A Study to Determine Pharmacokinetic Changes of Ceftriaxone in Patients With Liver Cirrhosis

The investigators designed an observational multicenter explorative in vivo study to investigate the changes in ceftriaxone pharmacokinetics in blood and ascites. The investigators will include a total of 20 patients with liver cirrhosis admitted to the ward of participating hospitals. Patients are eligible when receiving ceftriaxone and concomitantly receive paracentesis. The investigators will collect all available waste blood samples of each participant, starting from study entry up until 48 hours after the last dosing interval of ceftriaxone. The investigators will collect all available waste ascites samples of each participant up until 48 hours after the last dosing interval of ceftriaxone. Duration of the trial: The study duration is variable and depends on the duration of ceftriaxone treatment and duration of hospital admission, which both are determined by the treating physician and is not influenced by study participation. Patients will be eligible for study inclusion when patients received (a single dose of) ceftriaxone treatment and undergo paracentesis during ceftriaxone treatment. The study will end 48 hours after the last dosing interval of ceftriaxone or until hospital discharge, whichever comes first. Study timeline: The investigators expect to enrol 1-2 participants every month. The total enrolment time will thus be approximately 12 months.

Objective: The primary objective is to determine the changes in ceftriaxone pharmacokinetics in blood and ascites in patients with decompensated liver cirrhosis to guide ceftriaxone dosing in these patients.

Study design: Observational explorative multicentre study

Study population: Adults (\>18 years) with decompensated liver cirrhosis with the presence of ascites admitted to the clinical ward of participating centres who receive ceftriaxone and concomitantly undergo paracentesis during active antibiotic treatment.

Intervention: No intervention, the investigators will only collect the available waste blood and ascites samples.

Main study parameters/endpoints:

* Clearance (CL) of unbound ceftriaxone
* Volume of distribution (VD) of unbound ceftriaxone
* Penetration rate of unbound ceftriaxone from blood to ascites
* Elimination rate of unbound ceftriaxone from ascites by paracentesis

Secondary study parameters are:

* Target attainment of ceftriaxone in blood, defined as the unbound plasma concentration of ceftriaxone above at least one time the minimal inhibitory concentration (MIC) for 50% of the dosing interval (50%fT \> 1MIC).
* Target attainment of ceftriaxone in ascites, defined as the unbound ascites concentration of ceftriaxone above at least one time the minimal inhibitory concentration (MIC) for 50% of the dosing interval (50%fT \> 1MIC).
* Explorative analysis on the effects of liver disease severity (Child Pugh, MELD-score) and renal insufficiency (CKD-stage) on individual pharmacokinetic parameters

Eligibility Criteria:
Inclusion Criteria:

* Age ≥18 years
* Clinical, radiological and/or histological diagnosis of liver cirrhosis and portal hypertension
* Presence of ascites
* Receiving ceftriaxone in the context of prophylaxis or treatment of infection
* Indication for diagnostic and/or therapeutic paracentesis
* Providing oral informed consent

Exclusion Criteria:

* None