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Irene Urbino
Chiara Frairia
Alessandro Busca
Silvia Corcione
Stefano D'Ardia
Chiara Maria Dellacasa
Valentina Giai
Carolina Secreto
Roberto Freilone
Francesco Giuseppe De Rosa
Semra Aydin
Giovannino Ciccone
Rosalba Rosato
Marco Cerrano
Ernesta Audisio


acute myeloid leukemia, levofloxacin prophylaxis, bloodstream infections, induction death, antibiotic resistance


Background and objectives: acute myeloid leukemia (AML) patients are at high risk of infections during post induction neutropenia. Recently, the role of antibacterial prophylaxis has been reconsidered due to concerns about the emergence of multi-resistant pathogens. Aim of the present study was to evaluate the impact of prophylaxis omission on the rate of induction death (primary endpoint), neutropenic fevers, bloodstream infections (BSIs), resistant pathogens BSIs and septic shocks (secondary endpoints). Methods:  we performed a retrospective single center study including 373 AML patients treated with intensive induction chemotherapy, divided in two groups according to levofloxacin prophylaxis given (group A, gA) or not (group B, gB). Results: neutropenic fever was observed in 91% of patients in gA and 97% in gB (OR 0.35, IC95% 0.08 – 1.52, p=0162).The rate of BSIs was 27% in gA compared to 34% in gB (OR 0.69, 0.38 – 1.25, p=0.222). Induction death rate was 5% in gA and 3% in gB (OR 1.50, 0.34 – 6.70, p=0.284). Fluoroquinolones (FQ) resistant pathogens were responsible for 59% of total BSIs in gA and 22% in gB (OR 5.07, 1.87 – 13.73, p=0.001); gram-negative BSIs due to multi-drug resistant organisms were 31% in gA and 36% in gB (OR 0.75, 0.15 – 3.70, p=0.727). Conclusions: levofloxacin prophylaxis omission was not associated with an increased risk of induction death. Cumulative incidence of neutropenic fever was higher in non-prophylaxis group, while no difference was observed for BSIs. In the prophylaxis group we observed a higher incidence of FQ resistant organisms.


