title: Activities of trovafloxacin, gatifloxacin, clinafloxacin, sparfloxacin, levofloxacin, and ciprofloxacin against penicillin-resistant Streptococcus pneumoniae in an in vitro infection model.
abstract: We adapted an in vitro pharmacodynamic model of infection to incorporate infected fibrin clots. The bactericidal activities of various fluoroquinolones against two strains of penicillin-resistant Streptococcus pneumoniae were studied over a 48-h period. Bacteria were prepared in Muller-Hinton broth by using colonies from a 24-h tryptic soy agar plus 5% sheep blood plate and were added to a mixture of cryoprecipitate (80%) and thrombin (10%) to achieve approximately 10(6) CFU of organism per fibrin clot. The fibrin clots were suspended into the models and removed, in triplicate, at various time points over 48 h. Control models were also conducted to characterize the growth of S. pneumoniae in the growth medium without antibiotic. Trovafloxacin, gatifloxacin, clinafloxacin, sparfloxacin, levofloxacin, and ciprofloxacin were administered to simulate their pharmacokinetic profiles in humans. Fibrin clot samples were also plated onto antibiotic-containing tryptic soy agar plus 5% lysed horse blood to detect resistance. The newer fluoroquinolones demonstrated better activity than ciprofloxacin against both isolates. In conclusion, the newer quinolones demonstrated significant activity against penicillin-resistant S. pneumoniae, with standard dosing resulting in area under the concentration-time curve/MIC ratios and peak concentration/MIC ratios that resulted in 99.9% killing against these isolates.
authors.affiliation: Anti-Infective Research Laboratory, Wayne State University, and Department of Pharmacy Services, Detroit Receiving Hospital, University Health Center, Detroit, Michigan 48201, USA.
authors.forename: E
authors.initials: E
authors.lastname: Hershberger
authors.forename: M J
authors.initials: MJ
authors.lastname: Rybak
mesh_terms: D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001777:Blood Coagulation; D002939:Ciprofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology; D005337:Fibrin; D024841:Fluoroquinolones; D000077734:Gatifloxacin; D006801:Humans; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000493:pharmacokinetics / Q000494:pharmacology; D015242:Ofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology; D010403:Penicillin Resistance; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D002939:Ciprofloxacin; D064704:Levofloxacin; C057477:clinafloxacin; D005337:Fibrin; C080163:trovafloxacin; D015242:Ofloxacin; D000077734:Gatifloxacin; C061363:sparfloxacin