nodgoРоссийский журнал детской гематологии и онкологии (РЖДГиО)Russian Journal of Pediatric Hematology and Oncology2311-12672413-5496LTD “Graphica”10.21682/2311-1267-2021-8-2-61-72nodgo-721Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESЛечение тяжелых инфекционных осложнений, вызванных Klebsiella pneumoniae с множественной лекарственной устойчивостью, у детей со злокачественными новообразованиями кроветворной системы: опыт НИИ детской онкологии и гематологии ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава РоссииTreatment of severe infectious complications caused by multidrug-resistant Klebsiella pneumoniae in children with malignant neoplasms of the hematopoietic system: experience of the Research Institute of Pediatric Oncology and Hematology at N.N. Blokhin Russian Cancer Research Centerhttps://orcid.org/0000-0003-3797-5808СидороваН. В.SidorovaN. V.

Сидорова Наталья Валерьевна - заведующая отделением детской трансплантации костного мозга и гемопоэтических стволовых клеток НМИЦ онкологии им. Н.Н. Блохина.

115478, Москва, Каширское шоссе, 23.

SPIN-код: 7729-5713

Head of the Department of Pediatric Bone Marrow and Hematopoietic Stem Cell Transplantation of N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia.

23 Kashirskoe Shosse, Moscow, 115478.

SPIN-code: 7729-5713

valerevna25@mail.ruhttps://orcid.org/0000-0003-2395-4045МачневаЕ. Б.MachnevaE. B.

Кандидат медицинских наук, врач-гематолог отделения детской трансплантации костного мозга и гемопоэтических стволовых клеток НИИ детской онкологии и гематологии НМИЦ онкологии им. Н.Н. Блохина, врач-гематолог отделения трансплантации костного мозга Российской детской клинической больницы РНИМУ им. Н.И. Пирогова.

115478, Москва, Каширское шоссе, 23; 119571, Москва, Ленинский просп., 117.

SPIN-код: 6143-8644

Cand. of Sci. (Med.), Hematologist Department of Pediatric Bone Marrow and Hematopoietic Stem Cell Transplantation of the Research Institute of Pediatric Oncology and Hematology of N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, Hematologist Department of Bone Marrow Transplantation at the Russian Children's Clinical Hospital of the N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia.

23 Kashirskoe Shosse, Moscow, 115478; 117 Leninskiy Prosp., Moscow, 119571.

SPIN-code: 6143-8644

lena.machneva@yandex.ruhttps://orcid.org/0000-0002-1469-2365ВалиевТ. Т.ValievT. T.

Доктор медицинских наук, заведующий детским отделением химиотерапии гемобластозов отдела гематологии и трансплантации костного мозга НМИЦ онкологии им. Н.Н. Блохина.

115478, Москва, Каширское шоссе, 23.

SPIN-код: 9802-8610

Dr. of Sci. (Med.), Head of the Children's Department of Hemoblastosis Chemotherapy of the Department of Hematology and Bone Marrow Transplantation of N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia.

23 Kashirskoe Shosse, Moscow, 115478.

SPIN-code: 9802-8610

timurvaliev@mail.ruhttps://orcid.org/0000-0003-0179-2479КостареваИ. О.KostarevaI. O.

Врач-детский онколог отделения детской трансплантации костного мозга и гемопоэтических стволовых клеток НИИ детской онкологии и гематологии НМИЦ онкологии им. Н.Н. Блохина, младший научный сотрудник отдела оптимизации лечения и профилактики осложнений трансплантации гемопоэтических стволовых клеток НМИЦ ДГОИ им. Дмитрия Рогачева.

115478, Москва, Каширское шоссе, 23; 117198, Москва, ул. Саморы Машела, 1.

Pediatric Oncologist Department of Pediatric Bone Marrow and Hematopoietic Stem Cell Transplantation of N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, Researcher Department of Treatment Optimization and Prophylaxis of Hematopoietic Stem Cell Transplantation Associated Complications at Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of Russia.

