Mechanism of Action
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Penicillins inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), enzymes involved in the final stage of peptidoglycan cross-linking.
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This leads to weakened cell walls, osmotic instability, and ultimately bacterial cell lysis and death (bactericidal effect).
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Penicillins are only active against actively dividing bacteria.
Mechanism
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Imagine a brick wall (bacterial cell wall) being built. Penicillins act like “bricklayer inhibitors,” stopping the builder (PBPs) from joining bricks (peptidoglycan units), causing the wall to collapse.
Spectrum of Activity
| Class of Penicillin | Main Activity | Key Examples |
|---|---|---|
| Benzylpenicillin (Pen G) | Gram-positive cocci, some Gram-negatives (Neisseria) | Benzylpenicillin |
| Aminopenicillins | Improved Gram-negative, still Gram-positive | Amoxicillin, Ampicillin |
| Antistaphylococcal | Staphylococcus aureus (not MRSA) | Flucloxacillin |
| Extended-spectrum | Wider Gram-negative (e.g., Pseudomonas) | Piperacillin |
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Gram-positive coverage: Streptococci, pneumococci, enterococci, some staphylococci.
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Gram-negative coverage: Varies by penicillin type; aminopenicillins and extended-spectrum agents have improved coverage (e.g., E. coli, H. influenzae, Pseudomonas).
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Many Gram-negative bacteria produce beta-lactamases, limiting the spectrum of basic penicillins.
Beta-Lactamase Inhibitors
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Clavulanic acid and tazobactam are commonly combined with penicillins (e.g., co-amoxiclav = amoxicillin + clavulanic acid; piperacillin/tazobactam).
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These agents have little/no antibacterial activity alone but inhibit many beta-lactamases, protecting penicillins from enzymatic breakdown and broadening their spectrum.
Mnemonic:
“CAST” — Clavulanic acid, Amoxicillin, Sulbactam, Tazobactam
(CAST inhibitors shield penicillins!)
Side Effects
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Allergy: Rashes, urticaria, anaphylaxis (rare but serious).
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Gastrointestinal upset: Nausea, vomiting, diarrhoea, antibiotic-associated colitis.
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Neurotoxicity in renal impairment: High doses can cause seizures, confusion, encephalopathy—especially if renal function is impaired and drug accumulates.
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Other: Rarely, blood dyscrasias or liver enzyme abnormalities.
Mnemonic:
“ANGry GI tract” — Allergy, Neurotoxicity, Gastrointestinal upset
References
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British National Formulary, “Penicillins”
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NICE, “Antimicrobial stewardship: systems and processes for effective antimicrobial medicine use”
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NHS, “Penicillins”
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Oxford University Hospitals, “Antibiotic Guidelines”
