What is the recommended dosing regimen for intravenous polymyxin B and colistin (including loading and maintenance doses) in adults, and how should the doses be adjusted for renal impairment, extreme body weight, pediatric patients, and pulmonary infections?

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Polymyxin Dosing Recommendations

Polymyxin B: Preferred Agent for Renal Impairment

Polymyxin B is the preferred polymyxin in patients with any degree of renal dysfunction because it requires no dose adjustment regardless of creatinine clearance or dialysis status, and causes significantly less nephrotoxicity than colistin (11.8% vs 39.3%). 1, 2

Standard Polymyxin B Dosing (All Renal Functions)

  • Loading dose: 2.0–2.5 mg/kg IV (based on actual body weight), administered regardless of renal function 1, 3
  • Maintenance dose: 1.5–2.5 mg/kg/day IV divided every 12 hours 1, 3
    • FDA labeling states 15,000–25,000 units/kg/day (equivalent to 1.5–2.5 mg/kg/day) for adults and children with normal renal function 3
    • Infants may receive up to 40,000 units/kg/day (4 mg/kg/day) safely 3

Critical Advantage in Renal Impairment

  • No dose adjustment needed for any degree of renal insufficiency, including CRRT or intermittent hemodialysis 1, 4
  • Polymyxin B is administered as the active drug (not a prodrug), and plasma concentrations are not influenced by renal function 1, 4
  • Research confirms comparable drug exposures (AUC 63.5 ± 16.6 vs 56.0 ± 17.5 mg·h/L, p=0.42) in patients with normal versus impaired renal function receiving standard doses 4

Nephrotoxicity Profile

  • Polymyxin B nephrotoxicity occurs in 11.8% of patients versus 39.3% with colistin when both are dosed per current recommendations 2
  • Onset of nephrotoxicity averages 4.2 days, with 83.3% of affected patients recovering renal function within one week 2

Colistin: Alternative When Polymyxin B Unavailable

Colistin requires complex renal-based dose adjustments and causes substantially more nephrotoxicity than polymyxin B, making it a second-line choice for systemic therapy. 1, 2

Colistin Dosing for Normal Renal Function

  • Loading dose: 9 million IU (≈300 mg colistimethate sodium or 5 mg/kg colistin base activity) IV, administered to ALL patients regardless of renal function 5, 6, 7

    • The loading dose is mandatory because colistin's long half-life would otherwise result in subtherapeutic levels for 48–72 hours 5

  • Maintenance dose (CrCl ≥80 mL/min): 4.5 million IU IV every 12 hours (total 9 million IU/day) 5, 6

    • Alternative weight-based dosing: 2.5–5 mg/kg/day divided into 2–4 doses 6, 7
    • For critically ill patients with severe sepsis/septic shock: use the higher end (4.5 million IU q12h) 5

Colistin Dose Adjustment for Renal Impairment

Maintenance doses must be reduced based on creatinine clearance; failure to adjust markedly increases nephrotoxicity risk. 5

Creatinine Clearance Maintenance Dose
50–79 mL/min 2.5–3.8 mg/kg divided into 2 doses daily [5]
30–49 mL/min 2.5 mg/kg once daily or divided into 2 doses [5]
10–29 mL/min 1.5 mg/kg every 36 hours [5]
  • Formula-based alternative: Maintenance dose (mg CBA) = 2.5 × (1.5 × CrCl + 30) every 12 hours 5

Colistin Dosing for Renal Replacement Therapy

  • CRRT: Standard loading dose (9 million IU), then maintenance of at least 9 million IU/day (e.g., 3 million IU every 8 hours) 5

    • Do NOT reduce the dose for CRRT; full dosing is required to maintain therapeutic levels 5

  • Intermittent hemodialysis: Standard loading dose (9 million IU), then 2 million IU every 12 hours 5

    • Schedule dialysis toward the end of the dosing interval to minimize drug removal 5

