Antibiotic Allergy in Cystic Fibrosis (CF)
Tamariki (children) with Cystic Fibrosis (CF) are at risk of developing allergic reactions to antibiotics because they are exposed to repeated high dose intravenous antibiotics
Antibiotic allergy in Cystic Fibrosis (CF)
Tamariki (children) with CF are at risk of developing hypersensitivity reactions to antibiotics because they receive repeated high dose intravenous antibiotics. Ceftazidime and Piperacillin/Tazobactam are the antibiotics most commonly implicated in allergic reaction.
Acute allergic reactions to beta-lactam antibiotics are a particular issue for patients with CF. One study from Germany¹, reported 60% of CF patients had at least one reaction to intravenous antibiotics, most commonly to beta lactam based antibiotics. Clinical implications are important with a significant proportion of patients requiring discontinuation of treatment or a change in antibiotic. A recent Swedish study suggests that the risk is associated with cumulative antibiotic exposure and age.5
Drug reactions in CF represent a major challenge. The importance of accurate documentation in the medical record detailing the allergic reactions is crucial to reduce the risk of future adverse events or unnecessary avoidance of a drug.
Symptoms
Hypersensitivity reactions are classified as:
Immediate reactions - generally due to IgE dependent mast cell activation. Reactions usually occur within 1 hour and up to 6 hours after last drug administration and manifest as urticaria, angioedema or anaphylaxis.
Non immediate - occurring usually more than 6 hours after administration and sometimes starting days or weeks later. These reactions occur through a variety of mechanisms and can result in:
Rash - morbilliform, maculopapular, urticaria
Severe cutaneous adverse reactions (SCARs), which include acute generalised exanthematous pustulosis (AGEP), drug-induced hypersensitivity syndrome (DIHS) or drug reaction with eosinophilia and systemic symptoms (DRESS), and severe bullous exanthems such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
Other organ involvement - interstitial nephritis, pneumonitis, haemolytic anaemia, cytopenia, hepatitis, vasculitis, drug fever and serum sickness-like reaction.
Investigation
Documentation of precise details of adverse drug reaction including careful description of any rash, and information on timing (of onset in relation to drug doses, and in relation to duration of course) is essential.
Measuring serum tryptase may be useful if there is uncertainty about whether a patient has had anaphylaxis to a medication - tryptase is not always elevated with a severe allergic reaction but may be and will peak 1-2 hours after a reaction.
Antibiotic allergy testing is not available in community laboratories and is available only at a few hospital laboratories in Aotearoa New Zealand. Testing requires skin prick then graded intradermal testing. Testing is validated for penicillin, but there are limitations to testing for semi synthetic penicillins, cephalosporins, and other classes of antibiotics. Paediatric allergist input should be sought to assist with arranging appropriate investigation.
Management
Prevent further exposure to the drug in question. Appropriate alerts should be entered in to local medical records, and adverse drug reactions should be notified to CARM (Centre for Adverse Reactions Monitoring) www.://nzphvc.otago.ac.nz
If there is no appropriate alternate antibiotic (e.g., with multi-resistant organisms) then desensitisation may be an option, depending on the nature of the adverse drug reaction.
Desensitisation should be discussed with the paediatric allergy service.
Antibiotic desensitisation must be performed in a clinically appropriate environment equipped to treat acute anaphylaxis.
Cross reaction
Cross reactivity depends on the antibiotic in question.
If there has been an allergic reaction to a penicillin, then all penicillin based antibiotics should be avoided until further investigation. Allergy to a semi synthetic penicillin may be due to IgE directed against the side chain rather than the central beta lactam ring, so allergy skin testing may still be useful for these patients.
Cross reaction between penicillins and cephalosporins is less common than initially thought, particularly for 2nd, 3rd, and 4th generation cephalosporins. Side chain (particularly at the R1 position) similarity is important in predicting cross reactivity, with tables detailing groups of drugs to be aware of 2,4
Carbapenems (i.e., imipenem, meropenem, doripenem and ertapenem) share a common beta-lactam ring with penicillins so there is potential for cross-reactivity. Cautious use (e.g., with test dosing) may be appropriate in a safe setting. 2
Aztreonam does not cross react with penicillins and cephalosporins, but it shares a side chain with Ceftazidime. If allergy testing is not available, then cautious test dosing (with informed consent) may be appropriate.
Cross reactivity can occur within other classes of antibiotics including quinolones, macrolides, and aminoglycosides. Allergy tests are not reliable to diagnose or refute allergy to these drugs. Allergy consultation and consideration of cautious challenge with an alternate drug may be appropriate 4