Penicillin allergy

Antibiotic allergy history

• What antibiotic was the patient given? 
  • Was it an injection or a tablet? 
• When (was it >5 years ago)? 
• What happened (GI upset, facial swelling, anaphylaxis etc.)?  
• Where (community, GP practice, hospital) 
• Onset after taking antibiotic (Minutes, hours, weeks) 
• Treatment required (in particular, was adrenaline given)? 
• Has a Severe Cutaneous Adverse Reaction (SCAR) occurred? These include: 
  • Steven-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN) 
  • Drug Reaction with Eosinophilia & Systemic Symptoms (DRESS) 
  • Acute Generalised Exanthematous Pustulosis (AGEP) 

Features in history suggestive of different reactions: 

Other sources of information

Often patients are uncertain of the nature of the reaction, in which case consider these sources of information 

• GP: Phone to ask: 
  • Are there are details in the primary care record? 
  • Has the patient received other penicillins (amoxicillin/flucloxacillin/co-amoxiclav) since the documented reaction? 
• TRAK/HEPMA: Has the patient received other penicillins since the documented reaction? Check previous admissions notes/letters. 
• Collateral history from relatives 

Step 2.1: Assess suitability for direct de-labelling 

Step 2.2 Calculate penFAST score

Step 2.3: Interpretation of penFAST score 

This protocol must only be used for patients assessed as suitable for oral penicillin challenge by following Steps 1&2 above. 

Step 3.1: Pre-challenge checks 

1. Ensure discussion with senior clinician responsible for patient before proceeding. 
2. Ensure adequate medical staff available with training in the management of anaphylaxis. Resuscitation equipment must be available nearby. Medical staff should remain on-site for the first 20 minutes minimum. 
3. Ensure nursing staff available to undertaken required monitoring.
4. Patients taking antihistamines should temporarily stop these for 24 hours prior to challenge, where safe to do so. 
5. Inform the patient of the risks/benefits/alternatives of de-labelling which are outlined in the "Background" section, and provide Patient Information Leaflet, found here.
   • Inform the patient to seek medical attention if they develop symptoms of a delayed reaction. If they develop symptoms of a SCAR they should seek urgent review (see Step 1 for details). 
6. Document patient consent on TRAK. If written consent is preferred, the SAPG consent form can be used, found here.

Step 3.2: Exclusion criteria 

1. Clinically unstable or deteriorating patients (based on treating senior clinician’s judgement) 
2. Pregnant
3. <18 years old 
4. Patients receiving omalizumab (may mask reaction to challenge)
5. Uncontrolled asthma/COPD (complicates management of potential anaphylaxis)
6. Antihistamine use in past 24 hours (may mask reaction to challenge)
7. Previous urticaria, anaphylaxis or SCAR from a beta-lactam antimicrobial

If there are exclusion criteria present go to Step 5 and consider de-labelling at a future date if exclusion criteria no longer applicable. If uncertain, consider discussion with infection specialist. 

Step 3.3: Oral challenge protocol 

Printable checklists available here for clinicians and nursing staff.

1. Measure observations at 0 minutes. 
2. Administer oral penicillin challenge.
   1. Prescribe Amoxicillin 500mg oral on HEPMA (Flucloxacillin 500mg is an alternative, ideally use the antibiotic the reaction was reported to. If uncertain, use amoxicillin).
   2. Alternately prescribe on paper kardex if in non-HEPMA area.
3. Re-check observations at 20, 40, 60 minutes. 
4. Assess outcome at 120 minutes (see table below).

Step 3.4: Assessment of outcome

Clearly document the challenge has taken place and the outcome, by following the steps below: 

1. Document in TRAK patient notes, using “\penicillindelabelled” 
2. Update TRAK & HEPMA allergies field, removing the allergy label and adding the comment: 
   • “Successfully de-labelled DD/MM/YYYY following oral challenge: Patient is NOT penicillin-allergic" 
3. Inform patient and provide patient information leaflet here.
4. Inform patient’s GP by adding to immediate discharge letter/correspondence and sending standard letter via email to the GP practice clinical email address [accessable via intranet only]. 

If de-labelling was not deemed safe/suitable:

Clearly document the nature of the allergy and the reason de-labelling is not safe/suitable, by following the steps below: 

1. Document in patient notes, in particular the reason they are not suitable for de-labelling, using "\penicillinallergy"
2. Update TRAK & HEPMA allergies field, maintaining the allergy label and adding the comment: 
   • “Not suitable for allergy de-labelling on DD/MM/YYYY due to: XXXX" 
3. Inform patient and provide patient information leaflet here
4. Inform the patient’s GP and ask them to ensure the patient's ECS is updated with nature of allergy: 
   • Include nature of allergy in discharge letter/correspondence 
   • Consider sending a specific letter or email to the GP practice as appropriate 

Review the "Antimicrobial prescribing for patients with penicillin allergy" section for further advice.

If de-labelling was attempted and allergy confirmed:

Clearly document the challenge has taken place and the outcome, by following the steps below: 

1. Document in patient notes, using “\penicillinallergy” 
2. Update TRAK & HEPMA allergies field, maintaining the allergy label and adding the comment: 
   • “Allergy to XXXX confirmed DD/MM/YYYY following oral challenge: symptoms/signs XXXX" 
3. Inform patient and provide patient information leaflet here. 
4. Inform the patient’s GP and ask them to ensure ECS is updated with nature of allergy: 
   • Include nature of allergy in discharge letter/correspondence 
   • Consider sending a specific letter or email to the GP practice as appropriate

Review the "Antimicrobial prescribing for patients with penicillin allergy" section for further advice.

Within each section of the Body Systems guidelines, there will be antimicrobial treatment options suggested for patients with penicillin allergy.

Key points:

1. Penicillins, cephalosporins and carbapenems share a beta-lactam ring structure. However hypersensitivity is related to the side chains that differ significantly between different classes of beta-lactam antimicrobials.
2. Patients with a penicillin allergy should not receive other penicillin antibiotics, as they share similar side chains, and have similar metabolites which can lead to cross-reactivity.
3. The risk of cross-reactivity between a penicillin allergy and a cephalosporin is estimated at <1%, except for cephalexin as it shares a side chain with the penicillins.
4. Cephalosporins (apart from cephalexin) can be used in patients with a non-severe penicillin allergy (e.g. delayed onset reaction such as rash without SCAR).
5. Carbapenems can generally be safely used in patients with penicillin allergy regardless of severity, after discussion with an infection specialist.
6. Aztreonam can safely be used in most patients with penicillin allergy (noting the potential for cross-reactivity with certain cephalosporin allergies including cefuroxime and ceftazidime, see chart below)
7. Patients with severe penicillin allergy (e.g. features suggestive Type 1 Hypersensivity reaction or SCAR (see Table in Step 1)) should be discussed with an Infection Specialist if there is not a clear recommendation for empirical treatment in the relevant Body Systems section.

Cross-reactivity table

Further information on side-chain homology between different beta-lactam antimicrobials can be found in the chart below. This does not replace discussion with an Infection Specialist.

Click on the image to enlarge