Polymyxin Coverage Recommendations
For multidrug-resistant gram-negative bacterial infections, polymyxin combination therapy is strongly recommended over monotherapy, with a loading dose of 5 mg/kg colistin base activity followed by maintenance dosing of 2.5 mg CBA × (1.5 × CrCl + 30) every 12 hours. 1, 2
Dosing Recommendations
Colistin (Polymyxin E)
- Loading dose: 5 mg/kg colistin base activity (CBA) IV administered over 0.5-1 hour
- Maintenance dose: 2.5 mg CBA × (1.5 × CrCl + 30) IV every 12 hours
- Equivalent dosing: 9 million IU loading dose, followed by 4.5 million IU twice daily
- Dose conversion: 1 million IU = 33 mg CBA = 80 mg colistimethate sodium (CMS)
Polymyxin B
- Dosing: 15,000 to 25,000 units/kg/day for patients with normal renal function
- Administration: Dissolve 500,000 polymyxin B units in 300-500 mL of 5% Dextrose Injection for continuous drip
- Frequency: Can be given every 12 hours, but total daily dose must not exceed 25,000 units/kg/day 3
Indications for Polymyxin Use
Polymyxins are indicated for infections caused by:
- Carbapenem-resistant Acinetobacter baumannii (CRAB)
- Carbapenem-resistant Pseudomonas aeruginosa (CRPA)
- Difficult-to-treat Pseudomonas aeruginosa (DTR-PA)
- Carbapenem-resistant Enterobacterales (CRE)
Combination Therapy Recommendations
Polymyxin combination therapy is superior to monotherapy for:
- CRGNB infections: Strong recommendation, moderate-quality evidence 1
- CRE bloodstream infections: Reduces mortality compared to monotherapy (35.7% vs 55.5%) 1
Recommended Combinations:
- Colistin + carbapenem: When meropenem MIC is ≤8 mg/L for CRE or ≤32 mg/L for CRAB
- Colistin + tigecycline: Particularly for CRE bloodstream infections
- Colistin + fosfomycin: For CRAB infections
- Colistin + rifampicin: For XDR A. baumannii infections
Treatment Duration
| Infection Type | Recommended Duration |
|---|---|
| Pneumonia | 7-14 days |
| Bloodstream infections | 10-14 days |
| Complicated UTI | 5-7 days |
| Complicated intra-abdominal infections | 5-7 days |
Monitoring and Safety
- Renal function monitoring: Mandatory during treatment (Strong recommendation) 1
- Therapeutic drug monitoring: Encouraged where available due to high interpatient variability
- Nephrotoxicity risk:
- Colistin: 39.3% of patients
- Polymyxin B: 11.8% of patients 4
- Onset typically occurs 3-4 days after starting therapy
- Avoid concurrent nephrotoxic agents: Particularly vancomycin, which increases AKI risk 5
Alternative Therapies
When available and susceptible, newer agents are preferred over polymyxins due to better safety profiles:
- Ceftazidime-avibactam: 2.5g IV q8h (infused over 3h)
- Meropenem-vaborbactam: 4g IV q8h (infused over 3h)
- Imipenem-cilastatin-relebactam: 1.25g IV q6h
- Ceftolozane-tazobactam: For CRPA infections if susceptible
Clinical Pitfalls to Avoid
- Failure to administer loading dose: Results in delayed achievement of therapeutic concentrations
- Inconsistent dosing units: Pay attention to correct conversion between IU, CBA, and CMS
- Inadequate renal dose adjustment: Increases nephrotoxicity risk
- Monotherapy for high MIC pathogens: Use combination therapy when MIC >1 mg/L
- Overlooking antimicrobial susceptibility testing: Essential for guiding optimal combination therapy
Special Populations
- Pediatric patients: FDA/EMA recommends loading dose of 0.15 MU/kg followed by maintenance dose of 0.075 MU/kg every 12h, but may be inadequate when MIC ≥1 mg/L
- Renal impairment: Dose reduction required; polymyxin B may be preferred over colistin in patients with renal dysfunction 4
- Critical illness: Higher doses may be required due to augmented renal clearance
Polymyxins remain a critical last-line treatment option for multidrug-resistant gram-negative infections, but their use requires careful attention to dosing, monitoring, and combination strategies to optimize efficacy while minimizing toxicity.