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1.
Discrepancies in the management of Clostridioides difficile infections in patients after allogeneic haematopoietic cell transplantation: the results of the Infectious Diseases Working Party EBMT survey
Piekarska, A., Gil, L., Mikulska, M., Mensah-Glanowska, P., Sbianchi, G., Wendel, L., Knelange, N., Averbuch, D., de la Camara, R., Styczynski, J.
Bone marrow transplantation. 2022
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2.
8th European Conference on Infections in Leukaemia: 2020 guidelines for the use of antibiotics in paediatric patients with cancer or post-haematopoietic cell transplantation
Lehrnbecher, T., Averbuch, D., Castagnola, E., Cesaro, S., Ammann, R. A., Garcia-Vidal, C., Kanerva, J., Lanternier, F., Mesini, A., Mikulska, M., et al
The Lancet. Oncology. 2021;22(6):e270-e280
Abstract
Paediatric patients with cancer and those undergoing haematopoietic cell transplantation are at high risk of bacterial infections. The 8th European Conference on Infections in Leukaemia (ECIL-8) convened a Paediatric Group to review the literature and to formulate recommendations for the use of antibiotics according to the European Society of Clinical Microbiology and Infectious Diseases grading system. The evaluation of antibacterial prophylaxis included mortality, bloodstream infection, febrile neutropenia, emergence of resistance, and adverse effects as endpoints. Initial antibacterial therapy and antibiotic de-escalation or discontinuation focused on patients with a clinically stable condition and without previous infection or colonisation by resistant bacteria, and on patients with a clinically unstable condition or with previous infection or colonisation by resistant bacteria. The final considerations and recommendations of the ECIL-8 Paediatric Group on antibacterial prophylaxis, initial therapy, and de-escalation strategies are summarised in this Policy Review.
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3.
Legionellosis after hematopoietic stem cell transplantation
Mikulska, M., Tridello, G., Hoek, J., Gil, L., Yañez, L., Labussière-Wallet, H., Passweg, J., Xhaard, A., Pioltelli, P., Caillot, D., et al
Bone marrow transplantation. 2021
Abstract
Limited data are available on legionellosis after hematopoietic stem cell transplant (HSCT). The aim of this study was to report the cases of legionellosis and to identify predictors of legionellosis, legionellosis-associated death, and non-relapse mortality (NRM). All cases of post-HSCT legionellosis from the EBMT registry were included and matched with controls in a 3:1 ratio for the analyses of risk factors. In the years 1995-2016, 80 cases from 52 centers in 14 countries were identified (mainly from France, Italy, and Spain). Median time from HSCT to legionellosis was 203 days (range, 0-4099); 19 (23.8%) patients developed early legionellosis (within-day +30 post-HSCT). Patients were mainly male (70%), after allogeneic HSCT (70%), with acute leukemia (27.5%), lymphoma (23.8%), or multiple myeloma (21.3%), and the median age of 46.6 (range, 7.2-68.2). Predictors of legionellosis were allogeneic HSCT (OR?=?2.27, 95%CI:1.08-4.80, p?=?0.03) and recent other infection (OR?=?2.96, 95%CI:1.34-6.52, p?=?0.007). Twenty-seven (33.8%) patients died due to legionellosis (44% after early legionellosis), NRM was 50%. Predictors of NRM were female sex (HR?=?2.19, 95%CI:1.13-4.23, p?=?0.02), early legionellosis (HR?=?2.24, 95%CI:1.13-4.46, p?=?0.02), and south-eastern geographical region (HR?=?2.16, 95%CI:1.05-4.44, p?=?0.036). In conclusion, legionellosis is a rare complication after HSCT, mainly allogeneic, occurring frequently within 30 days after HSCT and associated with high mortality.
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4.
Intercontinental study on pre-engraftment and post-engraftment Gram-negative rods bacteremia in hematopoietic stem cell transplantation patients: Risk factors and association with mortality
Averbuch, D., Tridello, G., Hoek, J., Mikulska, M., Pabst, T., Segundo, L. Y. S., Akan, H., Özçelik, T., Donnini, I., Klyasova, G., et al
The Journal of infection. 2020
Abstract
OBJECTIVES We present here data on Gram-negative rods bacteremia (GNRB) rates, risk factors and associated mortality. METHODS Data on GNRB episodes were prospectively collected in 65 allo-/67 auto-HSCT centers in 24 countries (Europe, Asia, Australia). In patients with and without GNRB, we compared: demography, underlying disease, HSCT-related data, center` fluoroquinolone prophylaxis (FQP) policy and accreditation status, and involvement of infection control team (ICT). RESULTS The GNRB cumulative incidence among 2818 allo-HSCT was: pre-engraftment (pre-eng-allo-HSCT), 8.4 (95% CI 7-9%), post-engraftment (post-eng-allo-HSCT), 5.8% (95%CI: 5-7%); among 3152 auto-HSCT, pre-eng-auto-HSCT, 6.6% (95%CI: 6-7%), post-eng-auto-HSCT, 0.7% (95%CI: 0.4-1.1%). GNRB, especially MDR, was associated with increased mortality. Multivariate analysis revealed the following GNRB risk factors: (a) pre-eng-allo-HSCT: south-eastern Europe center location, underlying diseases not at complete remission, and cord blood source; (b) post-eng-allo-HSCT: center location not in northwestern Europe; underlying non-malignant disease, not providing FQP and never accredited. (c) pre-eng-auto-HSCT: older age, autoimmune and malignant (vs. plasma cell) disease, and ICT absence. CONCLUSIONS Benefit of FQP should be explored in prospective studies. Increased GNRB risk in auto-HSCT patients transplanted for autoimmune diseases is worrying. Infection control and being accredited are possibly protective against bacteremia. GNRB are associated with increased mortality.
