Polymyxin B Dosing and Indications for Multidrug-Resistant Gram-Negative Bacteria
Polymyxin B is indicated for treating serious infections caused by multidrug-resistant gram-negative bacteria, with a recommended loading dose of 2-2.5 mg/kg followed by maintenance dosing of 1.5-3 mg/kg/day divided into two doses, with dosing based on total body weight rather than renal function. 1, 2
Indications
- Polymyxin B is a drug of choice for treating infections caused by susceptible strains of Pseudomonas aeruginosa affecting the urinary tract, meninges, and bloodstream 2
- It is indicated for serious infections caused by multidrug-resistant gram-negative bacteria, including carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Enterobacterales (CRE), when less toxic drugs are ineffective or contraindicated 1, 2
- Other susceptible organisms include Haemophilus influenzae (meningeal infections), Escherichia coli (urinary tract infections), Aerobacter aerogenes (bacteremia), and Klebsiella pneumoniae (bacteremia) 2
Dosing Recommendations
General Dosing
- Loading dose: 2-2.5 mg/kg 1
- Maintenance dose: 1.5-3 mg/kg/day divided into two doses 1
- Continuous infusion may be suitable in some cases 1
- Loading dose should be administered in all patients, including those with renal dysfunction 1, 3
Special Populations
- Renal dysfunction: Unlike colistin, polymyxin B dosing does not require adjustment based on renal function 1, 3
- Patients on continuous renal replacement therapy (CRRT): Same dose as patients with normal renal function 1
- Liver dysfunction: No significant dose adjustment required based on Child-Pugh classification 4
Administration Considerations
- Polymyxin B is administered intravenously and is not a prodrug (unlike colistin methanesulfonate) 1
- Loading dose is critical to achieve optimal plasma levels on the first day of treatment 1, 3
- Dose should be calculated based on total body weight, not ideal body weight 3
- Therapeutic drug monitoring (TDM) is encouraged when available due to high interpatient variability 1
Combination Therapy
- Polymyxin B combination therapy is strongly recommended over monotherapy for treating multidrug-resistant gram-negative infections 1, 5
- For CRAB infections, if meropenem MIC is ≤32 mg/L, consider polymyxin B-carbapenem combination with extended-infusion of meropenem for 3 hours 1, 5
- For CRE bloodstream infections, polymyxin B can be combined with tigecycline or meropenem 1
- For complicated intra-abdominal infections due to CRE, polymyxin B can be combined with tigecycline or meropenem 1
Monitoring and Adverse Effects
- Monitor renal function during treatment, as nephrotoxicity occurs in approximately 14% of patients with normal baseline renal function 1, 6
- Nephrotoxicity risk increases with older age (significant association with age >75 years) 6
- Avoid concurrent use of other nephrotoxic or ototoxic drugs 1
- Common neurotoxicity-related adverse events include perioral paresthesia, dizziness, and numbness of extremities 7
- Acute toxicity is a dose-limiting factor for intravenous polymyxin B 7
Important Dosing Conversions
- Polymyxin B sulfate: 1 mg = 10,000 units 1
- For comparison with colistin: 1 million international units (IU) of colistin = 80 mg colistin methanesulfonate (CMS) = 33 mg colistin base activity (CBA) 1
Clinical Pearls
- Polymyxin B clearance is predominantly non-renal (median urinary recovery only 4.04%), explaining why dosing is not adjusted based on renal function 3
- The incidence of renal failure appears to be lower with polymyxin B than with colistin 1
- Combination therapy reduces treatment failure rates by approximately 119 cases per 1000 patients compared to monotherapy 1
- For intrathecal administration (meningeal infections), polymyxin B should ONLY be administered via the intrathecal route 2