Pharmacodynamics of fluoroquinolones in experimental models of endocarditis.
We calculated the magnitude of various serum pharmacodynamic parameters for fluoroquinolones in models of experimental endocarditis (EE) described in the literature. Nineteen publications contained data that allowed calculation of these parameters. Data were available for eight fluoroquinolones against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, methicillin-resistant Staphylococcus epidermidis, viridans streptococci, Enterobacter aerogenes, and Pseudomonas aeruginosa in rabbit or rat models. Enterococci were excluded because of poor bactericidal activity. A 24-hour area under the concentration curve (AUC)/minimal inhibitory concentration (MIC) ratio > or = 100, a peak level/MIC ratio > 8, and continuous levels above the time were associated with a significantly lower number of cfu per vegetation after 3-6 days of therapy. The 24-hour AUC/MIC exhibited the best linear correlation with cfu per vegetation after 3-6 days of therapy (r2 = 45%). The pharmacodynamic parameters predictive of efficacy for fluoroquinolones in the treatment of experimental endocarditis are similar to those for other infectious models.
William S. Middleton Memorial Veterans Affairs Hospital, Madison, Wisconsin, USA.
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Andes
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Craig
D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D004696:Endocarditis / Q000188:drug therapy*; D024841:Fluoroquinolones; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D011817:Rabbits; D051381:Rats
D000890:Anti-Infective Agents; D024841:Fluoroquinolones