Is Colistin Active Against Urinary Pseudomonas?
Yes, colistin is active against Pseudomonas aeruginosa in urinary tract infections and is FDA-approved for this indication, with particularly high efficacy for lower UTIs when the organism has low MIC values (≤2 mg/L). 1, 2
FDA-Approved Indication and Microbiological Activity
- Colistin (colistimethate sodium) is specifically FDA-approved for treating infections caused by sensitive strains of Pseudomonas aeruginosa, including urinary tract infections 1
- The drug demonstrates bactericidal activity against P. aeruginosa by disrupting the bacterial cell membrane 1
- Colistimethate sodium (the inactive prodrug) is primarily excreted in urine and converts to active colistin after glomerular filtration, resulting in much higher urinary concentrations than plasma levels 2
Clinical Efficacy Data for Urinary Pseudomonas
For lower complicated UTIs caused by multidrug-resistant P. aeruginosa:
- Clinical cure rates of 84.6% (11/13 patients) have been reported for urinary tract infections 3
- A more recent study showed 89.5% clinical cure in lower UTIs (predominantly with colistin monotherapy), with 76.9% microbiological eradication 2
- Good outcomes occurred in 20% of patients with various nosocomial infections, though this older study included mixed infection types 4
The efficacy is particularly strong when:
- The infection is a lower UTI (not pyelonephritis) 2
- The MIC is low (MIC50 and MIC90 values of 0.5 and 2 mg/L respectively) 2
- Patients are non-critically ill 2
Dosing Considerations for Urinary Infections
Standard dosing may be excessive for lower UTIs:
- Current data suggest that lower doses than the standard regimen (loading dose 9 MU, maintenance 4.5 MU twice daily) may be sufficient for lower UTIs to minimize nephrotoxicity 2
- In one study, 58.8% of patients with clinical cure showed colistin plasma concentrations above the MIC, but only 29.4% achieved the optimal plasma AUC/MIC ratio of ≥60 mg·h/L, suggesting urinary concentrations (not plasma) drive efficacy 2
- Average urine levels range from 270 mcg/mL at 2 hours to 15 mcg/mL at 8 hours following IV administration—far exceeding typical MIC values 1
Critical Nephrotoxicity Concerns
Renal toxicity is the major limiting factor:
- Nephrotoxicity occurred in 29.4% of patients in a recent UTI-specific study 2
- In patients with initially normal renal function, 27% developed renal failure, and 58% with baseline renal dysfunction worsened 4
- Another study reported 8.3% nephrotoxicity, with risk factors including pre-existing chronic renal insufficiency, diabetes mellitus, and concurrent aminoglycoside use 3
- Renal function must be closely monitored throughout treatment 5, 2
Monotherapy vs. Combination Therapy
- For lower UTIs with susceptible organisms (MIC ≤2 mg/L), colistin monotherapy is often sufficient, with 84.2% of successful cases in one series receiving monotherapy 2
- For difficult-to-treat resistant (DTR) Pseudomonas, combination therapy with one or more additional agents is suggested, even if the second agent lacks in vitro susceptibility 5
- Colistin-carbapenem combinations have shown high success rates (SUCRA 83.6% for clinical cure) in network meta-analyses, though this data primarily reflects non-urinary infections 6
Common Pitfalls to Avoid
- Do not use standard high-dose regimens for simple lower UTIs—this causes unnecessary nephrotoxicity given the high urinary drug concentrations achieved 2
- Do not assume efficacy for pyelonephritis equals that of lower UTI—outcomes are worse for upper tract infections 2
- Do not overlook MIC testing—efficacy drops significantly when MIC ≥2 mg/L 2
- Do not combine with aminoglycosides without compelling reason—this substantially increases nephrotoxicity risk 3