BACTROKANT

Indications

• Eradication of nasal carriage of Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA)
• Treatment of skin infections caused by susceptible bacteria, including impetigo and folliculitis

Dosage

Adults: For nasal carriage eradication, apply 2-3 times a day for 5 days, with the dose applied to the inner surface of each nostril. For

Mechanism of action

Mupirocin specifically and reversibly binds to bacterial isoleucyl transfer-RNA (tRNA) synthetase, inhibiting the enzyme that converts isoleucine and tRNA to isoleucyl-tRNA. This inhibition leads to decreased bacterial protein and RNA synthesis, resulting in bacteriostatic effects at lower concentrations and bactericidal effects with prolonged exposure, killing 90-99% of susceptible bacteria over 24 hours.

Pharmacodynamics

Mupirocin is effective against susceptible aerobic gram-positive cocci, particularly Staphylococcus aureus, Staphylococcus epidermidis, and beta-hemolytic streptococci such as Streptococcus pyogenes. Its antibacterial activity is attributed to its ability to inhibit protein synthesis, which is crucial for bacterial survival. Clinical studies have shown a therapeutic response rate of 94 to 98% after one week of treatment for conditions like impetigo, with over 90% of patients demonstrating clinical improvement in primary and secondary skin infections.

Pharmacokinetics

Mupirocin is primarily used topically, resulting in minimal systemic absorption. When applied to the skin, it is rapidly absorbed and achieves high local concentrations. The drug is metabolized in the liver and excreted in urine. Its pharmacokinetic profile supports its use for localized infections with minimal risk of systemic side effects.

Adverse effects

• Skin reactions
• Nasal mucosal disorder

Interactions

• Caution in patients with sensitivity to sulfonamides
• Caution with significant hepatic impairment
• Caution with significant renal impairment

Precautions

• Monitor for leucopenia
• Use with caution in patients with G6PD deficiency due to risk of hemolysis
• Avoid use in pregnancy unless potential benefit outweighs risk due to risk of neonatal hemolysis and methaemoglobinaemia in the third trimester

Pregnancy

Manufacturer advises avoiding unless potential benefit outweighs risk-no information available.

Breast-feeding

Small risk of kernicterus in jaundiced infants and of haemolysis in G6PD-deficient infants.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Mupirocin 20 mg per 1 gram cream
• Mupirocin nasal spray

Dosage

Children: Refer to the BNF for Children for appropriate dosing information in paediatric cases, especially in instances of overdose.

Adults: Refer to the BNF for specific dosing information based on clinical circumstances, particularly in cases of overdose.

Mechanism of action

Ethylene glycol is metabolized by alcohol dehydrogenase to glycoaldehyde, which is subsequently converted to glycolic, glyoxylic, and oxalic acids. These metabolites contribute to anion gap metabolic acidosis and are responsible for tissue injury through the formation of insoluble calcium oxalate crystals.

Pharmacodynamics

The toxicity of ethylene glycol arises from its metabolites, particularly glycolic and oxalic acids. These compounds induce metabolic acidosis, lead to renal failure through calcium oxalate crystal deposition in the kidneys, and can cause neurological impairment. The anion gap increases due to the accumulation of these acids, leading to complications such as cardiovascular instability and potential multi-organ failure.

Pharmacokinetics

Ethylene glycol is rapidly absorbed after oral ingestion. It undergoes first-pass metabolism primarily in the liver, where it is converted into its toxic metabolites. The elimination half-life of ethylene glycol varies but is generally prolonged in cases of renal impairment. Renal excretion of metabolites contributes to the duration of toxicity, necessitating prompt medical intervention in cases of overdose.

Adverse effects

• Metabolic acidosis
• Renal failure
• CNS depression
• Hypocalcemia
• Cardiovascular collapse
• Pulmonary edema

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of metabolic acidosis
• Evaluate electrolyte levels, particularly calcium

Pregnancy

There is limited data on the safety of ethylene glycol in pregnancy. It should only be used if clearly needed.

Breast-feeding

It is unknown if ethylene glycol is excreted in human milk. Caution is advised.

