Penicillins
Overview
Penicillins inhibit bacterial wall synthesis and are bactericidal. They do this by binding to penicillin-binding proteins (PBPs) and inhibit bacterial transpeptidase, preventing it from cross-linking and creating peptidoglycan walls.
Penicillins have a beta- (β-) lactam ring in their structure, along with cephalosporins, and can also be grouped as β-lactam antibiotics.
Examples include benzylpenicillin, flucloxacillin, and amoxicillin.
Adverse effects
General adverse effects of penicillins include:
- Allergy – skin rashes are seen in around 10% of people, and anaphylaxis is generally rare
- Gastrointestinal disturbance – nausea and vomiting
- Acute interstitial nephritis
- Stevens-Johnson syndrome (rare)
- Flucloxacillin can cause elevated transaminases
Resistance can occur if bacteria produce β-lactamase, which cleaves penicillin’s structure.
Cephalosporins
Overview
Cephalosporins (like penicillins) have a beta- (β-) lactam ring in their structure and can be grouped as β-lactam antibiotics, however, they are less susceptible toβ-lactamase. They are often used as empirical treatment.
They bind to penicillin-binding proteins (PBPs) and inhibit bacterial transpeptidase, preventing it from cross-linking and creating peptidoglycan walls.
They can also be classified into generations according to how well they have Gram-negative activity.
Examples include:
- First generation – cefalexin, cefazolin
- Second generation – cefuroxime, cefaclor
- Third generation – cefotaxime, ceftriaxone, ceftazidime
- Fourth generation – cefepime, cefpirome
- Fifth generation – ceftaroline
Adverse effects
General adverse effects of cephalosporins include:
- Allergy – around 10% of people with penicillin allergy are also allergic to cephalosporins
- Gastrointestinal disturbances – nausea, vomiting, diarrhoea, ceftriaxone can cause biliary sludging and biliary colic/cholecystitis, 2nd– and 3rd-generation cephalosporins can cause Clostridioides difficile diarrhoea
- Acute interstitial nephritis
Resistance can occur if bacteria produce β-lactamase, which cleaves cephalosporin’s structure.
Beta-Lactamase Inhibitors
Overview
Some examples of beta- (β-) lactamase inhibitors are clavulanic acid and tazobactam. If bacteria produce β-lactamase, they can destroy penicillins and cephalosporins, and become resistant. β-lactamase inhibitors can restore the activity of β-lactam antibiotics.
For example, co-amoxiclav is a combination of amoxicillin (a penicillin) and clavulanic acid. Its adverse effects are similar to penicillins, but it can also cause cholestatic jaundice.
Glycopeptides
Overview
The glycopeptide antibiotics include vancomycin and teicoplanin. They inhibit cell wall synthesis by binding to muramyl pentapeptide, preventing the polymerisation of peptidoglycans.
They can be used in the management of methicillin-resistant Staphylococcus aureus (MRSA) and Clostridioides difficile diarrhoea.
Adverse effects
The adverse effects of glycopeptides include:
- Nephrotoxicity – often seen with higher doses
- Ototoxicity
- Infusion reactions – such as ‘red man syndrome’ and vancomycin (causing an erythematous, pruritic rash of the face, neck, and upper torso)
Pre-dose (trough) levels are monitored to reduce the risk of adverse effects.
Aminoglycosides
Overview
Aminoglycoside antibiotics include gentamicin, streptomycin, and neomycin. They inhibit protein synthesis by binding to bacterial ribosome 30S subunits, causing them to change shape and impair mRNA translation.
Adverse effects
The adverse effects of aminoglycosides include:
- Nephrotoxicity – most common
- Ototoxicity – may cause sensorineural deafness and vestibular dysfunction that may be irreversible
Macrolides
Overview
Macrolide antibiotics include clarithromycin, erythromycin, and erythromycin. Lincosamides (such as clindamycin) are chemically unrelated but have similar properties. They inhibit bacterial protein synthesis by binding to the 50S ribosome subunit.
Adverse effects
Some general adverse effects of macrolides include:
- Allergy
- Gastrointestinal disturbance – nausea, vomiting, diarrhoea
- QT prolongation
- P450 inhibition – they can increase the risk of rhabdomyolysis with statins
Lincosamides
Overview
Lincosamide antibiotics include clindamycin and have similar properties to macrolides. They inhibit protein synthesis by binding to the 50S ribosomal subunit.
Adverse effects
General adverse effects of lincosamides include:
- Allergy – including erythema multiforme
- Gastrointestinal disturbance – nausea, vomiting, Clostridioides difficile diarrhoea
- Transient hepatitis
- Haematological disturbance – including neutropenia and thrombocytopenia
Chloramphenicol
Overview
Chloramphenicol inhibits protein synthesis by binding to the ribosomal 50S subunit, impairing protein synthesis.
