Safety and Efficacy of Tigecycline in Intensive Care Unit Patients Based on Therapeutic Drug Monitoring.

Objective: Tigecycline exerts significant beneficial effects against drug-resistant bacterial infections. The largely empirical medications used in clinical practice are often associated with wide individual differences in efficacy and safety. We investigated the associations between the pharmacokinetics of tigecycline and its efficacy and safety in intensive care unit (ICU) patients, with the aim of facilitating clinical applications of tigecycline.

Methods: ICU patients who were prescribed tigecycline in a hospital setting were prospectively included. Factors related to the clinical efficacy and safety of tigecycline were assessed by univariate and multivariate analyses.

Results: This study included 45 patients, from whom a total of 63 blood samples were collected to determine steady-state trough plasma concentrations (Cmin) of tigecycline. The Cmin of tigecycline was 417.1 ± 263.8 ng/mL (mean ± SD). The multivariate analysis showed that the APACHE II scores [odds ratio (OR) = 0.874, 95% confidence interval (CI) = 0.733-0.901, P = 0.048] were significantly correlated with the efficacy of tigecycline, whereas there was no correlation between Cmin of tigecycline and efficacy. In safety, the risk factors significantly associated with hepatotoxicity were sex (OR = 0.562, 95% CI = 0.191-0.774, P = 0.023), APACHE II score (OR = 1.061, 95% CI = 1.039-1.392, P = 0.045), and Cmin (OR = 1.210, 95% CI = 1.014-1.336, P = 0.008). The optimal cut-off for hepatotoxicity in ICU patients treated with tigecycline was 474.8 ng/mL.

Conclusions: There was considerable variability in the Cmin of tigecycline among the ICU patients in this study and it is at risk of high exposure in women. Cmin can be a useful predictor of hepatotoxicity with a cut-off of 474.8 ng/mL.