Colistin

Antibiotic Class:

Polymyxin

Antimicrobial Spectrum:

Acinetobacter baumannii and Pseudomonas aeruginosa, Klebsiella spp., Enterobacter spp., Escherichia coli, Salmonella spp., Shigella spp., Citrobacter spp., Yersinia pseudotuberculosis, and Haemophilus influenzae

Mechanism of Action:

Colsitin disrupts bacterial cell membrane phospholipids

Pharmacodynamics:

Peak:MIC and AUC:MIC ration correlate best with efficacy

Pharmacokinetics (150mg dose):

Cmax: 18mg//L; Tmax: 2 hours; Half-life: 2-3 hours

Adverse Effects:

Kidneys: Nephrotoxicity

Other: Neurotoxicity, drug fever

Skin: Pruritis, dermatoses

GI: gastrointestinal upset

Hematologic: leucopenia, granulocytopenia

FDA Warning: Colistin in Nebulizer Solution

Dosage:

Dosing in adults: 2.5-5mg/kg/day divided q6-12h

Dosing in pediatrics: 2.5-5mg/kg/day divided q6-12h

Disease state based dosing:

Renal failure: CrCl > 50mL/min: Standard dosing

                      CrCl 10-50mL/min: 50% of normal dose

                      CrCl < 10 mL/min: 25% of the normal dose

Hepatic failure:  No dosing changes recommended at this time.

Dosing during Continuous Renal Replacement Therapy

CVVH (Continuous venovenous hemofiltration): 2.5mg/kg IV q48h

CVVHD (Continuous venovenous hemodialysis): 2.5mg/kg IV q48h*

CVVHDF (Continuous venovenous hemodiafiltration) 2.5mg/kg IV q48h*

*A recent pharmacokinetic study suggests conventional dosing recommendations in CVVHD and CVVHDF are not appropriate in the critically ill and higher doses of 2-3 mg/kg IV q12h may be more appropriate. (Li J, et al. Antimicrob Agents Chemother 2005;49:4814-4815)

Note: CVVH is mainly for fluid removal alone. Many institutions will employ more CVVHD or CVVHDF which combine dialysis with fluid removal.

Contraindications/Warnings/Precautions:

Precautions: Renal impairment

Drug Interactions:

Non-depolarizing neuromuscular blockers: may lead to additive neuromuscular blockade

Pregnancy:

Category C: Risk unknown. Human studies inadequate

Monitoring Requirements:

Therapeutic:  Culture and sensitivities, serum levels, signs and symptoms of infection, white blood cell count

Toxic:  Nephrotoxicity (Serum creatinine, BUN)

Brand names/Manufacturer: 

Colymycin (various generic manufacturers worldwide)