3rd August 2023

Beta-lactams

Mechanism of action

Beta-lactams are bactericidal, meaning they directly kill bacteria, and work by disrupting bacterial cell wall synthesis. There are several different types of beta-lactam antibiotics, which are discussed in turn below.

Spectrum of activity

Penicillins

The first class of antibiotics first synthesised, which remain amongst the most commonly prescribed in healthcare today.

Benzylpenicillin (penicillin G)

• Narrow spectrum, with most activity against gram positive organisms, particularly Streptococci species
• Some activity against gram negative organisms, most importantly Neisseria and Leptospira species
• Also active against Treponema species
• Given IM or IV

Phenoxymethylpenicillin (penicillin V)

• Similar spectrum to benzylpenicillin, but given orally.

Amoxicillin

• A broader spectrum antibiotic that is commonly used to treat both gram positive and some gram negative organisms

Flucloxacillin

• Treats gram positive organisms and is the antibiotic of choice for Staphylococcus aureus.
• Especially used in skin and soft tissue infections

Co-amoxiclav (amoxicillin/clavulanic acid)

• Clavulanic acid is a beta lactamase inhibitor, which, when used in combination with amoxicillin, broadens the spectrum.
• Co-amoxiclav is used to treat a range of gram positive, gram negative, and anaerobic bacteria. It is a common first line antibiotic for many sources of infection, including sepsis of unknown origin.

Tazocin (piperacillin/tazobactam)

• Tazocin is a broad spectrum antibiotic that treats gram positive, gram negative, and anaerobic bacteria.
• Importantly, it has activity against Pseudomonas aeruginosa
• Generally first line for hospital-acquired infections and neutropenic sepsis

Cephalosporins

A category of beta-lactams, of which there exist several ‘generations’ with slightly different spectrums of actions.
Cross-react with penicillins (10%), and so therefore, should be avoided in severe penicillin allergy.

First generation:

• e.g. cefalexin
• Mainly active against Gram positive organisms

Second generation:

• e.g. cefuroxime
• Enhanced Gram negative activity compared to first generation

Third generation:

• e.g. ceftriaxone, cefotaxime
• Enhanced Gram negative activity compared to second generation, but not as good with Gram positive organisms, especially Staphylococcus aureus
• Ceftazidime in particular, has good activity against Pseudomonas species
• Reduced cross-reactivity with penicillin (2-3%) compared to first and second generation

Fourth generation:

• e.g. cefepime
• Broad spectrum –active against Gram positive and negative bacteria to a greater degree than cefotaxime (third generation)
• Active against Pseudomonas species

Fifth generation:

• e.g. ceftaroline
• Similar spectrum to cefotaxime (third generation) but has an extended activity against Gram positive organisms, including MRSA and multi-drug resistant Streptococcus pneumoniae, and hence reserved for these infections to decrease drug resistance

Carbapenems

Have a broad spectrum of activity against Gram positive, Gram negative and anaerobic bacteria. Less cross-reactivity with penicillin than cephalosporins (1% rather than 10%), so it may be safer to give in penicillin allergy.

Examples include imipenem, meropenem and ertapenem; the latter is not active against Pseudomonas aeruginosa, which separates it from other carbapenems.

Generally reserved for severe infections. Imipenem and meropenem are used for complicated hospital-acquired pneumonias, intra-abdominal, skin and soft tissue, and urinary tract infections. Ertapenem treats abdominal and gynaecological infections, community-acquired pneumonia, and skin and soft tissue infections in diabetics.

Carbapenems are not active against MRSA.

Important side effects, interactions and monitoring

Penicillins

Penicillin allergy is common and can range from mild skin reactions to life-threatening anaphylaxis. Side effects caused by penicillin are often mistakenly interpreted as an allergic reaction. It is important to establish the nature of symptoms to determine whether or not the reaction represents a true allergy. It is also crucial to clarify the severity of any allergic reactions, as this affects decision-making over whether cephalosporins would be safe to administer.
A common reaction with ampicillin and amoxicillin is a maculopapular rash, often mistaken for an allergic reaction. This rash generally manifests in patients with glandular fever or, more rarely, leukaemia or cytomegalovirus function. Broad spectrum penicillins are therefore contraindicated in patients presenting with sore throats, in case this is due to glandular fever, which triggers this reaction.

Caution should be taken when prescribing high doses in patients with renal failure, as accumulation may lead to encephalopathy. Interstitial nephritis may also be seen as a rare but important side effect of penicillins.

Penicillins do not require any special monitoring.

Cephalosporins

Hypersensitivity reactions are the most important side effect of cephalosporins. First and second generation cephalosporins have a cross-sensitivity with penicillin of 10% and 2-3% with third generation patients. Cephalosporins should therefore be avoided in penicillin-allergic patients, but if there are no suitable alternatives, then cefixime, cefotaxime, ceftazidime, ceftriaxone and cefuroxime may be used with caution. Caution should be taken when prescribing high doses in patients with renal failure, as accumulation may lead to encephalopathy.

Cephalosporins do not require any special monitoring.

Carbapenems

Common side effects of all meropenems include GI upset, headache, skin reactions and thrombophlebitis. Carbapenems are known to lower the seizure threshold (especially imipenem), so they should be used cautiously in people with seizure disorders and the elderly. Meropenem has less seizure-inducing potential and can be used to treat central nervous system infections.

Meropenem requires monitoring of LFTs, as it can cause hepatotoxicity. Dose reductions are necessary for all carbapenem antibiotics for renal impairment.

Imipenem is given in combination with the enzyme inhibitor cilastatin. This is because this enzyme can partially inactivate the kidney’s imipenem, reducing its effectiveness.