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Pharmacokinetics of Small Spectrum Beta-lactam Antibiotics (Amoxicillin/Clavulanic Acid and Cefuroxime) in Patients on Intensive Care Units

Completed
Conditions
Infection
Registration Number
NCT01581047
Lead Sponsor
University Hospital, Ghent
Brief Summary

Adequate antibiotic therapy is very important in the treatment of infections. Spectrum and dosing of the antibiotics are two factors of the therapy: the spectrum of an antibiotic can't be changed, but the dosing scheme can be optimized. Recent studies proved that an optimized dosing scheme can improve the efficacy of the treatment. Broad-spectrum antibiotics have unpredictable pharmacokinetics in patients on intensive care units. This is due to the pathophysiologic processes in the patients on intensive care units: increased distribution volume, hypoproteinemia, organ failure... The investigators guess that similar processes influence the pharmacokinetics of small spectrum antibiotics (like amoxicillin and cefuroxime), but data lacks. Because the pharmacokinetics of broad spectrum antibiotics in seriously ill patients are better known, physicians are more confident prescribing these drugs. Studying the pharmacokinetic interactions of small spectrum antibiotics in seriously ill patients, can help to give the physician the confidence to prescribe these small-spectrum antibiotics.

In this study, the investigators will study the pharmacokinetics of amoxicillin/clavulanic acid and cefuroxime, in 60 patients on intensive care. 8 blood samples will be drawn via a central catheter on different moments after one administration of the antibiotic in the steady state phase. All the patients are prescribed the antibiotics for the treatment of their infections: they get the antibiotic therapy anyway. By measuring the concentrations on different moments after one administration, the investigators can reconstruct the pharmacokinetic function.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
37
Inclusion Criteria
  • patients on the intensive care unit, who are treated with amoxicillin/clavulanic acid or cefuroxime for an infection
Exclusion Criteria
  • informed consent lacking
  • haematocrit < 21 %
  • arterial catheter lacking

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Area under the serum concentration versus time curve (AUC) of Amoxicillin/Clavulanic acid.Before and at 15, 30, 45, 60, 120, 240 and 360 minutes after administration

The concentrations of the antibiotic in serum samples, drawn at various times after one administration, will be measured. With these data, we can calculate the time above the minimal inhibitory concentration (MIC).

Area under the serum concentration versus time curve (AUC) of Cefuroxime.Before and at 15, 30, 45, 60, 120, 240 and 480 minutes after administration

The concentrations of the antibiotic in serum samples, drawn at various times after one administration, will be measured. With these data, we can calculate the time above the minimal inhibitory concentration (MIC).

Secondary Outcome Measures
NameTimeMethod
Rate of organ failure.At date of admission (day 1) and dismissal (up to 3 months).

This will be assessed using the Sequential Organ Failure Assessment score (SOFA-score).

Severity of disease classification.At date of admission (day 1) and dismissal (up to 3 months).

This will be assessed using the Acute Physiology and Chronic Health Evaluation II (APACHE2)-score.

24 hour urine creatinine clearanceAt 24 hours

Urine will be collected during 24 hours to measure the urine creatinine clearance.

Concentration serum albuminAt day 1.
Concentration serum creatininAt day 1.
Change in fluid balanceFrom 0 to 24 hours.

Change in fluid balance will be measured.

Trial Locations

Locations (1)

Ghent University Hospital

🇧🇪

Ghent, Belgium

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