title: Closed-chest microdialysis to measure antibiotic penetration into human lung tissue.
abstract: The majority of bacterial lung infections are localized to the interstitial space fluid, which is therefore an important target site for antimicrobial chemotherapy. Direct measurement of interstitial concentrations of antimicrobial agents in human lung tissue would allow for a more informed approach to appropriate dosing of antimicrobial agents, but until now this was beyond technical reach. In this exploratory pharmacokinetic study, we measured the time versus concentration profile of cefpirome after a single intravenous dose administration of 2 g in the lung interstitial fluid by flexible microdialysis catheters, which were implanted during lung surgery for pulmonary tumors in five patients. Cefpirome concentrations in lung interstitial fluid were 66% of corresponding plasma values within the first 240 min, and exceeded minimal inhibitory concentrations of most relevant bacteria. The experimental procedure was well tolerated by the patients and no adverse events were observed. The present study provides evidence for the first time that closed chest microdialysis of the human lung is a feasible and safe method to measure lung concentrations in patients in vivo. The present data also corroborate the use of cefpirome as a valuable agent in the treatment of lung infections with most extracellular bacteria.
authors.affiliation: Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, University of Vienna Medical School, Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Herkner
authors.forename: Michael Rolf
authors.initials: MR
authors.lastname: Müller
authors.forename: Nicole
authors.initials: N
authors.lastname: Kreischitz
authors.forename: Bernahrd X
authors.initials: BX
authors.lastname: Mayer
authors.forename: Martin
authors.initials: M
authors.lastname: Frossard
authors.forename: Christian
authors.initials: C
authors.lastname: Joukhadar
authors.forename: Nikolas
authors.initials: N
authors.lastname: Klein
authors.forename: Edith
authors.initials: E
authors.lastname: Lackner
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
mesh_terms: D000368:Aged; D019540:Area Under Curve; D002511:Cephalosporins / Q000493:pharmacokinetics*; D004867:Equipment Design; D005110:Extracellular Space / Q000378:metabolism*; D005240:Feasibility Studies; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008826:Microbial Sensitivity Tests; D017551:Microdialysis / Q000295:instrumentation / Q000379:methods*; D008875:Middle Aged; D013997:Time Factors; D000097572:Cefpirome
chemical_list: D002511:Cephalosporins; D000097572:Cefpirome