Vol 55, No 2 (2024)
Original research article
Published online: 2024-04-02
Evaluation of colonization and infection profile in allogeneic hematopoietic stem cell transplantation recipients
12
, 12, 2, 12, 12, 1, 12, 12
, 12, 2, 12, 12, 1, 12, 12
DOI: 10.5603/ahp.98671
Acta Haematol Pol 2024;55(2):112-122.
Abstract
Introduction: Infections are one of the main causes of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Material and methods: We conducted a single-center retrospective analysis of colonization and infection epidemiology in 44 patients who underwent matched related donor (MRD) allo-HSCT between 2012 and 2022.
Results: Colonization was observed in 84.1% of patients before allo-HSCT. The most common location was the anus, colonized in 55.4% of patients, mostly by Klebsiella pneumoniae ESBL (+) — 28.6%. Multi-drug resistant bacteria (MDR) accounted for 50.7% of positive colonization cultures before allo-HSCT. In the post-transplantation period (i.e. up to 100 days after allo-HSCT), infections occurred in 86.4% of patients. Bacteremia was observed in 47.7% of patients, mostly caused by methicillin-resistant coagulase-negative Staphylococcus epidermidis — 39.4%. Infection of the skin and soft tissue near the central line was found in 27.3% of patients, urinary tract infections in 56.8%, and gastrointestinal infections in 38.6%. Fungal infections were reported in 31.8%. MDR pathogens accounted for 58.1% of all infecting pathogens. The most common resistance was extended-spectrum beta-lactamase (ESBL), accounting for 50.8% of all MDR strains. Viral reactivations were detected in 29.5%.
59.5% of colonized patients developed an infection with the pathogen responsible for their previous colonization. Infections with such pathogens were significantly more frequent in colonized patients than with de novo pathogens (p = 0.04).
Conclusions: Colonization evaluation can be an effective tool to identify patients with a high risk of developing post-transplant infections with the colonizing pathogen, potentially resulting in a prompter implementation of targeted treatment and improved infection outcome.
Keywords: hematopoietic stem cell transplantationinfectionsbacteremia
References
- Passweg JR, Baldomero H, Ciceri F, et al. Hematopoietic cell transplantation and cellular therapies in Europe 2021. The second year of the SARS-CoV-2 pandemic. A Report from the EBMT Activity Survey. Bone Marrow Transplant. 2023; 58(6): 647–658.
- Styczyński J, Tridello G, Koster L, et al. Infectious Diseases Working Party EBMT. Death after hematopoietic stem cell transplantation: changes over calendar year time, infections and associated factors. Bone Marrow Transplant. 2020; 55(1): 126–136.
- Satwani P, Jin Z, Duffy D, et al. Transplantation-related mortality, graft failure, and survival after reduced-toxicity conditioning and allogeneic hematopoietic stem cell transplantation in 100 consecutive pediatric recipients. Biol Blood Marrow Transplant. 2013; 19(4): 552–561.
- Kong SG, Jeong S, Lee S, et al. Early transplantation-related mortality after allogeneic hematopoietic cell transplantation in patients with acute leukemia. BMC Cancer. 2021; 21(1): 177.
- Lindsay J, Kerridge I, Wilcox L, et al. Infection-related mortality in adults and children undergoing allogeneic hematopoietic cell transplantation: an Australian registry report. Transplant Cell Ther. 2021; 27(9): 798.e1–798.e10.
- Bolon YT, Atshan R, Allbee-Johnson M, et al. Current use and outcome of hematopoietic stem cell transplantation: CIBMTR summary slides, 2022. https://cibmtr.org/CIBMTR/Resources/Summary-Slides-Reports (1 May 2023).
- Heston SM, Young RR, Tanaka JS, et al. Risk factors for CMV viremia and treatment-associated adverse events among pediatric hematopoietic stem cell transplant recipients. Open Forum Infect Dis. 2022; 9(2): ofab639.
- Puerta-Alcalde P, Chumbita M, Charry P, et al. Risk factors for mortality in hematopoietic stem cell transplantation recipients with bloodstream infection: points to be addressed by future guidelines. Transplant Cell Ther. 2021; 27(6): 501.e1–501.e6.
