Polymyxin B

Polymyxin B is a polymyxin given directly as the active drug (not a prodrug), used IV for carbapenem-resistant Gram-negative infection and intrathecally for meningitis. Unlike colistin, it is cleared non-renally, so no dose reduction is needed in kidney impairment.

Classification. Polymyxin.

Mechanism. Binds lipopolysaccharide in the outer membrane of Gram-negative bacteria and disrupts the membrane; bactericidal.

Spectrum. Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Enterobacter. Not active against Proteus, Providencia, Serratia, Morganella, Burkholderia, Gram-positive bacteria or anaerobes. Cross-resistance with colistin is complete.

Pharmacokinetics. IV only for systemic use. Active drug with a half-life of 9 to 12 hours. Poor CSF, lung and bone penetration. Cleared by non-renal routes with minimal urinary excretion, so urinary levels are lower than colistin.

Reserve agent; combine with a second active drug. Maximum 3 mg/kg/day (30 000 units/kg/day). 1 mg = 10 000 units.

Adults, IV. - Loading dose 2 to 2.5 mg/kg (20 000 to 25 000 units/kg) over 60 minutes, based on actual body weight (cap total at 200 mg). - Maintenance, from 12 hours later: 1.25 to 1.5 mg/kg (12 500 to 15 000 units/kg) every 12 hours, over 60 minutes. - No dose adjustment in renal impairment (keep to the lower end with severe impairment). - Duration 7 to 14 days, depending on site and response.

Intrathecal or intraventricular (specialist, with IV therapy). Adults 50 000 units (5 mg) once daily for 3 to 4 days, then every 2 days for at least 2 weeks after cerebrospinal fluid cultures are negative. Children under 2 years 20 000 units once daily for 3 to 4 days, or 25 000 units every 2 days.

Children (IV). 1.5 to 2.5 mg/kg/day (15 000 to 25 000 units/kg/day) in 2 divided doses; neonates up to 4 mg/kg/day.

Alternatives. Colistin, ceftazidime avibactam, cefiderocol, meropenem vaborbactam, tigecycline.

Boxed-warning level risks. Nephrotoxicity, neurotoxicity and neuromuscular blockade; use in hospital with monitoring.

Contraindications. Hypersensitivity; concurrent use of other nephrotoxic or neurotoxic drugs unless unavoidable; myasthenia gravis (relative).

Adverse effects. Nephrotoxicity (dose related, often reversible), neurotoxicity (paraesthesia, dizziness, ataxia, confusion), neuromuscular blockade, skin hyperpigmentation (pigmentation reported with prolonged use), pain and thrombophlebitis at injection sites, fever, rash. Intrathecal: meningeal irritation, headache.

Interactions. Aminoglycosides, vancomycin, amphotericin B, NSAIDs, loop diuretics, contrast and other nephrotoxins; neuromuscular blockers and anaesthetics; colistin (never combine).

Common prescribing errors. Intramuscular injection (severe pain; avoid), unit confusion between units and milligrams, monotherapy, and concurrent nephrotoxins.

Special groups. - Pregnancy: avoid unless no alternative. Breastfeeding: avoid if possible. - Older adults: higher risk of kidney injury and neurotoxicity. - Kidney impairment: no adjustment; monitor creatinine daily. - Liver impairment: no adjustment. - Region: supply is limited in East Africa.

Preparation. Dilute the vial (500 000 units) in 300 to 500 mL of 5% glucose and infuse over 60 minutes. Intrathecal: reconstitute with preservative-free 0.9% sodium chloride; do not use IV solution containing preservatives.

Baseline and monitoring. - Baseline: creatinine, electrolytes, weight, neurological examination, medication review. - During treatment: creatinine daily to every 48 hours; neurological and respiratory status.

Stop rules. Stop for rising creatinine without another cause, neurotoxicity, neuromuscular weakness, apnoea or hypersensitivity.

Referral and escalation. Infectious diseases consultation before use; neurosurgery or intensive care for intraventricular therapy or respiratory depression.