Pharmacodynamics of levofloxacin and ciprofloxacin against Streptococcus pneumoniae.
An in-vitro pharmacokinetic model was used to compare the pharmacodynamics of levofloxacin and ciprofloxacin against four penicillin-susceptible and four penicillin-resistant Streptococcus pneumoniae. Logarithmic-phase cultures were exposed to the peak concentrations of levofloxacin or ciprofloxacin observed in human serum after 500 mg and 750 mg oral doses, human elimination pharmacokinetics were simulated, and viable bacterial counts were measured at 0, 1, 2, 4, 6, 8, 12, 24 and 36 h. Levofloxacin was rapidly and significantly bactericidal against all eight strains evaluated, with eradication of six strains occurring despite area under the inhibitory curve over 24 h (AUIC24) values of only 32-64 SIT(-1) x h (serum inhibitory titre over time). The pharmacodynamics of ciprofloxacin were more variable and the rate of bacterial killing was consistently slower than observed with levofloxacin. Ciprofloxacin eradicated five strains despite having an AUIC24 of only 44 SIT(-1) x h. These data suggest that the increased potency of levofloxacin and more favourable pharmacokinetics compared with ciprofloxacin provide enhanced pharmacodynamic activity against S. pneumoniae. Furthermore, these data suggest that the minimum AUIC required for clinical efficacy against and eradication of S. pneumoniae with levofloxacin and ciprofloxacin may be well below the 125 SIT(-1) x h identified by other studies.
Lister
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Center for Research in Anti-Infectives and Biotechnology, Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA. pdlister@creighton.edu
Sanders
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CC
D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D002939:Ciprofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D015242:Ofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology*; D010403:Penicillin Resistance; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000378:metabolism
D000890:Anti-Infective Agents; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin