Antipneumococcal Activity of Ertapenem Compared with Gatifloxacin in a Temperature-Sensitive Murine Model of Acute Pneumonia

• Published in: Journal of chemotherapy (Florence) Vol. 19; no. 4; pp. 392 - 397
• Main Authors: De Azavedo, J.C.S., Dresser, L., Duncan, C.L., Walker, S.E., Low, D.E., Bast, D.J.
• Format: Journal Article
• Language: English
• Published: Firenze Taylor & Francis 01-08-2007; EIFT
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacterial diseases; beta-Lactams - pharmacology; beta-Lactams - therapeutic use; Biological and medical sciences; Disease Models, Animal; DNA Topoisomerase IV - genetics; ertapenem; fluoroquinolone- resistance; Fluoroquinolones - pharmacology; Fluoroquinolones - therapeutic use; Human bacterial diseases; Infectious diseases; Medical sciences; Mice; Mice, Inbred Strains; Mutation; Pharmacology. Drug treatments; pneumonia; Pneumonia, Pneumococcal - drug therapy; Staphylococcal infections, streptococcal infections, pneumococcal infections; Streptococcus pneumoniae; Streptococcus pneumoniae - drug effects; Streptococcus pneumoniae - genetics; Temperature; Treatment Outcome; Animal model; Pneumonia; Temperature; Carbapenem derivatives; Fluoroquinolone derivatives; Streptococcal infection; Bacteria; Micrococcales; fluoroquinolone-resistance; Pneumococcal infection; Quinolone derivatives; Lung disease; Respiratory disease; β-Lactams; Acute; Rodentia; Ertapenem; Biological activity; Streptococcus pneumoniae; Infection; Resistance; Streptococcaceae; Vertebrata; Antibiotic; Mammalia; Mouse; Gatifloxacin; Bacteriosis; Antibacterial agent; Comparative study
• ISSN: 1120-009X; 1973-9478
• DOI: 10.1179/joc.2007.19.4.392

Fluoroquinolone-resistance among pneumococci is low; however the number of solates 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.