What is the difference between Polymyxin (Polymyxin B) and Colistin in treating infections, particularly in terms of dosing and potential nephrotoxicity?

Polymyxin B vs Colistin: Key Differences and Clinical Selection

Polymyxin B is the preferred polymyxin for patients with renal impairment or those at high risk for nephrotoxicity, as it causes significantly less kidney injury (11.8% vs 39.3% with colistin) and requires no dose adjustment in renal dysfunction or during continuous renal replacement therapy. 1

Critical Pharmacokinetic Distinctions

Administration Forms

• Polymyxin B is administered as the active drug directly, with plasma concentrations unaffected by renal function 1
• Colistin is given as colistimethate sodium (CMS), an inactive prodrug that must be converted to active colistin in the body 2, 3, 4
• One million IU of colistin equals 80 mg of CMS 1, 2

Nephrotoxicity Profile

• Polymyxin B demonstrates substantially lower nephrotoxicity rates (11.8% incidence) 1
• Colistin causes nephrotoxicity in 39.3% of patients, occurring earlier in treatment and more frequently than polymyxin B 1, 5
• In adjusted analyses, colistin treatment increases nephrotoxicity risk with a hazard ratio of 2.16 (95% CI 1.43-3.27) 5
• A 2024 study confirmed colistin as an independent risk factor for acute kidney injury (OR 3.882,95% CI 1.829-8.241) 6
• Loss of renal function episodes occur primarily with colistin (RR 8.55,95% CI 1.48-49.49) 5

Dosing Recommendations

Polymyxin B Dosing

• Loading dose: 2-2.5 mg/kg regardless of renal function 1
• Maintenance dose: 1.5-3 mg/kg/day 1
• No adjustment needed for renal impairment or CRRT 1
• Requires less dose modification than colistin across all renal function categories 1

Colistin Dosing

Normal Renal Function

• Loading dose: 9 million IU (equivalent to 5 mg/kg) regardless of renal function 2, 3
• Maintenance dose: 4.5 million IU every 12 hours 2, 3
• Alternative weight-based dosing: 2.5-5 mg/kg/day divided into 2-4 doses 3
• Consider 4-hour infusion to optimize pharmacokinetics 2, 3

Renal Impairment

• Loading dose: 6-9 million IU regardless of renal function 1, 2
• Maintenance dose: Individually adjusted according to creatinine clearance 1, 2
• CRRT patients: At least 9 million IU/day 2
• Intermittent hemodialysis: 2 million IU every 12 hours with normal loading dose; schedule dialysis toward end of dosing interval 2

Clinical Decision Algorithm

When to Choose Polymyxin B

• Any degree of renal impairment (no dose adjustment required) 1
• Patients on CRRT (no adjustment needed) 1, 2
• High nephrotoxicity risk (concomitant vasopressors, advanced age, baseline kidney disease) 6
• Critically ill patients where simplified dosing is advantageous 1

When Colistin May Be Acceptable

• Normal renal function with close monitoring capability 3
• Inhaled administration (colistin preferred over polymyxin B based on controlled study evidence) 1
• Polymyxin B unavailable (use with appropriate renal dose adjustments) 1

Critical Monitoring Requirements

Renal Function Surveillance

• Close monitoring mandatory for both agents 1, 3
• Watch for albuminuria, cellular casts, and azotemia with polymyxin B 7
• Monitor for diminishing urine output and rising BUN as indications to discontinue 7
• Most nephrotoxicity is reversible within one week, with 64.4% overall reversibility 6
• Acute kidney injury during treatment is a major factor related to clinical failure and mortality 1, 3

Neurotoxicity Monitoring

• Watch for irritability, weakness, drowsiness, ataxia, perioral paresthesia, numbness of extremities, and blurred vision 7
• Neurotoxicity risk increases with high serum levels in renal impairment 7
• Respiratory paralysis from neuromuscular blockade possible, especially post-anesthesia 7

Common Pitfalls to Avoid

• Never skip the loading dose for colistin—the long half-life requires it to rapidly achieve therapeutic levels 2, 3
• Avoid concurrent nephrotoxic agents (aminoglycosides, vancomycin) when possible 7
• Do not underdose colistin in renal impairment—high-dose colistin shows higher nephrotoxicity rates than polymyxin B (76.9% vs 25%) 6
• Avoid sequential use of other neurotoxic/nephrotoxic drugs including bacitracin, streptomycin, neomycin, kanamycin, gentamicin, tobramycin, amikacin, or cephaloridine 7

Efficacy Considerations

Comparative Effectiveness

• For carbapenem-resistant Pseudomonas aeruginosa (CRPA), very low-certainty evidence shows no mortality difference between agents 8
• In mixed MDR/XDR infections, ceftolozane-tazobactam shows superiority over polymyxin/aminoglycoside combinations with lower nephrotoxicity (adjusted OR 0.08,95% CI 0.03-0.22) 8
• A before-after study in critically ill patients showed higher RIFLE-defined nephrotoxicity with colistin (adjusted HR 2.27,95% CI 1.35-3.82) 8