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 Acinetobacter baumannii was the most common pathogen (64/130). The median tigecycline treatment length was 12 days. The median AUC was 14.0 mg h/L. The overall response rate and 28-day mortality rate were 50.0% and 36.2%, respectively. A lower fibrinogen level was the most common AE (51/130). ALB, PLT and combined use of cefoperazone-sulbactam were independent factors associated with clinical response, but AUC was negatively associated with clinical response.

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.