None listed
Conditions
Brief summary
Antibiotics are often implicated as the cause of drug allergy and many patients admitted to hospital will have a self-reported antibiotic allergy documented in their medical record during admission, and subsequently, the section of their inpatient medication chart specific to allergies and adverse drug reactions. This process has become known as ‘labelling’ and the patient is said to have an antibiotic allergy label. Documentation of allergy should protect the patient by alerting providers to avoid prescribing a drug that will result in a serious or life threatening reaction, however studies have shown that up to 90% of patients who report an allergy to penicillin, the most commonly reported antibiotic allergy, can tolerate the drug. This mistaken attribution of allergy by way of labelling has been shown to be harmful for patients directly, by limiting the selection of antibiotics for any given infection; and indirectly by increasing costs associated with alternative antibiotic choices; and increased hospital admissions. Clinicians have now recognised that a health strategy to verify or remove an antibiotic allergy label has an important role to play in increasing patient safety and reducing antibiotic resistance. The SPECIAL (Adult) study is supported by the WA Health Department. This study will allocate inpatients who report an antibiotic allergy, to either receive allergy assessment and an antibiotic challenge or an allergy assessment and usual medical care (control group). The allocation will be random so that participants have an equal chance of being in the intervention group or the control group. The intervention will be a medically supervised ‘drug challenge’. Participants will be given small doses of antibiotic in stages and their reactions will be monitored. Some participants will have skin testing first. Participants will be told the outcome of the challenge and whether they can safely take the antibiotic or that they are genuinely allergic and must completely avoid it. Documentation supporting this outcome will be provided to the participant and their GP. There will be one year of scheduled follow-up for all participants every three months by phone or email during which time participants will be asked about their health, specifically infections, and use of medical services, for example, GP visits and hospitalisations. At the end of one year participants in the control group will be offered an appointment in the allergy clinic to receive the antibiotic allergy provocation testing in line with the participants in the intervention group who received their challenge at the beginning of the study.
Interventions
Based on their allergy history, patients (N=768) will be randomised to receive a drug challenge (oral or IV) +/- skin testing (ARM 1), OR receive usual standard of in-patient care (control group, ARM 2). After discharge, both groups will be followed up for one year to record use of antibiotics, clinical events and the need for medical care. At the end of this period, patients who had been randomised to the control group will be offered the drug provocation testing following specialist assessment
Based on their allergy history, patients (N=768) will be randomised to receive a drug challenge (oral or IV) +/- skin testing (ARM 1), OR receive usual standard of in-patient care (control group, ARM 2). After discharge, both groups will be followed up for one year to record use of antibiotics, clinical events and the need for medical care. At the end of this period, patients who had been randomised to the control group will be offered the drug provocation testing following specialist assessment. The antibiotic allergy testing will be either an oral or intravenous challenge, with or without skin testing to be carried out in the hospital (inpatient) setting, under specialist guidance, where emergency equipment and medications are accessible and potential anaphylaxis can be treated. Management algorithms and the need for determination of a pre-test probability of IgE-mediated antibiotic allergy will be assessed against the clinical history of the patient. Skin testing will be carried out once in patients with a history that is suggestive of an IgE-mediated skin reaction (estimated to be approximately 40% of patients recruited). Skin Testing (Skin prick test and intradermal): The skin testing procedure for each participant will be carried out by a trained and qualified nurse. The Australasian Society of Clinical Immunology and Allergy (ASCIA) Manual for skin prick testing for the diagnosis of allergic disease: A manual for practitioners (March, 2016) describes the standard methodology for skin prick testing, and these recommendations will be followed. Departmental guidelines for routine clinical intradermal testing will be followed. Generally the most convenient and frequently used sites for skin testing are either the volar surface of the forearm, the outer upper arm or the back. The antibiotic challenge for people with a beta-lactam allergy label and history suggestive of an IgE mediated reaction, will involve the skin prick test followed by an intradermal skin test against the minor and major determinant of penicillins, benzylpenicillin, amoxicillin, ampicillin and the culprit antibiotic if different, followed by a two-dose oral antibiotic challenge. We will challenge with the culprit antibiotic, if it is known, and for patients with an unspecified penicillin allergy we will use amoxicillin. For the assessment of other antibiotic types (sulphonamides, macrolides or quinolones) no skin testing will be performed as it is less validated for these antibiotics, and 2-stage oral challenges will be performed instead. The hospital pharmacy (ies) will provide the solutions for skin testing. On the designated testing day, the study nurse will carry out the skin testing and/or oral provocation or IV challenge according to the medication orders from the study doctor whcih will be documented on the patient’s PBS Hospital Medication Chart. If an IV challenge is proposed the study doctor will cannulate the patient and administer the intravenous doses. In cases of unspecified ‘penicillin’ or ‘beta-lactam’ allergy, participants will be assessed with an amoxicillin challenge (a commonly used penicillin-antibiotic in the community). Oral challenges will be performed in 2-stages (10% followed by the rest of the dose); IV challenges will be performed as 3-dose challenges (1%, 10%, followed by the rest of the dose). The study nurse will record observations for 20-30 minutes following the challenge, thereafter ward nurses will be responsible for recording patient observations for a further two hours after administration of the last dose of the challenge. Drug reactions will be managed following hospital protocols for managing anaphylaxis. Post-discharge the patient will be contacted by the study nurse who will assess whether there is any delayed reaction or sequelae to the drug provocation. Thereafter, participants from both arms, will be followed up for one year by a clinical member of the research team who will ask them a series of questions concerning their clinical history since the last data collection. Questions will include: use of antibiotics, infections (including microbiological findings), GP and other primary care provider visits, readmission rates after discharge, presentation to ED, referrals and attendance at the Immunology/Allergy clinic.
Sponsors
Sir Charles Gairdner Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients (male or female), 16 years and above, presenting as medical or surgical inpatients with a self-reported allergy to beta lactam and/or sulphonamide antibiotics. Clinical examination will determine whether the patient with a disease state, for example a chronic medical condition, is well enough to undergo allergy testing. Any acute condition that necessitated admission will be resolved before allergy testing. Self-reported Antibiotic Allergy Label (AAL) Allergy to any beta-lactam, or allergy to any beta lactam and/or an allergy to one of the following: sulphonamide, macrolide or quinolone antibiotic Reported reaction to an intravenous or oral antibiotic Age >16 years
Exclusion criteria
Participants unable to give written informed consent A history of severe cutaneous adverse reactions Type II-IV reactions according to the ASCIA Criteria: Serum sickness, Stevens-Johnson Syndrome (SJS), Toxic epidermal necrolysis (TEN), Acute interstitial nephritis (AIN), Drug rash eosinophilia syndrome (DRESS), Acute Generalised Exanthematous Pustulosis (AGEP), haemolytic anaemia, Drug-induced liver injury (DILI). Participants with clinically established intolerances or allergy to an antibiotic. Females who are pregnant Antihistamine intake within 2 days prior to the scheduled challenge (including medications whose primary use is not as antihistamine but which are known to interact with histamine receptors). Daily antihistamine intake required for management of chronic disease, e.g. chronic idiopathic urticaria. Immunosuppressive treatment at the time of testing Patients on beta-blocker medication A relevant medical contraindication to testing
Outcome results
None listed