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Eur J Clin Microbiol Infect Dis. 2003 Apr;22(4):203-21. Epub 2003 Apr 1.

In vitro antibacterial activity and pharmacodynamics of new quinolones.

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  • 1Institute for Medical Microbiology and Virology, Universit√§tsklinikum Schleswig-Holstein, Brunswiker Strasse 4, 24105 Kiel, Germany. axel.dalhoff.ad@bayer-ag.de

Abstract

This synopsis of published literature summarises data on the in vitro antibacterial activity and pharmacodynamics of fluoroquinolones. Data were compiled for ciprofloxacin, levofloxcin, moxifloxacin, gatifloxacin, grepafloxacin, gemifloxacin, trovafloxacin, sitafloxacin and garenoxacin. All of these quinolones are almost equipotent against gram-negative bacteria but demonstrate improved activity against gram-positive species. The new quinolones are uniformly active against gram-positive species except Streptococcus pneumoniae; against which gemifloxacin, sitafloxacin and garenoxacin are one to two dilution steps more active than moxifloxacin. All of the new quinolones except gemifloxacin demonstrate enhanced activity against anaerobes. Since all the new quinolones show similar activity against the major respiratory tract pathogens except Streptococcus pneumoniae and members of the family Enterobacteriaceae, their pharmacokinetics and pharmacodynamics will be clinically relevant differentiators and determinants of their overall activity and efficacy. In vitro simulations of serum concentrations revealed that (i). gemifloxacin and levofloxacin were significantly and gatifloxacin moderately less active than moxifloxacin against Streptococcus pneumoniae and Staphylococcus aureus, and (ii). resistant subpopulations emerged following exposure to levofloxacin and gatifloxacin (gemifloxacin not yet published) but not to moxifloxacin. The emergence of resistance is a function of drug concentrations achievable in vivo and the susceptibility pattern of the target organisms. Therefore, the use of less potent fluoroquinolones with borderline or even suboptimal pharmacokinetic/pharmacodynamic surrogate parameters will inadvertently foster the development of class resistance. Drugs with the most favourable pharmacokinetic/pharmacodynamic characteristics should be used as first-line agents in order to preserve the potential of this drug class and, most importantly, to provide the patient with an optimally effective regimen.

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