Drug Monitoring of Antibiotics in Critical Care Patients

Completed

• Conditions: ARDS; Sepsis

• Registration Number: NCT01793012
• Lead Sponsor: Ludwig-Maximilians - University of Munich

Brief Summary

Infections are critical factors for the survival of critically ill patients. A broad, high-dose and early initial therapy of antibiotics is of particular relevance.

A serious problem is the high variability of antibiotic serum concentrations after administration of antibiotics in patients of the critical care units. This may result in the risk of underdosage with possible ineffective therapeutic levels as well as in the risk of overdosage with possible adverse and toxic effects. The goal of this study is to determine antibiotic concentrations in blood and to evaluate concentrations with the course of the therapy. The measurement of antibiotic concentrations in blood may allow an individual adaption of the dose in future.

100 - 200 patients will be included in this study. Only critically ill patients of the ICU of the Department of Anaesthesiology will be included that receive one or more of the following antibiotics: piperacillin/tazobactam, cefepime, meropenem, ciprofloxacin, linezolid, and colistin.

Detailed Description

Substantial variations of serum concentrations of different antibiotics with partly insufficient levels have been observed in critically ill patients. The high variabilities between the pharmacokinetic parameters in different patients argue for a therapeutic drug monitoring (TDM) in intensive care units. TDM may lower the risk of overdosage with possible adverse and toxic effects as well as the risk of underdosage with possible insufficient therapeutic effects and development of antibiotic resistance. The aim of this study is to evaluate variabilities of pharmacokinetic parameters of different widely used antibiotics and to correlate them with clinical and laboratory parameters. Therefore, numerous clinical and laboratory parameters including serum, urine and dialysate concentrations of 6 different antibiotics will be determined in 100 - 200 critically ill patients of the Department of Anaesthesiology, University Hospital of Munich. Laboratory parameters (e.g. inflammatory parameters) will be quantified by facilities of the Institute of Laboratory Medicine, University Hospital of Munich. Concentrations of antibiotics will be determined by liquid chromatography-mass spectrometry (LC-MS/MS). We expect that correlations between antibiotic serum concentrations and clinical and laboratory outcome parameters will be found.

Study Timeline

• Study First Submitted: 2013-01-24
• Study First Submitted QC: 2013-02-13
• Study First Posted: 2013-02-15
• Study Start: 2013-03
• Primary Completion: 2015-01
• Study Completion: 2015-01
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-01
• Last Update Posted: 2020-09-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 186

Inclusion Criteria

1. Hospitalisation in the critical care unit of the Department of Anaesthesiology of the University Hospital of Munich
2. Presence of infection by clinical assessment
3. Treatment of the patients with one or more of the following antibiotics: piperacillin/tazobactam, cefepime, meropenem, ciprofloxacin, linezolid, colistin
4. Bolus administration of selected antibiotics
5. Valid informed consent subscribed by the patient or by his or her legal guardian or - if only a provisional guardian is defined - by the provisional guardian.

Exclusion Criteria

1. Prophylactic antibiotics without clinical assessment for the presence of infection
2. Planned shorter hospital stay than 4 days
3. Administration of the selected antibiotic 14 days to 48 hours before the begin of the study
4. Only a single dose of an antibiotic per day
5. Subsequent withdrawal of the participation in the study by the patient or the guardian

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Variability of antibiotic serum concentrations in critically ill patients	2 Years	The primary goal of this study is to evaluate the variability of antibiotic serum concentrations in critically ill patients. In total, serum concentrations of 6 different antibiotics (piperacillin/tazobactam, cefepime, meropenem, ciprofloxacin, linezolid, and colistin) in 100-200 patients of the ICU will be determined by liquid chromatography mass spectrometry.

Secondary Outcome Measures

Name	Time	Method
correlate these serum concentrations with clinical and laboratory outcome Correlate serum concentrations with clinical and laboratory outcome parameters	2 Years	Moreover, we will evaluate if antibiotic serum concentrations differ between the different diseases (e.g. ARDS, sepsis) and the different therapies (e.g. different transplantation types (liver,lung) patients with and without renal replacement therapy).; Correlation between antibiotics serum concentrations and Apache II score / SOFA score. Correlation between antibiotics serum concentrations and CRP, procalcitonin, interleukin-6.; Finally minimal inhibitory concentrations (MIC) of antibiotics will be documented in case of detection of pathogens.

Trial Locations

Locations (1)

Department of Anaesthesiology of the University Hospital of Munich; 🇩🇪 Munich, Germany