Adverse effects
The adverse effects of chloramphenicol include:
- Bone marrow suppression – dose-dependent and occurs due to inhibiting mitochondrial protein synthesis, can cause anaemia, leukopenia, and thrombocytopenia
- Teratogenicity – can cause grey baby syndrome in neonates (ashen-grey skin, circulatory collapse, and abdominal distention)
- Optic neuritis
- Glossitis
- Stomatitis
Tetracyclines
Overview
Tetracycline antibiotics include tetracycline and doxycycline. They work by inhibiting protein synthesis by binding to the 30S ribosome subunit. They can also be used in eukaryotic parasites and protozoal infections.
Adverse effects
Some general adverse effects of tetracyclines include:
- Gastrointestinal disturbance – nausea, vomiting, diarrhoea
- Photosensitivity
- Deposition in growing bones – can suppress bone growth and cause tooth discolouration, avoid tetracyclines in children and pregnant/breastfeeding people
- Idiopathic intracranial hypertension
- Minocycline can cause skin, nail, and scleral pigmentation
- Renal impairment
- Demeclocycline can cause nephrogenic diabetes insipidus, hence it can be used as a treatment for syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Sulfonamides
Overview
Sulfonamide antibiotics include sulfamethoxazole and sulfadiazine. They inhibit DNA synthesis by inhibiting bacterial dihydropteroate synthetase which inhibits bacterial folic acid metabolism.
They are often used in combination products such as co-trimoxazole (trimethoprim and sulfamethoxazole).
Non-antibiotic sulfonamides include sulfasalazine (used in inflammatory disorders such as ulcerative colitis) and sulfonylureas (such as gliclazide in type 2 diabetes mellitus).
Adverse effects
Some general adverse effects of sulfonamides include:
- Allergy – reactions are common
- Rash – including erythema multiforme and Stevens-Johnson syndrome
- Gastrointestinal disturbance – nausea, vomiting, diarrhoea
- Haematological disturbance – anaemia, leukopenia, thrombocytopenia, agranulocytosis
- Acute haemolysis in G6PD deficiency
Trimethoprim
Overview
Trimethoprim inhibits DNA synthesis by inhibiting dihydrofolate reductase. Another trimethoprim drug is pyrimethamine (an anti-protozoal drug).
Adverse effects
Adverse effects of trimethoprim include:
- Blood dyscrasias – due to folate suppression, including bone marrow suppression
- Teratogenicity – avoid in pregnancy, as it is an antifolate drug
- Interactions – such as with methotrexate, which also inhibits dihydrofolate reductase, and can cause bone marrow suppression
- Transient elevation in creatinine – it can decrease tubular creatinine secretion
Quinolones
Overview
Quinolones directly inhibit DNA synthesis by inhibiting DNA gyrase and topoisomerase IV. Fluoroquinolones are the same, however, a fluorine atom is attached to the molecule, giving a wider spectrum of activity. Examples include ciprofloxacin, ofloxacin, and levofloxacin.
Adverse effects
Some general adverse effects of quinolones include:
- Gastrointestinal disturbance – nausea, vomiting, Clostridioides difficile diarrhoea
- Lowered seizure threshold – avoid in people with epilepsy
- Exacerbation of myasthenia gravis
- Tendinopathy and tendon rupture
- Cartilage damage – avoid in children
- QT prolongation and arrhythmia
- Acute interstitial nephritis
- Acute haemolysis in G6PD deficiency
Metronidazole
Overview
Metronidazole is an imidazole drug, which can have effects across bacteria, fungi, protozoa, and helminths. It is a prodrug and upon entering a bacterium, is activated when the bacterium reduces its nitro group, resulting in the formation of toxic compounds that kill the cell. For this reason, it is effective in anaerobic bacteria.
Adverse effects
Metronidazole is generally well-tolerated, however, some adverse effects include:
- Metallic mouth taste
- Disulfiram-like reaction when consuming alcohol
- P450 inhibition – for example, it can increase the levels of warfarin
Nitrofurantoin
Overview
Nitrofurantoin is a prodrug which is activated upon entering a bacterial cell, resulting in DNA damage and DNA repair inhibition. It is particularly effective in urinary tract bacterial infections.
Adverse effects
Adverse effects of nitrofurantoin include:
- Gastrointestinal disturbance – nausea, vomiting
- Pulmonary – hypersensitivity pneumonitis, pulmonary fibrosis
- Peripheral neuropathy
