Pharmacokinetic/pharmacodynamic modeling can help guide targeted antimicrobial therapy for nosocomial gram-negative infections in critically ill patients.

Critically ill patients have altered pharmacokinetics (PK) that need to be considered when choosing and dosing antibiotics. We conducted a prospective, observational study to assess clinical and microbiologic response rates in 19 critically ill patients with nosocomial Gram-negative infections. Antibiotics were dosed based on a mathematical pharmacodynamic (PD) model accounting for these altered kinetic parameters. The average APACHE II score +/- SE on intensive care unit admission and at the time of infection was 13.6 +/- 1.2 and 14.6 +/- 1.1, respectively. With targeted antimicrobial therapy adjusted to achieve an optimal PD profile, 17/19 (89%) patients had a clinical cure or improvement and 16/19 (84%) had either microbiologic eradication or presumed eradication. Modeling PD in these critically ill patients resulted in good clinical and microbiologic outcomes.