caa a22 4500 397591276 CHVBK 20180308164939.0 cr unu---uuuuu 161202e199610 xx s 000 0 eng 10.1093/jac/38.4.641 doi (NATIONALLICENCE)oxford-10.1093/jac/38.4.641 Efficacy of ABT-719, a 2-pyridone antimicrobial, against enterococci, Escherichia coli, and Pseudomonas aeruginosa in experimental murine pyelonephritis [Elektronische Daten] [Jonathan A. Meulbroek, Anatol Oleksijew, S. Ken Tanaka, Jeffrey D. Alder] ABT-719 is a 2-pyridone antimicrobial which inhibits DNA gyrase activity. It has considerable subcutaneous (sc) and oral efficacy in the treatment of experimental pyelonephritis induced in carrageenan-treated mice by clinical isolates of Enterococcus faecalis, Enterococcus faecium, Escherichia coli, and Pseudomonas aeruginosa. Therapeutic ED50s, defined here as producing a 2 log10 reduction in kidney bacterial burden, provide a reliable end point for comparison of drug efficacy in this experimental infection. Therapeutic ED50s for ABT-719 against these infections were equal to or up to ten-fold lower than those for ciprofloxacin, used as a reference because of similarity in mode of action. Against E. faecalis, the therapeutic ED50s for ABT-719 were 4.5-13.6 mg/kg.day for sc administration and 6.8-8.9 mg/kg.day for oral administration. ABT-719 was more potent than ciprofloxacin and vancomycin against the E. faecalis strains, which showed ciprofloxacin and vancomycin resistance covering a range of MICs. Against E. faecium, the therapeutic ED50s for ABT-719 were 8.8 mg/kg.day (sc) and 9.4 mg/kg.day (oral). Against an isolate of E. faecium showing ciprofloxacin and vancomycin resistance the ED50 for ABT-719 to achieve a 1 log10 reduction in kidney bacterial burden was 17.9 mg/kg.day by sc administration. While ABT-719 had lower efficacy against this isolate than against others, ciprofloxacin and vancomycin failed to show efficacy. Against E. coli, the therapeutic ED50, for ABT-719 was 1.1 mg/kg.day (oral), and against P. aeruginosa, this value was 2.7 mg/kg.day (oral) with values against both of these pathogens similar to those for ciprofloxacin. ABT-719, which represents the new 2-pyridone compound class, has promise for the treatment of urinary tract infections, as suggested by the significant efficacy seen against experimental pyelonephritis caused by E. coli, P. aeruginosa and susceptible and resistant enterococci. © 1995 The British Society for Antimicrobial Chemotherapy Original articles nationallicence Meulbroek Jonathan A. Anti-infective Research Division, Abbott Laboratories, Department 47T/Building AP3, One Abbott Park Road, Abbott Park, IL 60064-3500, USA aut Oleksijew Anatol Anti-infective Research Division, Abbott Laboratories, Department 47T/Building AP3, One Abbott Park Road, Abbott Park, IL 60064-3500, USA aut Tanaka S. Ken Anti-infective Research Division, Abbott Laboratories, Department 47T/Building AP3, One Abbott Park Road, Abbott Park, IL 60064-3500, USA aut Alder Jeffrey D. Anti-infective Research Division, Abbott Laboratories, Department 47T/Building AP3, One Abbott Park Road, Abbott Park, IL 60064-3500, USA aut Journal of Antimicrobial Chemotherapy Oxford University Press 38/4(1996-10), 641-653 0305-7453 38:4<641 1996 38 jac https://doi.org/10.1093/jac/38.4.641 text/html Onlinezugriff via DOI 1 other jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jac/38.4.641 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Meulbroek Jonathan A. Anti-infective Research Division, Abbott Laboratories, Department 47T/Building AP3, One Abbott Park Road, Abbott Park, IL 60064-3500, USA aut NATIONALLICENCE 700 1- Oleksijew Anatol Anti-infective Research Division, Abbott Laboratories, Department 47T/Building AP3, One Abbott Park Road, Abbott Park, IL 60064-3500, USA aut NATIONALLICENCE 700 1- Tanaka S. Ken Anti-infective Research Division, Abbott Laboratories, Department 47T/Building AP3, One Abbott Park Road, Abbott Park, IL 60064-3500, USA aut NATIONALLICENCE 700 1- Alder Jeffrey D. Anti-infective Research Division, Abbott Laboratories, Department 47T/Building AP3, One Abbott Park Road, Abbott Park, IL 60064-3500, USA aut NATIONALLICENCE 773 0- Journal of Antimicrobial Chemotherapy Oxford University Press 38/4(1996-10), 641-653 0305-7453 38:4<641 1996 38 jac Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford