Clinical Efficacy and Safety of Tigecycline Based on Therapeutic Drug Monitoring for Carbapenem- Resistant Gram Negative Bacterium Pneumonia in Intensive Care Units

Abstract

Abstract Background We investigated the associations between the different dose of tigecycline, its efficacy and safety, and the role of tigecycline therapeutic drug monitoring for patients in intensive care unit. Methods This was a single-center cohort study including patients with Multidrug-Resistant Acinetobacter baumannii, (MDR-AB)and Multidrug-Resistant Klebsiella pneumoniae(MDR-KP) pulmonary infections admitted to the ICU between October 2020 and December 2021. The steady-state plasma concentration after tigecycline administration was determined by the High Performance Liquid Chromatography (HPLC) method. Multivariate analysis of the clinical efficacy and safety of tigecycline were performed to control cofounding factors. Results This study included 45 patients, and a total of 45 blood samples were collected to determine steady-state trough concentrations of tigecycline. All patients were divided into High Dose (HD) group and Standard Dose (SD) group. The median trough concentration of tigecycline was 0.56µg/mL in the HD group, which was higher than in the SD group(0,21µg/mL),p = 0.000. There was no significant difference between the two groups of patients in terms of bacterial eradication rate, mortality rate and clinical efficacy. Multiple regression analysis showed that ICU days was correlated with mortality OR 1.030(1.005–1.056), p = 0.017. APACHE II was significantly associated with clinical efficacy OR 0.870(0.755–1.002),p = 0.045. The level of fibrinogen decline in the HD group was significantly higher than that in the SD group(-3.05 ± 1.67 vs -1.75 ± 1.90),p = 0.038. Age and tigecycline treatment duration were identified as influencing factors for fibrinogen decline. Conclusions Tigecycline plasma concentrations are significantly increased when using a high dose. However, the plasma concentration of tigecycline is not correlated with clinical efficacy and adverse reactions. Fibrinogen decline appears to be related to patient age and days of tigecycline. Large sample data are still needed to confirm the clinical guidance significance of tigecycline TDM.