23 Kashirskoe Shosse, Moscow, 115478; Samory Mashela St., Moscow, 117198.

kostareva_92@mail.ruhttps://orcid.org/0000-0003-1091-1521АлиевТ. З.AlievT. Z.

Врач-детский онколог отделения детской трансплантации костного мозга и гемопоэтических стволовых клеток НИИ детской онкологии и гематологии НМИЦ онкологии им. Н.Н. Блохина.

115478, Москва, Каширское шоссе, 23.

Pediatric Oncologist Department of Pediatric Bone Marrow and Hematopoietic Stem Cell Transplantation of the Research Institute of Pediatric Oncology and Hematology at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia.

23 Kashirskoe Shosse, Moscow, 115478.

timaliev118@gmail.comhttps://orcid.org/0000-0001-8143-5791ЕлфимоваА. Ю.ElfimovaA. Yu.

Врач-детский онколог отделения детской трансплантации костного мозга и гемопоэтических стволовых клеток НИИ детской онкологии и гематологии НМИЦ онкологии им. Н.Н. Блохина.

115478, Москва, Каширское шоссе, 23.

Pediatric Oncologist Department of Pediatric Bone Marrow and Hematopoietic Stem Cell Transplantation of the Research Institute of Pediatric Oncology and Hematology of N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia.

23 Kashirskoe Shosse, Moscow, 115478.

yelfimova.anna@mail.ruhttps://orcid.org/0000-0003-0600-8962ЛозованЮ. В.LozovanYu. V.

Врач-педиатр отделения детской трансплантации костного мозга и гемопоэтических стволовых клеток НИИ детской онкологии и гематологии НМИЦ онкологии им. Н.Н. Блохина.

115478, Москва, Каширское шоссе, 23.

Pediatrician Department of Pediatric Bone Marrow and Hematopoietic Stem Cell Transplantation at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia.

23 Kashirskoe Shosse, Moscow, 115478.

lyuriimd@mail.ruhttps://orcid.org/0000-0003-4999-5195ПавловаТ. Ю.PavlovaT. Yu.

Врач-детский онколог детского отделения химиотерапии гемобластозов отдела гематологии и трансплантации костного мозга НИИ детской онкологии и гематологии НМИЦ онкологии им. Н.Н. Блохина.

115478, Москва, Каширское шоссе, 23.

Pediatric Oncologist Children's Department of Hemoblastosis Chemotherapy of the Department of Hematology and Bone Marrow Transplantation of Research Institute of Pediatric Oncology and Hematology at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia.

23 Kashirskoe Shosse, Moscow, 115478.

md.pavlovaty@mail.ruhttps://orcid.org/0000-0002-8482-1863КоркинаЮ. С.KorkinaYu. S.

Врач-ординатор кафедры детской онкологии им. акад. Л.А. Дурнова РМАНПО.

125993, Москва, ул. Баррикадная, 2/1, стр. 11.

Resident of the Department of Pediatric Oncology named after Academician L.A. Durnov at Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia.

Bld. 1, 2/1 Barrikadnaya St., Moscow, 125993.

juliaskomorokhova@mail.ruhttps://orcid.org/0000-0001-5805-726XГорбуноваТ. В.GorbunovaT. V.

Кандидат медицинских наук, старший научный сотрудник отделения хирургического № 1 НИИ детской онкологии и гематологии НМИЦ онкологии им. Н.Н. Блохина.

115478, Москва, Каширское шоссе, 23.

SPIN-код: 9740-3687

Cand. of Sci. (Med.), Senior Researcher Surgical Department No. 1 of the Research Institute of Pediatric Oncology and Hematology at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia.

23 Kashirskoe Shosse, Moscow, 115478.

SPIN-code: 9740-3687

wasicsol@mail.ruhttps://orcid.org/0000-0003-4294-1995ГригорьевскаяЗ. В.GrigorievskayaZ. V.

Доктор медицинских наук, заведующая микробиологической лабораторией НИИ клинической онкологии НМИЦ онкологии им. Н.Н. Блохина.

115478, Москва, Каширское шоссе, 23.

Dr. of Sci. (Med.), Head of Microbiologic Laboratory of the Research Institute of Clinical Oncology at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia.

