Background: A documented penicillin allergy is associated with increased length of hospital stay and an increased incidence of Clostridium difficile, methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterocci. These findings are attributed to use of broader-spectrum ‘second-line’ antibiotics.  No clinical intervention has been shown to affect the above clinical outcomes to date. Hospitalization is an opportunity to affirm or deny a penicillin allergy however allergy testing may be affected by clinical factors related to hospitalization. The aim of this systematic review was to identify whether inpatient penicillin allergy testing affected clinical outcomes during hospitalization and following discharge.

Methods: We performed an electronic search of Ovid Medline/PubMed, Embase, Web of Science, Scopus and the Cochrane Library. We identified studies over the past 20 years in which subjects with a documented penicillin allergy were admitted for treatment of infection where a penicillin antibiotic was considered a ‘first-line’ antibiotic per Infectious Disease Society of America Guidelines. Any intervention to verify true penicillin allergy was performed during index admission. Studies in pediatric and surgical patients were excluded.

Results: Eight studies met eligibility criteria. Study sample size was between 44 and 183 patients (total of 783 patients). Seven were cohort studies while 1 was a case-control study. Penicillin skin testing with or without oral amoxicillin challenge was the main intervention in 7 studies. 1 study implemented a clinical guideline with ‘decision-tree’ for penicillin allergy testing versus administration of a test dose. The proportion of negative penicillin skin tests ranged between 88.1 to 100% (median 94.5%; 7 studies). Inpatient penicillin allergy testing led to a change in antibiotic selection (range 57-95%; 4 studies). An increased prescription of penicillin (range 9.9-49%) and cephalosporin (range 10.7-48%) antibiotics was reported. Vancomycin and quinolone use was decreased in all studies reporting antibiotic utilization as a clinical outcome. Inpatient penicillin allergy testing was associated with decreased healthcare cost (2 studies). No statistically significant difference in adverse drug reactions following testing was identified in any study.

Conclusions: Inpatient penicillin allergy testing is safe and effective at ruling out penicillin allergy. The rate of negative tests is comparable to outpatient and perioperative data. This suggests that all patients with a documented penicillin allergy who require penicillin should be tested during hospitalization. Further longitudinal studies should address the effect of inpatient penicillin allergy testing in relation to clinical outcomes including length of hospital stay, hospital-acquired infection, cost following index admission and 30-day readmission rate.