Penicillin allergy checklist

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Is a patient allergic to penicillin?

Bearded man receiving medical attention from a pharmacistThis guide will help pharmacists and other healthcare professionals to diagnose if a patient is allergic to penicillin or not.

Go to the Checklist

The scale of the problem

  • A 2019 study in England reported 5.9% of patients have a penicillin allergy recorded on their health record1
  • However, fewer than 10% of these patients are likely to have a true allergy to penicillin2
  • In a 2014 US study, penicillin-allergic hospital patients were found to have 23.4% more C. difficile and 14.1% more MRSA infections than expected compared with control subjects3
  • This means that up to four million people across the UK may have an incorrect allergy status record, putting them at increased risk of harm.

What is a true penicillin allergy?

  • Anaphylactic reactions to penicillin are mediated by IgE4
  • Rashes that involve hives (raised, intensely itchy spots that come and go over hours) or occur with other allergic symptoms like wheezing or swelling of the skin or throat suggest an IgE-mediated allergy5
  • Rashes that are flat, blotchy, and spread over days but do not change by the hour are less likely to represent a dangerous allergy5
  • Fatal anaphylaxis in patients treated with penicillin is rare: approximately 1 in 100,000 for parenteral exposure and 1 in 200,000 for oral exposure6, 7
  • Many people report an allergy, when they have actually experienced non-allergy adverse effects such as nausea, diarrhoea, or thrush.

What are the risks of a penicillin allergy?

  • For patients with a true Type 1 IgE mediated penicillin allergy, another (non-beta-lactam) antibiotic should be used for treatment8
  • The risk of cross-sensitivity to other beta-lactam antibiotics varies considerably, depending on the reaction to the index penicillin and the structure of the non-penicillin beta-lactam antibiotic4
  • The lowest rate of anaphylaxis is for oral penicillins, with a UK study reporting one case of fatal anaphylaxis from oral amoxicillin in 35 years and 100 million treatment courses9
  • In a 2019 US study involving 11.1 million patients, a recorded penicillin allergy was associated with a 14% increased risk of death10
  • Once a penicillin allergy is recorded, patients receive less effective and/or more toxic antibiotics for subsequent infections11, 12
  • Hospitalized patients with documented beta-lactam allergies are more likely to experience inferior outcomes, treatment failures, adverse events, and healthcare-associated infections7
  • In patients diagnosed with bacterial pneumonia, a penicillin allergy label is associated with an 11% increase in ICU admission and 8% increase in mortality compared to patients without a penicillin allergy label13
  • Patients with a penicillin allergy record were six times more likely to be prescribed meropenem than patients without a penicillin allergy record, increasing the selection pressure for the emergence and spread of multiresistant bacteria14
  • Most alternatives to penicillins, such as clarithromycin, doxycycline, fluoroquinolones, and linezolid have more extensive adverse effect profiles than penicillins
  • More healthcare associated infections: alternatives to penicillins tend to be broader-spectrum antibiotics. This both increases the risk of multi-drug resistance developing and causes increased collateral damage to the microbiota of the skin and intestines, associated with higher rates of MRSA carriage and Clostridioides difficile infection in patients with a penicillin allergy label.15, 16, 17

A 16-year-old boy presents at the pharmacy with decrease in appetite and abdominal pain. What is your next step?


How can pharmacy teams help?

The checklist

  • Ensure the patient record is accurate, in line with NICE guidance. An allergy history should include the drug name, date of reaction, nature of reaction and whether the patient was hospitalised or required intensive care admission
  • Review allergy status as part of Structured Medication Reviews
  • Review allergy status during New Medicine Service reviews
  • Check the patient medication record against the Summary Care Record
  • On admission to hospital, ensure allergy history is reviewed as part of the drug history and medicines reconciliation process
  • GP practice pharmacy teams can run searches to identify any patients with a documented allergy that have since received penicillin
  • Ensure that the records are updated for any patients with a penicillin allergy label that have since successfully received penicillin without an allergic reaction
  • If trained, carry out an allergy history assessment
  • Set up a penicillin allergy de-labelling service or clinic; the Resources below may help.



