steady state serum and epithelial lining fluid (elf) antibiotics concentrations under continous infusion

Conditions: Pneumonia; Bacteremia

Summary: 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.

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.

Eligibility criteria:
inclusion criteria: * patients of both gender \>0 18 years of age * patients of an icu with one or more of the following infections * bacteremia. sepsis * pneumonia * tracheo-bronchitis * mechanical ventilation * stay on the icu \>= 3 days * indication for bronchoscopy exclusion criteria: * pregnancy * allergy against the studied drug * known resistance of the involved pathogen against the study drug * simultaneous participation in other studies * former participation in the present study * probable stay on the icu \< 3 days * contra-indication against the study-drug * contra-indication for bronchoscopy

Keywords: continuous infusion epithelial lining fluid antibiotics pneumonia critical illness