title: Pharmacodynamics of moxifloxacin and levofloxacin simulating human serum and lung concentrations.
abstract: Fluoroquinolones are known to penetrate well into the infectious foci such as lung mucosa, epithelial lining fluid and alveolar macrophages achieving higher target site concentrations than the corresponding serum levels. In order to integrate the in vitro antibacterial activity and pharmacokinetics of moxifloxacin and levofloxacin, their bactericidal efficacy was assessed by simulating human serum and lung tissue concentrations using Streptococcus pneumoniae, Staphylococcus aureus and Klebsiella pneumoniae as indicator organisms. The bacteria were exposed to fluctuating moxifloxacin and levofloxacin concentrations simulating the drug levels in serum, lung mucosa, epithelial lining fluid and alveolar macrophages. The following parameters were deduced from the kill curves: area under the bactericidal kill curve normalized to the initial inoculum (AUBKC norm), the time needed to reduce the inoculum by 3 log(10) titers, and the initial bactericidal activity. In general, all these three parameters were for all the bacterial isolates having been exposed to moxifloxacin concentration dependent. In contrast, beyond a levofloxacin concentration of optimal bactericidal effect, higher drug concentrations did not further augment the bactericidal activity of levofloxacin. These data demonstrate that not all fluoroquinolones share the same pharmacodynamic targets needed to maximize their antibacterial effect.
authors.affiliation: Institute for Infection Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Brunswiker Str. 4, 24105 Kiel, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schubert
authors.forename: A
authors.initials: A
authors.lastname: Dalhoff
authors.forename: H
authors.initials: H
authors.lastname: Stass
authors.forename: U
authors.initials: U
authors.lastname: Ullmann
mesh_terms: D000900:Anti-Bacterial Agents / Q000097:blood* / Q000493:pharmacokinetics*; D001372:Aza Compounds / Q000097:blood* / Q000493:pharmacokinetics*; D024841:Fluoroquinolones; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects; D064704:Levofloxacin; D008168:Lung / Q000378:metabolism*; D008954:Models, Biological; D000077266:Moxifloxacin; D015242:Ofloxacin / Q000097:blood* / Q000493:pharmacokinetics*; D011804:Quinolines / Q000097:blood* / Q000493:pharmacokinetics*; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D064704:Levofloxacin; D015242:Ofloxacin; D000077266:Moxifloxacin