Antibiotic Treatment of Febrile Neutropenia in Patients with Acute Leukemia

Aim. To estimate the effi cacy of antibiotic treatment of febrile neutropenia in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Materials & Methods. The prospective study (2013 to 2015) included 66 AML and 44 ALL patients receiving 480 chemotherapy cycles within the period of 6 months. Results. Febrile neutropenia was registered during 242 (50 %) chemotherapy cycles occurring more frequently in AML than in ALL patients (93 % vs. 18 %, p < 0.0001). In AML patients infections were more common during induction and consolidation (98 and 89 %) phases compared to ALL patients who most commonly had infection during induction phase (55 %). Compared to ALL patients, AML patients had lower recovery rates after fi rst-line antibiotic monotherapy (24 % vs. 57 %, p < 0.0001), compared to combination therapy (37 % vs. 18 %, p = 0.01). The use of beta-lactam antibiotics in ALL patients was associated with lower recovery rates during the induction phase compared to consolidation phase (47 % vs. 72 %, p = 0.0004). In cases of granulocytopaenia longer that 14 days the clinical recovery rate with administration of the fi rst-line antibiotics and carbapenems accounted for 23–24 % compared to 47 % with other antimicrobials, more commonly with antifungal (21 %) administration. In patients with fever of unknown origin the monotherapy with fi rst-line antibiotics proved to be successful (45 %). In patients with clinically and microbiologically defi ned infections the best results were achieved by the combined treatment with the beta-lactam antibiotics and other drugs (43 %). Conclusion. Antibiotic escalation has proved to be the optimal strategy in treatment of ALL patients and in cases of fever of unknown origin. The effi cacy of the beta-lactam antibiotic monotherapy was lower in AML patients during the induction phase as well as in cases of continuous neutropenia (> 14 days) and clinically and microbiologically diagnosed infections. The adding of other antimicrobial administration resulted in the recovery in 37–48 % of cases. 101 ht tp : / /b lood journa l . ru / Лечение фебрильной нейтропении при острых лейкозах Ключевые слова: острый лейкоз, ОМЛ, ОЛЛ, фебрильная нейтропения, лихорадка неясной этиологии, клинически и микробиологически доказанная инфекция, антибиотики. Получено: 2 июля 2017 г. Принято в печать: 20 октября 2017 г. Для переписки: Владимир Александрович Охмат, канд. мед. наук, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167; тел.: +7(495)614-92-72; e-mail: okhmatvladimir@mail.ru Для цитирования: Охмат В.А., Клясова Г.А., Паровичникова Е.Н. и др. Применение антибиотиков при фебрильной нейтропении у больных острыми лейкозами. Клиническая онкогематология. 2018;11(1):100–9. DOI: 10.21320/2500-2139-2018-11-1-100-109

[1]  V. Mujeeb,et al.  Comparison of Efficacy of Piperacillin/Tazobactam Vs Cefoperazone/Sulbactam as Empirical Therapy in Patients with Febrile Neutropenia , 2017 .

[2]  Е. Н. Паровичникова,et al.  Спектр и этиология инфекционных осложнений у больных острыми миелоидными лейкозами на этапах индукции и консолидации ремиссии , 2017 .

[3]  А. В. Федорова,et al.  Следует ли назначать карбапенемы всем больным с фебрильной нейтропенией и колонизацией энтеробактериями с продукцией β-лактамаз расширенного спектра? , 2016 .

[4]  Quan-shun Wang,et al.  Piperacillin‐tazobactam vs. imipenem‐cilastatin as empirical therapy in hematopoietic stem cell transplantation recipients with febrile neutropenia , 2016, Clinical transplantation.

[5]  С. М. Куликов,et al.  Детекция энтеробактерий с продукцией бета-лактамаз расширенного спектра у больных острыми миелоидными лейкозами и лимфомами при поступлении в стационар , 2016 .

[6]  Russian Federation.  ОЦЕНКА АКТИВНОСТИ КАРБОАНГИДРАЗЫ И ЕЕ ВЛИЯНИЯ НА ПРОЦЕССЫ ОКСИГЕНАЦИИ ЭРИТРОЦИТОВ КРОВИ БЕРЕМЕННЫХ ПРИ ЦИТОМЕГАЛОВИРУСНОЙ ИНФЕКЦИИ М.Т.Луценко, И.А.Андриевская Дальневосточный научный центр физиологии и патологии дыхания, , 2015 .

[7]  D. Livermore,et al.  Aetiology and resistance in bacteraemias among adult and paediatric haematology and cancer patients. , 2014, The Journal of infection.

[8]  Е. Н. Паровичникова,et al.  Национальные клинические рекомендации по диагностике и лечению острых миелоидных лейкозов взрослых , 2014 .

[9]  E. Parovichnikova,et al.  [Treating patients with acute myeloid leukemias (AML) according to the protocol of the AML-01.10 Russian multicenter randomized trial: the coordinating center's results]. , 2014, Terapevticheskii arkhiv.

[10]  D. Livermore,et al.  Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European Conference on Infections in Leukemia (ECIL-4, 2011) , 2013, Haematologica.

[11]  D. Livermore,et al.  European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia , 2013, Haematologica.

[12]  A. Kara,et al.  Comparison of Sulbactam-Cefoperazone with Carbapenems as Empirical Monotherapy for Febrile Neutropenic Children with Lymphoma and Solid Tumors , 2011, Pediatric hematology and oncology.

[13]  Л. Н. Мищенко,et al.  Селекция яровой пшеницы в Амурской области , 2010 .

[14]  G. Fadda,et al.  Predictors of Mortality in Patients with Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae: Importance of Inadequate Initial Antimicrobial Treatment , 2007, Antimicrobial Agents and Chemotherapy.

[15]  M. Paesmans,et al.  Piperacillin-tazobactam monotherapy in high-risk febrile and neutropenic cancer patients. , 2006, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[16]  W. Hiddemann,et al.  Interventional antimicrobial therapy in febrile neutropenic patients , 1994, Annals of Hematology.

[17]  C. A. Усов,et al.  Лапароскопическая спленэктомия влечении иммунных заболеваний системы крови , 2004 .

[18]  F. Lacombe,et al.  [Treatment of acute myeloid leukemia in adults]. , 1996, La Revue du praticien.

[19]  P. Pizzo.  After empiric therapy: what to do until the granulocyte comes back. , 1987, Reviews of infectious diseases.

[20]  E. McFadden,et al.  Toxicity and response criteria of the Eastern Cooperative Oncology Group , 1982, American journal of clinical oncology.