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Last reviewed: March 2023

Author: Dr Amy Stanway MBChB, Department of Dermatology, Waikato Hospital, New Zealand, 2001.

Reviewing dermatologist: Dr Ian Coulson (2023)



Penicillin antibiotics are the most commonly used antibiotics in the treatment of skin infections. Penicillin was one of the first antibiotics used in clinical medicine and continues to be prescribed today. Unfortunately, its extensive use has resulted in increased resistance of some common bacteria to many forms of penicillin.

Penicillin antibiotics are effective against the common bacteria causing skin infections including:

In general, all streptococci are sensitive to simple penicillin. There has been increasing penicillin resistance in pneumococci, but penicillin remains the drug of choice even in localised pneumococcal skin infections.

Many staphylococci are no longer sensitive to simple penicillin due to the bacteria producing an enzyme that inactivates it, called penicillinase (also known as beta-lactamase). Penicillin antibiotics with penicillinase resistance include flucloxacillin and amoxicillin with clavulanic acid (amoxiclav). The latter is a broad-spectrum antibiotic that is best reserved for mixed bacterial infections. Some antibiotics are resistant to flucloxacillin as well (MRSA).

Penicillin antibiotics most commonly used in skin infections are:  

  • Flucloxacillin
  • Dicloxacillin
  • Penicillin V oral tablets
  • Penicillin G intravenous
  • Amoxicillin and clavulanic acid, oral or intravenous

It is recommended that flucloxacillin, dicloxacillin and penicillin be taken on an empty stomach but amoxicillin with clavulanic acid can be taken with meals.

Warnings, precautions and contraindications for penicillin

Penicillin antibiotics should be avoided in patients with suspected penicillin allergy. However, some studies suggest that true allergy may be present in only 1 in 10 individuals thought to be allergic. Penicillin may cross-react with cephalosporins in less than 1% of those with penicillin allergy.

Penicillin allergy can be assessed by skin testing.

Penicillin is one of the safer antibiotics to use in patients who have kidney or liver disease but the dose may need to be adjusted.

Flucloxacillin or amoxicillin with clavulanic acid should be used with caution in those with pre-existing liver disease. Dicloxacillin may be less likely to injure the liver.

Penicillins are not thought to have any adverse effect when used in pregnant or breastfeeding women.

What are the side effects of penicillin?

Penicillin antibiotics are generally well tolerated but occasionally result in:

  • Allergic reactions including urticaria, angioedema, erythema multiforme, toxic epidermal necrolysis, toxic erythema, exfoliative dermatitis, and anaphylaxis (collapse)
  • Gastrointestinal upset: stomatitis, glossitis, nausea, vomiting, diarrhoea (including the serious disease pseudomembranous colitis)
  • Liver disease (especially flucloxacillin and amoxicillin with clavulanic acid)
  • Blood reactions (very rare): haemolytic anaemia, thrombocytopenia, leucopenia (ie, low haemoglobin, platelet and white cell count)
  • Kidney reactions (very rare): interstitial nephritis
  • Neurotoxicity from very high dose treatment (very rare): confusion, twitching, seizures. This is more likely in those with renal failure.

Drug interactions with penicillin

Drug interactions are uncommon. Penicillin should be used with caution if the patient is taking the following drugs:

  • Anti-inflammatories, aspirin and probenecid, as these may compete for elimination and result in penicillin toxicity
  • Oral contraceptives, as penicillin antibiotics occasionally reduce their effectiveness.

Approved datasheets are the official source of information for medicines, including approved uses, doses, and safety information. Check the individual datasheet in your country for information about medicines.

We suggest you refer to your national drug approval agency such as the Australian Therapeutic Goods Administration (TGA), US Food and Drug Administration (FDA)UK Medicines and Healthcare products regulatory agency (MHRA) / emc, and NZ Medsafe, or a national or state-approved formulary eg, the New Zealand Formulary (NZF) and New Zealand Formulary for Children (NZFC) and the British National Formulary (BNF) and British National Formulary for Children (BNFC).



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