title: In vitro efficacy of the combination of ciprofloxacin and cefotaxime against nalidixic acid-resistant Salmonella enterica serotype Typhi.
abstract: Typhoid fever is a systemic intracellular infection caused by Salmonellaenterica serotype Typhi. The emergence and spread of nalidixic acid-resistant S. Typhi (NARST) is challenging for clinicians in many countries owing to the lack of suitable treatment options. The aim of this study was to identify in vitro synergistic combinations of antibiotics against S. Typhi. In vitro time-kill studies were performed on three clinical NARST isolates and one type strain of nalidixic acid-susceptible S. Typhi (NASST) ATCC 9992 with ciprofloxacin, cefotaxime and azithromycin in various combinations. The combination of ciprofloxacin (0.012-0.375 microg/mL) and cefotaxime (0.063-0.125 microg/mL) against all three NARST strains and the NASST strain was significantly more effective in vitro in reducing bacterial counts by >or=3log(10) colony-forming units at 24h and showed synergistic effects. Combination therapy with ciprofloxacin and cefotaxime might be the treatment of choice for patients with typhoid fever. The combination of a fluoroquinolone and a beta-lactam, which are directed against different targets, may improve efficacy compared with a fluoroquinolone alone and may reduce the chance of fluoroquinolone-resistant mutants emerging in patients with severe typhoid fever.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Chosun University College of Medicine, Clinical Research Institute, Gwangju, South Korea.
authors.forename: Dong-Min
authors.initials: DM
authors.lastname: Kim
authors.forename: Ganesh Prasad
authors.initials: GP
authors.lastname: Neupane
authors.forename: Sook Jin
authors.initials: SJ
authors.lastname: Jang
authors.forename: Sung Hun
authors.initials: SH
authors.lastname: Kim
authors.forename: Bok Kwon
authors.initials: BK
authors.lastname: Lee
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D002439:Cefotaxime / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004357:Drug Synergism; D006801:Humans; D008826:Microbial Sensitivity Tests; D009268:Nalidixic Acid / Q000494:pharmacology*; D012485:Salmonella typhi / Q000187:drug effects*; D014435:Typhoid Fever / Q000382:microbiology
chemical_list: D000890:Anti-Infective Agents; D009268:Nalidixic Acid; D002939:Ciprofloxacin; D002439:Cefotaxime