Direct Oral Penicillin Challenge Effective Among Those with Penicillin Allergies

Direct oral penicillin challenge (DOC) is effective for the removal of a penicillin allergy label, new findings suggest, and this delabeling may continue through to 6 months among most individuals.¹

The research letter detailing this analysis was authored in part by Ana Maria Copaescu, MD, from the Research Institute of the McGill University Health Centre in Quebec, Canada. Copaescu et al. noted that formal testing typically confirms less than 5% of penicillin allergies, though a negative test result can be followed by a failure to remove one’s penicillin allergy label or a mistaken label reinstatement.

“Few studies focus on the long-term follow-up and risk factors associated with the persistence or reinstatement of self-reported penicillin allergy (SRPA) following a successful oral challenge with penicillin and allergy label removal,” Copaescu and colleagues noted.

To address the lack of research in this specific area noted by the research team, the team explored long-term follow up and risks linked to allergy persistence in this secondary analysis of a previous study.

Background and Design

The investigators' secondary analysis looked at the results of the Penicillin Allergy Clinical Decision Rule (PALACE) study.² It represented the first international, randomized, multicenter clinical study to suggest that direct oral penicillin challenge may be as efficacious as the typical method of penicillin skin testing followed by an oral challenge.

Specifically, their analysis looked at adult subjects with a low-risk penicillin allergy, with a Penicillin Allergy Decision Rule (PEN-FAST) score of < 3. The team’s protocol for the study was given approval from an institutional review board at Austin Health.

The research team followed the CONSORT reporting guidelines. In the period 6 six months following their subjects’ randomization, they implemented a scripted telephone questionnaire that was given to participants for the purposes of assessing suspected recurrent penicillin allergy, the occurrence of adverse events (AEs), and other related elements.

In the investigators’ statistical analysis, they used univariable and multivariable logistic regression. They had a significance threshold of P < .05.

Findings

There were 377 individuals who were delabeled during the investigators’ first phase, with 93.1% reported to have completed the follow up interactions occurring during the 6-months afterward. The remaining subjects were noted by the research team as inaccessible through telephone communication.

It was found that 6.6% of the subjects who finished out the follow-up had experiences of suspected recurrent penicillin allergy. The team added that this occurred among 13 of the 178 featured in the study’s intervention cohort, and 10 of the 173 featured in the control cohort. They also concluded that 9.7% indicated that they did not take penicillin by the 6-month mark.

Among the 23 individuals noting suspected recurrent penicillin allergy, it was found by the research team that about 47.8% reported an AE within the initial study period lasting 5 days. The team also reported that 30.4% reported new occurrences of AEs, and that 21.7% noted suspected recurrent allergies without an AE accompanying the discovery.

Eleven of the 13 AEs linked to new penicillin-based therapies, following the first 5-day period, were noted as immune-mediated.

The existence of suspected recurrent allergies by the 6-month follow-up period was reported by the investigators to be strongly linked to immune-mediated AEs. These had been recorded after the initial study period (odds ratio, 35.44; 95% CI, 9.40-133.60; P < .001).

The research team found no baseline characteristics were linked to suspected recurrent penicillin allergies. 73.9% of the 23 aforementioned subjects with such allergies had taken an antibiotic within half a year of being delabeled. Additionally, 64.7% of these individuals had implemented penicillin-class antibiotics.

In contrast, the investigators reported that 37.5% of those without suspected recurrent allergies had been prescribed an antibiotic. They added that 53.6% of these were noted as penicillin-based.

“There are some limitations to this study,” they added. “A medical record review was not performed to directly document the allergy labels. Furthermore, despite successful delabeling and the absence of AEs, some patients were still reluctant to take penicillin.”

References

1. ^{Copaescu AM, Vogrin S, Douglas A, et al. Risk of Self-Reported Penicillin Allergy Despite Removal of Penicillin Allergy Label: Secondary Analysis of the PALACE Randomized Clinical Trial . JAMA Netw Open. 2024;7(8):e2429621. doi:10.1001/jamanetworkopen.2024.29621.}
2. ^{Copaescu AM, Vogrin S, James F, et al. Efficacy of a clinical decision rule to enable direct oral challenge in patients with low-risk penicillin allergy: the PALACE randomized clinical trial. JAMA Intern Med. 2023;183(9):944-952. doi:10.1001/jamainternmed.2023.2986.}