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5.
Multidrug-resistant bacterial infections in children undergoing hematopoietic stem cell transplantation over a 6-year period: analysis of the of Polish Pediatric Group for Hematopoietic Stem Cell Transplantation
Zajac-Spychala, O., Wachowiak, J., Fraczkiewicz, J., Salamonowicz, M., Kalwak, K., Gorczynska, E., Chybicka, A., Czyzewski, K., Dziedzic, M., Wysocki, M., et al
Journal of applied microbiology. 2019
Abstract
AIMS: Multidrug-resistant (MDR) bacteria are an emerging cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The aim of the study was to analyze the incidence, clinical characteristics and survival from bacterial infections caused by MDR pathogens in pediatric HSCT recipients. METHODS AND RESULTS Between 2012 and 2017, among 971 transplanted patients, bacterial infections were found in 416 children. Overall, there were 883 bacterial episodes, including 85.8% after allo-HSCT and 14.2% after auto-HSCT. MDR strains were responsible for half of the total number of bacterial episodes. Over 50% of MDR pathogens were Enterobacteriaceae causing mainly gut infections or urinary tract infections. CONCLUSIONS Regarding HSCT type, we did not find differences in the profile of MDR bacterial infections between allo- and auto-HSCT recipients. However, survival in MDR and non-MDR infections was comparable. SIGNIFICANCE AND IMPACT OF STUDY The large sample size enables unique analysis and makes our data more applicable to other pediatric HSCT centers. In case of the absence of local epidemiological data, presented clinical characteristic of MDR-caused infections may be used to optimize the prophylactic strategies, early identification of infectious complications of MDR etiology, and thus promptly initiate adequate antibiotic therapy and further improve patients' outcome.
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6.
Incidence, course, and outcome of Clostridium difficile infection in children with hematological malignancies or undergoing hematopoietic stem cell transplantation
Salamonowicz, M., Ociepa, T., Fraczkiewicz, J., Szmydki-Baran, A., Matysiak, M., Czyzewski, K., Wysocki, M., Galazka, P., Zalas-Wiecek, P., Irga-Jaworska, N., et al
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 2018
Abstract
Clostridium difficile infection (CDI) is one of the most common causes of nosocomial infectious diarrhea in children during anticancer therapy or undergoing hematopoietic stem cell transplantation (HSCT) in Europe. Immunosuppression in these patients is a risk factor for CDI. Malignant diseases, age, acute graft-versus-host disease (aGVHD), HLA mismatch, or use of total body irradiation may play an important role in CDI course. The aim of this study was to evaluate the incidence, course, and outcome of CDI in children treated for malignancy or undergoing HSCT. Between 2012 and 2015, a total number of 1846 patients were treated for malignancy in Polish pediatric oncological centers (PHO group) and 342 underwent transplantation (HSCT group). In PHO group, episodes of CDI occurred in 210 patients (14%). The incidence of CDI was higher in patients with hematological malignancies in comparison to that with solid tumors. Patients with acute myeloblastic leukemia had shorter time to episode of CDI than those with acute lymphoblastic leukemia. Patients over 5 years and treated for acute leukemia had more severe clinical course of disease in PHO group. In HSCT group, CDI occurred in 29 (8%) patients. The incidence of CDI was higher in patients transplanted for acute leukemia. The recurrence rate was 14.7% in PHO and 20.7% in HSCT patients. CDI incidence was highest in patients with hematological malignancies. Most of patients experienced mild CDI. Age < 5 years and diagnosis other than acute leukemia were the positive prognostic factors influencing clinical CDI course.
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7.
