Consequences of avoiding β-lactams in patients with β-lactam allergies

J Allergy Clin Immunol. 2016 Apr;137(4):1148-1153. doi: 10.1016/j.jaci.2015.10.026. Epub 2015 Dec 11.


Background: The choice of empiric antibiotics for the treatment of gram-negative bacilli (GNB) bloodstream infections (BSIs) in patients presenting with a β-lactam (BL) allergy is often a difficult decision given that these agents are first-line treatment in many guidelines.

Objective: We sought to compare rates of clinical failure between patients with a history of BL allergy who received either a BL or a non-β-lactam (NBL).

Methods: Adult patients with a past medical history of BL allergy and receipt of antibiotics for treatment of a GNB BSI were included from 3 academic medical centers. Treatment groups were classified as BL or NBL groups based on the empiric antibiotics received. Clinical failure was assessed 72 to 96 hours after initiation of empiric antibiotics. Hypersensitivity reactions during receipt of antibiotic therapy for the index BSI were recorded.

Results: A total of 552 patients were included for analysis: 433 patients in the BL group and 119 patients in the NBL group. Clinical failure was higher in the NBL group compared with the BL group (38.7% vs 27.4%, P = .030). The most common cause of clinical failure was a temperature of greater than 38.0°C 72 to 96 hours after receipt of empiric antibiotics (NBL group: 22.7% vs BL group: 13.9%, P = .016). Hypersensitivity occurred in 16 (2.9%) of 552 patients. Thirteen (2.5%) of 552 patients experiencing hypersensitivity reactions were exposed to a BL during treatment for GNB BSI.

Conclusion: Among patients with a BL allergy, use of BL antibiotics is associated with a lower rate of clinical failure. The low rate of hypersensitivity provides further evidence about the risk of cross-reactivity between BL classes. These results support the practice of using a BL from an alternative class for patients in need of gram-negative antibiotic coverage.

Keywords: bloodstream infection; empiric antibiotic; gram-negative; penicillin allergy; β-Lactam allergy.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Infections / drug therapy*
  • Bacterial Infections / mortality
  • Drug Hypersensitivity / etiology
  • Drug Hypersensitivity / mortality
  • Drug Hypersensitivity / prevention & control*
  • Female
  • Hospital Mortality
  • Humans
  • Length of Stay / statistics & numerical data
  • Logistic Models
  • Male
  • Middle Aged
  • Retrospective Studies
  • Severity of Illness Index
  • Treatment Failure
  • Young Adult
  • beta-Lactams / adverse effects*
  • beta-Lactams / therapeutic use


  • Anti-Bacterial Agents
  • beta-Lactams