Pharmacodynamics of moxifloxacin and levofloxacin simulating human serum and lung concentrations

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...

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Bibliographic Details
Published in:Infection 2005-12, Vol.33 Suppl 2 (S2), p.15-21
Main Authors: Schubert, S, Dalhoff, A, Stass, H, Ullmann, U
Format: Article
Language:English
Subjects:
Alveoli
Anti-Bacterial Agents - blood
Anti-Bacterial Agents - pharmacokinetics
Antibacterial activity
Antibiotics
Aza Compounds - blood
Aza Compounds - pharmacokinetics
Bactericidal activity
Fluoroquinolones
Humans
Inoculum
Klebsiella
Klebsiella pneumoniae - drug effects
Levofloxacin
Lung - metabolism
Lungs
Macrophages
Models, Biological
Moxifloxacin
Mucosa
Ofloxacin - blood
Ofloxacin - pharmacokinetics
Parameters
Pharmacodynamics
Pharmacokinetics
Pharmacology
Quinolines - blood
Quinolines - pharmacokinetics
Serum levels
Simulation
Staphylococcus aureus - drug effects
Streptococcus infections
Streptococcus pneumoniae - drug effects
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Summary: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.
ISSN:0300-8126
1439-0973
DOI:10.1007/s15010-005-8203-1