Safety and Efficacy of an Oral Penicillin Challenge in Low Risk Hospitalized Patients

Study Overview
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Brief Summary
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Penicillin allergy is the most common drug allergy reported by patients. Approximately 10% of the population and 20% of inpatients carry a label of penicillin allergy. However, less than 5%-10% of them have a confirmed allergy following comprehensive investigations. Reported penicillin allergy leads to higher medical costs and excess complications and presents a major challenge to antimicrobial stewardship. There is a high demand for allergy services however penicillin allergy testing (including skin testing and oral drug challenge) is not routinely available for inpatients even in major centres. Direct oral amoxicillin challenges are safe and effective in delabeling low risk patients who report penicillin allergy in large paediatric and adult studies and does not necessitate specialist referral. The study team seeks to determine the safety and efficacy of a single-dose oral penicillin challenge pilot program in adult in-patients with self-reported penicillin allergy admitted to hospital under the internal medicine Clinical Teaching Unit (CTU). The study investigators will determine the number of patients successfully delabelled of their penicillin allergy prior to discharge from hospital over a 12 month period. The study doctors will also assess the economic impact of the investigator's model and ease of implementation in the busy inpatient setting. In the future this model could be implemented generally as an inpatient or outpatient penicillin allergy program where low risk patients, who do not require referral to an allergist, are expeditiously delabelled.

Detailed Description
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Penicillin allergy is the most common drug allergy reported by patients. Approximately 10% of the population and 20% of inpatients carry a label of penicillin allergy. However, only <5%-10% of them have a confirmed allergy following comprehensive investigations. Reported penicillin allergy leads to higher medical costs and excess complications and presents a major challenge to antimicrobial stewardship. There is a high demand for allergy services however penicillin allergy testing (including skin testing and oral drug challenge) is not routinely available for inpatients even in major centres. Consequently, patients with a penicillin allergy label receive alternative antibiotics such as carbapenems, fluoroquinolones, and vancomycin for the treatment of common and serious infections and for pre-surgical prophylaxis. Patients with penicillin allergy label have longer hospital stays and higher rates of infections with Clostridioides (Clostridium) difficile, VRE and MRSA in comparison with patients without a documented allergy. Direct oral amoxicillin challenges are safe and effective in delabeling patients stratified as low risk for penicillin allergy in large pediatric and adult studies. Low-risk penicillin allergy histories include patients who have had isolated nonallergic symptoms (eg, gastrointestinal symptoms) or patients solely with a family history of a penicillin allergy, pruritus without rash, or remote (>10 years) unknown reactions without features suggestive of an IgE-mediated reaction. The study investigators seek to determine the safety and efficacy of a single-dose oral penicillin challenge pilot program in adult in-patients with self-reported penicillin allergy admitted to hospital under the internal medicine Clinical Teaching Unit (CTU). Identified patients that fulfill the exclusion and inclusion criteria will be reviewed at the time of discharge for suitability, as per the algorithm, modelled after a previous study of similar design. Based on patient's reported allergy, and upon obtaining informed consent, participants will receive a supervised challenge of amoxicillin 250 mg once orally and subsequently observed for 1 hour before discharge home. After antibiotic challenge, patient outcome will be defined as (1) tolerated oral challenge with no adverse drug reaction or (2) adverse drug reaction. By challenging carefully selected low risk patient that are unlikely to be truly allergic while in hospital, the study doctors can delabel patients of their penicillin allergy and as a result cut health care expenditures and promote good antimicrobial stewardship. In the future this model could be implemented generally as an inpatient or outpatient penicillin allergy program where low risk patients, who do not require referral to an allergist, are expeditiously delabeled.

Official Title
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Safety and Efficacy of an Oral Penicillin Challenge in Low Risk Hospitalized Patients

Conditions
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Penicillin Allergy

Intervention / Treatment
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* Drug: Amoxicillin 250 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Assessed to be low risk of having a penicillin allergy as per the risk stratification questionnaire One of the following: i) An unknown reaction >10 years before, ii) A type A adverse drug reaction (pharmacologically predictable drug side effect or intolerance), or iii) A history of a benign childhood rash, nonurticarial rash, or maculopapular exanthem more than 10 years ago Age 18 years or older Hemodynamically stable and suitable for discharge home Exclusion Criteria: Declines participation in the study Cognitive impairment and where a collateral history could not be obtained History of anaphylaxis or angioedema attributed to a penicillin-based antibiotic History of severe cutaneous adverse reactions attributed to a penicillin-based antibiotic History of acute kidney injury or severe liver impairment attributed to a penicillin-based antibiotic Currently taking an angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker or a beta blocker Hemodynamically unstable History of idiopathic urticaria or idiopathic anaphylaxis Currently taking an antibiotic(s) for treatment of an active infection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Patients reporting penicillin allergy will be enrolled based on eligibility criteria for direct oral amoxicillin challenge. There will be one treatment group of patients assigned low risk for penicillin allergy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Amoxicillin administration<br>Oral amoxicillin administered to study patients | Drug: Amoxicillin 250 MG<br>* Low dose oral amoxicillin will be administered to patients enrolled in the study meeting the inclusion and exclusion criteria.<br>* Other names: Amoxicillin 250 mg Capsule;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients tolerating oral amoxicillin challenge | The number of patients tolerating a single dose oral amoxicillin (250 mg) challenge without adverse reaction(s) up to one hour of administration | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients reporting a delayed reaction to amoxicillin | Number of patients reporting a delayed reaction to amoxicillin (between 1 hour - 12 weeks) following observation and discharge from hospital | 12 months | 
| Average delay in discharge attributable to amoxicillin challenge | Average delay in discharge (minutes) attributable to penicillin challenge, recorded by the resident or staff physician performing the questionnaire | 12 months | 
| The number of patients excluded from the study due to staff time constraints | Number of patients excluded from the study due to resident/staff time constraints | 12 months | 
| Type of immediate reaction attributed to the oral amoxicillin: maculopapular rash, urticaria, angioedema, airway compromise, diarrhea, vomiting or other (including subjective symptoms) | Nature of immediate adverse reaction if challenge unsuccessful | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypersensitivity, beta-lactam, penicillin, drug allergy