- Gill J, Busca A, Cinatti N, et al. Bacterial bloodstream infections after allogeneic hematopoietic stem cell transplantation: etiology, risk factors and outcome in a single-center study. Microorganisms. 2023; 11(3).
- Carreras E, Dufour C, Mohty M. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies [Internet]. 7th ed. Springer, Cham (CH) 2019.
- Averbuch D, Orasch C, Cordonnier C, et al. ECIL4, a joint venture of EBMT, EORTC, ICHS, ESGICH/ESCMID and ELN. 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): 1826–1835.
- Scheich S, Lindner S, Koenig R, 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; 124(2): 286–296.
- Pluta A, Krawiec K, Wieczorkiewicz-Kabut A, et al. P1535: Assessment of colonization and infection epidemiology in patients undergoing allogeneic stem cell transplantation – a prospective multi-center study of Polish Adult Leukemia Group (PALG). HemaSphere. 2023; 7(S3): 2981–2982.
- Bilinski J, Robak K, Peric Z, et al. Impact of gut colonization by antibiotic-resistant bacteria on the outcomes of allogeneic hematopoietic stem cell transplantation: a retrospective, single-center study. Biol Blood Marrow Transplant. 2016; 22(6): 1087–1093.
- van der Maas NG, Berghuis D, van der Burg M, et al. B cell reconstitution and influencing factors after hematopoietic stem cell transplantation in children. Front Immunol. 2019; 10: 782.
- Tomblyn M, Chiller T, Einsele H, et al. Center for International Blood and Marrow Research, National Marrow Donor program, European Blood and MarrowTransplant Group, American Society of Blood and Marrow Transplantation, Canadian Blood and Marrow Transplant Group, Infectious Diseases Society of America, Society for Healthcare Epidemiology of America, Association of Medical Microbiology and Infectious Disease Canada, Centers for Disease Control and Prevention. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009; 15(10): 1143–1238.
- Sahin U, Toprak SK, Atilla PA, et al. An overview of infectious complications after allogeneic hematopoietic stem cell transplantation. J Infect Chemother. 2016; 22(8): 505–514.
- Schuster MG, Cleveland AA, Dubberke ER, et al. Infections in hematopoietic cell transplant recipients: results from the organ transplant infection project, a multicenter, prospective, cohort study. Open Forum Infect Dis. 2017; 4(2): ofx050.
- 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; 35(6): 421–427.
- Srinivasan A, Wang C, Srivastava DK, et al. Timeline, epidemiology, and risk factors for bacterial, fungal, and viral infections in children and adolescents after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2013; 19(1): 94–101.
- Gjaerde LI, Moser C, Sengeløv H. Epidemiology of bloodstream infections after myeloablative and non-myeloablative allogeneic hematopoietic stem cell transplantation: A single-center cohort study. Transpl Infect Dis. 2017; 19(5).
- Mariggiò E, Iori AP, Micozzi A, et al. Peripherally inserted central catheters in allogeneic hematopoietic stem cell transplant recipients. Support Care Cancer. 2020; 28(9): 4193–4199.
- Santos KB, Neto AE, Silva GA, et al. Infection profile of patients undergoing autologous bone marrow transplantation in a Brazilian institution. Sao Paulo Med J. 2012; 130(1): 10–16.
- Czyż A. Infectious complications in hematology. Hematologia. 2015; 6(2): 136–154.
- Taplitz RA, Kennedy EB, Flowers CR. Antimicrobial prophylaxis for adult patients with cancer-related immunosuppression: ASCO and IDSA clinical practice guideline update summary. J Oncol Pract. 2018; 14(11): 692–695.
- Freifeld AG, Bow EJ, Sepkowitz KA, et al. 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): e56–e93.
- Dandoy CE, Kim S, Chen M, et al. Incidence, risk factors, and outcomes of patients who develop mucosal barrier injury-laboratory confirmed bloodstream infections in the first 100 days after allogeneic hematopoietic stem cell transplant. JAMA Netw Open. 2020; 3(1): e1918668.
