;11(3):381–99. https://doi.org/10.1517/14740338.2012.643866Иванчик НВ, Чагарян АН, Сухорукова МВ, Козлов РС, Дехнич АВ, Кречикова ОИ и др. Антибиотикорезистентность клинических штаммов Streptococcus pneumoniae в России: результаты многоцентрового эпидемиологического исследования «ПеГАС 2014–2017». Клиническая микробиология и антимикробная химиотерапия. 2019;21(3):230–7. [Ivanchik NV, Chagaryan АN, Sukhorukova МV, Kozlov RS, Dekhnich AV, Krechikova OI, et al. Antimicrobial resistance of clinical Streptococcus pneumoniae isolates in Russia: the results of multicenter epidemiological study «PEHASus 2014–2017». Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya = Clinical Microbiology and Antimicrobial Chemotherapy. 2019;21(3):230–7 (In Russ.)] https://doi.org/10.36488/cmac.2019.3.230-237Ivanchik NV, Chagaryan АN, Sukhorukova МV, Kozlov RS, Dekhnich AV, Krechikova OI, et al. Antimicrobial resistance of clinical Streptococcus pneumoniae isolates in Russia: the results of multicenter epidemiological study “PEHASus 2014– 2017”. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya = Clinical Microbiology and Antimicrobial Chemotherapy. 2019;21(3):230–7 (In Russ.) https://doi.org/10.36488/cmac.2019.3.230-237Imani S, Buscher H, Marriott D, Gentili S, Sandaradura I. Too much of a good thing: a retrospective study of β-lactam concentration–toxicity relationships. J Antimicrob Chemother. 2017;72(10):2891–7. https://doi.org/10.1093/jac/dkx209Imani S, Buscher H, Marriott D, Gentili S, Sandaradura I. Too much of a good thing: a retrospective study of β-lactam concentration–toxicity relationships. J Antimicrob Chemother. 2017;72(10):2891–7. https://doi.org/10.1093/jac/dkx209Field TS, Gurwitz JH, Harrold LR, Rotschield J, DeBellis KR, Seger AC, et al. Risk factors for adverse drug events among older adults in the ambulatory setting. J Am Geriatr Soc. 2004;52(8):1349–54. https://doi.org/10.1111/j.1532-5415.2004.52367.xField TS, Gurwitz JH, Harrold LR, Rotschield J, DeBellis KR, Seger AC, et al. Risk factors for adverse drug events among older adults in the ambulatory setting. J Am Geriatr Soc. 2004;52(8):1349–54. https://doi.org/10.1111/j.1532-5415.2004.52367.xMavros MN, Alexiou VG, Vardakas KZ, Tsokali K, Sardi TA, Falagas ME. Underestimation of Clostridium difficile infection among clinicians: an international survey. Eur J Clin Microbiol Infect Dis. 2012;31(9):2439–44. https://doi.org/10.1007/s10096-012-1587-9Mavros MN, Alexiou VG, Vardakas KZ, Tsokali K, Sardi TA, Falagas ME. Underestimation of Clostridium difficile infection among clinicians: an international survey. Eur J Clin Microbiol Infect Dis. 2012;31(9):2439–44. https://doi.org/10.1007/s10096-012-1587-9Zilberberg MD, Shorr AF, Wang Li, Baser O, Yu H. Development and validation of a risk score for Clostridium difficile infection in medicare beneficiaries: a population-based cohort study. J Am Geriatr Soc. 2016;64(8):1690–5. https://doi.org/10.1111/jgs.14236Zilberberg MD, Shorr AF, Wang Li, Baser O, Yu H. Development and validation of a risk score for Clostridium difficile infection in medicare beneficiaries: a population-based cohort study. J Am Geriatr Soc. 2016;64(8):1690–5. https://doi.org/10.1111/jgs.14236Rutter WC, Burgess DR, Talbert JC, Burgess DS. Acute kidney injury in patients treated with vancomycin and piperacillin–tazobactam: A retrospective cohort analysis. J Hosp Med. 2017;12(2):77–82. https://doi.org/10.12788/jhm.2684Rutter WC, Burgess DR, Talbert JC, Burgess DS. Acute kidney injury in patients treated with vancomycin and piperacillin–tazobactam: A retrospective cohort analysis. J Hosp Med. 2017;12(2):77–82. https://doi.org/10.12788/jhm.2684Cotner SE, Rutter WC, Burgess DR, Wallace KL, Martin CA, Burgess DS. Influence of β-Lactam Infusion Strategy on Acute Kidney Injury. Antimicrob Agents Chemother. 2017;61(10):e00871–17. https://doi.org/10.1128/AAC.00871-17Cotner SE, Rutter WC, Burgess DR, Wallace KL, Martin CA, Burgess DS. Influence of β-Lactam Infusion Strategy on Acute Kidney Injury. Antimicrob Agents Chemother. 2017;61(10):e00871–17. https://doi.org/10.1128/AAC.00871-17Deshayes S, Coquerel A, Verdon R. Neurological adverse effects attributable to beta-lactam antibiotics: a literature review. Drug Saf. 2017;40(12):1171–98. https://doi.org/10.1007/s40264-017-0578-2Deshayes S, Coquerel A, Verdon R. Neurological adverse effects attributable to beta-lactam antibiotics: a literature review. Drug Saf. 2017;40(12):1171–98. https://doi.org/10.1007/s40264-017-0578-2Noor S, Ismail M, Ali Z. Potential drug-drug interactions among pneumonia patients: do these matter in clinical perspectives? BMC Pharmacol Toxicol. 2019;20(1):45. https://doi.org/10.1186/s40360-019-0325-7Noor S, Ismail M, Ali Z. Potential drugdrug interactions among pneumonia patients: do these matter in clinical perspectives? BMC Pharmacol Toxicol. 2019;20(1):45. https://doi.org/10.1186/s40360-019-0325-7Vardakas KZ, Kalimeris GD, Triarides NA, Falagas ME. An update on adverse drug reactions related to β-lactam antibiotics. Expert Opin Drug Saf. 2018;17(5):499–508. https://doi.org/10.1080/14740338.2018.1462334Vardakas KZ, Kalimeris GD, Triarides NA, Falagas ME. An update on adverse drug reac tions related to β-lactam antibiotics. Expert Opin Drug Saf. 2018;17(5):499–508. https://doi.org/10.1080/14740338.2018.1462334

The authors declare that there are no conflicts of interest present.