Pharmacokinetic/pharmacodynamic evaluation of tigecycline dosing in a hollow fiber infection model against clinical bla-KPC producing Klebsiella Pneumoniae isolates.

The FDA announced a boxed warning for tigecycline due to progression of infections caused by Gram-negative bacteria and increased risk of mortality during treatment. Plasma exposure of tigecycline might not prevent bacteraemia in these cases from the focuses. Hence, we evaluated intensified dosing regimens and breakpoints that might suppress bloodstream infections, caused by progression of infection by e.

Pharmacokinetic/pharmacodynamic analysis of ceftazidime/avibactam and fosfomycin combinations in an hollow fiber infection model against multidrug-resistant .

Mechanistic understanding of pharmacodynamic interactions is key for the development of rational antibiotic combination therapies to increase efficacy and suppress the development of resistances. Potent tools to provide those insights into pharmacodynamic drug interactions are semi-mechanistic modeling and simulation techniques. This study uses those techniques to provide a detailed understanding with regard to the direction and strength of the synergy of ceftazidime-avibactam and ceftazidime-fosfomycin in a clinical isolate expressing extended spectrum beta-lactamase (CTX-M-15 and TEM-4) and carbapenemase (OXA-244) genes.

Operational characteristics of full random effects modelling ('frem') compared to stepwise covariate modelling ('scm').

An adequate covariate selection is a key step in population pharmacokinetic modelling. In this study, the automated stepwise covariate modelling technique ('scm') was compared to full random effects modelling ('frem'). We evaluated the power to identify a 'true' covariate (covariate with highest correlation to the pharmacokinetic parameter), precision, and accuracy of the parameter-covariate estimates.

Tigecycline Dosing Strategies in Critically Ill Liver-Impaired Patients.

This study investigated tigecycline exposure in critically ill patients from a population pharmacokinetic perspective to support rational dosing in intensive care unit (ICU) patients with acute and chronic liver impairment. A clinical dataset of 39 patients served as the basis for the development of a population pharmacokinetic model. The typical tigecycline clearance was strongly reduced (8.

Stability studies with tigecycline in bacterial growth medium and impact of stabilizing agents.

Purpose: This study aimed to examine the degradation of tigecycline in Mueller Hinton broth (ca-MHB), as knowledge about bacterial susceptibility is key for therapeutic decisions.

Methods: Antioxidative stabilizers were evaluated on tigecycline stability in a quantitative chromatography assay and tigecycline induced kill against Staphylococcus aureus (ATCC29213) was determined in time kill studies.

Results: Ascorbic acid caused rapid degradation of tigecycline and resulted in loss of antibacterial activity.