Clinical trial NCT01793012: Drug Monitoring of Antibiotics in Critical Care Patients
Official title: Drug Monitoring of Antibiotics in Critical Care Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: ARDS
Sepsis
Keywords: therapeutic drug monitoring
antibiotics
inflammation parameters
critically ill patients
septicaemia
intensive care unit
Lead sponsor: Ludwig-Maximilians - University of Munich
Sponsor class: OTHER
First posted: 2013-02-15
Enrollment: 186
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: Hospitalisation in the critical care unit of the Department of Anaesthesiology of the University Hospital 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.

Eligibility criteria: 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

Primary outcomes:
measure: Variability of antibiotic serum concentrations in critically ill patients
timeFrame: 2 Years
Secondary outcomes:
measure: correlate these serum concentrations with clinical and laboratory outcome Correlate serum concentrations with clinical and laboratory outcome parameters
timeFrame: 2 Years
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Department of Anaesthesiology of the University Hospital of Munich
Study officials:
affiliation: Department of Anaesthesiology of the University Hospital of Munich
name: Bernhard Zwissler, Prof.Dr.med.
role: STUDY_DIRECTOR
affiliation: Institute of Laboratory Medicine of the University Hospital of Munich
name: Daniel Teupser, Prof.Dr.med.
role: STUDY_DIRECTOR
affiliation: Institute of Laboratory Medicine of the University Hospital of Munich
name: Johannes Zander, Dr. med.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Anaesthesiology of the University Hospital of Munich
name: Michael Zoller, Dr. med.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Anaesthesiology of the University Hospital of Munich
name: Lorenz Frey, Dr. med.
role: STUDY_CHAIR
affiliation: Institute of Laboratory Medicine of the University Hospital of Munich
name: Michael Vogeser, Prof.Dr.med.
role: STUDY_CHAIR
affiliation: Institute of Laboratory Medicine of the University Hospital of Munich
name: Mathias Bruegel, Dr. med.
role: STUDY_CHAIR
affiliation: Institute of Laboratory Medicine of the University Hospital of Munich
name: Lesca Holdt, Dr.rer.nat.
role: STUDY_CHAIR
References:
citation: Ehmann L, Zoller M, Minichmayr IK, Scharf C, Maier B, Schmitt MV, Hartung N, Huisinga W, Vogeser M, Frey L, Zander J, Kloft C. Role of renal function in risk assessment of target non-attainment after standard dosing of meropenem in critically ill patients: a prospective observational study. Crit Care. 2017 Oct 21;21(1):263. doi: 10.1186/s13054-017-1829-4.
citation: Taubert M, Zoller M, Maier B, Frechen S, Scharf C, Holdt LM, Frey L, Vogeser M, Fuhr U, Zander J. Predictors of Inadequate Linezolid Concentrations after Standard Dosing in Critically Ill Patients. Antimicrob Agents Chemother. 2016 Aug 22;60(9):5254-61. doi: 10.1128/AAC.00356-16. Print 2016 Sep.
citation: Zander J, Dobbeler G, Nagel D, Maier B, Scharf C, Huseyn-Zada M, Jung J, Frey L, Vogeser M, Zoller M. Piperacillin concentration in relation to therapeutic range in critically ill patients--a prospective observational study. Crit Care. 2016 Apr 4;20:79. doi: 10.1186/s13054-016-1255-z.
citation: Zoller M, Maier B, Hornuss C, Neugebauer C, Dobbeler G, Nagel D, Holdt LM, Bruegel M, Weig T, Grabein B, Frey L, Teupser D, Vogeser M, Zander J. Variability of linezolid concentrations after standard dosing in critically ill patients: a prospective observational study. Crit Care. 2014 Jul 10;18(4):R148. doi: 10.1186/cc13984.