- Mikulska M, Del Bono V, Raiola AM, et al. Blood stream infections in allogeneic hematopoietic stem cell transplant recipients: reemergence of Gram-negative rods and increasing antibiotic resistance. Biol Blood Marrow Transplant. 2009; 15(1): 47–53.
- Gustinetti G, Mikulska M. Bloodstream infections in neutropenic cancer patients: A practical update. Virulence. 2016; 7(3): 280–297.
- Jia Y, Li Y, Liu Yi, et al. Epidemiology, antimicrobial resistance, and mortality risk factors of carbapenem resistant gram-negative bacteria in hematopoietic stem cell transplantation recipients. Front Cell Infect Microbiol. 2022; 12: 1098856.
- Girmenia C, Bertaina A, Piciocchi A, et al. Gruppo Italiano Trapianto di Midollo Osseo (GITMO) and Associazione Microbiologi Clinici Italiani (AMCLI). Incidence, risk factors and outcome of pre-engraftment gram-negative bacteremia after allogeneic and autologous hematopoietic stem cell transplantation: an Italian prospective multicenter survey. Clin Infect Dis. 2017; 65(11): 1884–1896.
- Averbuch D, Tridello G, Hoek J, et al. 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.
- Shi Jm, Pei Xy, Luo Yi, et al. Invasive fungal infection in allogeneic hematopoietic stem cell transplant recipients: single center experiences of 12 years. J Zhejiang Univ Sci B. 2015; 16(9): 796–804.
- Puerta-Alcalde P, Garcia-Vidal C. Changing epidemiology of invasive fungal disease in allogeneic hematopoietic stem cell transplantation. J Fungi (Basel). 2021; 7(10).
- Kontoyiannis DP, Marr KA, Park BJ, et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis. 2010; 50(8): 1091–1100.
- Biliński P, Seferyńska I, Warzocha K. Diagnostyka i leczenie układowych zakażeń grzybiczych w onkohematologii. Onkologia w praktyce klinicznej. 2008; 4(1): 15–24.
- Pagano L, Dragonetti G, Cattaneo C, et al. SEIFEM group (Sorveglianza Epidemiologica Infezioni Fungine in Ematologia). Changes in the incidence of candidemia and related mortality in patients with hematologic malignancies in the last ten years. A SEIFEM 2015-B report. Haematologica. 2017; 102(10): e407–e410.
- Bays DJ, Thompson GR. Fungal infections of the stem cell transplant recipient and hematologic malignancy patients. Infect Dis Clin North Am. 2019; 33(2): 545–566.
- Krawiec K, Czemerska M, Stelmach P, et al. Assessment of colonization and infection epidemiology in patients undergoing autologous hematopoietic stem cell transplantation: a single-center study. Acta Haematologica Polonica. 2022; 53(2): 133–140.
- Hierlmeier S, Eyrich M, Wölfl M, et al. Early and late complications following hematopoietic stem cell transplantation in pediatric patients - A retrospective analysis over 11 years. PLoS One. 2018; 13(10): e0204914.
- Pagano L, Caira M, Nosari A, et al. Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 study--Sorveglianza Epidemiologica Infezioni Fungine Nelle Emopatie Maligne. Clin Infect Dis. 2007; 45(9): 1161–1170.
- van Esser JW, van der Holt B, Meijer E, et al. Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation (SCT) and quantitatively predicts EBV-lymphoproliferative disease following T-cell--depleted SCT. Blood. 2001; 98(4): 972–978.
- Walker CM, van Burik JAH, De For TE, et al. Cytomegalovirus infection after allogeneic transplantation: comparison of cord blood with peripheral blood and marrow graft sources. Biol Blood Marrow Transplant. 2007; 13(9): 1106–1115.
- Zielonka K, Jasiński M, Jamroziak K. Influence of gut microbiota on efficacy and adverse effects of treatment of lymphoproliferative disorders. Acta Haematol Pol. 2022; 53(6): 363–375.
- Fałkowska A, Jakubas A, Surdacka L, et al. Safe use of fecal microbiota transplant in treatment of graft versus host disease in a 5-year-old child. Acta Haematol Pol. 2023; 54(4): 266–268.