Colistin Nephrotoxicity

  • Nephrotoxicity occurs in 39.3% of patients receiving currently recommended doses 2
  • Onset averages 3.8 days, with 75% of affected patients recovering within one week 2
  • Colistin nephrotoxicity is dose-dependent; daily doses ≥300 mg significantly increase risk 2
  • Acute kidney injury during colistin therapy is a major determinant of clinical failure and mortality 5

Critical Dosing Conversions for Colistin

  • 1 million IU colistimethate sodium = 80 mg CMS = 33 mg colistin base activity (CBA) 5, 6
  • Accurate conversion is essential to avoid 2–3-fold dosing errors 5

Special Populations and Situations

Obese Patients

  • Polymyxin B: Dose based on actual body weight 3
  • Colistin: Dose based on ideal body weight to avoid excessive exposure 7

Pediatric Patients

  • Polymyxin B:

    • Standard dosing: 15,000–25,000 units/kg/day (1.5–2.5 mg/kg/day) 3
    • Infants with normal renal function may safely receive up to 40,000 units/kg/day (4 mg/kg/day) 3
    • Premature and newborn infants with Pseudomonas sepsis: doses up to 45,000 units/kg/day have been used in limited studies 3

  • Colistin: Same weight-based dosing as adults (2.5–5 mg/kg/day), with loading dose of 5 mg/kg 5, 7

Pulmonary Infections (HAP/VAP)

For hospital-acquired or ventilator-associated pneumonia caused by carbapenem-resistant organisms susceptible only to polymyxins, add inhaled colistin to the intravenous regimen. 1, 5

  • Intravenous polymyxin B or colistin should be administered at standard doses 1
  • Adjunctive inhaled colistin is recommended based on pneumonia-specific guidelines 1, 5
  • Colistin is preferred over polymyxin B for inhaled administration based on controlled study evidence 1

Administration and Monitoring

Polymyxin B Administration

  • Administer as IV infusion over 1–2 hours 3
  • May divide total daily dose every 12 hours, but total must not exceed 25,000 units/kg/day 3
  • Intramuscular administration is not recommended due to severe injection site pain 3

Colistin Administration

  • Preferred method: 4-hour IV infusion to optimize pharmacokinetic/pharmacodynamic properties 5, 6
  • Alternative: Slow IV injection over 3–5 minutes for half the daily dose, followed by continuous infusion of the remaining half over 22–23 hours 7
  • Reconstituted solutions must be used within 24 hours 7

Mandatory Monitoring

  • Renal function: Check at baseline and 2–3 times per week during therapy 5
  • Close monitoring is essential because acute kidney injury is a major factor in treatment failure and mortality 5

Combination Therapy

For serious multidrug-resistant infections, polymyxins should be combined with at least one additional antimicrobial agent (e.g., carbapenem, sulbactam, tigecycline) to improve outcomes and reduce resistance selection. 5, 8

  • If no susceptible companion drug is available, combine with the nonsusceptible agent having the lowest MIC 5
  • Evidence for combination therapy superiority over monotherapy remains weak, but expert opinion strongly favors combination for severe infections 5, 8

Critical Pitfalls to Avoid

  • Never omit the loading dose of colistin—this results in 48–72 hours of subtherapeutic exposure and treatment failure 5
  • Never reduce colistin maintenance doses in CRRT patients—full dosing (≥9 million IU/day) is required 5
  • Always adjust colistin maintenance doses for renal impairment—failure to do so markedly increases nephrotoxicity 5
  • Avoid colistin in patients with renal dysfunction when polymyxin B is available—polymyxin B requires no dose adjustment and causes less nephrotoxicity 1, 2
  • Do not use polymyxin monotherapy for serious infections—combination therapy improves clinical outcomes 5, 8

References

1
Guideline

Polymyxin B in Renal Impairment

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

5
Guideline

Colistin Dosage Administration in Patients with Impaired Renal Function

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

6
Guideline

Colistin Dosage Guidelines for Patients with Normal Renal Function

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

8
Research

Intravenous polymyxins: Revival with puzzle.

Bioscience trends, 2017

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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