What is the recommended loading and maintenance dosing of colistimethate sodium for an adult with stage 5 chronic kidney disease (estimated glomerular filtration rate < 15 mL/min/1.73 m²), including adjustments for patients not on dialysis, on intermittent hemodialysis, and on continuous renal replacement therapy?

Colistin Dosing in Stage 5 CKD

For adults with stage 5 CKD (eGFR <15 mL/min/1.73 m²), always administer a loading dose of 9 million IU (5 mg CBA/kg) intravenously regardless of renal function, followed by maintenance dosing that varies based on whether the patient is on dialysis: for patients not on dialysis, use the formula-based approach [2.5 mg CBA × (1.5 × CrCL + 30)] every 12 hours; for intermittent hemodialysis, give 2 million IU every 12 hours after dialysis; and for continuous renal replacement therapy (CRRT), administer 3 million IU every 8 hours. 1

Loading Dose (Universal for All Stage 5 CKD Patients)

• Administer 9 million IU (≈5 mg CBA/kg) intravenously as a single loading dose to all patients, regardless of renal function status. 1
• This loading dose is critical because colistin has a relatively long half-life, and omitting it results in subtherapeutic plasma concentrations for 48-72 hours, increasing risk of treatment failure. 1
• The loading dose applies equally to patients not on dialysis, those on intermittent hemodialysis, and those receiving CRRT. 1

Maintenance Dosing: Patients NOT on Dialysis

• For stage 5 CKD patients not yet on renal replacement therapy (CrCL <15 mL/min), calculate the maintenance dose using the formula: 2.5 mg CBA × (1.5 × creatinine clearance + 30) mg, administered every 12 hours intravenously. 1
• For a patient with CrCL of 10 mL/min, this yields approximately 55 mg CBA (≈1.65 million IU) every 12 hours. 1
• Do not use fixed low doses (such as the older recommendation of 1-1.5 million IU/day total), as these create substantial risk of subtherapeutic exposure, particularly for pathogens with MIC ≥1 mg/L. 2

Maintenance Dosing: Intermittent Hemodialysis (IHD)

• After the standard 9 million IU loading dose, administer 2 million IU every 12 hours as the maintenance regimen. 1
• Schedule hemodialysis sessions toward the end of the colistin dosing interval to minimize premature drug removal during dialysis. 1
• Colistin is partially removed by intermittent hemodialysis, but supplemental post-dialysis dosing beyond the standard 2 million IU every 12 hours is not routinely required. 1

Maintenance Dosing: Continuous Renal Replacement Therapy (CRRT)

• Following the 9 million IU loading dose, give 3 million IU every 8 hours (total 9 million IU/day) for patients on CRRT. 1, 3
• Do not reduce the maintenance dose in CRRT patients—they require at least 9 million IU daily to maintain therapeutic plasma concentrations because CRRT significantly enhances colistin clearance (accounting for approximately 28% of total clearance). 3, 4
• CRRT settings matter: lower blood flow rates (e.g., 100 mL/min in continuous venovenous hemodialysis) may allow adequate drug exposure with this regimen, but higher flow rates or highly adsorptive membranes increase drug removal. 3, 4
• Consider therapeutic drug monitoring (TDM) in CRRT patients to ensure target steady-state concentrations of ≥2 mg/L are achieved, particularly if clinical response is suboptimal. 3, 5

Dosing Conversion Reference

• 1 million IU of colistimethate sodium = 80 mg CMS = 33 mg colistin base activity (CBA). 1
• Accurate conversion is essential to avoid 2-3 fold dosing errors that can lead to either toxicity or treatment failure. 1

Critical Monitoring and Safety Considerations

• Monitor renal function closely at baseline and 2-3 times per week during treatment, as acute kidney injury during colistin therapy is a major determinant of clinical failure and increased mortality. 1
• Paradoxically, despite higher colistin exposure in patients with severe renal impairment, dose reduction below therapeutic targets is not recommended because subtherapeutic dosing increases mortality risk more than nephrotoxicity does. 2
• For pathogens with MIC ≥1 mg/L (particularly Pseudomonas species), the recommended doses may be inadequate even with proper adjustment—strongly consider combination therapy with a carbapenem or another active agent in these cases. 1

Combination Therapy Recommendation

• Never use colistin as monotherapy for serious infections in stage 5 CKD patients. Combine with at least one additional antimicrobial (e.g., carbapenem via extended infusion, tigecycline) based on susceptibility testing to improve clinical outcomes and reduce resistance selection. 1
• If no susceptible companion drug is available, combine colistin with the nonsusceptible agent that has the lowest MIC to maximize therapeutic effect. 1

Common Pitfalls to Avoid

• Do not omit the loading dose in stage 5 CKD—this is the most common error and results in delayed therapeutic concentrations for 2-3 days. 1
• Do not use outdated fixed low-dose regimens (e.g., 1-1.5 million IU/day total) found in older references, as these are inadequate for modern multidrug-resistant pathogens. 2
• Do not reduce CRRT maintenance doses below 9 million IU/day—patients on CRRT have enhanced clearance and require full dosing. 1, 3
• Do not rely solely on serum creatinine to estimate renal function in critically ill or edematous patients; use calculated creatinine clearance (Cockcroft-Gault) or measured values when possible, as GFR can be substantially higher than SCr suggests. 6