antibioticsАнтибиотики и ХимиотерапияAntibiot Khimioter = Antibiotics and Chemotherapy0235-2990ООО «Издательство ОКИ»10.37489/0235-2990-2022-67-11-12-36-45antibiotics-986Research ArticleКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ И ПРАКТИКАGUIDELINES FOR PRACTITIONERSПервый опыт комбинированного применения цефепима/сульбактама и азтреонама в ОРИТ при нозокомиальных инфекциях, вызванных устойчивыми к карбапенемам грамотрицательными микроорганизмами, продуцирующими карбапенемазы классов B и DThe First Experience of Combined Use of Cefepime/Sulbactam and Aztreonam in ICU Patients with Nosocomial Infections Caused by Carbapenem-Resistant Gram-Negative Microorganisms Producing Class B and D Carbapenemaseshttps://orcid.org/0000-0002-1389-6454СувороваМ. П.SuvorovaM. P.

Суворова Маргарита Петровна — кандидат медицинских наук, доцент кафедры госпитальной терапии №2 Института  клинической медицины им. Н.В. Склифосовского ПМГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет); врач-клинический фармаколог ГКБ им. С.С. Юдина.

Москва

Margarita P. Suvorova — Ph. D. in Medicine, Associate  Professor at the Department of Hospital  Therapy No. 2 of the Institute of Clinical Medicine n. a. N.V. Sklifosovsky, I.M.  Sechenov First Moscow State  Medical University  (Sechenov University); clinical  pharmacologist, City  Clinical Hospital named  after S.S. Yudin.

Moscow

https://orcid.org/0000-0002-2970-3442СычевИ. Н.SychevI. N.

Сычев Игорь Николаевич — кандидат медицинских наук, заведующий отделом клинической фармакологии.

Москва

Igor N. Sychev — Ph. D. in Medicine, Head of the Clinical Pharmacology  Department, City Clinical Hospital named by S.S. Yudin.

Moscow

ИгнатенкоО. В.IgnatenkoO. V.

Игнатенко Ольга Викторовна — кандидат медицинских наук, заместитель главного врача по анестезиологии и реаниматологии.

Москва

Olga V. Ignatenko — Ph. D. in Medicine, Deputy  Chief  Physician for Anesthesiology and Intensive Care, City Clinical Hospital named  by S.S. Yudin.

Moscow

https://orcid.org/0000-0003-4757-3845БурмистроваЕ. Н.BurmistrovaE. N.

Бурмистрова Елена  Николаевна — заведующая бактериологической лабораторией.

Москва

Elena N. Burmistrova — Head  of the  Bacteriological Laboratory, City Clinical Hospital named by S.S. Yudin.

Moscow

МирзахамидоваС. С.MirzakhamidovaS. S.

Мирзахамидова Светлана Сергеевна — кандидат медицинских наук, заместитель главного врача по медицинской части.

Москва

Svetlana S. Mirzakhamidova — Ph. D. in Medicine, Deputy Chief  Physician  at the  Medical Unit, City  Clinical Hospital named  by S.S. Yudin.

Moscow

https://orcid.org/0000-0002-6417-9535ФединаЛ. В.FedinaL. V.

Федина Людмила Владимировна — врач-клинический фармаколог.

Москва

Lyudmila V. Fedina — Clinical pharmacologist, City Clinical Hospital named by S.S. Yudin.

Moscow

https://orcid.org/0000-0003-1160-0514ВаколюкР. М.VakolyukR. M.

Ваколюк Роза Михайловна — кандидат медицинских наук, кафедра госпитальной терапии №2.

Москва

Roza M. Vakolyuk — Ph. D. in Medicine, Department of Hospital Therapy No. 2, I.M. Sechenov First Moscow State Medical University (Sechenov  University).

Moscow

https://orcid.org/0000-0001-7606-8608ЯковлевС. В.YakovlevS. V.

Яковлев Сергей Владимирович — доктор медицинских наук, профессор кафедры госпитальной терапии №2 Института клинической медицины им. Н.В. Склифосовского ПМГМУ им. И. М. Сеченова Минздрава России (Сеченовский Университет); врач-клинический фармаколог ГКБ им. С.С. Юдина.

Коломенский пр., д, 4, Москва, 115446

Sergey V. Yakovlev — D. Sc. in Medicine, Professor at the Department of Hospital  Therapy No. 2 of the Institute of Clinical Medicine n. a. N.V. Sklifosovsky, I.M. Sechenov First Moscow State Medical University (Sechenov University), Clinical pharmacologist, City Clinical Hospital  named by S.S. Yudin.

