The Population Pharmacokinetics Study of Tigecycline and Pharmacokinetics- Pharmacodynamics Index in Patients With Carbapenem Resistant Enterobacteriaceae Bloodstream Infection

Overview

Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent global public health problem. Patients who were infected caused by CRE bloodstream infection were high mortality up to 40%. The National Antimicrobial Resistance Surveillance Center, Thailand (NARST) reported CRE increased from 1.1% to 17.9%. For carbapenemase producing CRE in Thailand was reported blaNDM 47.33%, blaOXA-48 43.33% and blaNDM+blaOXA-48 6.67%. Tigecycline (TGC) was a glycylcyclines antibiotics. High dose tigecycline (HD-TGC) loading dose 200 mg then TGC 100 mg q 12 h via intravenous improve clinical cure in critically ill patients and reduce mortality in carbapenem resistance Klebsiella pneumoniae bloodstream infection compared with standard dose therapy. TGC has susceptibility to CR-KP 79.6% and has an activity to blaNDM, blaKPC and blaOXA-48 carbapenemase producing CRE. However, TGC has clearance (CL) 0.2-0.3 L/h/kg, and high volume of distribution (vd) 2.8-13 L/kg resulted in low levels of TGC in plasma. Moreover, the pharmacokinetics of TGC in critically ill was limited and inconsistent with the previous study. Now pharmacokinetics-pharmacodynamics index (PK/PD index) of TGC for CRE bloodstream infection was not reported. This study aims to study the population pharmacokinetic and PK-PD index of TGC in patients who were CRE bloodstream infection to increase the success rate of treatment.

Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent global public health problem. Patients who were infected caused by CRE bloodstream infection were high mortality up to 40%. The National Antimicrobial Resistance Surveillance Center, Thailand (NARST) reported the carbapenem resistance Klebsiella pneumoniae (CR-KP) prevalence increased from 1.1% in 2000 to 17.9% in 2021 and the carbapenem resistance Escherichia coli was increased from 0.6% in 2000 to 5% in 2021. For carbapenemase producing CRE in Thailand was reported blaNDM 47.33%, blaOXA-48 43.33%, and blaNDM+blaOXA-48 6.67%. Ceftazidime-avibactam was first-line of treatment for CRE bloodstream infection recommended by Infectious Disease Society of America 2023 guidance on the treatment of antimicrobial resistant gram-negative infections but ceftazidime-avibactam was limited activity to blaNDM carbapenemase producing CRE. Tigecycline (TGC) was a glycylcyclines antibiotics. TGC was approved for U.S.FDA for complicated intra-abdominal infection, complicated skin and skin structure infection and community acquired pneumonia with loading dose TGC 100 mg then TGC 50 mg q 12 h via intravenous. High dose tigecycline (HD-TGC) loading dose 200 mg then TGC 100 mg q 12 h improve clinical cure in critically ill patients and reduce mortality in CR-KP bloodstream infection compared with standard dose therapy. TGC has susceptibility to CR-KP 79.6% and has an activity to blaNDM, blaKPC and blaOXA-48 carbapenemase producing CRE. However, TGC has clearance (CL) 0.2-0.3 L/h/kg, and high volume of distribution (vd) 2.8-13 L/kg resulted in low levels of TGC in plasma. Moreover, the pharmacokinetics of TGC in critically ill was limited and inconsistent with the previous study. Now pharmacokinetics-pharmacodynamics index (PK/PD index) of TGC for CRE bloodstream infection was not reported. This study aims to study the population pharmacokinetic and PK-PD index of TGC in patients who were CRE bloodstream infection to increase the success rate of treatment.