Guidelines for Using Colistin to Treat Multi-Drug Resistant Gram-Negative Bacterial Infections
Colistin (polymyxin E) should be used for treating infections caused by multi-drug resistant gram-negative bacteria when newer agents are not available or susceptible, with careful monitoring of renal function due to significant nephrotoxicity risk. 1
First-Line Treatment Options (In Order of Preference)
Newer β-lactam/β-lactamase inhibitors (if susceptible):
- Ceftolozane-tazobactam
- Ceftazidime-avibactam
- Imipenem-cilastatin-relebactam
- Cefiderocol
Colistin-based therapy (when newer agents are unavailable/resistant):
- Adult dosing: Loading dose of 9 MU (5 mg/kg) followed by maintenance dose of 4.5 MU twice daily 1
- Pediatric dosing: Loading dose of 0.15 MU/kg followed by maintenance dose of 0.075 MU/kg every 12 hours 1
- Note: FDA-recommended pediatric dosing may be inadequate when MIC ≥1 mg/L or in patients with augmented renal clearance 1
Combination vs. Monotherapy
The use of colistin-based combination therapy remains controversial with conflicting evidence:
- For critically ill patients with severe infections caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA), consider combination therapy with two in vitro active drugs when using colistin 1, 2
- If a susceptible second agent is not available, colistin may be combined with a non-susceptible agent (e.g., carbapenem) with the lowest MIC 1
- For non-severe infections, monotherapy with an in vitro active drug may be appropriate 1
Specific Combination Options
- Colistin + carbapenem: Evidence is mixed - one randomized controlled trial showed no superiority over colistin monotherapy 1
- Colistin + rifampin: Not recommended based on RCT evidence showing no advantage over colistin monotherapy 1
- Colistin + glycopeptide: Associated with higher nephrotoxicity without mortality benefit 1
- Colistin + ampicillin-sulbactam: May provide benefit for ventilator-associated pneumonia caused by susceptible Acinetobacter baumannii 1
Monitoring and Safety
- Renal function: Must be closely monitored during colistin therapy (strong recommendation) 1
- Nephrotoxicity risk: 14-20% of patients may develop acute kidney injury 1, 3
- Neurotoxicity risk: Reported in approximately 3.5% of patients 3
- Risk factors for toxicity: Advanced age, chronic kidney disease, concomitant nephrotoxic medications 1
Administration Routes
- Intravenous: Standard route for systemic infections 4
- Nebulized/inhaled: May be considered as adjunctive therapy for respiratory infections 5, 6
- Intrathecal/intraventricular: Option for CNS infections 5
Treatment Duration
Based on infection type:
- Complicated urinary tract infections: 5-10 days 2
- Complicated intra-abdominal infections: 5-10 days 2
- Ventilator-associated or hospital-acquired pneumonia: 10-14 days 2
- Bacteremia: 10-14 days 2
Clinical Pearls and Pitfalls
- Pitfall: Inadequate loading dose - Always start with appropriate loading dose to rapidly achieve therapeutic levels 1
- Pitfall: Failure to adjust for renal function - Dose must be adjusted based on creatinine clearance 1
- Pearl: Consider infectious disease consultation for management of CRPA infections 2
- Pearl: Antimicrobial susceptibility testing is essential to guide definitive therapy 2
- Pitfall: Delaying treatment - Early appropriate therapy is critical for improved outcomes 7
- Pearl: Clinical response rates of 51-85% have been reported with appropriate colistin therapy 3, 7
Special Populations
- Critically ill: Higher doses may be needed due to altered pharmacokinetics 1
- Renal impairment: Requires dose adjustment and more frequent monitoring 1
- Pediatric patients: Limited data on optimal dosing; FDA recommendations may be inadequate in certain scenarios 1
- Cystic fibrosis: Common indication for nebulized colistin 6
Remember that colistin should be reserved for infections proven or strongly suspected to be caused by susceptible bacteria to reduce the development of drug-resistant bacteria 4.