• Penicillins are bactericidal antibiotics that prevent cell-wall synthesis by preventing cross-linking of peptidoglycans by replacing the natural substrate with their β-lactam ring
  • Penicillins bind to penicillin binding proteins (PBPs) in the bacterial wall
  • Penicillins only rarely achieve complete eradication of sensitive organisms without addition of a synergistic antibiotic (such as gentamicin)

Common Features

Property Effect
Absorption Typically well absorbed orally. IM dosing tend to cause localised pain and irritation.
Distribution Typically have good tissue penetration. Only cross the blood-brain barrier and enter bone if it is inflamed. Typically low protein binding (exception is flucloxacillin, which is 95% protein bound).
Metabolism Typically small proportion is hepatically metabolised.
Elimination Majority (60-90%) is eliminated unchanged in urine predominantly by active tubular secretion, with renal clearance proportional to total renal plasma flow. A small quantity is secreted in bile.

Mechanisms of Resistance

  • Alteration or protection of PBPs
    • Gram negative bacteria may have altered permeability of porins in their outer membrane, which protects the PDP
  • Hydrolysis by β-lactamase-producing bacteria
    • Clavulanic acid and tazobactam inhibit β-lactamase, which can render otherwise resistant bacteria sensitive
    • Notably, flucloxacillin has a modified beta-lactam ring that is not sensitive to β-lactamases

Comparison of Penicillins

Narrow spectrum, naturally occurring Narrow spectrum, synthetic Extended-spectrum Antipseudomonal
Examples Benzylpenicillin, phenoxymethylpenicillin Flucloxacillin Ampicillin, amoxacillin Piperacillin, ticarcillin
Indications Gram positives and anaerobes, particularly streptococci and meningococci. Also listeria, Clostridia, and Treponema. Gram positive cocci, particularly staphylococci but also streptococci. Gram positive, particularly enterococci. Some gram negative. Gram positive, gram negative including pseudomonas.
Other bits Highly bactericidal Less active than benzylpenicillin on organisms sensitive to both. Can penetrate some gram-negatives. Gram negative cover.


  1. Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
  2. Barza M, Weinstein L. Pharmacokinetics of the penicillins in man. Clin Pharmacokinet. 1976;1(4):297-308.
  3. Brunton L, Chabner BA, Knollman B. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 12th Ed. McGraw-Hill Education - Europe. 2011.
  4. CICM July/September 2007
Last updated 2019-07-18

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