Penicillins
Examples
- Benzylpenicillin (Penicillin G)
- Phenoxymethylpenicillin (Penicillin V)
- Flucloxacillin
- Amoxicillin
- Co-amoxiclav (Combination of amoxicillin and the β-lactamase inhibitor Potassium Clavaulanate)
- Piperacillin with tazobactam (Combination of piperacillin and the ?-lactamase inhibitor tazobactam)
Indications
- Antibacterial spectrum is for most Gram-positive bacteria and Neisseria spp
- Benzylpenicillin and Phenoxymethylpenicillin are used clinically in the treatment of streptococcal and clostridial infections, syphilis, leptospirosis and actinomycosis. They are also used in sensitive staphylococcal and pneumococcal infections, but not enterococcal infections
- Flucloxacillin is part of the group of penicilinase-resistant penicillins, it is thus effective in infections caused by penicillin resistant staphylococci. MRSA, resistant to flucloxacillin, can be difficult to manage.
- Amoxicillin is a broad-spectrum penicillin. It has a similar spectrum of action to Penicillins G and V but, is also useful against sensitive strains of enterococci, Haemophilus Influenzae, E.Coli and Proteus mirabilis.
- Co-Amoxiclav affects the β-lactamase-producing bacteria resistant to Amoxicillin, this includes strains of Staph. Aureus and H. Influenzae, many Bacteroides and Klebsiella. Co-amoxiclav should be reserved for infections likely, or known, to be caused by Amoxicillin-resistant β-lactamase-producing strains.
- Piperacillin with tazobactam is usually restricted to treating severe infections where this is a broad spectrum of potential pathogens (including Pseudomonas aeruginosa) or where antibiotic resistance is likely or in immunocompromised patients.
Contraindications
Contraindications
- Penicillin hypersensitivity
- History of associated jaundice (co-amoxiclav)
- History of allergies; particularly those with a history of atopic allergy who are at a higher risk of anaphylactic reaction
- Glandular fever. Commonly results in erythematous rashes (amoxicillin)
- Some parenteral preparations of penicillins contain large amounts of sodium. Therefore care is needed in sodium-restricted patients such as those with heart failure.
- Renal and hepatic impairment.
Mechanism
The penicillins are bactericidal antibiotics. They inhibit cell wall synthesis by combining with the penicillin binding protein which, catalyses cross-linking of the bacterial cell wall peptidoglycan. The penicillins are dependent on an intact β-lactam ring to function and hydrolysation, by bacterial β-lactamase, of this ring is a common mechanism of penicillin resistance. Flucloxacillin is not inactivated by these penicillinases.
Potassium Clavulanate, as found in Co-Amoxiclav binds irreversibly with many β-lactamases preventing inactivation of Amoxicillin.
Potassium Clavulanate, as found in Co-Amoxiclav binds irreversibly with many β-lactamases preventing inactivation of Amoxicillin.
Administration
- Penicillin G - Intramuscular, Intravenous
- Penicillin V - Oral
- Flucloxacillin - Oral, Intramuscular, Intravenous
- Amoxicillin - Oral, Intramuscular, Intravenous
- Co-amoxiclav - Oral, Intramuscular, Intravenous
- Piperacillin with tazobactam- Intravenous
Adverse Reactions
- Hypersensitivity reactions are relatively common (1-10%) and true anaphylaxis is possible but rare (0.05% of exposed individuals)
- Diarrhoea occurs frequently with oral penicillin therapy. Broad-spectrum penicillins can cause antibiotic-associated colitis
- In very large doses there is a risk of neurotoxicity
- Cholestatic jaundice can occur during or shortly after use of Co-Amoxiclav, the incidence of acute liver toxicity being six times higher than with use of amoxicillin. Liver function should be monitored in patients with liver disease
- Amoxicillin should not be used for blind treatment of a sore throat, it puts the patient at risk of developing a maculopapular rash in those with glandular fever
Interactions
- Allopurinol may cause a rash when combined with penicillins
- Reduced excretion of methotrexate when taken alongside penicillins may cause serious side effects
- Penicillins can potentially alter the anticoagulant effect of warfarin. INR monitoring is recommended.
Education
Patients should be advised to complete the prescribed course of antibiotic therapy.
Pharmacokinetics
Penicillins diffuse well into body tissues and fluids but penetration into the CSF is poor except when the meninges are inflamed. They are excreted in the urine.
