Optimization of colistin dosing regimen for cystic fibrosis patients with chronic Pseudomonas aeruginosa biofilm lung infections

Objective The present study was performed to explore dosing regimens of colistin in patients of cystic fibrosis (CF) with Pseudomonas aeruginosa chronic biofilm lung infection. Methods Ten CF patients were involved. One dose colistimethate sodium (CMS) of 6 MIU (million international units) and 9 MIU were administered by intravenous infusion over 45 and 90 min. Venous blood was collected at different time points after the infusion of CMS. Pharmacokinetic parameters of colistin were calculated. Minimum inhibitory concentration for planktonic P. aeruginosa, minimum biofilm inhibitory concentration and minimum biofilm eradication concentration of P. aeruginosa were determined. Monte Carlo simulation was performed to determine the clinical probability of target attainment of different dosing regimens of colistin in CF patients. Results For 90 min (6 MIU), 45 min (6 MIU), and 45 min (9 MIU) intravenous infusion of colistin, C-max was 8.9 +/- 1.8, 15 +/- 5.5, and 31.7 +/- 5.3 mu g/mL, respectively; T-max was 1.2 +/- 0.4, 0.7 +/- 0.2, and 0.8 +/- 0.2 h, respectively; AUC(tot) were 31 +/- 3.8, 34 +/- 10, and 135 +/- 31mg center dot h/L, respectively; t(1/2) was 2.1 +/- 0.4, 2 +/- 0.3, and 3.3 +/- 0.4 h, respectively. MBIC and MBEC of colistin on biofilms at 24 h period treatment were 16-128 mu g/mL for non-mucoid and mucoid biofilms of P. aeruginosa. For 90 min (6 MIU), 45 min (6 MIU) and 45 min iv infusion (9 MIU) with one dose colistin, PTA was 49.8%, 53.8%, 99.4% for planktonic infection, and 11.3%, 14.6%, 65.3%, respectively for biofilm infection. Conclusions colistin treatment using 45 min iv infusion is better than 90 min iv infusion in this study. Colistin dosage of 9 MIU is better than 6 MIU on both planktonic and biofilm infections of P. aeruginosa in this study.