Cross-reactivity of penicillins and cephalosporins

A 73-year-old man collapsed at home. Ambulance officers noted impalpable blood pressure, shortness of breath and complaints of right-sided chest and epigastric pains.

The man had seen his family doctor earlier that day complaining of sore throat, cough and haemoptysis. He was prescribed cephalexin and had taken the first dose 10 minutes before collapsing. The man had a documented history of amoxycillin allergy with pruritis.

Oxygen and intravenous fluids were given and in the emergency department his blood pressure was 140/70. On examination he had a generalised erythematous rash that was pruritic. Wheeze and tongue swelling were absent and intra-abdominal pathology was excluded. A diagnosis of anaphylaxis to cephalexin was made. Hydrocortisone and antihistamines were given and he was admitted to hospital.

As he was taking propranolol it was ceased, as beta blockers can potentiate further anaphylactic reactions. He remained stable on oral antihistamines and was discharged after three days.

Penicillins and cephalosporins exhibit partial and incomplete cross-reactivity of up to 7% that may be related to the 'generation' of cephalosporin.¹In clinical practice it is not uncommon for cephalosporins to be given to penicillin-allergic patients, particularly if the history of penicillin reaction was not life-threatening. However, reports of adverse outcomes, including fatalities, appear to be increasing. Over the last six months, the authors know of four cases from western Sydney including two deaths.

Reactions to beta-lactam antibiotics can be classified into immediate and non-immediate. Immediate reactions are IgE mediated and classically manifest as anaphylaxis, urticaria, angioedema, bronchospasm and allergic rhinoconjunctivitis. Non-immediate reactions such as maculopapular or morbilliform rashes are probably T-cell mediated. The most common clinical manifestation of both penicillin and cephalosporin allergy is skin reactions, occurring with a frequency of 1-3% of courses given.¹In addition to anaphylaxis, less common but serious adverse reactions to cephalosporins include serum sickness-like reactions, acute interstitial nephritis and cytopenias.

While penicillin-induced anaphylaxis is rare (0.01-0.05% of courses), it may be fatal in 10% of cases.²It is difficult to obtain reliable data about the frequency of cephalosporin anaphylaxis, but published figures are 0.0001-0.1%.¹

Whether a penicillin-allergic patient can safely take cephalosporins remains a difficult question to answer - many people labelled penicillin-allergic can actually take penicillin. Patients with a history of penicillin allergy are four times more likely to have a reaction to cephalosporins than patients without a penicillin allergy, especially if the patient is penicillin skin prick test positive.²It is not known if a history of anaphylaxis predicts a more serious allergic reaction. A history of mild reactions to penicillin, such as rashes, does not imply that a reaction to cephalosporins will not be life-threatening.

Side chain specific antibodies may be responsible for cephalosporin allergies rather than antibodies to the core beta-lactam ring.^1,3This would explain the cross-reactivity between certain penicillins and cephalosporins which share similar side chains, for example, amoxycillin and cephalexin, aztreonam and ceftazidime, benzylpenicillin and cephalothin.

While the risk of a serious reaction to cephalosporins in patients with known penicillin allergy remains low, serious adverse reactions do occur, including fatalities. Before prescribing cephalosporins it is prudent to take a careful history as to the nature of the penicillin allergy and the specific drug involved. It would be sensible to avoid prescribing drugs with the same or similar side chains, especially if an alternative non-beta-lactam antibiotic is available. If a cephalosporin is prescribed, the first dose should be taken in a monitored setting.