Optimizing empiric antibiotic therapy in patients with severe β-lactam allergy

Antimicrob Agents Chemother. 2013 Dec;57(12):5918-23. doi: 10.1128/AAC.01202-13. Epub 2013 Sep 16.


Antibiotic selection is challenging in patients with severe β-lactam allergy due to declining reliability of alternate antibiotics. Organisms isolated from these patients may exhibit unique resistance phenotypes. The objective of this study was to determine which alternate antibiotics or combinations provide adequate empirical therapy for patients with β-lactam allergy who develop Gram-negative infections at our institution. We further sought to determine the effects of risk factors for drug resistance on empirical adequacy. A retrospective analysis was conducted for adult patients hospitalized from September 2009 to May 2010 who had a severe β-lactam allergy and a urine, blood, or respiratory culture positive for a Gram-negative organism and who met predefined criteria for infection. Patient characteristics, culture and susceptibility data, and predefined risk factors for antibiotic resistance were collected. Adequacies of β-lactam and alternate antibiotics were compared for all infections and selected subsets. The primary outcome was adequacy of each alternate antibiotic or combination for all infections. One hundred sixteen infections (40 pneumonias, 67 urinary tract infections, and 9 bacteremias) were identified. Single alternate agents were adequate less frequently than β-lactams and combination regimens. Only in cases without risk factors for resistance did single-agent regimens demonstrate acceptable adequacy rates; each factor conferred a doubling of risk for resistance. Resistance risk factors should be considered in selecting empirical antibiotics for Gram-negative pathogens in patients unable to take β-lactams due to severe allergy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / therapeutic use*
  • Bacteremia / drug therapy*
  • Bacteremia / immunology
  • Bacteremia / microbiology
  • Drug Hypersensitivity / drug therapy*
  • Drug Hypersensitivity / etiology
  • Drug Hypersensitivity / immunology
  • Drug Hypersensitivity / microbiology
  • Drug Resistance, Multiple, Bacterial
  • Drug Therapy, Combination
  • Empirical Research
  • Female
  • Fluoroquinolones / therapeutic use
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / growth & development
  • Gram-Negative Bacterial Infections / drug therapy*
  • Gram-Negative Bacterial Infections / immunology
  • Gram-Negative Bacterial Infections / microbiology
  • Humans
  • Middle Aged
  • Pneumonia, Bacterial / drug therapy*
  • Pneumonia, Bacterial / immunology
  • Pneumonia, Bacterial / microbiology
  • Retrospective Studies
  • Risk
  • Tetracycline / therapeutic use
  • Urinary Tract Infections / drug therapy*
  • Urinary Tract Infections / immunology
  • Urinary Tract Infections / microbiology
  • beta-Lactams / adverse effects


  • Anti-Bacterial Agents
  • Fluoroquinolones
  • beta-Lactams
  • Tetracycline