23 Kashirskoe Shosse, Moscow, 115478.

zlatadoc@list.ruhttps://orcid.org/0000-0003-3077-0447ПетуховаИ. Н.PetukhovaI. N.

Доктор медицинских наук, ведущий научный сотрудник микробиологической лаборатории микробиологической диагностики и лечения инфекций в онкологии НИИ клинической онкологии НМИЦ онкологии им. Н.Н. Блохина.

115478, Москва, Каширское шоссе, 23.

Dr. of Sci. (Med.), Leading researcher of Microbiologic Laboratory of the Research Institute of Clinical Oncology at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia.

23 Kashirskoe Shosse, Moscow, 115478.

irinapet@list.ruhttps://orcid.org/0000-0001-8198-7131ЕпифановаН. Ю.EpifanovaN. Yu.

Доктор медицинских наук, врач-клинический фармаколог, заведующая отделением клинической фармакологии НМИЦ онкологии им. Н.Н. Блохина.

115478, Москва, Каширское шоссе, 23.

Dr. of Sci. (Med.), Clinical Pharmacologist, Head of the Department of Clinical Pharmacology at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia.

23 Kashirskoe Shosse, Moscow, 115478.

ne_nato2007@mail.ruhttps://orcid.org/0000-0002-2945-284XКиргизовК. И.KirgizovK. I.

Кандидат медицинских наук, заместитель директора по научной и образовательной работе НИИ детской онкологии и гематологии НМИЦ онкологии им. Н.Н. Блохина.

115478, Москва, Каширское шоссе, 23.

SPIN-код: 3803-6370

Cand. of Sci. (Med.), Deputy Director for Scientific and Educational Work of Research Institute of Pediatric Oncology and Hematology at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia.

23 Kashirskoe Shosse, Moscow, 115478.

k.kirgizov@ronc.ruНМИЦ онкологии им. Н.Н. Блохина Минздрава РоссииРоссияN.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of RussiaRussian FederationНМИЦ онкологии им. Н.Н. Блохина Минздрава России; Обособленное структурное подразделение Российская детская клиническая больница ФГАОУ ВО «РНИМУ им. Н.И. Пирогова» Минздрава РоссииРоссияN.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia; Russian Children's Clinical Hospital of the N.I. Pirogov Russian National Research Medical University, Ministry of Health of RussiaRussian FederationНМИЦ онкологии им. Н.Н. Блохина Минздрава России; НМИЦ ДГОИ им. Дмитрия Рогачева Минздрава РоссииРоссияN.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia; Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of RussiaRussian FederationФГБОУ ДПО РМАНПО Минздрава РоссииРоссияRussian Medical Academy of Continuous Professional Education, Ministry of Health of RussiaRussian Federation202111072021826172Copyright © Сидорова Н.В., Мачнева Е.Б., Валиев Т.Т., Костарева И.О., Алиев Т.З., Елфимова А.Ю., Лозован Ю.В., Павлова Т.Ю., Коркина Ю.С., Горбунова Т.В., Григорьевская З.В., Петухова И.Н., Епифанова Н.Ю., Киргизов К.И., 20212021Сидорова Н.В., Мачнева Е.Б., Валиев Т.Т., Костарева И.О., Алиев Т.З., Елфимова А.Ю., Лозован Ю.В., Павлова Т.Ю., Коркина Ю.С., Горбунова Т.В., Григорьевская З.В., Петухова И.Н., Епифанова Н.Ю., Киргизов К.И.Sidorova N.V., Machneva E.B., Valiev T.T., Kostareva I.O., Aliev T.Z., Elfimova A.Y., Lozovan Y.V., Pavlova T.Y., Korkina Y.S., Gorbunova T.V., Grigorievskaya Z.V., Petukhova I.N., Epifanova N.Y., Kirgizov K.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nodgo.org/jour/article/view/721Введение

Введение. Тактика терапии бактериальных инфекций у пациентов со злокачественными заболеваниями кроветворной системы на этапе полихимиотерапии (ПХТ) и трансплантации гемопоэтических стволовых клеток (ТГСК) до настоящего момента не имеет четко сформулированного протокола. Разработанные в настоящее время рекомендации отдельных групп специалистов по изучению проблем антибиотикотерапии, таких как EMBT, NCCN, ECIL, Sepsis-3, зачастую не включают всего спектра клинических факторов риска развития тяжелых осложнений, обусловленных именно Klebsiella pneumoniae, обладающей множественной лекарственной устойчивостью (МЛУ).

