Guidance on Antibiotic Choice for Patients with Penicillin Hypersensitivity


The phrase ‘allergic to penicillin’ is commonly seen in medical notes and on medicine charts. The diagnosis of ‘penicillin allergy’ is often simply accepted without obtaining a detailed history of the reaction. It has been reported that a significant percentage of patients labelled as ‘penicillin allergic’ are not truly allergic to the drug. As a result, penicillins are unnecessarily withheld from these patients, which may subsequently affect their clinical outcomes.

What is the True Incidence of ‘Penicillin Allergy’?
General hypersensitivity reactions (e.g. rashes) to penicillin occur in between 1 and 10% of exposed patients but true anaphylactic reactions (which can be fatal) occur in less than 0.05% of treated patients. Please note that patients who have a vague history of symptoms or gastro-intestinal intolerance are probably not truly allergic to penicillins.

Who is at risk?
Patients with a history of atopic allergy (e.g. asthma, eczema, hay fever) are more likely to be allergic to penicillins.

Who should not be prescribed or administered penicillins?

ndividuals with a history of Type I allergy clinically recognisable by features of urticaria, laryngeal oedema, bronchospasm, hypotension or local swelling within 72 hours of administration, or development of a pruritic rash (even after 72 hours) should NOT receive a penicillin.

Are there situations where cephalosporins or other beta-lactam antibiotics can be prescribed for patients with penicillin hypersensitivity?
Clinical studies suggest that the incidence of cross-reactivity to cephalosporins in penicillin-allergic patients is around 10% but this is thought to be an overestimate. The true incidence of cross-sensitivity is uncertain. Second and third generation cephalosporins are unlikely to be associated with cross reactivity as they have different side chains to penicillin.

What about other types of antibiotics?
Tetracyclines (e.g. doxycycline), quinolones (e.g. ciprofloxacin), macrolides (e.g. clarithromycin), aminoglycosides (e.g. gentamicin) and glycopeptides (e.g. vancomycin) are all unrelated to penicillins and are safe to use in the penicillin allergic patient.

Prescribing Issues
lways identify and document the nature of the reported allergy and drug name on the medicine chart and in the medical notes. The prescriber has the primary responsibility for ensuring that the allergy/sensitivity details are completed on all relevant medicine charts and medical notes.

What should be prescribed for truly penicillin allergic patients?

Urinary Tract Infections
Female Lower UTI Trimethoprim or nitrofurantoin
Female Upper UTI Co-trimoxazole + gentamicin
Male UTI Trimethoprim or ciprofloxacin

Upper Respiratory Tract Infections
Sinusitis Doxycycline
Tonsillitis Erythromycin or clarithromycin
Otitis Media Erythromycin or clarithromycin

Lower Respiratory Tract Infections
Community Acquired Pneumonia (non-severe) Doxycycline
Community Acquired Pneumonia (severe) IV Levofloxacin then oral doxycycline
Aspiration or Hospital Acquired Pneumonia (severe) IV Vancomycin + metronidazole + gentamicin (and seek advice)
Aspiration or Hospital Acquired Pneumonia (non-severe) Co-trimoxazole (+metronidazole if aspiration suspected)
Infective Exacerbation of COPD Doxycycline

Peritonitis/Biliary Tract/Intra-abdominal Infections
Severe IV Vancomycin + metronidazole + gentamicin (and seek advice)
Step down to oral Cotrimoxazole

Skin Infections
Cellulitis (see separate protocol) Doxycycline
Animal bites Metronidazole + doxycycline
Surgical Prophylaxis See separate protocol

Click here for information on which antibiotics should be avoided in penicillin allergy, those that should be used with caution, and those that are safe.

Antimicrobial Management Group
Updated August 2008
Review August 2010

Ref: Pegler S, Healy B. BMJ 2007;335:991

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