What is the role of colistin in treating infections?

Role of Colistin in Treating Infections

Colistin is recommended primarily as a last-line treatment option for difficult-to-treat resistant Pseudomonas aeruginosa (DTR-PA) infections and other multidrug-resistant gram-negative bacterial infections when other antimicrobial options are limited. 1

Indications for Colistin Use

Colistin (polymyxin E) is indicated for:

• Treatment of infections caused by multidrug-resistant gram-negative bacteria, particularly:

  • Carbapenem-resistant Pseudomonas aeruginosa (CRPA)
  • Carbapenem-resistant Acinetobacter baumannii (CRAB)
  • Carbapenem-resistant Enterobacterales (CRE)
  • Other multidrug-resistant gram-negative bacilli 1, 2

• Specific FDA-approved indications include infections due to:

  • Pseudomonas aeruginosa
  • Enterobacter aerogenes
  • Escherichia coli
  • Klebsiella pneumoniae 2

Dosing Recommendations

Adult Dosing

• Loading dose: 9 MU (5 mg/kg colistin base activity) infused over 0.5-1 hour 1, 3
• Maintenance dose: 4.5 MU (2.5 mg/kg) twice daily, adjusted based on renal function 1, 3
• Formula for maintenance dose: 2.5 mg × (1.5 × CrCl + 30) twice daily 1

Critical Considerations

• Loading dose is essential to avoid suboptimal plasma concentrations for 2-3 days 3
• Renal function must be closely monitored during treatment 1, 3
• 1 million IU of colistin equals approximately 30 mg of colistin base activity 3

Efficacy and Clinical Outcomes

Colistin has demonstrated efficacy in treating multidrug-resistant infections:

• Survival rates of 39-83% have been reported in patients with CRPA or DTR-PA infections 1
• Better outcomes are observed in urinary tract infections and bloodstream infections compared to pneumonia 4
• In patients with hematologic malignancies, resolution of MDR-PA infections was achieved in 76.9% of patients receiving colistin 5

Combination Therapy vs. Monotherapy

Combination therapy is generally preferred over monotherapy:

• Colistin monotherapy rapidly selects for resistant subpopulations 6
• The combination of colistin with carbapenems showed the highest success rate for clinical cure (SUCRA 83.6%) and lowest mortality in network meta-analysis 1
• Recommended combinations include:
  • Colistin + carbapenem (even when the pathogen is carbapenem-resistant)
  • Colistin + tigecycline
  • Colistin + sulbactam 1

However, evidence is mixed:

• Some studies show no superiority of colistin-meropenem combination over colistin monotherapy 1
• Other studies demonstrate lower mortality with polymyxin B combination therapy for DTR-PA 1

Toxicity and Adverse Effects

Major concerns with colistin therapy include:

• Nephrotoxicity:

  • 27% of patients with normal baseline renal function may develop renal failure
  • 58% of patients with abnormal baseline renal function may experience worsening 4
  • However, nephrotoxicity is generally reversible and less frequent than historically reported 7

• Neurotoxicity:

  • Rare but can occur
  • May manifest as paresthesias, dizziness, or neuromuscular blockade 7

Treatment Duration

Recommended treatment durations:

• Complicated urinary tract infections: 5-10 days
• Complicated intra-abdominal infections: 5-10 days
• Hospital-acquired or ventilator-associated pneumonia: 10-14 days
• Bloodstream infections: 10-14 days 1, 3

Alternative Therapies

When available and susceptible, newer agents are preferred over colistin due to better safety profiles:

• Ceftolozane-tazobactam: 1.5-3g IV q8h (first-line for CRPA if susceptible) 3
• Ceftazidime-avibactam: 2.5g IV q8h 1
• Imipenem-cilastatin-relebactam: 1.25g IV q6h 1, 3

Practical Considerations

• Obtain infectious disease consultation for management of multidrug-resistant infections 3
• Perform antimicrobial susceptibility testing to guide therapy 3
• Be aware of inconsistent dosing units (IU vs. mg) that can lead to dosing errors 3
• Consider polymyxin B as an alternative to colistin in patients with renal impairment, as it doesn't require dosage adjustments based on renal function 3

Pitfalls to Avoid

• Failure to administer loading doses, resulting in suboptimal plasma concentrations 3
• Monotherapy with colistin, which may lead to rapid development of resistance 6
• Inappropriate use for infections not caused by susceptible bacteria 2
• Inadequate monitoring of renal function during treatment 1, 3
• Using colistin for pneumonia as a single agent (poorest outcomes observed) 4

In conclusion, while colistin remains an important last-line option for multidrug-resistant gram-negative infections, its use should be carefully considered, properly dosed, and monitored for toxicity to maximize efficacy while minimizing adverse effects.