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PLoS One. 2014 Jun 30;9(6):e101118. doi: 10.1371/journal.pone.0101118. eCollection 2014.

In vivo efficacy of the combination of ciprofloxacin and cefotaxime against Vibrio vulnificus sepsis.

Author information

1
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.
2
Department of Infectious diseases, Chonnam National University Medical School, Gwang-ju, Republic of Korea.
3
Microbiology, Chonnam National University Medical School, Gwang-ju, Republic of Korea.
4
Department of Biochemistry, School of Dentistry, Chonnam National University, Gwang-ju, Republic of Korea.
5
Department of Pharmaceutical Engineering, Dongshin University, Naju, Republic of Korea.
6
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.

Abstract

OBJECTIVES:

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.

PMID:
24978586
PMCID:
PMC4076242
DOI:
10.1371/journal.pone.0101118
[Indexed for MEDLINE]
Free PMC Article

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