Adverse reactions associated with oral and parenteral use of cephalosporins: A retrospective population-based analysis

J Allergy Clin Immunol. 2015 Mar;135(3):745-52.e5. doi: 10.1016/j.jaci.2014.07.062. Epub 2014 Sep 26.


Background: Few studies have provided population-based, route-specific data on allergy to cephalosporin or incidence of serious adverse drug reactions (ADRs).

Objective: We investigated the incidence of new reports of cephalosporin-associated "allergy" and serious ADRs.

Methods: We identified all members of the Kaiser Permanente Southern California health plan given cephalosporins (from January 1, 2010, through December 31, 2012), all new reports of cephalosporin-associated allergy, and all serious ADRs.

Results: There were 622,456 health plan members exposed to 901,908 courses of oral cephalosporins and 326,867 members exposed to 487,630 courses of parenteral cephalosporins over the 3-year study period. New reports of allergy to cephalosporin were more frequent among women (0.56%; 95% CI, 0.54% to 0.57%) than among men (0.43%; 95% CI, 0.41% to 0.44%) per course (P < .0001). The most frequent serious cephalosporin-associated ADRs were Clostridium difficile infection within 90 days (0.91%), nephropathy within 30 days (0.15%), and all-cause death within 1 day (0.10%). None correlated with history of drug allergy. Physician-documented cephalosporin-associated anaphylaxis occurred with 5 oral exposures (95% CI, 1/1,428,571-1/96,154) and 8 parenteral exposures (95% CI, 1/200,000-1/35,971) (P = .0761). There were 3 documented cephalosporin-associated serious cutaneous adverse reactions (95% CI, 0-1 in 217,291). All were associated with the use of another antibiotic at the same time as cephalosporin.

Conclusions: Cephalosporins are widely and safely used, even in individuals with a history of penicillin allergy. Physician-documented cephalosporin-associated anaphylaxis and serious cutaneous adverse reactions are rare compared with C difficile infection within 90 days, nephropathy within 30 days, and all-cause death within 1 day.

Keywords: Adverse drug reaction; Clostridium difficile; Stevens-Johnson syndrome; allergy; cephalosporin; death; hemolytic anemia; hospitalized; nephropathy; oral; outpatient; parenteral; serious cutaneous adverse reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Anti-Bacterial Agents / adverse effects*
  • California
  • Cephalosporins / adverse effects*
  • Clostridioides difficile / physiology
  • Drug Hypersensitivity / etiology*
  • Drug Hypersensitivity / immunology
  • Drug Hypersensitivity / physiopathology
  • Enterocolitis, Pseudomembranous / chemically induced*
  • Enterocolitis, Pseudomembranous / microbiology
  • Enterocolitis, Pseudomembranous / physiopathology
  • Female
  • Humans
  • Infusions, Parenteral
  • Male
  • Middle Aged
  • Nephritis / chemically induced*
  • Nephritis / physiopathology
  • Retrospective Studies
  • State Health Plans


  • Anti-Bacterial Agents
  • Cephalosporins