Anti-multidrug-resistant Acinetobacter baumannii activity of DS-8587: In vitro activity and in vivo efficacy in a murine calf muscle infection model

• Published in: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy Vol. 20; no. 5; pp. 312 - 316
• Main Authors: Higuchi, Saito, Kurosaka, Yuichi, Uoyama, Saori, Yoshida, Kumi, Chiba, Megumi, Ishii, Chiaki, Fujikawa, Katsuko, Karibe, Yukie, Hoshino, Kazuki
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.05.2014
• Subjects: Acinetobacter baumannii; Acinetobacter baumannii - drug effects; Acinetobacter Infections - drug therapy; Animals; Anti-Bacterial Agents - pharmacology; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Fluoroquinolones - pharmacology; Hematology, Oncology and Palliative Medicine; Male; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Multidrug-resistance; PK/PD; Quinolone; Acinetobacter baumannii; Quinolone; PK/PD; Multidrug-resistance
• ISSN: 1341-321X; 1437-7780
• DOI: 10.1016/j.jiac.2014.01.011

Abstract DS-8587 is a novel broad-spectrum fluoroquinolone with extended antimicrobial activity against both Gram-positive and Gram-negative pathogens. In this study, we evaluated the in vitro and in vivo antibacterial activity of DS-8587 against multidrug-resistant (MDR) Acinetobacter baumannii . The MIC range of DS-8587 against MDR A. baumannii was 0.25–2 mg/L. These DS-8587 MICs were a minimum of 16-fold or 8-fold more potent than ciprofloxacin or levofloxacin, respectively. Bactericidal activity, a 3 log10 reduction from the initial bacterial counts, was observed within 2 h for 1593644 and 4 h for 1593684 after exposure to DS-8587. Therapeutic efficacy of DS-8587 in the murine calf muscle model was observed at 256 mg/kg. The analysis of the pharmacokinetic and pharmacodynamic index revealed that the AUC/MIC ratio showed the best correlation with efficacy. The total and free drug AUC/MIC value required for a static effect was 29.4 and 14.1, respectively. These data indicate DS-8587 would be an effective agent against MDR A. baumannii infection.