Цель исследования — демонстрация опыта НИИ детской онкологии и гематологии ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России (НИИ ДОиГ), в рамках которого выбор антибактериальной терапии проводился с учетом спектра микроорганизмов, выявленных у пациента перед этапом противоопухолевой терапии, а также данных о МЛУ микроорганизмов, обнаруженных у детей со злокачественными новообразованиями (ЗНО) крови на фоне фебрильной нейтропении (ФН) на этапах ПХТ и ТГСК.

Материалы и методы

Материалы и методы. В исследование включены 5 пациентов, которым проводили ПХТ либо ТГСК по поводу ЗНО кроветворной системы с октября 2019 г. по октябрь 2020 г. в НИИ ДОиГ с доказанной колонизацией Klebsiella pneumoniae с МЛУ.

Результаты

Результаты. У 5 пациентов со ЗНО кроветворной системы с индуцированной аплазией кроветворения и в иммуносупрессивном статусе после ПХТ и на этапе ТГСК доказана колонизация Klebsiella pneumoniae с МЛУ. Принимая во внимание высокий риск летального исхода, данным больным требуется ранняя инициация терапии антибактериальными препаратами «резерва» вне текущих стандартных протоколов эмпирической антибактериальной терапии при развитии у них ФН. Наш опыт показал, что зачастую базовые протоколы могут быть неадекватными тяжести состояния таких пациентов в конкретный промежуток времени.

Выводы

Выводы. Суммируя наш ограниченный опыт можно сделать вывод о необходимости дополнительного изучения и выделения факторов риска развития тяжелых инфекционных осложнений, обусловленных Klebsiella pneumoniae с МЛУ, у пациентов на этапе ПХТ и ТГСК, и создания алгоритмов ведения такой группы крайне сложных пациентов.

Introduction

Introduction. So far there has been no clear protocol on the treatment of bacterial infections in hematopoietic cancer patients undergoing polychemotherapy (PCT) and hematopoietic stem cell transplantation (HSCT). Guidelines available from antibiotic therapy panels such as EMBT, NCCN, ECIL, Sepsis-3 often fail to cover the entire spectrum of clinical risk factors of severe complications caused specifically by multiresistant Klebsiella pneumoniae.

The aim of the study — is to showcase the clinical experience of demonstration of the experience of the Research Institute of Pediatric Oncology and Hematology at N.N. Blokhin Russian Cancer Research Center with respect to adjusting antibacterial therapy for the spectrum of microorganisms found in the patient before the onset of antitumor therapy, and for the multiresistant microorganism findings in patients with blood cancers and febrile neutropenia (FN) undergoing PCT and HSCT.

Materials and methods

Materials and methods. The study involved five patients undergoing either PCT or HSCT for hematopoietic cancers at Research Institute of Pediatric Oncology and Hematology in October 2019 — October 2020, multiresistant Klebsiella pneumonia colonies found in each case. Results. Five patients with hematopoietic cancers and induced bone marrow aplasia were found to have multiresistant Klebsiella pneumoniae colonies on top of post-PCT/HSCT immunosuppression. Given high risk of death, these patients need early antibacterial therapy with reserve antibiotics outside standard empirical antibacterial treatment protocols should they develop FN. The Center's practices have shown that baseline protocols are often inadequate to the severity of these patients' conditions in a certain timeframe.

Conclusions

Conclusions. To sum up the Center's limited experience, the finding is that additional research is required into the factors of risk of severe multiresistant Klebsiella pneumoniae infections in patients undergoing PCT and HSCT; algorithms must be developed for the treatment of patients in such a critical condition.

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