Antimicrobial resistance in Gram-negative rods causing bacteremia in hematopoietic stem cell transplant patients: intercontinental prospective study of Infectious Diseases Working Party of the European Bone Marrow Transplantation group
Averbuch, D., Tridello, G., Hoek, J., Mikulska, M., Akan, H., Yanez San Segundo, L., Pabst, T., Ozcelik, T., Klyasova, G., Donnini, I., et al
Clinical Infectious Diseases. 2017
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Abstract
Background: This intercontinental study aimed to study Gram-negative rods (GNR) resistance in hematopoietic stem cell transplantation (HSCT). Methods: GNR bacteremias occurring during six months post-HSCT (February/2014-May/2015) were prospectively collected, and analysed for rates and risk factors for resistance to fluoroquinolones, non-carbapenem anti-Pseudomonas beta-lactams (non-carbapenems), carbapenems and multidrug-resistance (MDR). Results: Sixty-five HSCT centers from 25 countries (Europe, Australia, Asia) reported data on 655 GNR episodes/704 pathogens in 591 patients (Enterobacteriaceae, 73%; non-fermentatives, 24% and 3% others). Half GNR were fluoroquinolone- and non-carbapenems-resistant; 18.5% carbapenem-resistant; 35.2% MDR. The total resistance rates were higher in allo-HSCT vs. auto-HSCT patients (p<0.001); but similar in community-acquired infections. Non-carbapenems-resistance and MDR were higher in auto-HSCT patients in centers providing vs. non-providing fluoroquinolone prophylaxis (p<0.01). Resistance rates were higher in southeast vs. north-west Europe; similar in children and adults; excluding higher fluoroquinolone- and beta-lactam beta-lactamase inhibitors-resistance rates in allo-HSCT adults. Non-Klebsiella Enterobacteriaceae were rarely carbapenem-resistant. Multivariable analysis revealed resistance risk factors in allo-HSCT patients: fluoroquinolone-resistance: adult, prolonged neutropenia, breakthrough on fluoroquinolones; non-carbapenems-resistance: hospital-acquired infection, breakthrough on non-carbapenems or other antibiotics (excluding fluoroquinolones, non-carbapenems, carbapenems), donor type; carbapenem-resistance: breakthrough on carbapenem, longer hospitalization, intensive care unit, previous other antibiotic therapy; MDR: longer hospitalization, breakthrough on beta-lactam beta-lactamase inhibitors and carbapenems. Inappropriate empirical therapy and mortality were significantly more common in infections caused by resistant bacteria. Conclusion: Our data question the recommendation for fluoroquinolone prophylaxis and call for reassessment of local empirical antibiotic protocols. Knowledge of pathogen-specific resistances enable early appropriate empirical therapy. Monitoring of resistance is crucial.
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Bacterial infections in pediatric hematopoietic stem cell transplantation recipients: incidence, epidemiology, and spectrum of pathogens: report of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation
Zajac-Spychala, O., Wachowiak, J., Pieczonka, A., Siewiera, K., Fraczkiewicz, J., Kalwak, K., Gorczynska, E., Chybicka, A., Czyzewski, K., Jachna-Sawicka, K., et al
Transplant Infectious Disease. 2016;18(5):690-698
Abstract
BACKGROUND Infectious complications are a significant cause of hematopoietic stem cell transplantation (HSCT) failure, especially allogeneic HSCT (allo-HSCT) because of delayed immune reconstitution and graft-versus-host disease (GVHD) occurrence. Identifying the factors responsible for bacterial infections (BI) in patients undergoing HSCT will provide much more effective empirical antimicrobial treatment in this group of patients. OBJECTIVE The aim of this study was to evaluate the epidemiology and profile of BI in patients after HSCT in 5 centers of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation in 2012-2013. PATIENTS AND METHODS In 308 HSCT recipients, we retrospectively analyzed 273 episodes of BI in 113 (36.7%) children aged 0.02-22 years (median age: 7 years), 92 after allo-HSCT and 22 after autologous HSCT (auto-HSCT). We assessed incidence of BI in different HSCT types by calculating the Index of Bacterial Infection (IBI) as a ratio of patients with at least 1 BI to all patients who underwent this type of HSCT in the analyzed period. We assessed the profile of BI with particular emphasis on multidrug-resistant organisms, and impact of underlying disease and of graft-versus-host disease on BI episodes. RESULTS In the studied group, 273 episodes of BI were diagnosed, including 237 episodes after allo-HSCT and 36 after auto-HSCT. Among allo-HSCT recipients diagnosed with at least 1 BI, the IBI was 0.4 (matched sibling donor-HSCT 0.3; matched donor-HSCT 0.4; mismatched unrelated donor [MMUD]-HSCT 0.8; P = 0.027) and after auto-HSCT 0.3 per 1 transplanted patient. In patient after allo-HSCT because of myelo- or lymphoproliferative diseases and bone marrow failures, the major cause of infections was Enterobacteriaceae, while gram-positive bacteria predominated in the group with primary immunodeficiencies. In all patients after auto-HSCT, the dominant pathogen of BI were Enterobacteriaceae (P = 0.011). Time from each type of HSCT to infection caused by different pathogens did not differ significantly. CONCLUSIONS The risk of BI does not depend on the underlying disease, but only on HSCT donor type and is the highest after MMUD-HSCT procedure. The profile of BI depends on the underlying disease and HSCT donor type, but does not depend on the occurrence of acute GVHD. Gram-negative bacteria predominated in patients with myelo- and lymphoproliferative diseases, while in patients with primary immunodeficiencies gram-positive strains were predominant. Copyright © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.