By Richard R. Watkins, MD, MS, FACP, FIDSA

Associate Professor of Internal Medicine, Northeast Ohio Medical University; Division of Infectious Diseases, Cleveland Clinic Akron General Medical Center, Akron, OH

Dr. Watkins reports that he has received research support from Actavis.

SYNOPSIS: A prospective cohort study from three hospitals determined that patients who did not receive a preferred beta-lactam antibiotic were at greater risk for an adverse event (adjusted odds ratio, 3.1; 95% confidence interval, 1.28-7.89) compared to controls without a beta-lactam allergy.

SOURCE: MacFadden DR, LaDelfa A, Leen J, et al. Impact of reported beta-lactam allergy on inpatient outcomes: A multicenter prospective cohort study. Clin Infect Dis 2016;63:904-910.

Many hospitalized patients report a beta-lactam allergy or have one documented in their medical record. This piece of history is important because it frequently prevents the use of a very safe and effective class of antibiotics. Indeed, beta-lactams are the “work horses” of contemporary antibiotic therapy. MacFadden and colleagues investigated the association between beta-lactam allergy labeling and outcomes in hospitalized patients.

The setting for the study was three hospitals in Toronto, Canada, and the population included all inpatients seen by the infectious disease (ID) consultation service between April 2014 and January 2015 on the days that the ID subspecialty residents were present. As part of a quality-improvement project, the investigators prospectively assessed beta-lactam allergy by collecting data on the type of previous allergic reaction such as IgE-mediated, bronchospasm, rash, anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrosis (TEN), drug rash eosinophilia and systemic symptoms (DRESS), angioedema, serum sickness, and “other.” Also, they collected patient demographic data (age, sex, pregnancy, and immunocompromised status), referring service, duration of antibiotic therapy, Charlson comorbidity index, and information on antibiotic therapy, including the preferred antibiotic and what antibiotic was chosen initially. Outcome data were recorded later in a second data collection step. The primary outcome measured was the occurrence of any treatment-related adverse event, defined as acute kidney injury while on antibiotics, Clostridium difficile infection (CDI) within three months of treatment, suspected drug-related adverse event that required discontinuation, or readmission due to the same infection.

Of the 507 patients who received antibiotic therapy during the study period, 95 (19%) reported a beta-lactam allergy. In the group that reported a beta-lactam allergy and a beta-lactam was considered optimal therapy, 47 (65%) received a beta-lactam, while 25 (35%) received a non-beta-lactam drug. There was an increased likelihood of an adverse event for the patients who did not receive preferred beta-lactam therapy (adjusted odds ratio [OR], 3.18; 95% confidence interval [CI], 1.28-7.89). The adverse events were mostly due to increased rates of readmission and adverse drug reactions, although there were no significant differences in mortality between the beta-lactam-allergic and non-allergic patients. Moreover, there were no significant differences in outcomes between those patients who reported a beta-lactam allergy yet were given a beta-lactam, compared to patients who did not report a beta-lactam allergy. Further analysis to adjust for possible confounding due to a diagnosis of bacteremia from an unknown primary source did not result in any significant changes to the findings.


This study is noteworthy because it showed that patients with a reported beta-lactam allergy who did not receive preferred beta-lactam therapy had three times the chance of an adverse event compared to those without a reported allergy. According to the Centers for Disease Control and Prevention, 10% of the population reports a penicillin allergy, but < 1% of the whole population is truly allergic.1 Furthermore, approximately 80% of patients with IgE-mediated penicillin allergy lose their sensitivity after 10 years. The findings reported by MacFadden and colleagues support the notion that beta-lactam antibiotics might be appropriate in select patients who report beta-lactam allergies, such as those with non-severe allergy histories. Also, increasing beta-lactam usage in these patients may lead to more cures and fewer adverse events.

One way to objectively assess for beta-lactam allergy is by skin testing. A recent study in which ID fellows at the University of Maryland Medical Center performed penicillin skin testing (PST) showed that 96% of patients tested negative, leading to changes in antibiotic therapy in 84% of cases.2 As these investigators mentioned, PST can help antibiotic stewardship efforts, reduce antibiotic costs (e.g., less aztreonam use), lead to better clinical outcomes (e.g., using ampicillin instead of vancomycin for enterococcal endocarditis), and is a potential revenue source for ID practices. The study by MacFadden and colleagues, therefore, adds to the growing body of evidence that PST can be used to potentially improve patient outcomes.

There were a few limitations that may have affected the study results. To generate sufficient power, a composite endpoint was used, making it challenging to analyze for individual outcomes. Also, the small sample size may have influenced the incidence of CDI. This is because no increased risk was reported for the beta-lactam-allergic patients, despite receiving alternative antibiotics that are associated with a higher risk for developing CDI, such as clindamycin and fluoroquinolones. Despite these limitations, MacFadden and colleagues have provided robust data about the clinical consequences of reported beta-lactam allergies. Thus, when treating a patient with a beta-lactam allergy for whom a beta-lactam antibiotic would be the best option, clinicians should take a detailed history of the allergy and pursue PST if available.


  1. Centers for Disease Control and Prevention. Is It Really a Penicillin Allergy? Available at: Accessed Oct. 17, 2016.
  2. Heil EL, Bork JT, Schmalzle SA, et al. Implementation of an infectious disease fellow-managed penicillin allergy skin testing service. Open Forum Infect Dis 2016;3:ofw155. [First published online July 22, 2016.]