The Antibiotic De-escalation Strategy in Patients with Multidrug-resistant Bacterial Colonization After Allogeneic Stem Cell Transplantation

Overview

Journal Front Microbiol

Date 2025 Jan 20

PMID 39831122

Authors

Roberto Bono

Giuseppe Sapienza

Stefania Tringali

Cristina Rotolo

Alessandra Santoro

Laura Di Noto

Angelo Pirrera

Floriana Schiro

Raffaella Rubino

Antonio Cascio

Sergio Siragusa

Carmen Tommaselli

Orazia DiQuattro

Caterina Patti

Luca Castagna

Affiliations

Soon will be listed here.

Abstract

Colonization by multidrug-resistant (MDR) bacteria and related bloodstream infections (BSI) are associated with a high rate of mortality in patients with hematological malignancies after intensive chemotherapy and allogeneic stem cell transplantation (allo-SCT). In this retrospective study, we analyzed the outcomes of patients colonized with MDR bacteria (primarily carbapenem-resistant , KPC), before allo-SCT. We also investigated the feasibility and safety of an antimicrobial de-escalating approach in these patients. Since 2021, 106 patients have been undergoing allo-SCT in our department, and 34 (32%) of them were colonized by MDR bacteria before allo-SCT. In the pre-engraftment period, 84% received an empiric antibiotic therapy (EAT) active against MDR bacteria and 16% were treated with a conventional EAT. The MDR translocation rate was null, and the overall de-escalation rate was 79%, with 75% in patients with fever of unknown origin (FUO). Among the cohort of patients with MDR-positive rectal swabs just before allo-SCT ( = 18), the de-escalation rate was 100%. The all-cause mortality rates at 30 and 100 days for the whole MDR patient population were 6% (2/34) and 12% (4/34), respectively. Day +30 infection-related mortality rate was 3%. In this study, we confirm the safety of the de-escalation approach in patients with previous MDR infection after allo-SCT. This could reduce the exposure time to EAT antibiotics, reducing the selective pressure.

References

Verlinden A, Mikulska M, Knelange N, Averbuch D, Styczynski J . Current antimicrobial practice in febrile neutropenia across Europe and Asia: the EBMT Infectious Disease Working Party survey. Bone Marrow Transplant. 2020; 55(8):1588-1594. PMC: 7391284. DOI: 10.1038/s41409-020-0811-y. View

Paul M, Carrara E, Retamar P, Tangden T, Bitterman R, Bonomo R . European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine). Clin Microbiol Infect. 2021; 28(4):521-547. DOI: 10.1016/j.cmi.2021.11.025. View

Przepiorka D, Weisdorf D, MARTIN P, Klingemann H, Beatty P, Hows J . 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995; 15(6):825-8. View

Micozzi A, Gentile G, Santilli S, Minotti C, Capria S, Moleti M . Reduced mortality from KPC-K.pneumoniae bloodstream infection in high-risk patients with hematological malignancies colonized by KPC-K.pneumoniae. BMC Infect Dis. 2021; 21(1):1079. PMC: 8524821. DOI: 10.1186/s12879-021-06747-8. View

Girmenia C, Rossolini G, Piciocchi A, Bertaina A, Pisapia G, Pastore D . Infections by carbapenem-resistant Klebsiella pneumoniae in SCT recipients: a nationwide retrospective survey from Italy. Bone Marrow Transplant. 2014; 50(2):282-8. DOI: 10.1038/bmt.2014.231. View

Petteys M, Kachur E, Pillinger K, He J, Copelan E, Shahid Z . Antimicrobial de-escalation in adult hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin. J Oncol Pharm Pract. 2019; 26(3):632-640. DOI: 10.1177/1078155219865303. View

Gustinetti G, Raiola A, Varaldo R, Galaverna F, Gualandi F, Del Bono V . De-Escalation and Discontinuation of Empirical Antibiotic Treatment in a Cohort of Allogeneic Hematopoietic Stem Cell Transplantation Recipients during the Pre-Engraftment Period. Biol Blood Marrow Transplant. 2018; 24(8):1721-1726. DOI: 10.1016/j.bbmt.2018.03.018. View

Spyridonidis A, Labopin M, Savani B, Niittyvuopio R, Blaise D, Craddock C . Redefining and measuring transplant conditioning intensity in current era: a study in acute myeloid leukemia patients. Bone Marrow Transplant. 2020; 55(6):1114-1125. DOI: 10.1038/s41409-020-0803-y. View

Bonifazi F, Solano C, Wolschke C, Sessa M, Patriarca F, Zallio F . Acute GVHD prophylaxis plus ATLG after myeloablative allogeneic haemopoietic peripheral blood stem-cell transplantation from HLA-identical siblings in patients with acute myeloid leukaemia in remission: final results of quality of life and long-term.... Lancet Haematol. 2019; 6(2):e89-e99. DOI: 10.1016/S2352-3026(18)30214-X. View

10.

Aguilar-Guisado M, Espigado I, Martin-Pena A, Gudiol C, Royo-Cebrecos C, Falantes J . Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol. 2017; 4(12):e573-e583. DOI: 10.1016/S2352-3026(17)30211-9. View

11.

Micozzi A, Minotti C, Capria S, Cartoni C, Trisolini S, Assanto G . Benefits and Safety of Empiric Antibiotic Treatment Active Against KPC- in Febrile Neutropenic Patients with Acute Leukemia Who are Colonized with KPC-. A 7-Years Retrospective Observational Cohort Study. Infect Drug Resist. 2023; 16:695-704. PMC: 9899007. DOI: 10.2147/IDR.S393802. View

12.

Averbuch D, Orasch C, Cordonnier C, Livermore D, Mikulska M, Viscoli C . 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. Haematologica. 2013; 98(12):1826-35. PMC: 3856957. DOI: 10.3324/haematol.2013.091025. View

13.

Filipovich A, Weisdorf D, Pavletic S, Socie G, Wingard J, Lee S . National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005; 11(12):945-56. DOI: 10.1016/j.bbmt.2005.09.004. View

14.

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

15.

Gutierrez-Gutierrez B, Salamanca E, Cueto M, Hsueh P, Viale P, Pano-Pardo J . Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study. Lancet Infect Dis. 2017; 17(7):726-734. DOI: 10.1016/S1473-3099(17)30228-1. View

16.

Forcina A, Lorentino F, Marasco V, Oltolini C, Marcatti M, Greco R . Clinical Impact of Pretransplant Multidrug-Resistant Gram-Negative Colonization in Autologous and Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2018; 24(7):1476-1482. DOI: 10.1016/j.bbmt.2018.02.021. View

17.

Kroger N, Solano C, Wolschke C, Bandini G, Patriarca F, Pini M . Antilymphocyte Globulin for Prevention of Chronic Graft-versus-Host Disease. N Engl J Med. 2016; 374(1):43-53. DOI: 10.1056/NEJMoa1506002. View

18.

Pizzo P . Management of fever in patients with cancer and treatment-induced neutropenia. N Engl J Med. 1993; 328(18):1323-32. DOI: 10.1056/NEJM199305063281808. View

19.

Korula A, Perumalla S, Devasia A, Abubacker F, Lakshmi K, Abraham A . Drug-resistant organisms are common in fecal surveillance cultures, predict bacteremia and correlate with poorer outcomes in patients undergoing allogeneic stem cell transplants. Transpl Infect Dis. 2020; 22(3):e13273. DOI: 10.1111/tid.13273. View

20.

Patriarca F, Cigana C, Massimo D, Lazzarotto D, Geromin A, Isola M . Risk Factors and Outcomes of Infections by Multidrug-Resistant Gram-Negative Bacteria in Patients Undergoing Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2016; 23(2):333-339. DOI: 10.1016/j.bbmt.2016.11.005. View