title: In vivo efficacy of the combination of ciprofloxacin and cefotaxime against Vibrio vulnificus sepsis.
abstract: OBJECTIVE
  The in vivo efficacy of a cefotaxime-ciprofloxacin combination against Vibrio vulnificus and the effects on rtxA1 expression of commonly used antibiotics are unknown.
  
  
  METHODS
  In vitro time-kill studies were performed to evaluate synergism. Female BALB/c mice were injected subcutaneously with 1×10(7) or 1×10(8) cfu of V. vulnificus. Antibiotic therapy was initiated at 2 h after inoculation in the following four therapy groups: cefotaxime; ciprofloxacin; cefotaxime-plus-ciprofloxacin; and cefotaxime-plus-minocycline. The cytotoxicity of V. vulnificus for HeLa cells was measured using the lactate dehydrogenase assay; rtxA1 transcription was measured in a transcriptional reporter strain using a β-galactosidase assay.
  
  
  RESULTS
  In vitro time-kill assays exhibited synergism between cefotaxime and ciprofloxacin. In the animal experiments, the 96-h survival rate for the cefotaxime-plus-ciprofloxacin group (85%; 17/20) was significantly higher than that of the cefotaxime-plus-minocycline (35%; 7/20) and cefotaxime alone (0%; 0/20) groups (P<0.05 for both). Bacterial counts in the liver and spleen were significantly lower in the cefotaxime-plus-ciprofloxacin group 24 and 48 h after treatment, relative to the other groups. At sub-inhibitory concentrations, ciprofloxacin inhibited more effectively rtxA1 transcription and mammalian cell cytotoxicity than either minocycline or cefotaxime (P<0.05 for both).
  
  
  CONCLUSIONS
  Ciprofloxacin is more effective at reducing rtxA1 transcription and subsequent cytotoxicity than either minocycline or cefotaxime, and the combination of ciprofloxacin and cefotaxime was more effective in clearing V. vulnificus in vivo than previously used regimens. These data suggest that the combination of ciprofloxacin and cefotaxime is an effective option for the treatment of V. vulnificus sepsis in humans.
authors: Department of Infectious diseases, Chonnam National University Medical School, Gwang-ju, Republic of Korea; Research Institute of Vibrio Infection and Genome Research Center for Enteropathogenic Bacteria, Gwang-ju, Republic of Korea.
authors: Hee-Chang
authors: HC
authors: Jang
authors: Department of Infectious diseases, Chonnam National University Medical School, Gwang-ju, Republic of Korea.
authors: Su-Mi
authors: SM
authors: Choi
authors: Department of Infectious diseases, Chonnam National University Medical School, Gwang-ju, Republic of Korea.
authors: Hee Kyung
authors: HK
authors: Kim
authors: Department of Infectious diseases, Chonnam National University Medical School, Gwang-ju, Republic of Korea.
authors: Sung-Eun
authors: SE
authors: Kim
authors: Department of Infectious diseases, Chonnam National University Medical School, Gwang-ju, Republic of Korea.
authors: Seung-Ji
authors: SJ
authors: Kang
authors: Department of Infectious diseases, Chonnam National University Medical School, Gwang-ju, Republic of Korea.
authors: Kyung-Hwa
authors: KH
authors: Park
authors: Microbiology, Chonnam National University Medical School, Gwang-ju, Republic of Korea.
authors: Phil Youl
authors: PY
authors: Ryu
authors: Department of Biochemistry, School of Dentistry, Chonnam National University, Gwang-ju, Republic of Korea.
authors: Tae-Hoon
authors: TH
authors: Lee
authors: Department of Pharmaceutical Engineering, Dongshin University, Naju, Republic of Korea.
authors: Young Ran
authors: YR
authors: Kim
authors: Research Institute of Vibrio Infection and Genome Research Center for Enteropathogenic Bacteria, Gwang-ju, Republic of Korea; Microbiology, Chonnam National University Medical School, Gwang-ju, Republic of Korea.
authors: Joon Haeng
authors: JH
authors: Rhee
authors: Department of Infectious diseases, Chonnam National University Medical School, Gwang-ju, Republic of Korea.
authors: Sook-In
authors: SI
authors: Jung
authors: Research Institute of Vibrio Infection and Genome Research Center for Enteropathogenic Bacteria, Gwang-ju, Republic of Korea; Microbiology, Chonnam National University Medical School, Gwang-ju, Republic of Korea.
authors: Hyon E
authors: HE
authors: Choy
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D001427:Bacterial Toxins / Q000235:genetics; D002439:Cefotaxime / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D002939:Ciprofloxacin / Q000494:pharmacology / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology*; D016019:Survival Analysis; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014735:Vibrio Infections / Q000188:drug therapy* / Q000382:microbiology*; D041261:Vibrio vulnificus / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D002939:Ciprofloxacin; D002439:Cefotaxime