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.


  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