title: A Multicenter Study of Bacterial Blood Stream Infections in Pediatric Allogeneic Hematopoietic Cell Transplantation Recipients: The Role of Acute Gastrointestinal Graft-versus-Host Disease.
abstract: Blood stream infections (BSI) caused by enteric organisms are associated with a particularly high mortality rate in allogeneic hematopoietic cell transplantation (alloHCT) recipients. We conducted a retrospective multicenter study aiming to analyze the risk factors associated with antibiotic resistance and impact of BSI on transplantation-related mortality (TRM) in children after alloHCT. During the study period from 2004 to 2014, 395 children (mean age, 9.4 years) with at least 1 BSI were included. The incidences of resistant gram-negative rods were 20.7% to piperacillin-tazobactam, 10.9% to cefepime, 21% to ceftazidime, 11.4% to levofloxacin, and 8.16% to meropenem. Thirty-eight percent of Enterococcus spp. isolates were resistant to vancomycin. More than 1 episode of BSI was associated with significant increase in the risk of resistance to piperacillin-tazobactam, cefepime, and vancomycin. On multivariate analysis of risk factors for TRM, achievement of neutrophil engraftment by day 30 was associated with lower TRM (P = .002). However, infection with an antibiotic-resistant organism was not associated with TRM. Development of enteric bacterial BSI after the onset of acute gastrointestinal graft-versus-host disease (GVHD) was the strongest predictor of TRM (hazard ratio, 4.786; 95% confidence interval, 2.833 to 8.087; P < .001). In patients with acute gastrointestinal GVHD who subsequently developed enteric bacterial BSI, the incidence of 1-year TRM was 33.4% (SE = 7%), compared with 15.3% (SE = 2%) for those without acute gastrointestinal GVHD (P = .004). Primary prevention of a first episode of BSI is arguably the most important intervention to decrease antibiotic resistance. It is also imperative that we develop strategies to maintain gastrointestinal health, especially in patients with gastrointestinal GVHD, in an effort to prevent subsequent enteric bacterial BSI and improve survival.
authors.affiliation: Department of Pediatrics, Columbia University, New York, New York. Electronic address: ps2087@columbia.edu.
authors.forename: Prakash
authors.initials: P
authors.lastname: Satwani
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Freedman
authors.affiliation: Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
authors.forename: Sonali
authors.initials: S
authors.lastname: Chaudhury
authors.affiliation: Department of Pediatrics, Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Zhezhen
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Pediatrics, Columbia University, New York, New York.
authors.forename: Anya
authors.initials: A
authors.lastname: Levinson
authors.affiliation: Department of Pediatrics, Columbia University, New York, New York.
authors.forename: Marc D
authors.initials: MD
authors.lastname: Foca
authors.affiliation: Department of Pediatrics, Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Krajewski
authors.affiliation: Department of Pediatrics, The Steven and Alexandra Cohen Children's Medical Center of New York, New Hyde Park, New York.
authors.forename: Indira
authors.initials: I
authors.lastname: Sahdev
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Mala Kiran
authors.initials: MK
authors.lastname: Talekar
authors.affiliation: Department of Pediatrics, Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Aliza
authors.initials: A
authors.lastname: Gardenswartz
authors.affiliation: Department of Pediatrics, Columbia University, New York, New York.
authors.forename: Justin
authors.initials: J
authors.lastname: Silverman
authors.affiliation: Department of Pharmacy, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
authors.forename: Meghan
authors.initials: M
authors.lastname: Hayes
authors.affiliation: Department of Pediatrics, UCSF Benioff Children's Hospital, San Francisco, California.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Dvorak
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D016470:Bacteremia / Q000209:etiology* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D004352:Drug Resistance, Microbial; D005260:Female; D005767:Gastrointestinal Diseases / Q000209:etiology / Q000382:microbiology*; D000069196:Gastrointestinal Microbiome; D006086:Graft vs Host Disease / Q000382:microbiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality*; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D014184:Transplantation, Homologous
keywords: Antibiotic resistance; Bone marrow transplantation; Children; Transplantation-related mortality