Penicillin and cephalosporin allergies

Penicillins are some of the most frequently prescribed antibiotics in clinical practice. The following list includes the penicillins available in Australia, and the common brand names:

  • Amoxicillin - Alphamox, Amoxil, Cilamox, Ibiamox, Fisamox
  • Ampicillin - Agpen, Alphacyn, Ampicyn, Austrapen, Ibimicyn, Penamp
  • Benzylpenicillin (Penicillin G) - BenPen
  • Benzathine benzylpenicillin - Bicillin-LA
  • Dicloxacillin - Dicloxsig, Distaph
  • Flucloxacillin - Flubiclox, Flucil, Flopen, Flucil, Staphylex
  • Phenoxymethylpenicillin (Penicillin V) - Aspecillin, Cilicaine VK, Cilicaine V, Cilopen
  • Piperacillin with tazobactam - Tazopip, PiperTaz, Tazocin, Piptaz Procaine benzylpenicillin Cilicaine

Cross-reactivity between beta-lactamclasses

A history of penicillin allergy should not rule out the use of cephalosporins. The prevalence of cross-reactivity between beta-lactams is lower than originally thought. An estimated 1-2% of patients with a penicillin allergy react to cephalosporins. 1

Antibiotics with shared structural similarities, such as those with the same or similar R1-group side-chains are more likely to cross-react:


  • Identical - Cefaclor, Cefalexin
  • Similar - Amoxicillin


  • Similar - Ampicillin, Cefaclor, Cefalexin


  • Identical - Cefepime, Cefotaxime
  • Similar - Cefuroxime


  • Similar - Cefepime, Ceftriaxone, Cefotaxime, Ceftazidime


  • Similar - Cefuroxime


  • Cefazolin has no common side-chains with other beta-lactam antibiotics, so can often be tolerated in patients with a penicillin or a cephalosporin allergy
  • Cefalexin and cefaclor have a similar side chain to amoxicillin: Avoid cefalexin or cefaclor if the patient has a history of serious amoxicillin or ampicillin allergy
  • Ceftriaxone allergy – avoid cefotaxime, cefepime and cefuroxime. These cephalosporins all have the same or similar side chains.
  • Ceftazidime and aztreonam have the same side chain. Avoid one where there is a history of allergy to the other.

In patients with a history of delayed severe penicillin hypersensitivity [e.g. drug rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN), Acute generalised exanthematous pustulosis (AGEP)], avoid all penicillins and cephalosporins – Do not use cross-reactivity to guide treatment as further drug exposure can be fatal.

An algorithm for the suggested management of patients reporting a hypersensitivity to penicillins in whom a beta-lactam is the preferred drug is available in the Therapeutic Guidelines:Antibiotic2:

Investigating / De-labelling antibiotic allergies

Many patients who believe they have a ‘penicillin allergy’ are not allergic when tested. Testing involves initial risk stratification based on history and available information, with subsequent either direct de-labelling, oral challenge testing (in low risk cases), or skin testing followed by oral challenge if negative (in higher risk cases). 7 Some patients are confirmed to be allergic either by available information, or after testing.

In patients with a confirmed beta-lactam allergy, or those who have a high-risk history when there is no opportunity for testing, desensitisation can be attempted under specialist care, which will allow temporary tolerance of the antibiotic.

Prioritisation for testing and potential de-labelling will take into account the likely antibiotic requirements of the patient including factors such as:

History of bacterial infection and antibiotic requirement in the recent past

  • Conditions predisposing to bacterial infection such as bronchiectasis, chronic sinusitis
  • Immunodeficiency, or compromised immunity due to immunosuppressive drugs or other medical conditions
  • Allergy or intolerance to several antibiotics or antibiotic classes which is limiting antibiotic choice
  • Patients who have had infections for which penicillins are the optimal choice.

Antibiotic allergy oral challenge guideline

The National Antibiotic Allergy Network (NAAN) has developed guidance for clinicians on antibiotic allergy assessment and management of an oral antibiotic challenge in patients who have an antibiotic allergy. 

Patient information 

The National Antibiotic Allergy Network (NAAN) has developed these patient information leaflets:

Patients can also use this Antibiotic Allergy Alert Card


  1. Yuson CL et al (2018). ‘Cephalosporin allergy’ label is misleading’. Aust Pres, 41: 37-41
  2. Antibiotic Expert Groups (2019). Therapeutic Guidelines:Antibiotic (version 16)

Hospital contacts - adults

Royal Adelaide Hospital (RAH) 

Department of Clinical Immunology and Allergy

Outpatient general enquiries: 1300 153 853

Urgent phone consultations: RAH immunology on-call registrar via Switchboard: (08) 7074 0000

Flinders Medical Centre (FMC)

Allergy & Clinical Immunology Services

General enquiries: (08) 8204 7201

Hospital contacts - paediatric

Women’s and Children’s Hospital (WCH)

Department of Allergy and Clinical Immunology

General enquiries: (08) 8161 8638