FEVER OF UNKNOWN ORIGIN AND MULTIDRUG-RESISTANT ORGANISMS COLONIZATION IN AML PATIENTS.
Main Article Content
Keywords
Acute Myeloid leukemia, fever of unknown origin, Colonization, Multidrug-resistant organisms
Abstract
Abstract. Background: Colonization by multidrug-resistant organisms (MDRO) is a frequent complication in hematologic departments, which puts patients at risk of life-threatening bacterial sepsis. Fever of unknown origin (FUO) is a condition related to the delivery of chemotherapy in hematologic malignancies, in which the use of antibiotics is debated. The incidence, risk factors, and influence on the outcome of these conditions in patients with acute myeloid leukemia (AML) are not clearly defined.
Methods: We retrospectively analyzed 132 consecutive admissions of non-promyelocytic AML patients at the Hematology Unit of the University Tor Vergata in Rome between June 2019 and February 2022. MDRO swab-based screening was performed in all patients on the day of admission and once weekly after that. FUO was defined as fever with no evidence of infection.
Results: Of 132 consecutive hospitalizations (69 AML patients), MDRO colonization was observed in 35 cases (26%) and resulted independently related to a previous MDRO colonization (p=0.001) and length of hospitalization (p=0.03). The colonization persistence rate in subsequent admissions was 64%. MDRO-related bloodstream infection was observed in 8 patients (23%) and correlated with grade III/IV mucositis (p=0.008) and length of hospitalization (p=0.02). FUO occurred in 68 cases (51%) and correlated with an absolute neutrophilic count <500μ/L at admission (0.04).
Conclusion: In our experience, MDRO colonization is a frequent and difficult-to-eradicate condition that can arise at all stages of treatment. Prompt discharge of patients as soon as clinical conditions allow could limit the spread of MDRO. In addition, the appropriate use of antibiotics, especially in the case of FUO, and the contraction of hospitalization length, when feasible, are measures to tackle the further spread of MDRO.
Downloads
Abstract 888
PDF Downloads 861
HTML Downloads 341
References
2. Palmieri R, Paterno G, De Bellis E, Mercante L, Buzzatti E, Esposito F, et al. Therapeutic choice in older patients with acute myeloid leukemia: A matter of fitness. Cancers (Basel). 2020;12(1):1–19.
3. Ballo O, Tarazzit I, Stratmann J, Reinheimer C, Hogardt M, Wichelhaus TA, et al. Colonization with multidrug resistant organisms determines the clinical course of patients with acute myeloid leukemia undergoing intensive induction chemotherapy. PLoS One. 2019;14(1):e0210991.
4. Rice LB. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE. Vol. 197, The Journal of infectious diseases. United States; 2008. p. 1079–81.
5. Bronzwaer SLAM, Cars O, Buchholz U, Mölstad S, Goettsch W, Veldhuijzen IK, et al. A European study on the relationship between antimicrobial use and antimicrobial resistance. Emerg Infect Dis. 2002 Mar;8(3):278–82.
6. Hyde TB, Gay K, Stephens DS, Vugia DJ, Pass M, Johnson S, et al. Macrolide resistance among invasive Streptococcus pneumoniae isolates. JAMA. 2001 Oct;286(15):1857–62.
7. Averbuch D, Orasch C, Cordonnier C, Livermore DM, Mikulska M, Viscoli C, 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. Vol. 98, Haematologica. 2013. p. 1826–35.
8. Heinz WJ, Buchheidt D, Christopeit M, von Lilienfeld-Toal M, Cornely OA, Einsele H, et al. Diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Hematol. 2017 Nov;96(11):1775–92.
9. Villa A, Vollemans M, De Moraes A, Sonis S. Concordance of the WHO, RTOG, and CTCAE v4.0 grading scales for the evaluation of oral mucositis associated with chemoradiation therapy for the treatment of oral and oropharyngeal cancers. Support care cancer Off J Multinatl Assoc Support Care Cancer. 2021 Oct;29(10):6061–8.
10. Kolonen A, Sinisalo M, Huttunen R, Syrjänen J, Aittoniemi J, Huhtala H, et al. Bloodstream infections in acute myeloid leukemia patients treated according to the Finnish Leukemia Group AML-2003 protocol - a prospective nationwide study. Infect Dis (London, England). 2017;49(11–12):799–808.
11. Malik IA, Cardenas-Turanzas M, Gaeta S, Borthakur G, Price K, Cortes J, et al. Sepsis and Acute Myeloid Leukemia: A Population-Level Study of Comparative Outcomes of Patients Discharged From Texas Hospitals. Clin Lymphoma Myeloma Leuk. 2017 Dec;17(12):e27–32.
12. Cattaneo C, Di Blasi R, Skert C, Candoni A, Martino B, Di Renzo N, et al. Bloodstream infections in haematological cancer patients colonized by multidrug-resistant bacteria. Ann Hematol. 2018 Sep;97(9):1717–26.
