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