Enterococcal Bacteremia in Children With Malignancies and Following Hematopoietic Stem Cell Transplantation: A 15-Year Single-Center Experience.
Adolescent
Ampicillin
/ therapeutic use
Anti-Bacterial Agents
/ therapeutic use
Bacteremia
/ drug therapy
Child
Child, Preschool
Cross Infection
/ drug therapy
Drug Resistance, Multiple, Bacterial
Enterococcus
/ drug effects
Gram-Positive Bacterial Infections
/ complications
Hematologic Neoplasms
/ complications
Hematopoietic Stem Cell Transplantation
/ adverse effects
Humans
Immunocompromised Host
Infant
Infant, Newborn
Retrospective Studies
Tertiary Care Centers
/ statistics & numerical data
Time Factors
Vancomycin
/ therapeutic use
Vancomycin-Resistant Enterococci
/ drug effects
Journal
The Pediatric infectious disease journal
ISSN: 1532-0987
Titre abrégé: Pediatr Infect Dis J
Pays: United States
ID NLM: 8701858
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
pubmed:
29
1
2020
medline:
10
2
2021
entrez:
29
1
2020
Statut:
ppublish
Résumé
Data on enterococcal bacteremia (EB) in immunocompromised children are scarce. We aimed to describe EB in children with hematologic malignancies (HM), solid tumors and/or following allogeneic hematopoietic stem cell transplantation (HSCT) and analyze their ampicillin and vancomycin resistance. We conducted an observational retrospective study in the tertiary-care Hadassah University Medical Center (2001-2015). We collected demographic, clinical and laboratory data on EB and compared ampicillin and vancomycin sensitive with resistant episodes. Fifty-six of 1123 children developed 74 episodes of EB; 62.1% Enterococcus faecium, 36.5% Enterococcus faecalis; and 1.4% Enterococcus gallinarum. EB developed in 12.1% of HSCT patients, 5.1% of HM, 6.3% of neuroblastoma and 1.0% of other solid tumors patients. Of these episodes, 85.1% were nosocomial, and 71.6% developed while on antibiotic therapy. Resistance rates were: to ampicillin, 57.6%; to vancomycin (vancomycin-resistant enterococci), 21.6%; and higher rates among E. faecium. Among vancomycin-resistant enterococci, 1 of 16 was linezolid and 2 of 10 daptomycin resistant. Overall 7- and 30-day mortality rates were 2.7% and 5.4%, respectively. Thirty-day mortality was 18.2% in recurrent episodes and 0% in the first-time EB episodes (P = 0.006). In multivariate analysis, high treatment intensity was associated with ampicillin resistance [odds ratio (OR) = 3.18, 95% confidence interval (CI): 1.31-9.12], prior penicillin exposure (OR = 7.50, 95% CI: 1.41-39.81) and breakthrough on vancomycin (OR = 18.83, 95% CI: 3.31-101.14) with vancomycin resistance. EB occurs mainly as a nosocomial infection in children receiving high-intensity chemotherapy, especially in those with neuroblastoma, HM and following HSCT. Antibiotic resistance is common. Vancomycin resistance can occur regardless of previous vancomycin use. Prognosis in immunocompromised children with EB is better than previously reported. Recurrent EB is associated with increased mortality.
Sections du résumé
BACKGROUND
Data on enterococcal bacteremia (EB) in immunocompromised children are scarce. We aimed to describe EB in children with hematologic malignancies (HM), solid tumors and/or following allogeneic hematopoietic stem cell transplantation (HSCT) and analyze their ampicillin and vancomycin resistance.
METHODS
We conducted an observational retrospective study in the tertiary-care Hadassah University Medical Center (2001-2015). We collected demographic, clinical and laboratory data on EB and compared ampicillin and vancomycin sensitive with resistant episodes.
