A randomized clinical trial found that direct oral penicillin challenge in patients with a low-risk penicillin allergy was non-inferior to the standard-of-care skin test, investigators reported today in JAMA Internal Medicine.
For the trial, investigators in the United States, Canada, and Australia randomly assigned patients with a PEN-FAST score lower than 3 to receive either direct oral challenge with penicillin (the intervention arm) or a skin test followed by an oral challenge (the control arm). While the skin test is the standard-of-care in most countries, it is resource-intensive, and observational data support direct oral challenge, which is the necessary final step to remove the penicillin allergy label. The primary outcome of the trial was a physician-verified positive immune-mediated oral penicillin challenge within 1 hour post-intervention in the intention-to-treat population.
A total of 377 patients (median age, 51 years; 247 [65.5%] female) were included in the analysis, with 187 in the intervention group and 190 in the control group. Most patients had a PEN-FAST score of 0 or 1. The primary outcome occurred in 1 patient (0.5%) in the intervention group and 1 patient (0.5%) in the control group, with a risk difference (RD) of 0.0084 percentage points (90% confidence interval [CI], −1.22 to 1.24 percentage points). The 1-sided 95% CI was below the non-inferiority margin of 5 pp.
Compared with skin testing, a direct oral penicillin challenge is less resource and time intensive, is less expensive, and has the potential to be performed outside of the specialist allergy setting.
In the 5 days following the oral penicillin challenge, 9 immune-mediated adverse events were recorded in the intervention group and 10 in the control group (RD, −0.45 percentage points; 95% CI, −4.87 to 3.96 percentage points). No serious adverse events occurred.
Although many patients report having penicillin allergies, only 95% are truly allergic, thus making penicillin allergy testing an important component of antibiotic stewardship.
"Compared with skin testing, a direct oral penicillin challenge is less resource and time intensive, is less expensive, and has the potential to be performed outside of the specialist allergy setting, providing a scalable approach to address low-risk, unverified penicillin allergy in diverse treatment settings internationally," the study authors wrote.