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Summary for secondary care

Guideline for the Set-up of Penicillin Allergy De-labelling Services by Non-allergists Working in a Hospital Setting

This specialist Guidelines summary provides a framework for the set-up and delivery of penicillin allergy de-labelling services by non-allergists. It details appropriate patient selection, risk stratification, minimum safety standards, conduct of a drug provocation test, and the degree of oversight required from allergy or immunology specialists. The guideline is intended to supplement the 2015 British Society for Allergy & Clinical Immunology (BSACI) guideline Management of allergy to penicillin and other beta-lactams.

This summary is intended for use by non-allergists with an interest in clarifying the penicillin allergy status of their patients. The target population is adults and children with an untested label of penicillin allergy. For the complete set of recommendations, please refer to the full guideline.

Risk Stratification

  • A detailed drug allergy history, including review of prescription records where possible, will allow the clinician to stratify the risk of allergy. Patients may report symptoms and/or signs:
    • in keeping with non-immunological side effects from penicillin antibiotics and probable non-allergic phenomena (see Table 1). This group is often referred to as ‘low risk;’ however, there is wide variation within this definition and the Guideline Writing Group preferred to consider patients as either ‘suitable’ or ‘not suitable’ for direct drug provocation testing (DPT)
    • consistent with either type 1 (IgE-mediated) immediate hypersensitivity reactions or type 4 (typically T cell-mediated) delayed reactions (see Table 2). These patients are considered not suitable for direct DPT by non-allergists and require evaluation by an allergy specialist
    • entirely in keeping with side effects and other non-allergic phenomena, in whom no allergy testing is indicated (see Table 1). However, such patients may require reassurance from a test as proof of tolerance and, in this situation, a DPT could be considered.
  • There are patients in groups 1 and 2 (see above) in whom there is a clinical imperative for treatment with penicillin but a DPT is not appropriate—for example, treatment of syphilis in pregnancy. These patients must be evaluated and treated by an allergy specialist who may perform desensitisation
  • All patients labelled as ‘penicillin allergic’ attending secondary or tertiary care should be considered for penicillin allergy testing
  • Non-allergists providing de-labelling services should be networked with a specialist allergy immunology service for advice and support.

Table 1: Low-risk Symptoms in Adults and Children

  • Minor gastrointestinal symptoms (nausea, abdominal pain, diarrhoea)[A]
  • Candidiasis (thrush)[A]
  • Minor symptoms unrelated to any form of allergic reaction, for example, headache, arthralgia, strange taste in mouth[A]
  • Family history of penicillin allergy but without personal history of allergy[A]
  • Patient has taken and tolerated the same penicillin subsequent to the index reaction[A]
  • Patient reports ‘benign’[B] rash which developed more than 1 hour after the first dose of a course of penicillin
  • Patient reports a childhood rash with no other history available[C]
  • Patient cannot remember what happened during index reaction but was told it was not serious and did not require hospital treatment.
Note: Patients with symptoms listed in Table 1 but none of the exclusion criteria listed in Table 2 are suitable for direct DPT performed by a non-allergist outside an allergy clinic setting
[A] These patients do not require allergy testing in the form of either skin tests or DPT. However, some patients may continue avoiding penicillin if they do not have the reassurance of a negative allergy test. In these circumstances, a DPT should be considered.
[B] Benign defined as non-urticarial, non-itchy, non-blistering, short-lived (less than 24 hours), and did not require treatment.
[C] ‘No other history available’ assumes that such information has been sought from patients, carers, relatives, and healthcare records where possible.

Table 2: Exclusion Criteria for DPT in Adults and Children

  • Rash occurring within 1 hour of the first dose of penicillin
  • Rash lasting more than 24 hours and/or affecting more than 10% of body surface
  • Rash associated with blisters, skin peeling, mucosal inflammation (eyes, mouth, genitals), purpura
  • Patients reporting any symptoms suggestive of a type 1 immediate hypersensitivity reaction to penicillin, including swelling, urticaria, angioedema, shortness of breath, wheeze, loss of consciousness, or collapse
  • Patients who required hospital treatment due to their reaction
  • Patients who required treatment with adrenaline for their reaction
  • Patients who cannot remember what happened during the index reaction but were told it was serious and/or required medical intervention
  • Unable to give informed consent
  • Severe or uncontrolled asthma
  • Severe chronic obstructive airways disease
  • Severe aortic stenosis
  • Patients who, at the time they are being considered for DPT, are acutely unwell or clinically unstable. This includes patients with respiratory and/or cardiac compromise
  • Pregnancy
  • Previous penicillin allergy testing which concluded that the patient was allergic to penicillin.
DPT=drug provocation testing.

Conduct of DPT

  • Where a patient reports a reaction to penicillin in which only symptoms from Table 1 occurred, and none of the exclusion criteria from Table 2, a direct DPT can be performed
  • See Table 3 for the safe conduct of DPT. A single or graded DPT may be used, depending on local preference of the allergy team supporting the set-up of the de-labelling service
  • Amoxicillin is the drug of choice unless the index penicillin is known to be different, in which the index penicillin should be used. Amoxicillin is widely used in routine NHS practice for direct oral penicillin challenge (DPC) and has a more favourable side effect profile compared with other penicillins such as co-amoxiclav
  • All personnel administering a DPT should have up-to-date training in advanced life support and management of anaphylaxis, and immediate access to on-site resuscitation facilities, including provision of critical care
  • All patients identified as low risk for true penicillin allergy should be offered direct DPT, providing no exclusion criteria are met
  • Non-allergists should perform DPT in low-risk patients in a setting where allergic reactions, including anaphylaxis, can be treated.

Table 3: Principles for the Conduct of a Drug Provocation Test 

  • Written informed consent is required
  • If the index penicillin is not known, amoxicillin should be used
  • Blood pressure, heart rate, and oxygen saturations should be checked prior to commencing the DPT and after each dose given
  • Single or divided dose DPT may be used according to local preference
  • Single dose DPC 
    • Administer 100% of a full dose of amoxicillin (500 mg)
  • Graded DPC
    • Administer 10% of a full dose of amoxicillin (50 mg)
    • Observe for 30 min
    • Administer 50% of a full dose of amoxicillin (250 mg)
    • Observe for 30 min
    • Administer remainder of a full dose of amoxicillin (200 mg)
  • If an alternative penicillin is used for the DPT, follow the same percentage dosing schedules as above
  • Peak flow should be included in the observations measured, depending on local guidelines in place during the COVID-19 pandemic
  • Should symptoms consistent with anaphylaxis develop during the test, treat the patient in accordance with the Resuscitation Council Guidelines for management of anaphylaxis
  • The patient should be observed for 1 hour after the last dose (if an in-patient, ensure this observation is conducted by a member of the de-labelling team)
  • The patient should be provided with clear written instructions about what to do if symptoms develop after leaving the hospital
  • If a prolonged course is required (see Use of Prolonged DPT), this should be provided to the patient. They must be contacted at the end of the course to check for delayed reactions
  • A system should be in place to inform the GP and other relevant healthcare professionals about the result of the DPT. The patient should receive clear written information about the test result and its implications.
Note: Training for those delivering the service should be developed in collaboration with the allergy/immunology service providing support for the de-labelling service

DPC=direct oral penicillin challenge; DPT=drug provocation testing. 

Use of Prolonged DPT

  • Consultation with the local/regional allergy service providing oversight for the de-labelling service should be sought to define which patients require a prolonged DPT and how long this should be
  • A prolonged (multiple doses) DPT should be considered when the index reaction occurred after the second or subsequent dose of a course of penicillin (or where the timing of the reaction is unknown)
  • Where indicated, a prolonged DPT lasting 3 days is sufficient in the majority of patients. If the index reaction is clearly remembered to have occurred after more than 3 days, advice should be sought from the local or regional allergy service as to how long to extend the DPT.


  • True allergic reactions to penicillin are less common than in adults
  • Reactions, if they develop, are usually mild–moderate and occur 3–4 days from the start of the challenge. Recommendations for children of all ages are the same as those for adults, in terms of risk stratification and the conduct of DPT (see Tables 1–3)
  • Doses of medication should be age adjusted.