title: Variation in Risk of Hospital-Onset Clostridium difficile Infection Across β-Lactam Antibiotics in Children With New-Onset Acute Lymphoblastic Leukemia.
abstract: BACKGROUND
  Antibiotic exposure is common among children with leukemia. However, limited data exist regarding the risk of Clostridium difficile infection (CDI) across anti-pseudomonal β-lactam antibiotics commonly used for fever and neutropenia.
  
  
  METHODS
  A multicenter cohort of children with newly diagnosed acute lymphoblastic leukemia (ALL) was established from 43 freestanding children's hospitals from 1999 to 2009. Patients were followed until their index CDI event, defined by the CDI ICD-9 code plus a C difficile test charge, or until 180 days from ALL diagnosis. Cox proportional hazards models were performed to identify the hazards of CDI after exposure to anti-pseudomonal β-lactams, adjusting for demographics, other antibiotic exposures, severity of illness, antacids, gastrointestinal manipulation, and confounding by hospital.
  
  
  RESULTS
  A cohort of 8268 ALL patients was assembled; median age was 5.5 years (interquartile range, 3.26-10.58). Two-hundred sixty-eight (3.2%) patients developed CDI within 180 days of ALL diagnosis. Each 1-day increase in exposure to an anti-pseudomonal β-lactam within the prior 30 days was associated with a significantly increased risk for CDI (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01, 1.09). Ceftazidime (HR, 1.05; 95% CI, 1.02, 1.08) and cefepime (HR, 1.07; 95% CI, 1.02, 1.12) were each independently associated with CDI.
  
  
  CONCLUSIONS
  Efforts to reduce total exposure to anti-pseudomonal β-lactam agents may help to reduce the risk of CDI in children with newly diagnosed ALL. Cefepime and ceftazidime were independently associated with CDI, whereas anti-pseudomonal penicillins and carbapenems were not. These findings, if confirmed, have potential implications for antibiotic choice during periods of fever and neutropenia.
authors.affiliation: Division of Infectious Diseases Center for Pediatric Clinical Effectiveness, The Children's Hospital of Philadelphia, Pennsylvania Department of Pediatrics, and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Fisher
authors.affiliation: Division of Infectious Diseases Department of Infection Prevention and Control Center for Pediatric Clinical Effectiveness, The Children's Hospital of Philadelphia, Pennsylvania Department of Pediatrics, and.
authors.forename: Julia Shaklee
authors.initials: JS
authors.lastname: Sammons
authors.affiliation: Division of Oncology, and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors.forename: Yimei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Pediatric Hematology and Oncology, Rainbow Babies & Children's Hospital Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Peter
authors.initials: P
authors.lastname: de Blank
authors.affiliation: Division of Oncology, and Department of Pediatrics, and.
authors.forename: Alix E
authors.initials: AE
authors.lastname: Seif
authors.affiliation: Department of Pediatrics, and.
authors.forename: Yuan-Shung
authors.initials: YS
authors.lastname: Huang
authors.affiliation: Division of Oncology, and.
authors.forename: Marko
authors.initials: M
authors.lastname: Kavcic
authors.affiliation: Division of Infectious Diseases.
authors.forename: Sarah
authors.initials: S
authors.lastname: Klieger
authors.affiliation: Division of Oncology, and.
authors.forename: Tracey
authors.initials: T
authors.lastname: Harris
authors.affiliation: Division of Oncology, and.
authors.forename: Kari
authors.initials: K
authors.lastname: Torp
authors.affiliation: Division of Oncology, and.
authors.forename: Douglas
authors.initials: D
authors.lastname: Rheam
authors.affiliation: Division of Oncology, and.
authors.forename: Ami
authors.initials: A
authors.lastname: Shah
authors.affiliation: Division of Oncology, and Center for Pediatric Clinical Effectiveness, The Children's Hospital of Philadelphia, Pennsylvania Department of Pediatrics, and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors.forename: Richard
authors.initials: R
authors.lastname: Aplenc
keywords: Clostridium difficile; leukemia; pediatrics.