SPECTRUM AND EPIDEMIOLOGY OF INFECTION COMPLICATIONS IN PATIENTS WITH ACUTE MYELOID LEUKEMIA DURING INDUCTION AND CONSOLIDATION CHEMOTHERAPY

The aim of the study is to evaluate the spectrum and epidemiology of infectious complications in patients with acute myeloid leukemia (AML) during induction and consolidation chemotherapy. Prospective study (2013–2015) included 66 patients with de novo AML (median age: from 39 (17–64) years. Patients received 208 chemotherapy courses (94 inductions, 114 consolidations). Patients were followed up for 180 days. Most patients were admitted from other hospitals (89%). On admission hyperleukocytosis was revealed in 33% of patients, ECOG score 3–4 points had 65% of patients, 38% of patients had severe infections, including pneumonia (21%) and cellulitis (17%). The mean number of febrile neutropenic episodes (FNE) per patient was 2.9 (1–4). FNE occurred in 93% of chemotherapy courses (98% of induction chemotherapy and 93% of consolidation chemotherapy; OR = 5.9; p = 0.01). The majority of FNE were attributable to clinically documented infections (44%), followed by fever of unknown origin (39%) and bloodstream infection (BSI) (17%). Gram-negative and Gram-positive bacteria accounted for 53% and 47% of BSI pathogens, consequently. Most prevalent BSI isolates were Escherichia coli (25%) and Streptococcus viridans (22%). Among Enterobacteriacae (n = 12) the production of β-lactamases of the extended spectrum was detected in 42% of positive isolates. Invasive mycoses (IM) were in 23% of patients. Invasive aspergillosis (IA) was the most frequent (60% of all invasive mycoses) (14% in the induction – 9%, 6% in the consolidation). Thus, infection complications were dominated both in the induction and consolidation and were caused by bacteria and fungi.

1. Rolston K.V.I., Raad I., Whimbey E., Bodey G.P. The changing spectrum of bacterial infections in febrile neutropenic patients. In: Klastersky J.A., eds. Febrile Neutropenia. Berlin: Springer; 1997: 53–6. doi: 10.1007/978-3-642-60443-0.

2. Klyasova G.A., Savchenko V.G., Parovichnikova E.N., Isaev V.G., Tolkacheva, T.V., Maslova E.R., et al. Empirical antibiotic therapy in patients with acute leukemia: results of a multicenter trial. Therapeutic archive. Russian Journal (Terapevticheskiy arkhiv). 1998; 70(7): 15–21. (in Russian)

3. Klyasova G. A. Infections in patients with hematological malignancies: clinical features, diagnosis and treatment. Dis. Moscow; 2009. (in Russian)

4. Savchenko V.G., Parovichnikova E.N., Afanasyev B.V., Gritsaev S.V., Semochkin S.V., Bondarenko S.N., et al. Russian experts’ clinical guidelines for acute myeloid leukemia treatment in patients less than 60 years of age. Therapeutic archive. Russian Journal (Terapevticheskiy arkhiv). 2014; 86(7): 4–13. (in Russian)

5. Oken M.M., Creech R.H., Tormey D.C., Horton J., Davis T.E., McFadden E.T., et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am. J. Clin. Oncol. 1982; 5(6): 649–55.

6. Guidelines for Susceptibility testing of microorganisms to antibacterial agents. Clinical Microbiology and antimicrobial chemotherapy. Russian Journal (Klinicheskaya Mikrobiologiya i Antimikrobnaya Himioterapiya). 2004; 6(4): 306–59. (in Russian)

7. De Pauw B., Walsh T.J., Donnelly J.P., Stevens, D.A., Edwards J.E., Calandra T., et al. Revised definitions of invasive fungal disease from the European organization for research and treatment of cancer/invasive fungal infections cooperative group and the national institute of allergy and infectious diseases mycoses study group (EORTC/MSG) consensus group. Clin. Infect. Dis. 2008; 46(12): 1813–21. doi:10.1086/588660.

8. Bodey G.P., Rodriguez V., Chang, H.Y., Narboni G. Fever and infection in leukemic patients. A study of 494 consecutive patients. Cancer. 1978; 41(4): 1610–22. doi:10.1002/1097-0142(197804)41:4<1610::AIDCNCR2820410452>3.0.CO;2-B.

9. Pizzo P.A., Robichaud K.J., Wesley R., Commers J.R. Fever in the pediatric and young adult patient with cancer: a prospective study of 1001 episodes. Medicine. 1982; 61(3): 153–65.

10. Pagano L., Caira M., Rossi G., Tumbarello M., Fanci R., Garzia M.G., et al. A prospective survey of febrile events in hematological malignancies. Ann. Hematol. 2012; 91(5): 767–74. doi: 10.1007/s00277-011-1373-2.

11. Pagano L., Caira M., Nosari A., Rossi G., Viale P., Aversa F., et al. Etiology of febrile episodes in patients with acute myeloid leukemia: results from the Hema e-Chart Registry. Arch. Intern. Med. 2011; 171(16): 1502–3.

12. Di Blasi R., Lewis E.R., Busca A., Candoni A., Caramatti C., Cattaneo C., et al. Seifem B 2012. A prospective, multicentric, observational study on febrile events in acute lymphoblastic leukaemia. In: Infections in patients with cancer and/or stem cell transplantation: Proc. 25th European Congress of Clin. Microbriol. Infect. Dis. 2015, Apr. 25–28; Copenhagen. Available at: https://www.escmid.org/escmid_publications/escmid_elibrary/material/?mid=21027 (accessed 12 Jan 2017).

13. Mikulska M., Viscoli C., Orasch C., Livermore D.M., Averbuch D., Cordonnier C., et al. Aetiology and resistance in bacteraemias among adult and paediatric haematology and cancer patients. J. Infect. 2013; 68(4): 321—31. doi: 10.1016/j.jinf.2013.12.006.

14. Kara Ö., Zarakolu P., Aşçioğlu S., Etgül S., Uz B., Büyükaşik Y., et al. Epidemiology and emerging resistance in bacterial bloodstream infections in patients with hematologic malignancies. Infect. Dis. 2015; 47(10): 686–93. doi:10.3109/23744235.2015.1051105.

15. Trecarichi E.M., Pagano L., Candoni A., Pastore D., Cattaneo C., Fanci R., et al. Current epidemiology and antimicrobial resistance data for bacterial bloodstream infections in patients with hematologic malignancies: an Italian multicentre prospective survey. Clin. Microbiol. Infect. 2015; 21(4): 337–43. doi:10.1016/j.cmi.2014.11.022.

16. Klyasova G.A., Speranskaya L.L., Mironova A.V., Maschan M.A., Baydildina D.D., Vereshchagina S.A., et al. The pathogens causing sepsis in immunocompromized patients: structure and problems of antibiotic resistance. Results of a multi-center cooperative study. Hematology and Transfusiology. Russian Journal (Gematologiya i transfusiologiya). 2007; 52(1): 11–8. (in Russian)

17. Panina M.V., Klyasova G.A., Novichkova G.A., Myakova N.V., Litvinov D.V., Baidildina D.D., et al. Etiological structure of bacteremias in children with oncohematological diseases and bone marrow failure syndromes in a “University type” multiprofile hospital. Pediatric Haematology, Oncology and Immunopatology. Russian Journal (Voprosy Gematologii, Onkologii i Immunopatologii v Pediatri)i. 2014; 13(3): 49–56. (in Russian)

18. Khrulnova S.A., Fedorova A.V., Klyasova G.A. Virulence genes in Enterococcus spp. strains, isolated from blood cultures of patients with hematological malignancies in Russia. Immunopathology, Allergology, Infectology. Russian Journal. 2016; 1: 78–82. doi:10.14427/ jipai.2016.1.78. (in Russian)

19. Brilliantova A.N., Kliasova G.A., Mironova A.V., Tishkov V.I., Novichkova G.A., Bobrynina V.O., et al. Spread of vancomycin-resistant Enterococcus faecium in two haematological centres in Russia. Int. J. Antimicrob. Agents. 2010; 35(2): 177–81. doi: 10.1016/j.ijantimicag.2009.10.006.

20. Pagano L., Caira M., Candoni A., Offidani M., Fianchi L., Martino B., et al. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica. 2006; 91(8): 1068–75.

21. Klyasova G.A., Blokhina E.V., Gracheva A.N., Kravchenko S.K., Parovichnikova E.N., Okhmat V.A., et al. Factors influencing recovery in patients with hemoblastoses and candidemia. Therapeutic archive. Russian Journal (Terapevticheskiy arkhiv). 2015; 87(7): 77–87. (in Russian)

22. Nucci M., Garnica M., Gloria A.B., Lehugeur D.S., Dias V.C., Palma L.C., et al. Invasive fungal diseases in haematopoietic cell transplant recipients and in patients with acute myeloid leukaemia or myelodysplasia in Brazil. Clin. Microbiol. Infect. 2013; 19(8): 745–51. doi: 10.1111/1469-0691.12002.

23. Klyasova G.A., Okhmat V.A., Vasilyeva V.A., Popova M.O., Kaporskaya T.S., Sveshnikova U.V., et al. Invasive mycoses in patients with acute leukemia and hematopoietic stem cell transplant recipients. Results of prospective observational multicenter study in Russia (RIFI). Hematology and Transfusiology. Russian Journal (Gematologiya i transfusiologiya). 2016; 61(1, Suppl. 1): 19. (in Russian)