Storage

Store in a tightly closed container at room temperature, away from heat and moisture.

Formulations

• Liquid

Indications

• Constipation
• Bowel preparation prior to surgical procedures or diagnostic tests

Dosage

Children: Refer to specific guidelines or BNF for Children for dosing information.

Adults: Refer to specific guidelines or BNF for detailed dosing information.

Mechanism of action

Polyethylene glycol works by osmotically retaining water in the intestinal lumen, which increases the water content of the stool. This enhances the passage of stool through the intestines and promotes bowel movements. The high molecular weight of polyethylene glycol prevents its absorption in the gastrointestinal tract, ensuring that it remains in the lumen to exert its effects.

Pharmacodynamics

The pharmacodynamic profile of polyethylene glycol involves its ability to increase stool water content, thereby reducing stool consistency and facilitating easier passage. It does not stimulate intestinal motility directly but rather relies on the osmotic effect to promote bowel evacuation. The onset of action typically occurs within 24 to 96 hours after ingestion.

Pharmacokinetics

Polyethylene glycol is not absorbed systemically, and its pharmacokinetics are characterized by its presence solely in the gastrointestinal tract. It is excreted unchanged in the stool. The volume of polyethylene glycol administered can influence the effectiveness and timing of its action, but its absorption is negligible, making systemic side effects rare.

Adverse effects

• Abdominal cramping
• Diarrhea
• Nausea
• Vomiting
• Bloating
• Flatulence

Precautions

• Use with caution in patients with gastrointestinal disorders or bowel obstruction.
• Ensure adequate hydration during use to prevent dehydration.

Pregnancy

Polyethylene glycol is generally considered safe during pregnancy, but should be used under medical supervision.

Breast-feeding

Polyethylene glycol is excreted in breast milk in very small amounts and is generally regarded as safe during breastfeeding.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Powder for oral solution
• Liquid formulation

Mechanism of action

Ethylene glycol is metabolized by alcohol dehydrogenase to glycoaldehyde, which is then metabolized to glycolic, glyoxylic, and oxalic acids. These acids, along with excess lactic acid are responsible for the anion gap metabolic acidosis. Oxalic acid readily precipitates with calcium to form insoluble calcium oxalate crystals. Tissue injury is caused by widespread deposition of oxalate crystals and the toxic effects of glycolic and glyoxylic acids.

Mechanism of action

Mupirocin specifically and reversibly binds to bacterial isoleucyl transfer-RNA (tRNA) synthetase, which is an enzyme that promotes the conversion of isoleucine and tRNA to isoleucyl-tRNA. Inhibition of this enzyme subsequently leads to the inhibition of the bacterial protein and RNA synthesis. Mupirocin is bacteriostatic at lower concentrations but it exerts bactericidal effects with prolonged exposure, killing 90-99% of susceptible bacteria over a 24 hour period.

Pharmacodynamics

Mupirocin is reported to be active against susceptible aerobic gram-positive cocci, such as _Staphylococcus aureus_, _Staphylococcus epidermidis_, and other beta-hemolytic streptococci_Streptococcus pyogenes_. It mediates its antibacterial activity by inhibiting the bacterial protein synthesis and formation of bacterial proteins essential for survival. The minimum bactericidal concentration (MBC) against relevant pathogens is generally eight-fold to thirty-fold higher than the minimum inhibitory concentration (MIC). In one clinical study investigating the therapeutic effectiveness of topical mupirocin in impetigo, the therapeutic response rate was about 94 to 98% after one week following the end of therapy. In clinical studies of patients with primary and secondary skin infections, both elimination of the bacterial pathogen and clinical cure or improvement hav been demonstrated in over 90% of patients receiving topical mupirocin. Mupirocin resistance as high as 81% has been reported previously. Resistance to mupirocin, which occurs more frequently in methicillin-resistant than methicillin-susceptible staphylococci, may occur with the production of a modified isoleucyl-tRNA synthetase, or the acquisition of, by genetic transfer, a plasmid mediating a new isoleucyl-tRNA synthetase.