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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.
AuthorsHarald Herkner, Michael Rolf Müller, Nicole Kreischitz, Bernahrd X Mayer, Martin Frossard, Christian Joukhadar, Nikolas Klein, Edith Lackner, Markus Müller
JournalAmerican journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 165 Issue 2 Pg. 273-6 (Jan 15 2002) ISSN: 1073-449X [Print] United States
PMID11790667 (Publication Type: Clinical Trial, Journal Article)
Chemical References
  • Cephalosporins
  • cefpirome
Topics
  • Aged
  • Area Under Curve
  • Cephalosporins (pharmacokinetics)
  • Equipment Design
  • Extracellular Space (metabolism)
  • Feasibility Studies
  • Humans
  • Lung (metabolism, surgery)
  • Male
  • Microbial Sensitivity Tests
  • Microdialysis (instrumentation, methods)
  • Middle Aged
  • Time Factors

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