Polymyxin B 

Introduction

Polymyxin B is a last-line bactericidal antibiotic used in ICUs for multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative infections.

  • Carbapenem-resistant Enterobacterales (CRE)
  • MDR Pseudomonas
  • MDR Acinetobacter

 

 Mechanism of Action Target: Lipopolysaccharide (LPS) of Gram-negative outer membrane

 Bactericidal and concentration-dependent killing(Infuse over 60 minutes)

Also:Neutralizes endotoxin (LPS binding effect)

 

Spectrum of Activity

 Active Against

  • Carbapenem-resistant Klebsiella
  • CRE (NDM, KPC producers)
  • MDR Pseudomonas aeruginosa
  • MDR Acinetobacter baumannii
  • Some Enterobacter species

 Not Active Against

  • Gram positives
  • Anaerobes
  • Proteus
  • Serratia
  • Providencia
  • Morganella
  • Burkholderia cepacia

 

 Polymyxin B vs Colistin 

Feature

Polymyxin B

Colistin

Form

Active drug

Prodrug (CMS)

Loading dose

Not required

Required

Renal adjustment

No

Yes

Urinary concentration

Low

High

PK predictability

Better

Variable

Nephrotoxicity

Similar

Similar

✔ Polymyxin B is preferred in bloodstream infections
✔ Colistin preferred in UTI

 

 Pharmacokinetics 

Absorption

  • IV route for systemic infections

Distribution

  • Moderate tissue penetration
  • Poor lung epithelial lining fluid levels
  • Poor CSF penetration

Elimination

  • Non-renal clearance predominant
  • Minimal urinary excretion (~1%)

 Therefore:

  • No renal dose adjustment required
  • Can still cause nephrotoxicity

 

 

 Combination therapy preferred to:

  • Prevent resistance
  • Improve mortality

Used with:

  • Carbapenems (even if resistant)
  • Tigecycline
  • Fosfomycin
  • Aminoglycosides

 Adverse Effects 

1️⃣ Nephrotoxicity (Dose-Limiting)

Mechanism:

  • Acute tubular necrosis

 

2️⃣ Neurotoxicity

  • Paresthesias
  • Neuromuscular blockade
  • Muscle weakness
  • Respiratory paralysis (rare)

 Avoid with:

  • Neuromuscular blockers
  • Myasthenia gravis

 

3️⃣ Electrolyte Disturbances

  • Hypomagnesemia
  • Hypokalemia

 

 Resistance Mechanisms

  1. mcr-1 gene mediated plasmid resistance
  2. Modification of Lipid A
  3. Efflux pumps

mcr gene is a major global concern.

 

 Therapeutic Drug Monitoring (TDM)

Not widely available.

Target:

  • AUC/MIC optimization

 

 Current Guideline Position (2024–2025)

IDSA recommends:

⚠ Avoid polymyxins if newer beta-lactam/beta-lactamase inhibitors are active.

Use only when:

  • No alternative
  • Resource-limited settings

In India:

  • Still widely used due to cost issues