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[1] Vento S, Cainelli F. Infections in patients with cancer undergoing chemotherapy: aetiology, prevention, and treatment. Lancet Oncol. 2003;4(10):595-604. DOI: 10.1016/s1470-2045(03)01218-x
[2] Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR. Infectious Diseases Society of America. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011;52(4). DOI: 10.1093/cid/ciq147
[3] Bucaneve G, Micozzi A, Menichetti F, Martino P, Dionisi MS, Martinelli G, Allione B, D'Antonio D, Buelli M, Nosari AM, Cilloni D, Zuffa E, Cantaffa R, Specchia G, Amadori S, Fabbiano F, Deliliers GL, Lauria F, Foà R, Del Favero A. Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) Infection Program. Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. N Engl J Med. 2005;353(10):977-87. DOI: 10.1056/NEJMoa044097
[4] Bucaneve G, Castagnola E, Viscoli C, Leibovici L, Menichetti F. Quinolone prophylaxis for bacterial infections in afebrile high risk neutropenic patients. EJC Suppl. 2007;5(2):5-12. DOI: 10.1016/j.ejcsup.2007.06.002
[5] European Centre for Disease Prevention and Control. Surveillance of antimicrobial resistance in Europe 2018. Stockholm: ECDC; 2019. DOI: 10.2900/22212
[6] De Rosa FG, Motta I, Audisio E, Frairia C, Busca A, Di Perri G, Marmont F. Epidemiology of bloodstream infections in patients with acute myeloid leukemia undergoing levofloxacin prophylaxis. BMC Infect Dis. 2013;13:563. DOI: 10.1186/1471-2334-13-563
[7] Mikulska M, Averbuch D, Tissot F, Cordonnier C, Akova M, Calandra T, Ceppi M, Bruzzi P, Viscoli C. European Conference on Infections in Leukemia (ECIL). Fluoroquinolone prophylaxis in haematological cancer patients with neutropenia: ECIL critical appraisal of previous guidelines. J Infect. 2018;76(1):20-37. DOI: 10.1016/j.jinf.2017.10.009
[8] Owattanapanich W, Chayakulkeeree M. Efficacy of levofloxacin as an antibacterial prophylaxis for acute leukemia patients receiving intensive chemotherapy: a systematic review and meta-analysis. Hematology. 2019;24(1):362-368. DOI: 10.1080/16078454.2019.1589706
[9] Phillips R, Hancock B, Graham J, Bromham N, Jin H, Berendse S. Prevention and management of neutropenic sepsis in patients with cancer: summary of NICE guidance. BMJ. 2012;345:e5368. DOI: 10.1136/bmj.e5368
[10] Christopeit M, Schmidt-Hieber M, Sprute R, Buchheidt D, Hentrich M, Karthaus M, Penack O, Ruhnke M, Weissinger F, Cornely OA, Maschmeyer G. Prophylaxis, diagnosis and therapy of infections in patients undergoing high-dose chemotherapy and autologous haematopoietic stem cell transplantation. 2020 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Hematol. 2021;100(2):321-336. DOI: 10.1007/s00277-020-04297-8
[11] Taplitz RA, Kennedy EB, Bow EJ, Crews J, Gleason C, Hawley DK, Langston AA, Nastoupil LJ, Rajotte M, Rolston KV, Strasfeld L, Flowers CR. Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update. J Clin Oncol. 2018;36(30):3043-3054. DOI: 10.1200/JCO.18.00374
[12] Tallman MS, Wang ES, Altman JK, Appelbaum FR, Bhatt VR, Bixby D, Coutre SE, De Lima M, Fathi AT, Fiorella M, Foran JM, Hall AC, Jacoby M, Lancet J, LeBlanc TW, Mannis G, Marcucci G, Martin MG, Mims A, O'Donnell MR, Olin R, Peker D, Perl A, Pollyea DA, Pratz K, Prebet T, Ravandi F, Shami PJ, Stone RM, Strickland SA, Wieduwilt M, Gregory KM; OCN; Hammond L, Ogba N. Acute Myeloid Leukemia, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2019;17(6):721-749. DOI: 10.6004/jnccn.2019.0028
[13] Slavin MA, Lingaratnam S, Mileshkin L, Booth DL, Cain MJ, Ritchie DS, Wei A, Thursky KA; Australian Consensus Guidelines 2011 Steering Committee. Use of antibacterial prophylaxis for patients with neutropenia. Australian Consensus Guidelines 2011 Steering Committee. Intern Med J. 2011;41(1b):102-9. DOI: 10.1111/j.1445-5994.2010.02341.x
[14] Klastersky J, de Naurois J, Rolston K, Rapoport B, Maschmeyer G, Aapro M, Herrstedt J. ESMO Guidelines Committee. Management of febrile neutropaenia: ESMO Clinical Practice Guidelines. Ann Oncol. 2016;27(suppl 5):v111-v118. DOI: 10.1093/annonc/mdw325
[15] Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz M, Sierra J, Tallman MS, Tien HF, Wei AH, Löwenberg B, Bloomfield CD. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424-447. DOI: 10.1182/blood-2016-08-733196
[16] Parker JE, Pagliuca A, Mijovic A, Cullis JO, Czepulkowski B, Rassam SM, Samaratunga IR, Grace R, Gover PA, Mufti GJ. Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of poor-risk myelodysplastic syndromes and acute myeloid leukaemia. Br J Haematol. 1997;99(4):939-44. DOI: 10.1046/j.1365-2141.1997.4763281.x
[17] Cerrano M, Candoni A, Crisà E, Dubbini MV, D'Ardia S, Zannier ME, Boccadoro M, Audisio E, Bruno B, Ferrero D. FLAI induction regimen in elderly patients with acute myeloid leukemia. Leuk Lymphoma. 2019;60(13):3339-3340. DOI: 10.1080/10428194.2019.1620943
[18] Lichtman MA. A historical perspective on the development of the cytarabine (7days) and daunorubicin (3days) treatment regimen for acute myelogenous leukemia: 2013 the 40th anniversary of 7+3. Blood Cells Mol Dis. 2013;50(2):119-30. DOI: 10.1016/j.bcmd.2012.10.005
[19] Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O'Grady NP, Raad II, Rijnders BJ, Sherertz RJ, Warren DK. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;49(1):1-45. DOI: 10.1086/599376
[20] Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-10. DOI: 10.1001/jama.2016.0287
[21] Cattaneo C, Di Blasi R, Skert C, Candoni A, Martino B, Di Renzo N, Delia M, Ballanti S, Marchesi F, Mancini V, Orciuolo E, Cesaro S, Prezioso L, Fanci R, Nadali G, Chierichini A, Facchini L, Picardi M, Malagola M, Orlando V, Trecarichi EM, Tumbarello M, Aversa F, Rossi G, Pagano L. SEIFEM Group. Bloodstream infections in haematological cancer patients colonized by multidrug-resistant bacteria. Ann Hematol. 2018;97(9):1717-1726. DOI: 10.1007/s00277-018-3341-6
[22] Vehreschild MJ, Hamprecht A, Peterson L, Schubert S, Häntschel M, Peter S, Schafhausen P, Rohde H, Lilienfeld-Toal MV, Bekeredjian-Ding I, Libam J, Hellmich M, Vehreschild JJ, Cornely OA, Seifert H. A multicentre cohort study on colonization and infection with ESBL-producing Enterobacteriaceae in high-risk patients with haematological malignancies. J Antimicrob Chemother. 2014;69(12):3387-92. DOI: 10.1093/jac/dku305