What is the appropriate colistin dosing regimen (loading dose, maintenance dose, renal adjustments, and duration) for an adult with a multidrug‑resistant liver abscess and no severe renal impairment?

Colistin for Multidrug-Resistant Liver Abscess

For an adult with a multidrug-resistant liver abscess and normal renal function, administer colistin with a loading dose of 9 million IU (5 mg/kg colistin base activity) intravenously, followed by a maintenance dose of 4.5 million IU every 12 hours, combined with at least one additional active antimicrobial agent, and ensure aggressive source control with drainage of the abscess. 1, 2, 3

Loading Dose (Critical First Step)

• All patients must receive a loading dose of 9 million IU (equivalent to 5 mg/kg colistin base activity) intravenously, regardless of renal function. 1, 3
• This loading dose is non-negotiable because colistin has a long half-life; omitting it results in subtherapeutic plasma concentrations for 48-72 hours, significantly increasing treatment failure risk. 1
• Administer the loading dose slowly over 3-5 minutes as a direct intravenous injection. 3

Maintenance Dosing for Normal Renal Function

• For patients with normal renal function (creatinine clearance ≥80 mL/min), administer 4.5 million IU every 12 hours. 1, 3
• Alternatively, use the formula-based approach: 2.5 mg CBA × (1.5 × creatinine clearance + 30) mg every 12 hours, which automatically adjusts for renal function. 1
• The FDA-approved dosing range is 2.5-5 mg/kg per day of colistin base divided into 2-4 doses, but higher doses (9 million IU daily) are recommended for severe infections. 3, 1

Renal Function Adjustments

Mild Renal Impairment (CrCl 50-79 mL/min)

• Reduce maintenance dose to 2.5-3.8 mg/kg divided into 2 doses per day. 3
• Always give the full loading dose of 9 million IU. 1

Moderate Renal Impairment (CrCl 30-49 mL/min)

• Reduce maintenance dose to 2.5 mg/kg once daily or divided into 2 doses. 3

Severe Renal Impairment (CrCl 10-29 mL/min)

• Reduce maintenance dose to 1.5 mg/kg every 36 hours. 3

Continuous Renal Replacement Therapy (CRRT)

• Do not reduce the dose for patients on CRRT. 1
• Administer the standard loading dose of 9 million IU, followed by maintenance of 3 million IU every 8 hours (total 9 million IU daily). 1
• CRRT patients require full dosing because colistin is significantly cleared by dialysis. 1

Intermittent Hemodialysis

• Give the standard loading dose of 9 million IU, then 2 million IU every 12 hours. 1
• Schedule dialysis toward the end of the dosing interval to minimize drug removal. 1

Combination Therapy (Mandatory for Serious Infections)

• Colistin should never be used as monotherapy for a liver abscess. 2, 1
• Combine colistin with at least one additional antimicrobial agent selected based on in vitro susceptibility testing. 2, 4
• If no susceptible companion drug is available, combine colistin with a nonsusceptible agent that has the lowest minimum inhibitory concentration. 1, 2
• For carbapenem-resistant Enterobacterales (common in liver abscesses), the preferred combination is colistin plus tigecycline (100 mg IV loading dose, then 50 mg IV every 12 hours). 2
• Combination therapy improves clinical outcomes, reduces mortality, and prevents emergence of resistance. 2, 1

Source Control (Absolutely Essential)

• Source control is mandatory and must be prioritized to optimize outcomes and shorten antibiotic duration. 4, 2
• For liver abscess, this means percutaneous or surgical drainage of the abscess cavity. 4, 2
• Without adequate drainage, antibiotic therapy alone—even with optimal dosing—will likely fail. 4

Duration of Therapy

• Treat for 7-14 days depending on clinical response and adequacy of source control. 2
• Continue therapy until clinical improvement is documented, the abscess cavity resolves or significantly decreases in size, and inflammatory markers normalize. 2

Administration Methods

• Administer maintenance doses as a slow intravenous infusion over 4 hours to optimize pharmacokinetic/pharmacodynamic properties. 1
• Alternatively, for continuous infusion: inject half the total daily dose over 3-5 minutes, then infuse the remaining half over 22-23 hours. 3
• Compatible intravenous solutions include 0.9% NaCl, 5% dextrose in water, 5% dextrose in 0.9% NaCl, lactated Ringer's solution. 3
• Prepare fresh infusion solutions and use within 24 hours. 3

Critical Monitoring Requirements

• Monitor renal function daily with serum creatinine and creatinine clearance calculations. 2, 1
• Nephrotoxicity occurs in 10.9-53.7% of patients receiving colistin, though most cases are reversible. 2, 5
• Check renal function at baseline and 2-3 times per week during treatment. 1
• Acute kidney injury during colistin therapy is a major determinant of treatment failure and increased mortality. 1, 2
• Monitor for neurotoxicity (rare but serious), including paresthesias, muscle weakness, and respiratory depression. 6

Important Dosing Conversions

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

Common Pitfalls to Avoid

• Never omit the loading dose—this is the most common error and leads to delayed therapeutic concentrations for 2-3 days. 1
• Do not reduce maintenance doses in CRRT patients—they require full dosing despite dialysis. 1
• Do not use colistin monotherapy for serious infections—combination therapy is essential for liver abscesses. 2, 1
• Do not neglect source control—antibiotics alone will not cure an undrained abscess. 4, 2
• Failure to adjust maintenance doses for renal impairment markedly increases nephrotoxicity risk. 1

Special Considerations for Liver Abscess

• While the evidence primarily addresses pneumonia and bacteremia, the principles apply to deep-seated infections like liver abscesses. 4, 2
• Colistin penetration into abscess cavities may be suboptimal, making adequate drainage even more critical. 4
• Consider therapeutic drug monitoring if available to ensure adequate plasma concentrations, particularly in critically ill patients with altered pharmacokinetics. 4, 1