13. Jaiswal SR, Gupta S, Kumar RS, Sherawat A, Rajoreya A, Dash SK, et al. Gut Colonization with Carbapenem-resistant Enterobacteriaceae Adversely Impacts the Outcome in Patients with Hematological Malignancies: Results of A Prospective Surveillance Study. Mediterr J Hematol Infect Dis. 2018;10(1):e2018025.
14. Scheich S, Lindner S, Koenig R, Reinheimer C, Wichelhaus TA, Hogardt M, et al. Clinical impact of colonization with multidrug-resistant organisms on outcome after allogeneic stem cell transplantation in patients with acute myeloid leukemia. Cancer. 2018 Jan;124(2):286–96.
15. Tatarelli P, Mikulska M. Multidrug-resistant bacteria in hematology patients: emerging threats. Future Microbiol. 2016 Jun;11:767–80.
16. Mikulska M, Viscoli C, Orasch C, Livermore DM, Averbuch D, Cordonnier C, et al. Aetiology and resistance in bacteraemias among adult and paediatric haematology and cancer patients. J Infect. 2014 Apr;68(4):321–31.
17. Wingard JR, Eldjerou L, Leather H. Use of antibacterial prophylaxis in patients with chemotherapy-induced neutropenia. Curr Opin Hematol. 2012 Jan;19(1):21–6.
18. Cometta A, Calandra T, Bille J, Glauser MP. Escherichia coli resistant to fluoroquinolones in patients with cancer and neutropenia. Vol. 330, The New England journal of medicine. United States; 1994. p. 1240–1.
19. Castañón C, Fernández Moreno A, Fernández Verdugo AM, Fernández J, Martínez Ortega C, Alaguero M, et al. The Value of Adding Surveillance Cultures to Fluoroquinolone Prophylaxis in the Management of Multiresistant Gram Negative Bacterial Infections in Acute Myeloid Leukemia. J Clin Med. 2019 Nov;8(11).
20. Galloway-Peña JR, Smith DP, Sahasrabhojane P, Ajami NJ, Wadsworth WD, Daver NG, et al. The role of the gastrointestinal microbiome in infectious complications during induction chemotherapy for acute myeloid leukemia. Cancer. 2016 Jul;122(14):2186–96.
21. Galloway-Peña JR, Shi Y, Peterson CB, Sahasrabhojane P, Gopalakrishnan V, Brumlow CE, et al. Gut Microbiome Signatures Are Predictive of Infectious Risk Following Induction Therapy for Acute Myeloid Leukemia. Clin Infect Dis an Off Publ Infect Dis Soc Am. 2020 Jun;71(1):63–71.
22. Yang C, Gong G, Jin E, Han X, Zhuo Y, Yang S, et al. Topical application of honey in the management of chemo/radiotherapy-induced oral mucositis: A systematic review and network meta-analysis. Int J Nurs Stud. 2019 Jan;89:80–7.
23. Kern W, Behre G, Rudolf T, Kerkhoff A, Grote-Metke A, Eimermacher H, et al. Failure of fluconazole prophylaxis to reduce mortality or the requirement of systemic amphotericin B therapy during treatment for refractory acute myeloid leukemia: results of a prospective randomized phase III study. German AML Cooperative Group. Cancer. 1998 Jul;83(2):291–301.
24. Link H, Freund M, Diedrich H, Wilke H, Austein J, Henke M, et al. Mitoxantrone, cytosine arabinoside, and VP-16 in 36 patients with relapsed and refractory acute myeloid leukemia. Haematol Blood Transfus. 1990;33:322–5.
25. Palmieri S, Sebastio L, Mele G, Annunziata M, Annunziata S, Copia C, et al. High-dose cytarabine as consolidation treatment for patients with acute myeloid leukemia with t(8;21). Leuk Res. 2002 Jun;26(6):539–43.
26. Gil L, Styczynski J, Komarnicki M. Infectious complication in 314 patients after high-dose therapy and autologous hematopoietic stem cell transplantation: risk factors analysis and outcome. Infection. 2007 Dec;35(6):421–7.
27. Hämäläinen S, Kuittinen T, Matinlauri I, Nousiainen T, Koivula I, Jantunen E. Neutropenic fever and severe sepsis in adult acute myeloid leukemia (AML) patients receiving intensive chemotherapy: Causes and consequences. Leuk Lymphoma. 2008 Mar;49(3):495–501.
28. Loizidou A, Aoun M, Klastersky J. Fever of unknown origin in cancer patients. Crit Rev Oncol Hematol. 2016 May;101:125–30.
29. Kawano Y, Fukui C, Shinohara M, Wakahashi K, Ishii S, Suzuki T, et al. G-CSF-induced sympathetic tone provokes fever and primes antimobilizing functions of neutrophils via PGE2. Blood. 2017 Feb;129(5):587–97.
30. Macedo-Viñas M, De Angelis G, Rohner P, Safran E, Stewardson A, Fankhauser C, et al. Burden of meticillin-resistant Staphylococcus aureus infections at a Swiss University hospital: excess length of stay and costs. J Hosp Infect. 2013 Jun;84(2):132–7.