Colistin Monotherapy for Urinary Tract Infections
Colistin monotherapy can be appropriate for UTIs caused by multidrug-resistant Gram-negative bacteria when no other susceptible agents are available, though combination therapy is generally preferred for severe infections. 1
Clinical Appropriateness
When to Consider Colistin for UTI
Colistin should be reserved for infections caused by carbapenem-resistant Enterobacterales (CRE) or difficult-to-treat resistant Pseudomonas aeruginosa (DTR-PA) when the organism shows resistance to all beta-lactams, fluoroquinolones, and other first-line agents 1, 2
For uncomplicated lower UTIs caused by multidrug-resistant organisms with low MIC values (≤0.5-1 mg/L), colistin monotherapy has demonstrated clinical cure rates of approximately 89.5% in non-critically ill patients 3
The evidence suggests colistin monotherapy may be more appropriate for lower UTIs than for pyelonephritis or complicated UTIs, where combination therapy should be strongly considered 1, 3
Monotherapy vs. Combination Therapy
The evidence on combination versus monotherapy remains controversial and of very low quality 1:
One randomized controlled trial showed no superiority of colistin-meropenem combination over colistin monotherapy for Pseudomonas or other carbapenem-resistant Gram-negative bacteria (14-day mortality: 25% vs 31%, p=1.0) 1
However, other studies demonstrated lower mortality with polymyxin B combination therapy compared to monotherapy, even when the combined agent lacked in vitro activity 1
Expert consensus recommends combination therapy when a susceptible second agent is available; if not available, colistin may be combined with a nonsusceptible agent (e.g., carbapenem) with the lowest MIC 1
Recommended Dosing
Standard Adult Dosing (Normal Renal Function)
Loading dose: 6-9 million IU (MU) of colistimethate sodium (CMS), followed by maintenance dose of 4.5 MU every 12 hours 1, 2
The FDA-approved dosing range is 2.5-5 mg/kg/day of colistin base activity divided into 2-4 doses 4
For critically ill patients and those with severe sepsis/septic shock with creatinine clearance >50 mL/min, use the higher dosing regimen with loading dose 2
The loading dose is critical because without it, plasma colistin concentrations remain suboptimal for 2-3 days before reaching steady state 2
Dosing in Renal Impairment
Dose adjustment is mandatory based on creatinine clearance 4:
- CrCl 50-79 mL/min: 2.5-3.8 mg/kg divided into 2 doses per day 4
- CrCl 30-49 mL/min: 2.5 mg/kg once daily or divided into 2 doses 4
- CrCl 10-29 mL/min: 1.5 mg/kg every 36 hours 4
For patients on continuous renal replacement therapy (CRRT): At least 9 million IU/day is suggested 2
For intermittent hemodialysis: 2 million IU CMS every 12 hours with normal loading dose; dialysis should be performed toward the end of dosing interval 2
Special Considerations for UTI
Recent evidence suggests that for lower uncomplicated UTIs with low MIC organisms, lower doses than currently recommended may be sufficient and could minimize nephrotoxicity 3
Colistin concentrations in urine are much higher than plasma because CMS is mainly excreted unchanged in urine and converts to active colistin after glomerular filtration 3, 5
In one study of lower UTIs, clinical cure was achieved even when only 29.4% of patients attained optimal plasma AUC/MIC ratios, suggesting urinary concentrations may be adequate despite suboptimal plasma levels 3
Monitoring Requirements
Renal Function Monitoring
Renal function must be closely monitored during colistin therapy (strong recommendation) 1:
Acute kidney injury is one of the most important factors related to clinical failure and mortality 1
Nephrotoxicity rates range from 10.9% to 33% depending on patient population and concomitant nephrotoxic agents 2, 6
Patients at higher risk include elderly, those with chronic kidney disease, and those receiving concomitant aminoglycosides 1
Despite common combination use with aminoglycosides (48% in one study), nephrotoxicity remained relatively uncommon (10.9%) when monitored appropriately 6
Neurological Monitoring
Patients should be warned about potential neurological adverse effects 4:
Transient neurological disturbances may include circumoral paresthesia, tingling of extremities, generalized pruritus, vertigo, dizziness, and slurring of speech 4
Patients should not drive vehicles or use hazardous machinery while on therapy 4
Dose reduction may alleviate symptoms without requiring discontinuation 4
Clinical Efficacy Data
UTI-Specific Outcomes
In a study of 60 patients with various infections (8.3% UTI), colistin showed a favorable response in 71.7% of cases with 26.7% overall mortality 6
For lower complicated UTIs caused by extremely drug-resistant P. aeruginosa, clinical cure was achieved in 89.5% with monotherapy and microbiological eradication in 76.9% 3
Susceptibility rates for carbapenem-resistant organisms from UTIs: 83.5% for CR-E. coli and 88.6% for CR-K. pneumoniae 7
Important Caveats
A concerning trend shows decreasing colistin susceptibility in CR-E. coli UTI isolates and CR-K. pneumoniae from intra-abdominal infections between 2015-2017 7
Biofilm-producing strains (present in 90% of chronic UTIs) require much higher concentrations for eradication (MBEC 32 to >512 mg/L) compared to planktonic bacteria 8
For biofilm-related UTIs, parenteral colistin success is unpredictable despite high urinary concentrations; intravesical instillation may be considered 8
Alternative Considerations
When susceptibility allows, sulbactam may be preferable to colistin for A. baumannii UTIs due to better safety profile 2:
- Sulbactam has intrinsic activity against A. baumannii at MIC ≤4 mg/L 2
- Studies showed comparable clinical cure rates with lower nephrotoxicity (15.3% vs 33%) compared to colistin 2
New beta-lactam/beta-lactamase inhibitors (ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relebactam) should be considered when available and susceptible 1:
- These agents show better cure rates with less acute kidney injury compared to polymyxin-based regimens 1