4 Kolomensky drive, Moscow, 115446

antimicrob@yandex.ruПервый МГМУ им. И.М. Сеченова МЗ России (Сеченовский Университет); Городская клиническая больница имени С.С. Юдина ДЗ МосквыРоссияI.M. Sechenov First Moscow State Medical University; City Clinical Hospital named after S.S. YudinRussian FederationГородская клиническая больница имени С.С. Юдина ДЗ Москвы; Российская медицинская академия непрерывного последипломного образования Минздрава РоссииРоссияCity Clinical Hospital named after S.S. Yudin; Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian FederationRussian FederationГородская клиническая больница имени С.С. Юдина ДЗ МосквыРоссияCity Clinical Hospital named after S.S. YudinRussian FederationПервый МГМУ им. И.М. Сеченова МЗ России (Сеченовский Университет)РоссияI.M. Sechenov First Moscow State Medical UniversityRussian FederationПервый МГМУ им. И.М. Сеченова МЗ России (Сеченовский Университет); Городская клиническая больница имени С.С. Юдина ДЗ МосквыРоссияI.M. Sechenov First Moscow State Medical University; City Clinical Hospital named after S.S. YudinRussian Federation2022110220236711-123645Copyright © Суворова М.П., Сычев И.Н., Игнатенко О.В., Бурмистрова Е.Н., Мирзахамидова С.С., Федина Л.В., Ваколюк Р.М., Яковлев С.В., 20232023Суворова М.П., Сычев И.Н., Игнатенко О.В., Бурмистрова Е.Н., Мирзахамидова С.С., Федина Л.В., Ваколюк Р.М., Яковлев С.В.Suvorova M.P., Sychev I.N., Ignatenko O.V., Burmistrova E.N., Mirzakhamidova S.S., Fedina L.V., Vakolyuk R.M., Yakovlev S.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.antibiotics-chemotherapy.ru/jour/article/view/986

В связи с высоким риском летальности при инфекциях, вызванных устойчивыми к карбапенемам Enterobacterales, в последние годы проведено большое количество клинических  исследований  по изучению  оптимальных опций антибактериальной терапии таких инфекций. Показано, что летальность  при комбинированной антибактериальной терапии ниже, чем при монотерапии.

Цель исследования — изучение эффективности комбинированного применения цефепима/сульбактама и азтреонама при нозокомиальных инфекциях, вызванных грамотрицательными бактериями, устойчивыми к карбапенемам за счёт продукции карбапенемаз класса D и В.

Материал и методы

Материал и методы. Исследование в скоропомощном стационаре в период с марта 2021 г. по июнь 2022 г. Дизайн исследования: проспективное открытое несравнительное. Все пациенты, включенные в исследование, находились на лечении в отделениях реанимации  и интенсивной  терапии.

Результаты и заключение

Результаты и заключение. Проведённое исследование впервые продемонстрировало достоверную клиническую  и микробиологическую эффективность комбинации цефепим/сульбактам и азтреонам  при лечении в ОРИТ нозокомиальных инфекций, осложнённых сепсисом или септическим шоком и вызванных Klebsiella pneumoniae, продуцирующей карбапенемазы класса D и В — OXA-48, NDM и NDM + OXA-48. Полученные данные показали  уникальность  данной  комбинации,  демонстрирующей  достоверную  эффективность  даже  в случае устойчивости возбудителя к обоим антибиотикам (азтреонаму и цефепиму) in vitro.

Background

Background. The difficulties of antibacterial therapy of infections caused by carbapenemase-producing  gram-negative bacteria are associated with limited options for adequate therapy since, in addition to resistance to carbapenems and other beta-lactams, these microorganisms are often characterized by associated resistance to other classes of antibiotics, including polymyxins. In vitro data support the idea of combined use of inhibitor-protected cephalosporins with aztreonam for the treatment of such infections. The aim of the study was to investigate the effectiveness of cefepime/sulbactam (FEP/SB) in combination with aztreonam (ATM) in infections caused by class B and D carbapenemase producers.

Methods

Methods. A prospective observational study evaluated the effectiveness of the combination of FEP/SB + ATM in ICU patients with nosocomial infections complicated by sepsis or septic shock caused by carbapenem-resistant pathogens with documented production of class B or D carbapenemase. The ineffectiveness of previous treatment and the absence of other options for adequate therapy were used as inclusion criteria. Microbiological, clinical efficacy, and 30-day mortality were indicators of therapy evaluation.

Results

Results. The study included 25 patients with nosocomial infection (76% of them was VAP), with sepsis (60%) or septic shock (40%) and an average SOFA score of 6 points caused by Klebsiella pneumoniae (23 patients) or Pseudomonas aeruginosa (2) producing carbapenemases OXA-48 (56%), NDM (20%), NDM + OXA-48 (16%), and class B carbapenemase in two strains of P. aeruginosa. The average daily dose of FEP/SB and ATM was 6.6 g, the duration of therapy was 9.9 days. As a result of the treatment, eradication was achieved in 68% of patients, clinical efficacy was 72%, and the 30-day mortality rate was 28%.

Conclusion

Conclusion. Our results show good clinical and bacteriological efficacy of the combination of FEP/SB and ATM in infections caused by extremely resistant K. pneumoniae, non-susceptible to carbapenems and producing class B or D carbapenemase.

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