Polymyxin — Last-Resort MDR / Carbapenem-Resistant Gram-Negatives Pregnancy: Avoid — nephrotoxicity and neurotoxicity risk; use only for life-threatening MDR infections with no alternative

Colistin (Polymyxin E)

Brand names: Colomycin, Promixin (nebulised)

Adult dose

Dose: IV: loading dose 9 million units (MU) then 4.5 MU every 12 hours; adjust by renal function; Nebulised (cystic fibrosis/bronchiectasis): 1–2 MU twice daily

Route: IV infusion or nebulised

Frequency: Every 12 hours (IV); twice daily (nebulised)

Max: 9 MU/day IV (renal function-dependent)

LAST-RESORT antibiotic for carbapenem-resistant Acinetobacter, Klebsiella, Pseudomonas (CRAB, CRKP, CRPA). Prodrug colistimethate sodium (CMS) — converted to active colistin in vivo. Must ALWAYS use in combination (resistance emerges rapidly on monotherapy). TDM available but not universally standardised. Note: 1 million units ≈ 80 mg colistimethate sodium.

Paediatric dose

Dose: Loading: 75,000–150,000 units/kg then 50,000–75,000 units/kg every 8 hours units/kg

Route: IV

Frequency: Every 8 hours (children)

Max: 9 MU/day

BNFc: specialist use only; always in combination; TDM essential

Dose adjustments

Renal

CrCl 50–79: 4.5 MU every 12 hours; CrCl 30–49: 4.5 MU every 18 hours; CrCl <30: 4.5 MU every 24 hours; CRRT: specialist dosing required; dialysis patients — specialist guidance

Hepatic

No dose adjustment required

Paediatric weight-based calculator

Patient weight (kg)

BNFc: specialist use only; always in combination; TDM essential

Clinical pearls

Used only when all other options exhausted — MDR/XDR gram-negative infections; never use as monotherapy (resistance develops rapidly)
IV colistin (CMS prodrug) has complex pharmacokinetics — slow conversion to active colistin means loading dose essential to achieve rapid therapeutic levels
Nebulised colistin for chronic Pseudomonas colonisation in bronchiectasis/CF — systemic absorption minimal; can be used alongside IV antibiotics
Combination regimens: colistin + carbapenem (synergy even against resistant strains via membrane permeabilisation allowing carbapenem entry) or colistin + rifampicin or colistin + fosfomycin
Nephrotoxicity monitoring critical: daily U&E; reduce dose or consider alternative if AKI develops

Contraindications

Myasthenia gravis
Hypersensitivity to colistin/polymyxins

Side effects

Nephrotoxicity (dose-limiting — acute kidney injury in 40–60%)
Neurotoxicity (dizziness, perioral paraesthesia, confusion, neuromuscular blockade)
Apnoea (with neuromuscular blocking agents)
Bronchospasm (nebulised)
Hyponatraemia

Interactions

Aminoglycosides — additive nephrotoxicity
Neuromuscular blocking agents — additive blockade and apnoea risk
Vancomycin — additive nephrotoxicity
Loop diuretics — additive nephrotoxicity

Monitoring

Renal function daily (mandatory)
Colistin serum levels if available (target Css,avg 2–4 mg/L)
Neurotoxicity (perioral paraesthesia, confusion)
Respiratory function during nebulisation
FBC

Reference: BNFc; BNF 90; EUCAST Colistin Guidelines; PHE MDR Organism Guidelines; Daikos et al. (Colistin Combinations); MHRA SPC Colomycin. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways