Factors Associated with Gram-Negative Bacteremia and Mortality in Neutropenic Patients with Hematologic Malignancies in a High-Resistance Setting

Overview

Journal Infect Dis Clin Microbiol

Date 2024 Apr 18

PMID 38633337

Authors

Caglayan Merve Ayaz

Gulsen Hazirolan

Banu Sancak

Gulsen Hascelik

Murat Akova

Affiliations

Soon will be listed here.

Abstract

Objective: Patients with hematological malignancies (HMs) have a substantial incidence of febrile neutropenic episodes. Gram-negative bacteremia (GNB) is still the major cause of these episodes. We evaluated the factors associated with GNB and mortality of bacteremic patients with HMs in a high-resistance setting.

Materials And Methods: We conducted a prospective cohort study from March 2018 to June 2019 with 66 bacteremic and 132 non-bacteremic patients. Regression analyses were used to identify factors associated with GNB and 30-day mortality.

Results: The mean age was 53.83±15.21 years, and 129 (65.2%) of the patients were male. In multivariable analysis, factors independently associated with GNB were male gender, duration of hospitalization and neutropenia before the febrile neutropenic episode, leukemias and allogeneic transplant recipients, radiotherapy, receiving glucocorticosteroids, colonization with resistant microorganisms. All-cause mortality and 30-day mortality were 47.0% and 30.3% in cases of GNB, compared to non-bacteremic controls 25.0% and 10.6%, respectively. Sepsis, duration of hospitalization before the febrile neutropenic episode, carbapenem-resistant GNB, and inappropriate empirical antibiotic treatment was found as factors associated with 30-day mortality. Prior antibiotic exposure particularly beta-lactamase inhibitor combinations and carbapenems during the past 30 days was more frequent in the bacteremic group. An increasing trend was observed in multidrug-resistant (MDR) bacteria (=0.03) and carbapenem-resistant Enterobacterales (=0.02) over the years.

Conclusion: By considering the risk factors associated with GNB and 30-day mortality that we detected in our study among neutropenic patients, a personalized approach for the management of febrile neutropenic patients can be designed by means of an effective antimicrobial stewardship program including the appropriate use of broad-spectrum antibiotics.

Citing Articles

Development and Validation of a Machine Learning Model for the Prediction of Bloodstream Infections in Patients with Hematological Malignancies and Febrile Neutropenia.

Gallardo-Pizarro A, Teijon-Lumbreras C, Monzo-Gallo P, Aiello T, Chumbita M, Peyrony O Antibiotics (Basel). 2025; 14(1).

PMID: 39858299 PMC: 11760484. DOI: 10.3390/antibiotics14010013.

References

Apostolopoulou E, Raftopoulos V, Terzis K, Elefsiniotis I . Infection Probability Score, APACHE II and KARNOFSKY scoring systems as predictors of bloodstream infection onset in hematology-oncology patients. BMC Infect Dis. 2010; 10:135. PMC: 2890000. DOI: 10.1186/1471-2334-10-135. View

Al-Otaibi F, Bukhari E, Badr M, Alrabiaa A . Prevalence and risk factors of Gram-negative bacilli causing blood stream infection in patients with malignancy. Saudi Med J. 2016; 37(9):979-84. PMC: 5039618. DOI: 10.15537/smj.2016.9.14211. View

Klastersky J, de Naurois J, Rolston K, Rapoport B, Maschmeyer G, Aapro M . Management of febrile neutropaenia: ESMO Clinical Practice Guidelines. Ann Oncol. 2016; 27(suppl 5):v111-v118. DOI: 10.1093/annonc/mdw325. View

Garcia-Vidal C, Cardozo-Espinola C, Puerta-Alcalde P, Marco F, Tellez A, Aguero D . Risk factors for mortality in patients with acute leukemia and bloodstream infections in the era of multiresistance. PLoS One. 2018; 13(6):e0199531. PMC: 6023133. DOI: 10.1371/journal.pone.0199531. View

Marin M, Gudiol C, Ardanuy C, Garcia-Vidal C, Calvo M, Arnan M . Bloodstream infections in neutropenic patients with cancer: differences between patients with haematological malignancies and solid tumours. J Infect. 2014; 69(5):417-23. DOI: 10.1016/j.jinf.2014.05.018. View

