Serum Ceftazidime Concentrations in Hemodialysis Patients

Summary

There is evidence that the current dosing recommendations of ceftazidime in hemodialysis patients may not reach the critical pharmacokinetic/pharmacodynamics thresholds associated with maximal efficacy.

The primary objective is to assess whether the standard doses of ceftazidime (1 or 2 g) administered at the end of the dialysis session (intermittent dialysis) allow to obtain a trough level equal or superior to 8 mg/L if the causative organism is not identified or 1 x the MIC if it is identified and its in vitro susceptibility to ceftazidime established. The secondary objectives will be (i) to assess whether a trough level equal or superior to 32 mg/L (if the causative organism is not identified) and 4 x its MIC (if identified and its in vitro susceptibility established) can be obtained; (ii) whether the criteria mentioned above also apply to the free fractions of ceftazidime; (iii) to assess whether reaching the desired free and total trough concentrations impacts the clinical outcome of the patient; (iv) to assess whether the main hemodialysis parameters impact on ceftazidime total and free serum concentrations; (v) to assess the impact of patient's residual renal function on the ceftazidime serum free and total concentrations; (vi) to assess the impact of potential drug-drug interactions on ceftazidime serum free and total concentrations; (vii) to assess how the MIC of the causative organism (if known) affects the expected effectiveness of ceftazidime.

The study will be prospective and monocentric. Drug assay will be made High Performance Liquid Chromatography (HPLC) and UV photometric detection (confirmed by tandem mass spectrometry detection\[HPLC-MS-MS\]). Free concentration will be measured after separation by membrane sieving.

The expected number of enrolled patients will be 20 (arbitrarily chosen but compatible with previous studies and the possibilities of the Institution in which the study will be performed. The standard dose of ceftazidime will be (i) a loading dose of 2 g followed by a maintenance dose of 1 g (the dose may be modified by the clinician in charge if deemed necessary and recorded accordingly).

The data obtained will be used for pharmacokinetic modelling and population pharmacokinetics, followed by Monte-Carlo simulations to obtain population-wide predictions and to draw conclusions that could be applicable to a larger population.

Conditions

• Bacterial Infections
• Ceftazidime
• Renal Failure Chronic Requiring Hemodialysis

Interventions

DRUG

Drug bood sampling

Total: 6 per patient * after the first administration of ceftazidime (loading dose): sampling #1: at trough before 1st dialysis; sampling #2: after the end of the dialysis session; * after the second administration of ceftazidime (maintenance dose): sampling #3: at trough before 2d dialysis session; * after the third administration of ceftazidime (maintenance dose): sampling #4: at trough before 3d dialysis session; * after the fourth third administration of ceftazidime (maintenance dose): sampling #5: at trough before 4th dialysis session; sampling #6: after the end of the dialysis session

Sponsors & Collaborators

• Université Catholique de Louvain

  collaborator OTHER

• Centre Hospitalier Universitaire de Charleroi

  lead OTHER

Principal Investigators

• Remy Demeester, MD · Centre Hospitalier Universitaire de Charleroi

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-09-15

Primary Completion

2020-09-15

Completion

2021-09-15