Steady State Serum and Epithelial Lining Fluid (ELF) Antibiotics Concentrations Under Continous Infusion

University Hospital Tuebingen

Status

Terminated

Conditions

Bacteremia

Pneumonia

Treatments

Drug: Piperacillin/Tazobactam

Drug: Linezolid

Drug: Vancomycin

Drug: Meropenem

Drug: Ceftazidim

Drug: Cefepim

Study type

Observational

Funder types

Other

Identifiers

NCT00435305

2005-002128-32

Details and patient eligibility

About

The purpose of our study is to determine the penetration of continuously infused antibiotics at steady state, mainly Meropenem, Vancomycin, Linezolid, Piperacillin/tazobactam and additionally cefepim and ceftazidim, into epithelial lining fluid.

Full description

Severe infectious disease may be the cause for admitting a patient to an ICU, but more often they constitute a complication of the intensive care and turn out to be caused by nosocomial pathogens.

Nosocomial infections are associated with a high lethality. The appropriate antibiotic therapy determines in part the outcome of the patients. Especially this antibiotic therapy implicates a number of problems for the physician.

He has to ensure that the chosen antibiotics are effective against the most common and presumed pathogens and that the reached concentrations of antibiotics in plasma and epithelial lining fluid are reliably and permanently above the minimal inhibitory concentration (MIC) for the given pathogens.

All the antibiotics included in our clinical trial are so called "time dependent" antibiotics. They are most effective if there concentrations reach a certain level (MIC) at the infected site (epithelial lining fluid in our study) over the entire period of treatment.

To achieve this aim, many authors already suggested that the continuous infusion might solve the problem of too low antibiotic plasma and ELF levels. Studies about pharmacokinetics of continuous infused antibiotics, which were conducted in healthy volunteers or patients with normal organ function, cannot be assigned to critical ill patients. Rationales for this statement are that data about plasma and tissue levels of antibiotics in critical ill patients are highly influenced by modified volume of distribution, elimination half-life period and impaired tissue perfusion compared to healthy volunteers. These physiological variances implicate that the response to the antibiotic treatment remains doubtful. Under these pathophysiological conditions, data about antibiotics plasma and ELF levels may provide additional information in order to adjust the dosing regime of antibiotics.

Studies conducted in critical ill patients showed that under the circumstances of continuous infused antibiotics, the reached levels in plasma are above the MIC. However there is little data about penetration into ELF of continuous infused antibiotics.

Our study intends to provide data about plasma and ELF levels of continuous infused antibiotics in steady state, determine a penetration coefficient for these antibiotics into ELF and to compare the reached levels in ELF to the MIC.

To demonstrate the efficiency of continuous infused antibiotics, we will conduct quantitative microbiological measurements before and after treatment if applicable.

Enrollment

40 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria