Is Intravenous Colistin Nephrotoxic?
Yes, intravenous colistin is definitively nephrotoxic, with nephrotoxicity occurring in approximately 36% of critically ill patients, representing a 2.4-fold increased risk compared to β-lactam-based regimens. 1, 2
Magnitude of Nephrotoxicity Risk
- The nephrotoxicity incidence is substantial at 36.2% in randomized controlled trials comparing colistin to β-lactam antibiotics, with a number needed to harm of only 5 patients 2
- Observational studies report nephrotoxicity rates ranging from 31.9% to 48% in various patient populations 3, 4, 5
- Polymyxin B demonstrates significantly lower nephrotoxicity (11.8% vs 39.3% with colistin) and should be considered as a safer alternative when polymyxin therapy is necessary 1, 6
Impact on Clinical Outcomes
- Nephrotoxicity during colistin treatment is a major factor related to clinical failure and increased mortality 1, 7
- Most nephrotoxicity is reversible within one week after discontinuation, with 90% of patients recovering renal function within one month 4
- The kidney injury typically presents with preserved urine output, which may delay recognition 4
Risk Factors for Enhanced Nephrotoxicity
Patient-specific factors that increase risk include: 4, 5
- Hypoalbuminemia (suggesting free colistin causes renal toxicity)
- Body mass index ≥31.5 kg/m² (odds ratio 3.1)
- Diabetes mellitus (odds ratio 2.11)
- Advanced age (odds ratio 1.08 per year)
- Longer hospitalization prior to colistin (odds ratio 1.04 per day)
Concomitant nephrotoxic exposures: 4
- NSAIDs (significant independent risk factor)
- Aminoglycosides (cumulative dose-related)
- Shock states
Dose-Dependent Toxicity
- Total cumulative colistin dose is directly associated with kidney damage, suggesting that shortening treatment duration could decrease nephrotoxicity incidence 3
- The mean dosage at time of nephrotoxicity development was 2.25 g colistimethate sodium (22.5 defined daily doses) 4
Critical Clinical Pitfall to Avoid
Do not underdose colistin in an attempt to reduce nephrotoxicity. Subtherapeutic levels lead to treatment failure and increased mortality while still carrying nephrotoxic risk 1. The FDA-approved dosing is 2.5 to 5 mg/kg per day in 2 to 4 divided doses for patients with normal renal function 8, though current guidelines recommend a loading dose of 9 million IU followed by 4.5 million IU every 12 hours 1, 7.
Mandatory Monitoring Requirements
- Renal function must be monitored closely, with assessment 2-3 times per week during treatment 1
- Monitor for subjective symptoms in adults; pediatric patients may not report symptoms, requiring heightened vigilance 8
Preferred Alternatives When Possible
Colistin should be regarded as a last-line agent 2. When treating carbapenem-resistant infections:
- Strongly consider ceftolozane-tazobactam over polymyxin-based regimens due to superior efficacy and dramatically lower nephrotoxicity (adjusted OR 0.08) 6
- If polymyxin therapy is necessary, polymyxin B is preferable to colistin due to lower nephrotoxicity rates and no requirement for dose adjustment during continuous renal replacement therapy 1, 6
- Sulbactam may be preferable for Acinetobacter baumannii with MIC ≤4 mg/L, based on better safety profile 9
Special Considerations in Renal Impairment
- Always administer the loading dose regardless of renal function to rapidly achieve therapeutic levels 7, 8
- Adjust only the maintenance dose (not loading dose) based on creatinine clearance 8
- For patients with creatinine clearance 10-29 mL/min, reduce to 1.5 mg/kg every 36 hours 8
Historical Context
While earlier European consensus guidelines from 2000 reported "low frequency of nephrotoxicity" with intravenous colistin 9, this assessment has been definitively contradicted by modern randomized controlled trial data showing substantially higher rates 2. The drug was actually abandoned from clinical use in the 1970s specifically because of significant renal toxicity and has only been reintroduced due to the emergence of multidrug-resistant organisms 3.