Clinical outcomes and their relationship with tigecycline exposure in critically ill patients with drug resistant infections.

Background: Dosing tigecycline, an important last resort for carbapenem-resistant organisms, should be under the guidance of pharmacokinetic/pharmacodynamic (PK/PD) theory. However, tigecycline has shown large interindividual variability in PK among different patients, and its PK/PD target has limited data support. This study aimed to evaluate the clinical outcome and the relationship with exposure in critically ill patients with drug-resistant infections. Methods: A single center, prospective observational, single-arm cohort study was performed to assess the outcome and its relationship with exposure in critically ill patients with drug-resistant pathogen infections. Patients were enrolled according to the inclusion and exclusion criteria. The clinical outcomes, including clinical response rate, 28-day mortality rate, and major adverse events (AEs), were followed up. Plasma concentrations in steady status were intensively collected and determined for tigecycline concentration, and the 24-hour area-under-curves (AUCs) were calculated. The exposure-clinical outcome relationship was analyzed, and multivariate logistic regressions were performed to identify risk factors that associated with outcome. Results: A total of 130 patients were included. The most common infection type was low respiratory tract infection (76/130), and carbapenem-resistant Conclusion: The clinical outcome of tigecycline in critically ill patients with resistant pathogen infection was satisfactory, but negative relationship between tigecycline exposure and outcome was found and the PK/PD profile in these patients should be revisited.