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Clinical Practice Guidelines

Antibiotic prescribing in children with reported penicillin or cephalosporin allergy

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    PIC Endorsed

  • See also

    Local antimicrobial guidelines
    Anaphylaxis
    Urticaria
    Serum Sickness and Serum Sickness like reactions (SSLRs)

    Key points

    1. A detailed drug allergy history should be taken to help make appropriate antibiotic choices
    2. Children with a history of an immediate or severe reaction to either a penicillin or cephalosporin should avoid drugs from both β-lactam classes
    3. Children with a history of non-immediate and non-severe reactions can be prescribed an antibiotic from an alternate β-lactam class
    4. Drug allergy testing (drug challenge or skin testing) should take place in controlled settings

    Background

    • Up to a quarter of all children presenting to hospital will report an antibiotic allergy
    • β-lactam antibiotics (including penicillins, cephalosporins, carbapenems) are the most commonly implicated
    • More than 90% of children with non-immediate β-lactam reactions do not have a reproducible ‘allergic’ reaction when re-challenged with the same drug

    Assessment

    A detailed history of the timing, nature and severity of the previous reaction (including the potential for a severe, IgE-mediated reaction) is essential

    History

    • Timing of reaction
      • Symptoms occur <1 hour after ingestion (= immediate)
      • Occur >1 hour after ingestion (= delayed)
      • Duration of symptoms and time to recovery

    • Type of reaction
      • Rash (eg non-specific, maculopapular, urticarial)
      • Respiratory symptoms (eg wheeze, stridor or increased work of breathing)
      • Dizziness or collapse
      • Airway angioedema (mouth, eyes, lips, or tongue)
      • Mucous membrane involvement
      • Gastrointestinal symptoms
      • Joint and muscle pain
    • Other
      • Required immediate treatment (eg adrenaline auto injector, bronchodilator)
      • Previous episode of anaphylaxis
      • Concurrently administered drugs
      • Concurrent illness (eg possible viral infection)
      • Antibiotics previously tolerated (especially those after the reported reaction)
      • Past history of other drug and non-drug allergies
      • Atopic disease

    Examination

    No specific examination required – be guided by current presentation

    Management

    Approach to the child with reported penicillin or cephalosporin allergy

     

    Type of reaction

     

    Appropriate alternative antibiotic

     

    Immediate (<1 hour)
    • For severe reactions (airway angioedema, bronchospasm or anaphylaxis): avoid all drugs from the same β-lactam class and those with potential for cross reactivity (see table)
    • For non-severe reactions (eg isolated urticaria, pruritus): may consider non-cross reactive drug from alternate β-lactam class
    • Refer for drug allergy assessment and document allergy in the medical record pending outcome

    Delayed (>1 hour)
    • For suspected severe cutaneous adverse reaction (SCAR)*: avoid all β-lactams
    • For cytopenias, acute kidney or drug-induced liver injury: discuss with local paediatric team or drug allergy service
    • Safe to prescribe all non β-lactam antibiotics or aztreonam
    • For non-severe reactions (eg pruritus or isolated exanthem), it is safe to prescribe β-lactam from alternative class
    • Refer for drug allergy assessment and document allergy in the medical record pending outcome

    Timing unknown
    • Severe reaction: treat as per immediate, severe reaction
    • Non-severe reaction: treat as per delayed, non-severe reaction
    • Refer for drug allergy assessment and document allergy in the medical record pending outcome

    Timing known but unlikely allergy:

    • Known drug side effects (eg nausea, headache)
    • family history only
    • Safe to administer all β-lactam drugs
    • Remove drug allergy label
      •  

    * SCARs include: Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis

    Consider consultation with local paediatric team when

    • Any child with a clear history of immediate or severe antibiotic allergy
    • Children with history of non-severe reactions who require urgent or ongoing antibiotic therapy
    • Children with either immediate or non-immediate reactions may be referred to an outpatient allergy clinic for formal drug allergy assessment

    Additional notes

    • Three quarters of all children who identify as “allergic” to penicillin will do so by 3 years of age
    • For children with an immediate reaction to a penicillin or cephalosporin, the highest chance of cross reactivity is with a β-lactam that shares an R1-side chain (see table)
    •  Antibiotics to avoid based on shared R1-side chain:
      • For suspected amoxicillin or ampicillin allergy - avoid cefalexin and cefaclor (except for non-immediate and non-severe reactions - see above)
      • Suspected ceftriaxone allergy – avoid cefotaxime and cefepime
      • ceftazidime and aztreonam
    • Cross reactivity between penicillin and carbapenems (eg imipenem, meropenem) is rare – around 1%

     

    Last updated January 2022

  • Reference List

    1. Blumenthal KG, Peter JG, Trubiano JA, et al. Antibiotic allergy. Lancet. 2019;393(10167):183-98
    2. Grinlington L, Cranswick N, Gwee A. What is the risk of a repeat reaction to amoxicillin or a cephalosporin in children with a history of a non-immediate reaction to amoxicillin? Arch Dis Child. 2017;102(3):285-8.
    3. Macy E, Poon KYT. Self-reported antibiotic allergy incidence and prevalence: age and sex effects. Am J Med. 2009;122(8):778 e1-7.
    4. Romano A, Gaeta F, Poves M, Valluzzi R. Cross-Reactivity Among Beta-Lactams. Curr Allergy Asthma Rep (2016) 16: 24
    5. Romano A, Viola M, Gueant-Rodriguez R, et al. Brief communication: tolerability of meropenem in patients with IgE-mediated hypersensitivity to penicillins. Ann Intern Med. 2007 Feb 20;146(4):266-9.
    6. Trubiano JA et al. The Three C’s of Antibiotic Allergy – Classification, Cross-Reactivity and Collaboration. J Allergy Clin Immunol Pract. 2017; Vol 5, Number 6
    7. Vyles D, Chiu A, Simpson P, Nimmer M, Adams J, Brousseau DC. Parent-Reported Penicillin Allergy Symptoms in the Pediatric Emergency Department. Acad Pediatr. 2017;17(3):251-5.