title: In vivo measurement of levofloxacin penetration into lung tissue after cardiac surgery.
abstract: Nosocomial pneumonia is a severe complication after cardiac surgery (CS). Levofloxacin, a fluoroquinolone, qualifies for the therapy of postoperative pneumonia. However, penetration properties of levofloxacin into the lung tissue could be substantially affected by CS: atelectasis, low cardiac output after CS, high volume loads, and inflammatory capillary leak potentially influence drug distribution. The aim of our study was to gain information on interstitial antibiotic concentrations in lung tissue in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. Therefore, six patients undergoing elective CS participated in this prospective study. A dose of 500 mg of levofloxacin was administered intravenously in addition to standard antibiotic prophylaxis immediately after the end of surgery. Time versus concentration profiles of levofloxacin in the interstitial lung tissue and plasma were determined. A microdialysis technique was used for lung interstitial concentration measurements. The microdialysis procedure was well tolerated in all patients and no adverse events were observed. The median area under the concentration curve (AUC) of levofloxacin in interstitial lung fluid was 18.6 microg.h/ml (range, 10.1 to 33.6). The median AUC for tissue (AUC(tissue)) of unbound levofloxacin/AUC(total) in plasma was 0.6 (range, 0.4 to 0.9). The median unbound AUC(tissue)/MIC was 2.4 (range, 1.3 to 4.2) for Pseudomonas aeruginosa. Our study demonstrated the feasibility and safety of microdialysis in human lung tissue in vivo after CS. The unbound AUC/MIC ratio revealed that levofloxacin used in the described manner was borderline sufficient for the treatment of nosocomial pneumonia caused by Klebsiella pneumoniae and insufficient for the treatment of pneumonia caused by Pseudomonas aeruginosa, because the breakpoint of 30 to 40 for AUC/MIC could not be reached by the conventionally used dosage schema in our post-CS setting. Penetration was lower than in previous reports.
authors.affiliation: Department of Cardiothoracic and Vascular Anaesthesia & Critical Care Medicine, University of Vienna, General Hospital, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Doris
authors.initials: D
authors.lastname: Hutschala
authors.forename: Keso
authors.initials: K
authors.lastname: Skhirtladze
authors.forename: Andreas
authors.initials: A
authors.lastname: Zuckermann
authors.forename: Wilfried
authors.initials: W
authors.lastname: Wisser
authors.forename: Peter
authors.initials: P
authors.lastname: Jaksch
authors.forename: Bernhard Xaver
authors.initials: BX
authors.lastname: Mayer-Helm
authors.forename: Heinz
authors.initials: H
authors.lastname: Burgmann
authors.forename: Ernst
authors.initials: E
authors.lastname: Wolner
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
authors.forename: Edda M
authors.initials: EM
authors.lastname: Tschernko
mesh_terms: D000368:Aged; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001026:Coronary Artery Bypass; D004305:Dose-Response Relationship, Drug; D006801:Humans; D064704:Levofloxacin; D008168:Lung / Q000378:metabolism*; D008875:Middle Aged; D015242:Ofloxacin / Q000493:pharmacokinetics*; D011014:Pneumonia / Q000378:metabolism; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000890:Anti-Infective Agents; D064704:Levofloxacin; D015242:Ofloxacin