Influence of continuous renal replacement therapy on the plasma concentration of tigecycline in patients with septic shock: A prospective observational study

Objective: The influence of continuous renal replacement therapy (CRRT) on the steady-state plasma concentration of high-dose tigecycline was investigated in septic shock patients to provide references for drug dosing. Methods: In this prospective observational study, 17 septic shock patients presenting with severe infections needing a broad-spectrum antibiotic therapy with high-dose tigecycline (100 mg per 12 h) in the intensive care unit were included and divided into CRRT group (n = 6) or non-CRRT group (n = 11). The blood samples were collected and plasma drug concentration was determined by SHIMADZU LC-20A and SHIMADZU LCMS 8040. The steady-state plasma concentration was compared between groups using unpaired t-test. Furthermore, between-groups comparisons adjusted for baseline value was also done using multivariate linear regression model. Results: Peak concentration (C-max) of tigecycline was increased in CRRT group compared to non-CRRT group, but there were no statistical differences (505.11 +/- 43.84 vs. 406.29 +/- 108.00 ng/mL, p-value: 0.129). Trough concentration (C-min) of tigecycline was significantly higher in CRRT group than in non-CRRT group, with statistical differences (287.92 +/- 41.91 vs. 174.79 +/- 33.15 ng/mL, p-value: 0.000, adjusted p-value: 0.000). In safety, C-min was reported to be a useful predictor of hepatotoxicity with a cut-off of 474.8 ng/mL. In our studies, C-min of all patients in CRRT group was lower than 474.8 ng/mL. Conclusion: The plasma concentration of tigecycline was increased in septic shock patients with CRRT treatment and only C-min shown statistical differences. No dose adjustment seems needed in the view of hepatotoxicity.