title: Protective effect of trovafloxacin, ciprofloxacin and ampicillin against Streptococcus pneumoniae in a murine sepsis model.
abstract: Trovafloxacin is a new fluoroquinolone that has potent microbiological activity against the pneumococcus, including penicillin-resistant strains. To evaluate the protective effect of trovafloxacin, ciprofloxacin and ampicillin against penicillin-susceptible, -intermediate and -resistant strains of Streptococcus pneumoniae, an intraperitoneal, immunocompetent mouse model of sepsis was used. The minimum lethal dose (MLD) for each isolate was determined in duplicate. A single sc dose of each antibiotic was administered over a wide range of doses 1 h after the ip inoculation of the test isolate at the MLD. The assessment of the protective dose for 50% of the population (PD50) for each antimicrobial/bacteria combination was performed in triplicate and the PD50 value was calculated at the end of 5 days. Results showed that trovafloxacin provided PD50 values that were significantly lower than those of ciprofloxacin for all isolates. For the penicillin-susceptible and -intermediate isolates, the PD50 values of ampicillin were significantly lower than those for either of the fluoroquinolones studied; however, trovafloxacin was statistically superior to both ciprofloxacin and ampicillin against the penicillin-resistant strain. Therefore, regardless of penicillin susceptibility, trovafloxacin has potent activity against Streptococcus pneumoniae and may be a viable alternative for the treatment of penicillin-resistant isolates.
authors.affiliation: Department of Pharmacy Practice, School of Pharmacy, The University of Kansas Medical Center, Kansas City 66160-7231, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Lacy
authors.forename: D P
authors.initials: DP
authors.lastname: Nicolau
authors.forename: M A
authors.initials: MA
authors.lastname: Banevicius
authors.forename: C H
authors.initials: CH
authors.lastname: Nightingale
authors.forename: R
authors.initials: R
authors.lastname: Quintiliani
mesh_terms: D000667:Ampicillin / Q000627:therapeutic use*; D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000627:therapeutic use*; D024841:Fluoroquinolones; D051379:Mice; D009287:Naphthyridines / Q000627:therapeutic use*; D010403:Penicillin Resistance; D011008:Pneumococcal Infections / Q000188:drug therapy*; D013296:Streptococcus pneumoniae / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D002939:Ciprofloxacin; D000667:Ampicillin; C080163:trovafloxacin