Polymyxin B
Formulary Guideline for Use of IV Polymyxin B
- Polymyxin B, when administered intravenously, is restricted to Infectious Disease and Pulmonary Services. Use by other services requires consultation with Infectious Disease or Pulmonary. The drug will be distributed for 24 hours only unless one of those groups has been formally consulted and approved the use.
Criteria for Use
- Polymyxin B is recommended over Colistin for treatment of systemic gram negative infections, generally in combination with other antimicrobials.
- Polymyxin B is preferred due to more predictable pharmacokinetics compared to colistin and less associated nephrotoxicity.
- Polymyxin B should NOT be used for urinary tract infections because it achieves low concentrations in the urine.
- Colistin is preferred for UTIs since high concentrations occur in the urine.
Dosing Guidance
- Loading dose
- A loading dose should be considered for critically ill patients (e.g., sepsis, septic shock) to reach pharmacodynamics targets for organisms with an MIC <2 mg/L
- Up to 25,000 units/kg administered over 1-2 hours using an adjusted body weight is preferred (e.g. 1,500,000 – 2,000,000 units x1)
- There is not a specific maximum or dose cap recommended, however, experience with doses over 2 million units is limited
- Infusion-related adverse events may occur with higher doses (thoracic pain, paresthesias, dizziness, dyspnea, hypoxemia)
- Maintenance dose
- For severe infections, a maintenance dose of 12,500 units/kg (12,500 to 15,000 units/kg) 12 hours is recommended
- Round to the nearest 50,000 units and administer over 1 hour (e.g. 750,000 – 1 million units)
- Dose Adjustments
- No dose adjustments are recommend for patients with renal impairment.
- For patients on renal replacement therapy (CRRT), no dose adjustments are required. This applied to both the loading and the maintenance doses.
- Concomitant therapy
- Nephrotoxic agents should be avoided when possible (e.g., calcineurin inhibitors, loop diuretics, vasopressors, IV contrast media, NSAIDs, ACEI, and other nephrotoxic antibiotics like vancomycin)
- The routine use of antioxidants for renal protection is not recommended
| Loading Dose | Maintenance Dose | |
|---|---|---|
| Dosing regimen | 20,000-25,000 units/kg x 1 | 12,500 to 15,000 units/kg Q12 hours |
| Duration of infusion | 1 hour | 1 hour |
| Dose adjustment for renal dysfunction | No | No |
| Dose adjustment for patients on CRRT | No | No |
The body weight that is to be used for the loading dose and the maintenance dose should be adjusted body weight in obese patients.
Reference: Tsuji BT, Pogue JM, Zavascki AP, et al. International Consensus Guidelines for the Optimal Use of the Polymyxins: Endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). Pharmacotherapy. 2019 Jan;39(1):10-39. doi: 10.1002/phar.2209.