Clinical trial NCT01581047: Pharmacokinetics of Small Spectrum Beta-lactam Antibiotics (Amoxicillin/Clavulanic Acid and Cefuroxime) in Patients on Intensive Care Units
Official title: Pharmacokinetics of Small Spectrum Beta-lactam Antibiotics (Amoxicillin/Clavulanic Acid and Cefuroxime) in Patients on Intensive Care Units
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Infection
Keywords: amoxicillin
clavulanic acid
cefuroxime
Patients in the intensive care unit, with an infection which requires amoxicillin/clavulanic acid or cefuroxime
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
First posted: 2012-04-19
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients on the intensive care unit, with an infection (which requires amoxicillin/clavulanic acid or cefuroxime).

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.


Eligibility criteria: 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

Primary outcomes:
measure: Area under the serum concentration versus time curve (AUC) of Amoxicillin/Clavulanic acid.
timeFrame: Before and at 15, 30, 45, 60, 120, 240 and 360 minutes after administration
measure: Area under the serum concentration versus time curve (AUC) of Cefuroxime.
timeFrame: Before and at 15, 30, 45, 60, 120, 240 and 480 minutes after administration
Secondary outcomes:
measure: Severity of disease classification.
timeFrame: At date of admission (day 1) and dismissal (up to 3 months).
measure: Rate of organ failure.
timeFrame: At date of admission (day 1) and dismissal (up to 3 months).
measure: Concentration serum creatinin
timeFrame: At day 1.
measure: 24 hour urine creatinine clearance
timeFrame: At 24 hours
measure: Change in fluid balance
timeFrame: From 0 to 24 hours.
measure: Concentration serum albumin
timeFrame: At day 1.
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Ghent University Hospital
Study officials:
affiliation: University Hospital, Ghent
name: Jan De Waele, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: