The safety and feasibility of an oral test-dose challenge to assess low-risk penicillin allergy in critically ill hospital patients.

A 12-month study period is anticipated. The intervention is 250mg of oral amoxicillin* (capsule or liquid via enteral route, including nasogastric, with mode of enteral administration at the discretion of the treating clinician) following baseline observations being performed (i.e. temperature, heart rate, blood pressure, respiratory rate, skin check). The amoxicillin test doses will be charted by the study clinician following approval by the treating ICU clinician and admitting unit (review of baseline observations) and administered via bedside nursing staff, with dosing directly observed by bedside nursing staff. Patients in the intervention arm will have the same observations performed by the beside nursing staff at +30, +60, +90 and +120 minutes post oral provocation. If at any stage an antibiotic associated adverse event is noted the treating and study clinicians will be informed and treatment of the adverse event will be at the discretion of the treating clinician. If patients are randomised to the intervention arm they will also undergo a repeat single-dose oral amoxicillin (250mg) provocation at least 48 hours post initial provocation, if they remain an inpatient. The repeat challenge is to ensure that a false negative oral provocation secondary to critical illness did not occur with the first challenge. Patients will be reviewed post each provocation at 24 hours and 5 days, and at 90 days post randomisation [in person if inpatient or alternatively via phone if discharged] for any serious or antibiotic-associated adverse events.