Department of Medicine

Penicillin Allergy: A Comorbidity Worth Exploring

Mar 6, 2019
Dr. Christine Song

Dr. Christine SongDr. Christine Song Although penicillin allergies are reported in 5-15% of the population, over 90% of individuals tested for penicillin allergy are found not to be allergic (1,2). Because true penicillin allergies can be life-threatening, healthcare providers must still use alternative antimicrobials in patients reporting penicillin allergies. Avoidance of β-lactam antibiotics, however, is not without its own risks. Recent data has emerged showing that a penicillin allergy label is associated with higher rates of methicillin-sensitive staphylococcus aureus (MSSA), Clostridium difficile, vancomycin-resistant enterococcus (VRE), increased healthcare utilization, and longer hospital stays (2-4). In one study assessing patients admitted to hospital with haematologic malignancies, a β-lactam allergy label was even associated with increased mortality (4). Certain infections, such as MSSA bacteremia, are associated with higher mortality when treated with a non-β-lactam antibiotic compared with treatment with a β-lactam 5.

The reported “penicillin allergy” is now considered a comorbidity worth investigating. Taking a detailed history and performing penicillin skin testing, when appropriate, is important in assessing individuals reporting a penicillin allergy. Because certain hypersensitivity reactions to medications are life-threatening, patients need to first be screened for contraindications to skin testing and future drug provocation challenges. Studies are currently underway in assessing the impact of large-scale penicillin allergy testing programs.


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  2. Macy E, Contreras R. Health care use and serious infection prevalence associated with penicillin "allergy" in hospitalized patients: A cohort study. J Allergy Clin Immunol. 2014;133(3):790-796.
  3. Blumenthal KG, Lu N, Zhang Y, Li Y, Walensky RP, Choi HK. Risk of methicillin resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy: population based matched cohort study. BMJ. 2018;361:k2400.
  4. Huang KG, Cluzet V, Hamilton K, Fadugba O. The Impact of Reported Beta-Lactam Allergy in Hospitalized Patients With Hematologic Malignancies Requiring Antibiotics. Clin Infect Dis. 2018;67(1):27-33.
  5. McDanel JS, Perencevich EN, Diekema DJ, et al. Comparative effectiveness of beta-lactams versus vancomycin for treatment of methicillin-susceptible Staphylococcus aureus bloodstream infections among 122 hospitals. Clin Infect Dis. 2015;61(3):361-367.