Colistimethate Sodium (IV) — How to Prepare and Administer
• Bold recommendation: For IV use, reconstitute colistimethate sodium (CMS) with sterile water, then dilute in 0.9% normal saline (NS) or other approved IV fluids; infuse as per label (intermittent slow IV or continuous infusion). 1
Step-by-step (maximize survival, minimize toxicity)
Choose CMS vial: 150 mg colistin base activity (CBA) per vial. Reconstitute each vial with 2 mL Sterile Water for Injection to 75 mg CBA/mL; swirl gently (avoid froth). Inspect for particulates/discoloration. 1
Diluent (answer to “NS?”): Yes—after reconstitution, dilute in one of:
- 0.9% NaCl (normal saline), D5W, D5NS, D5½NS, D5¼NS, Lactated Ringer’s, or 10% invert sugar. Use only these solutions. Prepare fresh; use within 24 h. 1
- Rationale: stability is acceptable in NS or D5W when refrigerated; CMS hydrolyzes faster at room temperature after dilution—limit hang time to 24 h to reduce colistin generation and nephrotoxicity risk. 2
Administration options (pick one):
- Intermittent IV: Inject one-half of the total daily dose slowly over 3–5 minutes every 12 h. 1
- Continuous infusion: Inject half the daily dose over 3–5 minutes, then add the remaining half to the approved diluent and infuse over the next 22–23 hours; start 1–2 hours after the initial dose. Adjust rate if renal impairment. 1
Dosing (optimize mortality/QOL while limiting AKI)
- FDA label (adults/peds): 2.5–5 mg CBA/kg/day IV in 2–4 divided doses; base dosing on ideal body weight; reduce for renal impairment per label table. 1
- Critically ill HAP/VAP (IDSA/ATS, high-MDRO settings): Use a loading dose followed by renal-adjusted maintenance (doses expressed as colistin-based formula): LD 5 mg/kg once, then 2.5 mg × (1.5 × CrCl + 30) q12h (institution-specific; dosing units can vary—use your pharmacy’s CBA/IU conversion). Reserve polymyxins for high-MDR prevalence and with local expertise. 3
- Acinetobacter ICU guidance: Loading 6–9 million IU, then 4.5 million IU q12h with CrCl >50 mL/min; adjust to CrCl. This improves early target attainment and outcomes in severe sepsis/VAP. 4
- Pitfall to avoid: unit confusion (CBA mg vs IU vs CMS mg). 1 million IU ≈ 30 mg CBA ≈ 80 mg CMS. Confirm units with pharmacy to prevent under/overdosing. 3, 4
Special situations
- Renal dysfunction: Strictly reduce dose/extend interval per label or guideline algorithms; monitor creatinine daily; avoid concomitant nephrotoxins. 1, 3
- Hemodialysis/CRRT: Follow ICU guideline adjustments; dialysis timing relative to dosing matters. 4
- Inhaled adjunct (for HAP/VAP): If used, each dose is diluted in 5 mL sterile NS for nebulization per guideline; this is adjunctive to IV in select cases. 5
Safety and monitoring (prevent morbidity)
- Nephrotoxicity is the main risk; use shortest effective duration, therapeutic drug guidance when available, and avoid prolonged room-temperature storage of diluted solutions. 3, 2
- Neuromuscular blockade risk: avoid rapid IV push beyond recommended; adhere to slow administration. 1
Common pitfalls and how to avoid them
- Wrong diluent: Use only the approved solutions (NS is appropriate). Do not mix with unlisted fluids/drugs in the same bag. 1
- Skipping the loading dose in severe infection: leads to delayed target levels and worse outcomes—give LD when treating severe MDR infections as per guidelines. 4, 3
- Dose unit mismatch (IU vs mg CBA vs mg CMS): double-check conversions. 3
Minimal pragmatic regimen example (adult, severe MDR HAP/VAP, normal kidneys)
- Loading dose: 9 million IU (≈270 mg CBA) once, reconstituted with sterile water then diluted in NS; administer per facility practice (e.g., short infusion). 4, 3
- Maintenance: 4.5 million IU (≈135 mg CBA) IV q12h, each dose prepared as above and infused per label (intermittent slow injection or continuous infusion strategy). Adjust if CrCl declines. 4, 3, 1