title: Peripheral blood eosinophilia and hypersensitivity reactions among patients receiving outpatient parenteral antibiotics.
abstract: BACKGROUND
  Although drug-induced peripheral eosinophilia complicates antimicrobial therapy, little is known about its frequency and implications.
  
  
  OBJECTIVE
  We aimed to determine the frequency and predictors of antibiotic-induced eosinophilia and subsequent hypersensitivity reactions (HSRs).
  
  
  METHODS
  We evaluated a prospective cohort of former inpatients receiving intravenous antibiotic therapy as outpatients with at least 1 differential blood count. We used multivariate Cox proportional hazards models with time-varying antibiotic treatment indicators to assess the effect of demographic data and antibiotic exposures on eosinophilia and subsequent HSRs, including documented rash, renal injury, and liver injury. Possible drug rash with eosinophilia and systemic symptoms (DRESS) syndrome cases were identified and manually validated.
  
  
  RESULTS
  Of 824 patients (60% male; median age, 60 years; median therapy duration, 41 days), 210 (25%) had eosinophilia, with median peak absolute eosinophil counts of 726/mL (interquartile range, 594-990/mL). Use of vancomycin, penicillin, rifampin, and linezolid was associated with a higher hazard of having eosinophilia. There was a subsequent HSR in 64 (30%) of 210 patients with eosinophilia, including rash (n = 32), renal injury (n = 31), and liver injury (n = 13). Patients with eosinophilia were significantly more likely to have rash (hazard ratio [HR], 4.16; 95% CI, 2.54-6.83; P < .0001) and renal injury (HR, 2.13; 95% CI, 1.36-3.33; P = .0009) but not liver injury (HR, 1.75; 95% CI, 0.92-3.33; P = .09). Possible DRESS syndrome occurred in 7 (0.8%) of 824 patients; 4 (57%) were receiving vancomycin.
  
  
  CONCLUSIONS
  Drug-induced eosinophilia is common with parenteral antibiotics. Although most patients with eosinophilia do not have an HSR, eosinophilia increases the hazard rate of having rash and renal injury. DRESS syndrome was more common than previously described.
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, Mass; Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, Mass; Harvard Medical School, Boston, Mass. Electronic address: kblumenthal1@partners.org.
authors.forename: Kimberly G
authors.initials: KG
authors.lastname: Blumenthal
authors.affiliation: Harvard Medical School, Boston, Mass; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Mass; Division of Infectious Diseases, Department of Pediatrics, Boston Children's Hospital, Boston, Mass.
authors.forename: Ilan
authors.initials: I
authors.lastname: Youngster
authors.affiliation: Biostatistics Center, Massachusetts General Hospital, Boston, Mass.
authors.forename: Dustin J
authors.initials: DJ
authors.lastname: Rabideau
authors.affiliation: Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, Mass; Harvard Medical School, Boston, Mass; Biostatistics Center, Massachusetts General Hospital, Boston, Mass; Division of General Medicine, Department of Medicine, Massachusetts General Hospital, Boston, Mass.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Parker
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Mass.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Manning
authors.affiliation: Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, Mass; Harvard Medical School, Boston, Mass; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Mass; Division of General Medicine, Department of Medicine, Massachusetts General Hospital, Boston, Mass.
authors.forename: Rochelle P
authors.initials: RP
authors.lastname: Walensky
authors.affiliation: Harvard Medical School, Boston, Mass; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Mass.
authors.forename: Sandra B
authors.initials: SB
authors.lastname: Nelson
mesh_terms: D000485:Allergens / Q000276:immunology; D000553:Ambulatory Care; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001775:Blood Circulation; D015331:Cohort Studies; D063926:Drug Hypersensitivity Syndrome / Q000453:epidemiology* / Q000209:etiology; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies
chemical_list: D000485:Allergens; D000900:Anti-Bacterial Agents
keywords: Allergy; antibiotic; drug; drug rash with eosinophilia and systemic symptoms syndrome; eosinophilia; hypersensitivity; metronidazole; outpatient parenteral antimicrobial therapy; vancomycin