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In Vivo Efficacy of the Combination of Ciprofloxacin and Cefotaxime against Vibrio vulnificus Sepsis

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...

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Autores principales: Jang, Hee-Chang, Choi, Su-Mi, Kim, Hee Kyung, Kim, Sung-Eun, Kang, Seung-Ji, Park, Kyung-Hwa, Ryu, Phil Youl, Lee, Tae-Hoon, Kim, Young Ran, Rhee, Joon Haeng, Jung, Sook-In, Choy, Hyon E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076242/
https://www.ncbi.nlm.nih.gov/pubmed/24978586
http://dx.doi.org/10.1371/journal.pone.0101118
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author Jang, Hee-Chang
Choi, Su-Mi
Kim, Hee Kyung
Kim, Sung-Eun
Kang, Seung-Ji
Park, Kyung-Hwa
Ryu, Phil Youl
Lee, Tae-Hoon
Kim, Young Ran
Rhee, Joon Haeng
Jung, Sook-In
Choy, Hyon E
author_facet Jang, Hee-Chang
Choi, Su-Mi
Kim, Hee Kyung
Kim, Sung-Eun
Kang, Seung-Ji
Park, Kyung-Hwa
Ryu, Phil Youl
Lee, Tae-Hoon
Kim, Young Ran
Rhee, Joon Haeng
Jung, Sook-In
Choy, Hyon E
author_sort Jang, Hee-Chang
collection PubMed
description 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.
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spelling pubmed-40762422014-07-02 In Vivo Efficacy of the Combination of Ciprofloxacin and Cefotaxime against Vibrio vulnificus Sepsis Jang, Hee-Chang Choi, Su-Mi Kim, Hee Kyung Kim, Sung-Eun Kang, Seung-Ji Park, Kyung-Hwa Ryu, Phil Youl Lee, Tae-Hoon Kim, Young Ran Rhee, Joon Haeng Jung, Sook-In Choy, Hyon E PLoS One Research Article 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. Public Library of Science 2014-06-30 /pmc/articles/PMC4076242/ /pubmed/24978586 http://dx.doi.org/10.1371/journal.pone.0101118 Text en © 2014 Jang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Jang, Hee-Chang
Choi, Su-Mi
Kim, Hee Kyung
Kim, Sung-Eun
Kang, Seung-Ji
Park, Kyung-Hwa
Ryu, Phil Youl
Lee, Tae-Hoon
Kim, Young Ran
Rhee, Joon Haeng
Jung, Sook-In
Choy, Hyon E
In Vivo Efficacy of the Combination of Ciprofloxacin and Cefotaxime against Vibrio vulnificus Sepsis
title In Vivo Efficacy of the Combination of Ciprofloxacin and Cefotaxime against Vibrio vulnificus Sepsis
title_full In Vivo Efficacy of the Combination of Ciprofloxacin and Cefotaxime against Vibrio vulnificus Sepsis
title_fullStr In Vivo Efficacy of the Combination of Ciprofloxacin and Cefotaxime against Vibrio vulnificus Sepsis
title_full_unstemmed In Vivo Efficacy of the Combination of Ciprofloxacin and Cefotaxime against Vibrio vulnificus Sepsis
title_short In Vivo Efficacy of the Combination of Ciprofloxacin and Cefotaxime against Vibrio vulnificus Sepsis
title_sort in vivo efficacy of the combination of ciprofloxacin and cefotaxime against vibrio vulnificus sepsis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076242/
https://www.ncbi.nlm.nih.gov/pubmed/24978586
http://dx.doi.org/10.1371/journal.pone.0101118
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