Long Term Consequences of ß-lactam Allergies

Reviewed by David Cluck, PharmD, East Tennessee State University

Bottom Line: In a study that followed patients for up to 10 years, reported beta-lactam allergy was not associated with increased all-cause mortality, but did increase risk of drug-resistant infection.

Gray and colleagues evaluated the long-term clinical outcomes associated with reported allergy to beta-lactams1 in a longitudinal retrospective cohort conducted at a regional health system in western Pennsylvania. Patients with a diagnosis of sepsis, pneumonia or UTI between 2007 and 2008 were enrolled in the study and followed until death or the end of 2018. The primary outcome was all-cause mortality according to the Social Security Death Index, since other studies have shown an association with increased mortality.2 Secondary outcomes included infection with methicillin-resistant Staphylococcus aureus (MRSA), Clostridioides difficile (CDI), vancomycin-resistant Enterococci (VRE) or acute kidney injury.

A total of 20,092 patients (most common patient included was a White female in her 60s) of whom 21% had a documented beta-lactam allergy while 79.0% did not. Using generalized estimating equations, the analysis revealed documented beta-lactam allergies were not significantly associated with the odds of mortality ([OR], 1.02; 95% CI, 0.96-1.09). Beta-lactam allergies were associated with higher odds of MRSA infection (OR, 1.44; 95% CI, 1.36-1.53), VRE infection (OR, 1.18; 95% CI, 1.05-1.32), and the pooled rate of the 3 evaluated antibiotic-resistant infections (OR, 1.33; 95% CI, 1.30-1.36) but were not associated with CDI (OR, 1.04; 95% CI, 0.94-1.16), stage 2 and 3 AKI (OR, 1.02; 95% CI, 0.96-1.10), or stage 3 AKI (OR, 1.06; 95% CI, 0.98-1.14). Over the course of follow-up, 955 patients had their allergy status change from the index encounter, this was considered as a dynamic variable in the sensitivity analysis which did show an increased risk of all-cause mortality with a reported beta-lactam allergy; however, the authors caution this is a subgroup of patients, thus clinical conclusions should not be drawn from this finding. The findings are limited by lack of ability to discern infectious etiology as cause of death and inability to stratify the severity of beta-lactam allergy. 

References:

  1. Gray MP, Kellum JA, Kirisci L, Boyce RD, Kane-Gill SL. Long-Term Outcomes Associated With β-Lactam Allergies. JAMA Netw Open. 2024;7(5):e2412313. 
  2. Blumenthal KG, Lu N, Zhang Y,Walensky RP, Choi HK. Recorded penicillin allergy and risk of mortality: a population-based matched cohort study. J Gen Intern Med. 2019;34(9):1685-1687.
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