Fig. 1.

Nebulization of polymyxin B and E (colistimethate sodium) for treating ventilator-associated pneumonia caused by extensive drug resistant Gram-negative bacteria A Optimization of nebulization and recommended doses; B PK/PD after nebulization of high-dose polymyxin B. Very high doses are attained in the infected lung parenchyma and there is a massive systemic absorption. Because 80% of plasma polymyxin B binds to the proteins, plasma unbound polymyxin B Is not different after intravenous administration or nebulization of 4.25 mg/kg (square shows plasma concentrations according to time). Unbound polymyxin B is filtered and massively reabsorbed by the kidney so that hepatic elimination is predominant; C PK/PD after nebulization of high dose of colistimethate sodium. Very high doses are attained in the infected lung parenchyma and there is a low systemic absorption (yellow square shows individual plasma concentrations according to time after the first nebulization (a and b) of 0.5 and 2 million International Units 3/24H and blue square shows individual plasma concentrations after multiple nebulizations (c and d) of 4 million International Units 3/24H). Fifty five % of plasma colistin binds to the proteins and is eliminated by the liver. Thirty % of colistimethate sodium is hydrolyzed into colistin in the kidney and eliminated by the liver. PK/PD data are reproduced from reference 14 with permission of the publisher