The findings of a recent randomized controlled trial (ORACLE Study) affirmed the safety and effectiveness of direct oral challenge (DOC) in alleviating low-risk penicillin allergy cases in intensive care units. This study by Morgon Rose and other investigators sought to determine the effectiveness, feasibility, and safety of DOC for low-risk penicillin allergy cases in critical care settings. 

In this open-label, pilot study, adults suffering from documented penicillin allergy were identified. Patients deemed low-risk (PEN-FAST score <3) were randomly allocated in a 1:1 ratio to either receive a single dose of Penicillin (250 mg Amoxicillin or the implicated Penicillin) via DOC or undergo routine care (with a 2-hour observation period for both groups). Those in the intervention group underwent a repeat oral challenge post-discharge (with a minimum 48-hour interval from the initial challenge).

The enrolled subjects were assessed at 24 hours and 5 days post each challenge, with follow-ups at 90 days. Out of 575 patients screened, 80 (14%) were recruited, with a median age of 65 years and a median PEN-FAST score of 1. The median APACHE2 score was 11. Among those enrolled, 50% were randomized to undergo DOC. Only one positive challenge out of 40 (2.5%) was observed, characterized by a mild rash treated with oral antihistamine. No severe adverse events related to antibiotics were reported.

Eighty percent (32/40) of participants who underwent the initial challenge proceeded to the repeat challenge, none of which yielded positive results. The notably low ratio of screened-to-enrolled patients raises concerns about current feasibility and underscores the necessity for broader eligibility criteria and the integration of allergy assessment into routine intensive care unit protocols to facilitate wider delabelling efforts in critical care contexts.