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. 1999 May;43 Suppl B:51-9.
doi: 10.1093/jac/43.suppl_2.51.

Pharmacodynamics of Fluoroquinolones

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Pharmacodynamics of Fluoroquinolones

A Dalhoff. J Antimicrob Chemother. .

Abstract

Fluctuating concentrations of three fluoroquinolones (moxifloxacin, sparfloxacin and ofloxacin) and a beta-lactam (amoxycillin) were used in vitro to simulate antibiotic concentrations in human serum after oral doses of antibiotics. The antibiotics were tested against Staphylococcus aureus 12241 and Streptococcus pneumoniae 4241. Moxifloxacin and sparfloxacin were also tested against Escherichia coli Neumann. Human serum concentrations of moxifloxacin and ciprofloxacin were also simulated in an in-vivo murine thigh muscle model against S. aureus, S. pneumoniae and E. coli. Ciprofloxacin, sparfloxacin and ofloxacin had a dose-independent effect on gram-positive organisms beyond their optimal dose that gave a maximum effect, as did amoxycillin. In contrast, moxifloxacin had a dose-dependent and therefore concentration-dependent effect on both gram-positive and beta-lactam-susceptible and-resistant gram-negative organisms. The marked activity of moxifloxacin against both gram-positive and gram-negative organisms was confirmed in an in-vivo model. A human dose equivalent of 200 mg moxifloxacin reduced viable counts of S. pneumoniae below the limit of detection and regrowth did not occur. S. aureus was eliminated almost as effectively as S. pneumoniae. A 200 mg dose of moxifloxacin completely eliminated the original inoculum of E. coli within 6 h. Treatment of S. aureus with ciprofloxacin (250 or 500 mg) resulted in a dose-independent decrease in viable counts by approximately 3.5 log10 cfu/mL. A 125 mg dose of ciprofloxacin almost completely eliminated the original inoculum of E. coli within 8 h, whereas both the 250 mg and 500 mg doses reduced viable counts below the limit of detection. Thus, the in-vitro and in-vivo pharmacodynamic models used in this study established that moxifloxacin was highly effective against both gram-negative and gram-positive bacteria.

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