What is the recommended dosage of Colistin (Polymyxin E) for treating multi-drug resistant gram-negative bacterial infections in patients with Impaired renal function?

From the Guidelines

For patients with impaired renal function, the recommended dosage of Colistin (Polymyxin E) is an initial loading dose of 9 million international units (MIU) followed by maintenance doses adjusted according to creatinine clearance (CrCl).

Key Considerations

• The maintenance dose should be adjusted based on the degree of renal impairment, with close monitoring of renal function to minimize the risk of nephrotoxicity 1.
• For patients with CrCl 50-90 mL/min, maintenance doses of 4.5-7.5 MIU daily divided into two doses are appropriate.
• With CrCl 10-50 mL/min, reduce to 2.5-4.5 MIU daily in two divided doses.
• For severe impairment (CrCl <10 mL/min) including hemodialysis patients, 1.5-2.5 MIU daily is recommended, with supplemental dosing after dialysis sessions.
• Continuous renal replacement therapy patients typically require 4-6 MIU daily in two divided doses.

Important Notes

• Plasma level monitoring should be performed when available to optimize dosing 1.
• Treatment duration typically ranges from 7-14 days depending on infection severity, site, and clinical response, with careful assessment of benefit versus risk of further renal damage.
• The use of colistin-based combination therapy is controversial, and clinicians should weigh the benefits and risks of such therapy 1.
• It is essential to pay attention to the correct conversion of dosage, as the dose unit of polymyxin is expressed in different ways 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION ... The daily dose and frequency should be reduced for the patients with renal impairment Suggested modifications of dosage schedule for patients with renal impairment are presented in Table 1. TABLE 1 Suggested Modification of Dosage Schedules of Colistimethate for Injection, USP for Adults with Impaired Renal Function Degree of Renal Impairment | Creatinine Clearance (mL/min) | Dosage Schedule Normal | ≥80 | 2.5 to 5 mg/kg, divided into 2 to 4 doses per day Mild | 50-79 | 2.5 to 3.8 mg/kg, divided into 2 doses per day Moderate | 30-49 | 2.5 mg/kg, once daily or divided into 2 doses per day Severe | 10-29 | 1.5 mg/kg every 36 hours

The recommended dosage of Colistin for treating multi-drug resistant gram-negative bacterial infections in patients with impaired renal function is as follows:

• Mild renal impairment: 2.5 to 3.8 mg/kg, divided into 2 doses per day
• Moderate renal impairment: 2.5 mg/kg, once daily or divided into 2 doses per day
• Severe renal impairment: 1.5 mg/kg every 36 hours 2

From the Research

Colistin Dosage for Multi-Drug Resistant Gram-Negative Bacterial Infections

• The recommended dosage of Colistin (Polymyxin E) for treating multi-drug resistant gram-negative bacterial infections is not explicitly stated in the provided studies, but it is emphasized that dosage alterations are imperative in patients with impaired renal function to achieve maximal efficacy and minimal toxicity 3, 4.
• Colistin is mainly distributed within the extracellular space, and its renal clearance is very low, but the dosing regimen should be adapted to the renal function of the patient because CMS is partly eliminated by the kidney 4.
• Therapeutic drug monitoring of colistin is warranted because the pharmacokinetics of colistin are very variable, and its therapeutic window is narrow 4.
• The use of a loading dose might reduce the emergence of resistance, but the use of colistin in combination also seems necessary 4.
• International consensus guidelines for the optimal use of the polymyxins, including colistin, have been established, which provide recommendations for agent selection, dosing, dosage adjustment, and monitoring of colistin 5.

Dosage Considerations in Patients with Impaired Renal Function

• Patients with impaired renal function may require dosage adjustments to minimize the risk of toxicity, particularly nephrotoxicity 3, 4.
• The dosing regimen should be adapted to the renal function of the patient, as CMS is partly eliminated by the kidney 4.
• Therapeutic drug monitoring is crucial in patients with impaired renal function to ensure optimal dosing and minimize the risk of toxicity 4.

Clinical Evidence and Guidelines

• Clinical studies have shown that colistin can be effective in treating multi-drug resistant gram-negative bacterial infections, but its use is often associated with renal toxicity 6, 7.
• International consensus guidelines recommend careful consideration of the pharmacokinetic and pharmacodynamic properties of colistin, as well as the use of therapeutic drug monitoring to optimize dosing and minimize toxicity 5.
• The guidelines also recommend the use of colistin in combination with other antibiotics to reduce the emergence of resistance 5.