Improving Clinical Outcomes in Patients With Methicillin-Sensitive Staphylococcus aureus Bacteremia and Reported Penicillin Allergy

Clin Infect Dis. 2015 Sep 1;61(5):741-9. doi: 10.1093/cid/civ394. Epub 2015 May 19.


Background: Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia is a morbid infection. First-line MSSA therapies (nafcillin, oxacillin, cefazolin) are generally avoided in the 10% of patients reporting penicillin (PCN) allergy, but most of these patients are not truly allergic. We used a decision tree with sensitivity analyses to determine the optimal evaluation and treatment for patients with MSSA bacteremia and reported PCN allergy.

Methods: Our model simulates 3 strategies: (1) no allergy evaluation, give vancomycin (Vanc); (2) allergy history-guided treatment: if history excludes anaphylactic features, give cefazolin (Hx-Cefaz); and (3) complete allergy evaluation with history-appropriate PCN skin testing: if skin test negative, give cefazolin (ST-Cefaz). Model outcomes included 12-week MSSA cure, recurrence, and death; allergic reactions including major, minor, and potentially iatrogenic; and adverse drug reactions.

Results: Vanc results in the fewest patients achieving MSSA cure and the highest rate of recurrence (67.3%/14.8% vs 83.4%/9.3% for Hx-Cefaz and 84.5%/8.9% for ST-Cefaz) as well as the greatest frequency of allergic reactions (3.0% vs 2.4% for Hx-Cefaz and 1.7% for ST-Cefaz) and highest rates of adverse drug reactions (5.2% vs 4.6% for Hx-Cefaz and 4.7% for ST-Cefaz). Even in a "best case for Vanc" scenario, Vanc yields the poorest outcomes. ST-Cefaz is preferred to Hx-Cefaz although sensitive to input variations.

Conclusions: Patients with MSSA bacteremia and a reported PCN allergy should have the allergy addressed for optimal treatment. Full allergy evaluation with skin testing seems to be preferred, although more data are needed.

Keywords: Staphylococcus aureus; allergy; decision analysis; penicillin; vancomycin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Bacterial Agents* / adverse effects
  • Anti-Bacterial Agents* / therapeutic use
  • Bacteremia / complications
  • Bacteremia / drug therapy*
  • Bacteremia / epidemiology
  • Bacteremia / microbiology
  • Decision Support Systems, Clinical
  • Drug Hypersensitivity / complications*
  • Drug Hypersensitivity / epidemiology
  • Humans
  • Methicillin-Resistant Staphylococcus aureus*
  • Models, Biological
  • Models, Statistical
  • Penicillins / adverse effects*
  • Staphylococcal Infections / complications
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / epidemiology
  • Staphylococcal Infections / microbiology
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Penicillins