Pharmacodynamics of 750 mg and 500 mg doses of levofloxacin against ciprofloxacin-resistant strains of Streptococcus pneumoniae.
An in vitro pharmacokinetic model (IVPM) was used to evaluate the pharmacodynamics of the 750 mg and 500 mg doses of levofloxacin against 4 ciprofloxacin-nonsusceptible Streptococcus pneumoniae. Levofloxacin MICs ranged from 1.4 to 3.2 micro g/ml. Log-phase cultures (5 x 10(7) cfu/ml) were inoculated into the IVPM and exposed to the peak free-drug concentrations of levofloxacin achieved in human serum with each dose. Levofloxacin was dosed at 0 and 24 h, elimination pharmacokinetics were simulated, and viable counts were measured over 30 h. The 750 mg dose was rapidly bactericidal against all 4 strains, achieving eradication within 30 h. Against strains with levofloxacin MICs of 1.4 and 1.8 micro g/ml, the 500 mg dose exhibited pharmacodynamics similar to the 750 mg dose. In contrast, against strains with levofloxacin MICs of 2.6 and 3.2 micro g/ml, viable counts never fell below 10(4) cfu/ml. The rapid killing and eradication of these pneumococci by the 750 mg dose warrant the clinical evaluation of this new dose in the treatment of pneumococcal infections.
Lister
Philip D
PD
Department of Medical Microbiology and Immunology, Creighton University School of Medicine, 2500 California Plaza, Omaha, Nebraska 68178, USA. pdlister@creighton.edu
D002939:Ciprofloxacin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial; D006801:Humans; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000493:pharmacokinetics* / Q000494:pharmacology; D012680:Sensitivity and Specificity; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000302:isolation & purification
D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin