Colistin Treatment for Acinetobacter Infections in Post-BMT Children
For Acinetobacter infections in post-bone marrow transplant children, colistin (polymyxin E) is recommended with a loading dose of 5 mg/kg colistin base activity (CBA) followed by a maintenance dose of 2.5 mg CBA/kg/day divided every 12 hours, with careful monitoring of renal function. 1, 2
Dosing Recommendations for Pediatric Patients
- The FDA recommends a loading dose of 0.15 MU/kg (equivalent to 5 mg/kg CBA) followed by a maintenance dose of 0.075 MU/kg every 12 hours (equivalent to 2.5-5 mg CBA/kg/day) 2, 1
- Dose adjustment is required based on renal function, with close monitoring throughout treatment 1, 2
- For critically ill children, higher dosing may be necessary when the MIC of the infecting Acinetobacter strain is ≥1 mg/L or when the patient has augmented renal clearance 1
- Administration should be via slow intravenous infusion over 3-5 minutes for direct intermittent administration, or as a continuous infusion over 22-23 hours 2
Monotherapy vs. Combination Therapy
- For carbapenem-resistant Acinetobacter baumannii (CRAB) infections, colistin-based therapy is recommended as the backbone of treatment 1
- Combination therapy with colistin plus a carbapenem has shown the best outcomes in network meta-analyses, with a higher survival rate compared to colistin monotherapy 1, 3
- For bloodstream infections, colistin with or without a carbapenem is recommended for a duration of 10-14 days 1
- For pneumonia, colistin with or without a carbapenem plus adjunctive inhaled colistin is recommended for at least 7 days 1
Site-Specific Considerations
- For central nervous system infections (meningitis/ventriculitis), which can occur in post-BMT patients, combination therapy with intravenous and intraventricular colistin may be necessary for effective treatment 4, 5
- For pneumonia, consider adding adjunctive inhaled colistin at a dose of 1.25-5 MIU/day in 2-3 divided doses 1
- For bloodstream infections, a longer treatment duration of 10-14 days is recommended 1
Alternative Treatment Options
- If the Acinetobacter strain is susceptible to sulbactam, this may be considered as an alternative to colistin due to its better safety profile (nephrotoxicity rates of 15.3% for sulbactam vs. 33% for colistin) 6, 3
- For strains with tigecycline MIC ≤1 mg/L, tigecycline may be considered as part of combination therapy, but should not be used as monotherapy 1, 3
Monitoring and Adverse Effects
- Renal function should be closely monitored during colistin treatment, as nephrotoxicity is a major concern and is associated with clinical failure and mortality 1, 6
- Acute kidney injury during colistin treatment is one of the most important factors related to clinical failure and mortality 1
- There is no current consensus regarding frequency of dose adjustment and timing of withdrawal of therapy in the presence of acute kidney injury 1
Common Pitfalls and Considerations
- Underdosing colistin in pediatric patients with good renal function or when treating strains with MIC ≥1 mg/L may lead to treatment failure 1, 6
- Heteroresistance to colistin is a concern, with rates varying widely in clinical isolates 6, 7
- Previous use of colistin might be a risk factor for higher rates of heteroresistance 6
- Not considering local resistance patterns and MIC values when selecting therapy 6, 8
- Failure to adjust dosing based on renal function can increase toxicity risk 1, 2
Treatment Algorithm
- Obtain cultures and susceptibility testing before initiating therapy 8
- For confirmed Acinetobacter infection in a post-BMT child:
- Adjust dose based on renal function and monitor renal parameters closely 1, 2
- For specific sites of infection, consider:
- Continue treatment for at least 7 days for pneumonia and 10-14 days for bloodstream infections 1