Meyer E, Beyersmann J, Bertz H, Wenzler-Rottele S, Babikir R, Schumacher M . Risk factor analysis of blood stream infection and pneumonia in neutropenic patients after peripheral blood stem-cell transplantation. Bone Marrow Transplant. 2007; 39(3):173-8. DOI: 10.1038/sj.bmt.1705561. View

Trecarichi E, Tumbarello M, Spanu T, Caira M, Fianchi L, Chiusolo P . Incidence and clinical impact of extended-spectrum-beta-lactamase (ESBL) production and fluoroquinolone resistance in bloodstream infections caused by Escherichia coli in patients with hematological malignancies. J Infect. 2009; 58(4):299-307. DOI: 10.1016/j.jinf.2009.02.002. View

Kang C, Chung D, Ko K, Peck K, Song J . Risk factors for infection and treatment outcome of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae bacteremia in patients with hematologic malignancy. Ann Hematol. 2011; 91(1):115-21. DOI: 10.1007/s00277-011-1247-7. View

Worth L, Slavin M . Bloodstream infections in haematology: risks and new challenges for prevention. Blood Rev. 2008; 23(3):113-22. DOI: 10.1016/j.blre.2008.10.003. View

10.

Carena A, Laborde A, Roccia-Rossi I, Palacios C, Jordan R, Valledor A . Proposal of a clinical score to stratify the risk of multidrug-resistant gram-negative rods bacteremia in cancer patients. Braz J Infect Dis. 2019; 24(1):34-43. PMC: 9392047. DOI: 10.1016/j.bjid.2019.11.001. View

11.

Cattaneo C, Di Blasi R, Skert C, Candoni A, Martino B, Di Renzo N . 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. View

12.

Montassier E, Batard E, Gastinne T, Potel G, de La Cochetiere M . Recent changes in bacteremia in patients with cancer: a systematic review of epidemiology and antibiotic resistance. Eur J Clin Microbiol Infect Dis. 2013; 32(7):841-50. DOI: 10.1007/s10096-013-1819-7. View

13.

Cornejo-Juarez P, Perez-Jimenez C, Silva-Sanchez J, Velazquez-Acosta C, Gonzalez-Lara F, Reyna-Flores F . Molecular analysis and risk factors for Escherichia coli producing extended-spectrum β-lactamase bloodstream infection in hematological malignancies. PLoS One. 2012; 7(4):e35780. PMC: 3335120. DOI: 10.1371/journal.pone.0035780. View

14.

Islas-Munoz B, Volkow-Fernandez P, Ibanes-Gutierrez C, Villamar-Ramirez A, Vilar-Compte D, Cornejo-Juarez P . Bloodstream infections in cancer patients. Risk factors associated with mortality. Int J Infect Dis. 2018; 71:59-64. DOI: 10.1016/j.ijid.2018.03.022. View

15.

Tumbarello M, Spanu T, Caira M, Trecarichi E, Laurenti L, Montuori E . Factors associated with mortality in bacteremic patients with hematologic malignancies. Diagn Microbiol Infect Dis. 2009; 64(3):320-6. DOI: 10.1016/j.diagmicrobio.2009.02.008. View

16.

Averbuch D, Tridello G, Hoek J, Mikulska M, Akan H, Yanez San Segundo L . Antimicrobial Resistance in Gram-Negative Rods Causing Bacteremia in Hematopoietic Stem Cell Transplant Recipients: Intercontinental Prospective Study of the Infectious Diseases Working Party of the European Bone Marrow Transplantation Group. Clin Infect Dis. 2017; 65(11):1819-1828. DOI: 10.1093/cid/cix646. View

17.

Mert D, Ceken S, Iskender G, Iskender D, Merdin A, Duygu F . Epidemiology and mortality in bacterial bloodstream infections in patients with hematologic malignancies. J Infect Dev Ctries. 2020; 13(8):727-735. DOI: 10.3855/jidc.11457. View

18.

Baker T, Satlin M . The growing threat of multidrug-resistant Gram-negative infections in patients with hematologic malignancies. Leuk Lymphoma. 2016; 57(10):2245-58. PMC: 5027842. DOI: 10.1080/10428194.2016.1193859. View

19.

Russell J . Management of sepsis. N Engl J Med. 2006; 355(16):1699-713. DOI: 10.1056/NEJMra043632. View

20.

Magiorakos A, Srinivasan A, Carey R, Carmeli Y, Falagas M, Giske C . Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2011; 18(3):268-81. DOI: 10.1111/j.1469-0691.2011.03570.x. View