RESULTS
Fifty-six of 1123 children developed 74 episodes of EB; 62.1% Enterococcus faecium, 36.5% Enterococcus faecalis; and 1.4% Enterococcus gallinarum. EB developed in 12.1% of HSCT patients, 5.1% of HM, 6.3% of neuroblastoma and 1.0% of other solid tumors patients. Of these episodes, 85.1% were nosocomial, and 71.6% developed while on antibiotic therapy. Resistance rates were: to ampicillin, 57.6%; to vancomycin (vancomycin-resistant enterococci), 21.6%; and higher rates among E. faecium. Among vancomycin-resistant enterococci, 1 of 16 was linezolid and 2 of 10 daptomycin resistant. Overall 7- and 30-day mortality rates were 2.7% and 5.4%, respectively. Thirty-day mortality was 18.2% in recurrent episodes and 0% in the first-time EB episodes (P = 0.006). In multivariate analysis, high treatment intensity was associated with ampicillin resistance [odds ratio (OR) = 3.18, 95% confidence interval (CI): 1.31-9.12], prior penicillin exposure (OR = 7.50, 95% CI: 1.41-39.81) and breakthrough on vancomycin (OR = 18.83, 95% CI: 3.31-101.14) with vancomycin resistance.
CONCLUSIONS
EB occurs mainly as a nosocomial infection in children receiving high-intensity chemotherapy, especially in those with neuroblastoma, HM and following HSCT. Antibiotic resistance is common. Vancomycin resistance can occur regardless of previous vancomycin use. Prognosis in immunocompromised children with EB is better than previously reported. Recurrent EB is associated with increased mortality.
Identifiants
pubmed: 31990889
doi: 10.1097/INF.0000000000002579
pii: 00006454-202004000-00013
doi:
Substances chimiques
Anti-Bacterial Agents
0
Vancomycin
6Q205EH1VU
Ampicillin
7C782967RD
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
318-324Références
Mikulska M, Viscoli C, Orasch C, et al.; Fourth European Conference on Infections in Leukemia Group (ECIL-4), a joint venture of EBMT, EORTC, ICHS, ELN and ESGICH/ESCMID. Aetiology and resistance in bacteraemias among adult and paediatric haematology and cancer patients. J Infect. 2014;68:321–331.
Satlin MJ, Soave R, Racanelli AC, et al. The emergence of vancomycin-resistant enterococcal bacteremia in hematopoietic stem cell transplant recipients. Leuk Lymphoma. 2014;55:2858–2865.
Gudiol C, Ayats J, Camoez M, et al. Increase in bloodstream infection due to vancomycin-susceptible Enterococcus faecium in cancer patients: risk factors, molecular epidemiology and outcomes. PLoS One. 2013;8:e74734.
DiazGranados CA, Zimmer SM, Klein M, et al. Comparison of mortality associated with vancomycin-resistant and vancomycin-susceptible enterococcal bloodstream infections: a meta-analysis. Clin Infect Dis. 2005;41:327–333.
Vydra J, Shanley RM, George I, et al. Enterococcal bacteremia is associated with increased risk of mortality in recipients of allogeneic hematopoietic stem cell transplantation. Clin Infect Dis. 2012;55:764–770.
Tsiatis AC, Manes B, Calder C, et al. Incidence and clinical complications of vancomycin-resistant enterococcus in pediatric stem cell transplant patients. Bone Marrow Transplant. 2004;33:937–941.
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:e56–e93.
Avery R, Kalaycio M, Pohlman B, et al. Early vancomycin-resistant enterococcus (VRE) bacteremia after allogeneic bone marrow transplantation is associated with a rapidly deteriorating clinical course. Bone Marrow Transplant. 2005;35:497–499.
Liss BJ, Vehreschild JJ, Cornely OA, et al. Intestinal colonisation and blood stream infections due to vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) in patients with haematological and oncological malignancies. Infection. 2012;40:613–619.
Mikulska M, Del Bono V, Raiola AM, et al. Enterococcal bloodstream infection after hematopoietic stem cell transplant: experience of a center with a low prevalence of vancomycin-resistant enterococci. Clin Infect Dis. 2012;55:1744.
Papanicolaou GA, Ustun C, Young JH, et al. Bloodstream infection (BSI) due to Vancomycin-Resistant Enterococcus (VRE) is associated with increased mortality after hematopoietic cell transplantation for acute leukemia and myelodysplastic syndrome: a multicenter, retrospective cohort study. Clin Infect Dis. 2019;69:1771–1779.
Webb BJ, Healy R, Majers J, et al. Prediction of bloodstream infection due to vancomycin-resistant Enterococcus in patients undergoing leukemia induction or hematopoietic stem-cell transplantation. Clin Infect Dis. 2017;64:1753–1759.
