title: Antipneumococcal activity of ertapenem compared with gatifloxacin in a temperature-sensitive murine model of acute pneumonia.
abstract: Fluoroquinolone-resistance among pneumococci is low; however the number of isolates with a single ParC mutation has increased. Consequently, more potent agents are needed to minimize resistance selection. We investigated the efficacy of ertapenem versus gatifloxacin in a temperature-sensitive mouse model of pneumonia caused by a wildtype Streptococcus pneumoniae strain (A66) and an isogenic mutant with a ParC mutation (R222). Treatment started at 24 h and lasted for 5 days. Temperature was used to assess disease progression before and during treatment. Of mice infected with either strain and treated at an early stage of infection, 79-94% of those given ertapenem survived compared with 56-61% given gatifloxacin. If treated at a later stage, the results were similar for ertapenem (71-84%) but were considerably lower for gatifloxacin (17-33%). Ertapenem was as bactericidal as gatifloxacin against A66 (94-100% vs 92-100%) but was superior to gatifloxacin against R222 (95-100% vs 50-77%). Ertapenem is a promising new treatment for patients with pneumococcal pneumonia, including those at risk of infection with a fluoroquinolone-resistant strain.
authors.affiliation: Toronto Centre for Antimicrobial Research and Evaluation (ToCare), Mount Sinai Hospital, Canada. jdeazavedo@mtsinai.on.ca
authors.forename: J C S
authors.initials: JC
authors.lastname: De Azavedo
authors.forename: L
authors.initials: L
authors.lastname: Dresser
authors.forename: C L
authors.initials: CL
authors.lastname: Duncan
authors.forename: S E
authors.initials: SE
authors.lastname: Walker
authors.forename: D E
authors.initials: DE
authors.lastname: Low
authors.forename: D J
authors.initials: DJ
authors.lastname: Bast
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D027101:DNA Topoisomerase IV / Q000235:genetics; D004195:Disease Models, Animal; D000077727:Ertapenem; D024841:Fluoroquinolones / Q000494:pharmacology / Q000627:therapeutic use*; D000077734:Gatifloxacin; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics; D013696:Temperature; D016896:Treatment Outcome; D047090:beta-Lactams / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D047090:beta-Lactams; D027101:DNA Topoisomerase IV; D000077727:Ertapenem; D000077734:Gatifloxacin