Penicillin Allergy: Assessment and Overview

Background

Approximately 10% of in-patients have a penicillin allergy label.
Of those, only 10% are actually allergic, and 1% will have a severe allergy (e.g. anaphylaxis).
Removing a penicillin allergy can benefit the patient and simplify treatment with antibiotics in the future.

Why remove a penicillin allergy label?

Using non-beta lactam antibiotics is associated with:

Treatment failure
Side effects from the drug
Admission to intensive care
Death on intensive care
Healthcare-associated infection: MRSA, Clostridioides Difficile infection or VRE infection

Open all

Definition of Severity

Severe allergy

Anaphylaxis OR
Angioedema OR
Severe Cutaneous Adverse Reaction (SCAR):
- Steven-Johnson Syndrome/Toxic Epidermal Necrolysis
- Drug Reaction with Eosinophilia and Systemic Symptoms
- Acute Generalised Exanthematous Pustulosis

Patients with a history of SCAR, anaphylaxis or angioedema should NOT be challenged or delabelled.

Non-severe allergy

Any reaction other than anaphylaxis/angioedema or SCAR

Non-allergy

Side effect of the drug (e.g. nausea with co-amoxiclav)

DRUG	What antibiotic was the patient given? Was it an injection or a tablet?
REACTION	When (Days, weeks, years ago)? What (GI upset, facial swelling, anaphylaxis etc.)? Was it anaphylaxis, angioedema or a SCAR? Site (community, GP practice, hospital) Onset after taking antibiotic (Minutes, hours, weeks) Treatment required (in particular, was adrenaline given)?
OTHER SOURCES OF HISTORY	GP practice notes: If there are details in the primary care record. If the patient has received other penicillins (amoxicillin/flucloxacillin/co-amoxiclav) since the documented reaction. Secondary care notes: Has the patient ever received another type of penicillin? Check previous admissions Patient’s family

At this point, Non-allergies (Side effects) can be directly delabelled:

Example

Action

Tolerated treatment with a penicillin since penicillin allergy was documented

‘Allergy’ is a known side effect of a drug (e.g. nausea)

Penicillin allergy label can be removed with patient consent.

PENFAST is a validated scoring system for assessing reported penicillin allergy.

PEN	Penicillin allergy reported by patient? If so, proceed with assessment	Points
F	Five years or less since reaction?	2
A	Anaphylaxis/angioedema?	2
S	Severe cutaneous adverse reaction?	2
T	Treatment (any) given?	1

Interpret as follows

Score	Risk of true hypersensitivity reaction/allergy	Recommendations
0	less than 1%	Suitable for delabelling
1-2	5%	Suitable for delabelling (unless SCAR)
3	20%	Do not use penicillins Continue to label as ‘penicillin-allergic’
4-5	50%	Do not use penicillins or cephalosporins Continue to label as ‘penicillin-allergic’

If delabelling is indicated, proceed with penicillin challenge.
If PENFAST score is 3 or more, consider referral to the immunology clinic for allergy assessment: email referral to Immunology secretaries (ImmunologySecretaries@ouh.nhs.uk).

Cephalosporins	Low risk ( Approximately 2% overall)
Carbapenems	Very low risk
Aztreonam	Very low risk

Notable cross-reactivity between other groups:
- Aztreonam and Ceftazidime
- Aztreonam and Cefiderocol
- 3^rd and 4^th generation cephalosporins with each other

Shenoy ES, Macy E, Rowe T, Blumenthal KG. Evaluation and Management of Penicillin Allergy: A Review. JAMA. 2019;321(2):188–199. doi:10.1001/jama.2018.19283
Wijnakker R, van Maaren MS, Bode LGM, et al. The Dutch Working Party on Antibiotic Policy (SWAB) guideline for the approach to suspected antibiotic allergy. Clin Microbiol Infect. 2023;29(7):863-875. doi:10.1016/j.cmi.2023.04.008
Mirakian R., Leech S.C., Krishna M.T., et al. BSACI Guideline. Management of allergy to penicillins and other beta-lactams. Clinical & Experimental Allergy. 2015;45:300-327
Trubiano JA, Vogrin S, Chua KYL, et al. Development and Validation of a Penicillin Allergy Clinical Decision Rule. JAMA Intern Med. 2020;180(5):745–752. doi:10.1001/jamainternmed.2020.0403
Farkas J. Approach to beta-lactam allergy in critical care. The internet book of Critical Care. 2024. Available at: Approach to beta-lactam allergy in critical care - EMCrit Project. Accessed January 2025.

Definition of Severity