Baran J Jr, Riederer KM, Ramanathan J, et al. Recurrent vancomycin-resistant Enterococcus bacteremia: prevalence, predisposing factors, and strain relatedness. Clin Infect Dis. 2001;32:1381–1383.
Werba BE, Hobbie W, Kazak AE, et al. Classifying the intensity of pediatric cancer treatment protocols: the intensity of treatment rating scale 2.0 (ITR-2). Pediatr Blood Cancer. 2007;48:673–677.
Firth D. Bias reduction of maximum likelihood estimates. Biometrika. 1993;80:27–38.
Heinze G, Schemper M. A solution to the problem of separation in logistic regression. Stat Med. 2002;21:2409–2419.
Mikulska M, Del Bono V, Prinapori R, et al. Risk factors for enterococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients. Transpl Infect Dis. 2010;12:505–512.
Dubberke ER, Hollands JM, Georgantopoulos P, et al. Vancomycin-resistant enterococcal bloodstream infections on a hematopoietic stem cell transplant unit: are the sick getting sicker? Bone Marrow Transplant. 2006;38:813–819.
Zajac-Spychala O, Wachowiak J, Szmydki-Baran A, et al. Infectious complications in children treated for Hodgkin and non-Hodgkin lymphomas in polish pediatric leukemia/lymphoma study group: incidence, epidemiology and etiology. Leuk Lymphoma. 2019;60:124–132.
Satwani P, Freedman JL, Chaudhury S, et al. A Multicenter study of bacterial blood stream infections in pediatric allogeneic hematopoietic cell transplantation recipients: the role of acute gastrointestinal graft-versus-host disease. Biol Blood Marrow Transplant. 2017;23:642–647.
Cho SY, Lee DG, Choi SM, et al. Impact of vancomycin resistance on mortality in neutropenic patients with enterococcal bloodstream infection: a retrospective study. BMC Infect Dis. 2013;13:504.
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;15:47–53.
Tamma PD, Hsu AJ. Optimizing therapy for vancomycin-resistant enterococcal bacteremia in children. Curr Opin Infect Dis. 2014;27:517–527.
Fossati M, Cappelli B, Biral E, et al. Fatal vancomycin- and linezolid-resistant Enterococcus faecium sepsis in a child undergoing allogeneic haematopoietic stem cell transplantation for beta-thalassaemia major. J Med Microbiol. 2010;59(Pt 7):839–842.
Verma N, Clarke RW, Bolton-Maggs PH, et al. Gut overgrowth of vancomycin-resistant enterococci (VRE) results in linezolid-resistant mutation in a child with severe congenital neutropenia: a case report. J Pediatr Hematol Oncol. 2007;29:557–560.
Tavadze M, Rybicki L, Mossad S, et al. Risk factors for vancomycin-resistant enterococcus bacteremia and its influence on survival after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2014;49:1310–1316.
Worth LJ, Thursky KA, Seymour JF, et al. Vancomycin-resistant Enterococcus faecium infection in patients with hematologic malignancy: patients with acute myeloid leukemia are at high-risk. Eur J Haematol. 2007;79:226–233.
Kamboj M, Chung D, Seo SK, et al. The changing epidemiology of vancomycin-resistant Enterococcus (VRE) bacteremia in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Biol Blood Marrow Transplant. 2010;16:1576–1581.
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;98:1826–1835.
Al-Mulla NA, Taj-Aldeen SJ, El Shafie S, et al. Bacterial bloodstream infections and antimicrobial susceptibility pattern in pediatric hematology/oncology patients after anticancer chemotherapy. Infect Drug Resist. 2014;7:289–299.
Castagnola E, Conte M, Parodi S, et al. Incidence of bacteremias and invasive mycoses in children with high risk neuroblastoma. Pediatr Blood Cancer. 2007;49:672–677.
Averbuch D, Avaky C, Harit M, et al. Non-fermentative Gram-negative rods bacteremia in children with cancer: a 14-year single-center experience. Infection. 2017;45:327–334.
Zirakzadeh A, Gastineau DA, Mandrekar JN, et al. Vancomycin-resistant enterococcal colonization appears associated with increased mortality among allogeneic hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 2008;41:385–392.