title: Drug Fever: a descriptive cohort study from the French national pharmacovigilance database.
abstract: BACKGROUND
  Although known as a rare adverse drug reaction (ADR), drug fever (DF) remains an important issue in medicine, with the risk of leading to inappropriate and potentially harmful diagnostic and therapeutic interventions. Only sparse data regarding DF have been published.
  
  
  OBJECTIVE
  The aim of the study was to investigate which drugs were associated with DF, and report outcomes.
  
  
  METHODS
  Cases of DF without skin reactions were selected from all ADRs reported from 1986 to 2007 in the French National Pharmacovigilance Database. Drugs potentially responsible for DF were assessed using a qualitative case-by-case analysis (Naranjo's criteria) and quantitative measurement (proportional reporting ratio [PRR]). A drug was implicated as the cause of DF when the following criteria were validated: three or more cases and PRR of at least two with a Chi-squared value of at least four.
  
  
  RESULTS
  A total of 167 DF cases involving 115 drugs were eligible. Based on the PRR, 22 drugs were significantly associated with DF. Antibacterials represented the most frequently reported drugs, including amikacin (PRR 39.6 [95% CI 23.6, 69.0], oxacillin (9.1 [3.6, 23.4]), cefotaxime (5.5 [2.0, 15.3]), ceftriaxone (5.4 [2.6, 11.3]), rifampicin (4.0 [1.8, 9.2]), vancomycin (4.0 [1.4, 11.5]), ciprofloxacin (3.1 [1.2, 8.0]), isoniazid (3.9 [1.4, 11.4]), pristinamycin (3.1 [1.0, 9.1]) and cotrimoxazole (2.6 [1.2, 5.8]). Median time [interquartile range] from drug administration to fever onset was 2 days [1.0-10.5]. A diagnosis of DF was made following cessation of the suspected drugs (3 days [1.0-11.5] after fever onset. Drug rechallenge was performed (38.0%), resulting in recurrence of DF in all cases. DF resulted in life-threatening events (0.6%), hospitalization or prolonged hospital stay (24.5%) and persistent disability (0.6%). Final outcome was favourable in 96.9% of cases after drug discontinuation.
  
  
  CONCLUSIONS
  Diagnosing DF is challenging. Based on this large series, antibacterials remain the major class of drugs responsible for DF.
authors: Department of Internal Medicine, AP-HP, Ambroise Par Hospital, Boulogne-Billancourt, France.
authors: Dominique
authors: D
authors: Vodovar
authors: Christine
authors: C
authors: LeBeller
authors: Bruno
authors: B
authors: Mégarbane
authors: Agnes
authors: A
authors: Lillo-Le-Louet
authors: Thomas
authors: T
authors: Hanslik
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D015331:Cohort Studies; D016208:Databases, Factual; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005334:Fever / Q000139:chemically induced*; D005602:France; D006801:Humans; D008297:Male; D008875:Middle Aged; D060735:Pharmacovigilance; D055815:Young Adult