Recommended Intrathecal Colistin Dosing
For intrathecal (IT) or intraventricular (IVT) administration of colistin, a dose of 10 mg per day is recommended for treating central nervous system infections caused by multidrug-resistant gram-negative bacteria. 1
Dosing Considerations for Intrathecal Administration
- Intrathecal colistin at 10 mg/day has been successfully used to sterilize multidrug-resistant Pseudomonas aeruginosa meningitis and ventriculoperitoneal shunt infections 1
- When administered intraventricularly at doses ≥5.22 mg/day, colistin concentrations in cerebrospinal fluid (CSF) remain continuously above the MIC of 2 μg/ml, with trough concentrations ranging from 2.0-9.7 μg/ml 2
- For optimal coverage against resistant pathogens, the Infectious Diseases Society of America suggests a daily dose of 10 mg for intrathecal administration, which provides a prudent margin of safety and efficacy 2
Pharmacokinetics of Intrathecal Colistin
- Colistin is administered as colistimethate sodium (CMS), an inactive prodrug that undergoes spontaneous hydrolysis to active colistin in the CSF 3
- After intraventricular administration, colistin has an estimated CSF terminal half-life of approximately 7.8 ± 3.2 hours 2
- Peak concentration of colistin in CSF is reached approximately 3.7 ± 0.9 hours after administration 2
- External CSF drainage can influence the clearance of colistin, potentially requiring dose adjustments 2
Clinical Efficacy and Safety
- Intrathecal colistin administration has demonstrated high rates of microbiological cure (8/9 patients in one study) for multidrug-resistant gram-negative CNS infections 2
- Intrathecal colistin represents a viable treatment option when intravenous administration is not feasible due to nephrotoxicity or inadequate CSF penetration 1
- This route of administration may help avoid the systemic nephrotoxicity associated with intravenous colistin therapy 1
Important Considerations
- One million international units (IU) of colistin is equivalent to 80 mg of colistimethate sodium (CMS) 4
- Renal function should be monitored during colistin therapy, even when administered intrathecally, as some systemic absorption may occur 5
- For patients with external ventricular drains or significant CSF drainage (40-300 ml), clearance of colistin may be increased, potentially requiring dose adjustments 2
Comparison with Systemic Administration
- Intravenous colistin has poor penetration across the blood-brain barrier, making intrathecal administration preferable for CNS infections 3
- Standard systemic dosing for colistin (loading dose of 9 million IU followed by 4.5 million IU every 12 hours) is insufficient for treating CNS infections without direct intrathecal administration 5, 6