Deferasirox plus ciprofloxacin combination therapy after rapid diagnosis of Vibrio vulnificus sepsis using real-time polymerase chain reaction

Kim, Dong-Min; Cho, Hong Sung; Kang, Ji-In; Kim, Hyong Sun; Park, Chi Young

doi:10.1016/j.jinf.2008.08.003

Cited by 8 publications

(11 citation statements)

References 18 publications

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“…DFO‐treated patients with iron overload conditions such as hemochromatosis or thalassemia are known to be susceptible to fulminant Y. enterocolitica septicemia and Mucorales 10,20,22 . They are also susceptible to V. vulnificus infection 13 . Similarly our in vitro study data showed DFS or DFP have more potential clinical application rather than DFO for the patients who needed iron chelation therapy, especially living in those areas where habit of eating raw seafood or in exposure to sea water is more common.…”

Section: Discussionsupporting

confidence: 57%

“…However, there have been case reports in which Mucorales , for which iron availability is critical for growth, was successfully treated with DFS 22,23 . Similarly, V. vulnificus sepsis developed during DFO therapy for transfusional iron overload due to secondary hemochromatosis of myelodysplastic syndrome was also successfully treated with adjuvant DFS in combination with ciprofloxacin 13 . Hence, we compared two other oral chelators which have completely different chemical structures than DFO.…”

Section: Discussionmentioning

confidence: 99%

“…In both in vitro and in vivo iron‐limited conditions V. vulnificus can use DFO from transferrin‐bound iron for efficient iron uptake and growth via the specific receptor Des A 12 . We encountered a patient with hemochromatosis who had V. vulnificus sepsis that developed after consumption of raw fish during iron chelation therapy with DFO against secondary hemochromatosis 13 . Thus iron chelation therapy can do harm by promoting microbial growth, or do good by inhibiting their growth, and there has long been interest in developing new therapeutics or novel preventive measures for V. vulnificus septicemia 14 .…”

mentioning

confidence: 99%

“…12 We encountered a patient with hemochromatosis who had V. vulnificus sepsis that developed after consumption of raw fish during iron chelation therapy with DFO against secondary hemochromatosis. 13 Thus iron chelation therapy can do harm by promoting microbial growth, or do good by inhibiting their growth, and there has long been interest in developing new therapeutics or novel preventive measures for V. vulnificus septicemia. 14 However, the effect of DFS on the growth of V. vulnificus remains unknown.…”

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confidence: 99%

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Comparison of the effects of deferasirox, deferiprone, and deferoxamine on the growth and virulence of Vibrio vulnificus

Neupane

Kim

2009

Transfusion

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Comparison of the effects of deferasirox, deferiprone, and deferoxamine on the growth and virulence of Vibrio vulnificus

Neupane

Kim

2009

Transfusion

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“…Among these, the combinations of a third-generation cephalosporin with tetracycline or quinolone monotherapy are most often recommended, based on the results of in vitro [12] and in vivo research [13], [14] and several retrospective clinical studies [15], [16]. However, the mortality rates remain high, suggesting the need for adjuvant therapies [17], [18] and more effective antibiotic regimens.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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ObjectivesThe 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 1×107 or 1×108 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).ConclusionsCiprofloxacin 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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In vitro time-kill activities of ciprofloxacin alone and in combination with the iron chelator deferasirox against Vibrio vulnificus

Neupane

Kim

2010

Eur J Clin Microbiol Infect Dis

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Iron plays a major role in the growth and virulence of ferrophilic organisms like Vibrio vulnificus. People who reside in the coastal areas with raw fish eating habits have a high risk of Vibrio infection and aggressive therapy can only reduce their mortality. We investigated the in vitro efficacy of ciprofloxacin, a bactericidal drug used in V. vulnificus patients, and the orally active iron chelator deferasirox against V. vulnificus infection. We performed in vitro time-kill studies on two ATCC strains and one clinical isolate of V. vulnificus collected from a patient admitted to Chosun University Hospital with either ciprofloxacin or iron chelator deferasirox alone and the two drugs in combination. The combination of an iron chelator plus an antibiotic creates a novel form of synergism at 24 h. The antimicrobial effect of deferasirox may be ascribed to its ability to deplete iron that would otherwise be used for bacterial growth. Combination therapy with ciprofloxacin plus deferasirox has potential clinical application by lowering the iron availability against a ferrophilic organism like V. vulnificus infections.

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Deferasirox plus ciprofloxacin combination therapy after rapid diagnosis of Vibrio vulnificus sepsis using real-time polymerase chain reaction

Cited by 8 publications

References 18 publications

Comparison of the effects of deferasirox, deferiprone, and deferoxamine on the growth and virulence of Vibrio vulnificus

Comparison of the effects of deferasirox, deferiprone, and deferoxamine on the growth and virulence of Vibrio vulnificus

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

In vitro time-kill activities of ciprofloxacin alone and in combination with the iron chelator deferasirox against Vibrio vulnificus

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