1 West RM, Smith CJ, Pavitt SH, et al. Warning: allergic to penicillin: association between penicillin allergy status in 2.3 million NHS general practice electronic health records, antibiotic prescribing and health outcomes. J Antimicrob Chemo. 2019; 74(7): 2075-2082.

2 NICE. Drug Allergy: Diagnosis and Management of Drug Allergy in Adults, Children and Young People. NICE Clinical Guideline 183. 2014.

3 Macy E, Contreras R. Health care use and serious infection prevalence associated with penicillin ‘allergy’ in hospitalized patients: a cohort study. J Allergy Clin Immunol 2014; 133: 790–6.

4 Castells M, Khan DA, Phillips EJ. Penicillin Allergy. N Engl J Med. 2019 Dec 12; 381(24):2338-2351.

5 Solensky, R. Patient education: Allergy to penicillin and related antibiotics (Beyond the Basics). In: UpToDate, Post, AF (Ed). Retrieved from Patient education: Allergy to penicillin and related antibiotics (Beyond the Basics) - UpToDate.

6 P Lee, D Shanson. Results of a UK survey of fatal anaphylaxis after oral amoxicillin. J Antimicrob Chemo. 60 (2007), pp. 1172-1173.

7 MH Thornhill et al. Incidence and nature of adverse reactions to antibiotics used as endocarditis prophylaxis. J Antimicrob Chemo. 70 (2015), pp. 2382-2388.

8 Patterson RA, Stankewicz HA. Penicillin Allergy. [Updated 2023 Jun 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023

9 Paul Lee, David Shanson, Results of a UK survey of fatal anaphylaxis after oral amoxicillin, J Antimicrob Chemo, Volume 60, Issue 5, November 2007, Pages 1172–1173.

10 Blumenthal KG, Lu N, Zhang Y, Walensky RP, Choi HK. Recorded Penicillin Allergy and Risk of Mortality: A Population-Based Matched Cohort Study. J Gen Intern Med. 2019 Sep; 34(9):1685-1687.

11 MacFadden DR, LaDelfa A, Leen J, Gold WL, Daneman N, Weber E, Al-Busaidi I, Petrescu D, Saltzman I, Devlin M, Andany N, Leis JA. Impact of Reported Beta-Lactam Allergy on Inpatient Outcomes: A Multicenter Prospective Cohort Study. Clin Infect Dis. 2016 Oct 1; 63(7):904-910.

12 Jeffres MN, Narayanan PP, Shuster JE, Schramm GE. Consequences of avoiding β-lactams in patients with β-lactam allergies. J Allergy Clin Immunol. 2016 Apr;137(4):1148-1153

13 Kaminsky, Lauren W et al. Penicillin Allergy Label Is Associated with Worse Clinical Outcomes in Bacterial Pneumonia. J Allergy Clin Immunol. In practice vol. 10, 12 (2022): 3262-3269.

14 Powell, N et al. “Impact of penicillin allergy records on carbapenem prescribing: an observational retrospective cohort study.” The Journal of Hospital Infection vol. 101, 4 (2019): 467-470.

15 Blumenthal KG, Lu N, Zhang Y, Li Y, Walensky RP, Choi HK. Risk of meticillin resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy: population based matched cohort study. BMJ. 2018 Jun 27; 361: k2400.

16 de Nies, L., Kobras, C.M. & Stracy, M. Antibiotic-induced collateral damage to the microbiota and associated infections. Nat Rev Microbiol (2023). Epub ahead of print. PMID: 37542123.

17 Maier, L., Goemans, C.V., Wirbel, J. et al. Unravelling the collateral damage of antibiotics on gut bacteria. Nature 599, 120–124 (2021).