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
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.
Department of Infectious diseases, Chonnam National University Medical School, Gwang-ju, Republic of Korea.
PLoS One. 2014 Jun 30;9(6):e101118. doi: 10.1371/journal.pone.0101118. eCollection 2014.
The in vivo efficacy of a cefotaxime-ciprofloxacin combination against Vibrio vulnificus and the effects on rtxA1 expression of commonly used antibiotics are unknown.
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.
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).
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.
头孢噻肟-环丙沙星联合用药对创伤弧菌的体内疗效以及常用抗生素对rtxA1表达的影响尚不清楚。
进行体外时间杀菌研究以评估协同作用。将雌性BALB/c小鼠皮下注射1×10⁷或1×10⁸cfu的创伤弧菌。在接种后2小时开始对以下四个治疗组进行抗生素治疗：头孢噻肟；环丙沙星；头孢噻肟加环丙沙星；以及头孢噻肟加米诺环素。使用乳酸脱氢酶测定法测量创伤弧菌对HeLa细胞的细胞毒性；使用β-半乳糖苷酶测定法在转录报告菌株中测量rtxA1转录。
体外时间杀菌试验显示头孢噻肟和环丙沙星之间具有协同作用。在动物实验中，头孢噻肟加环丙沙星组的96小时存活率（85%；17/20）显著高于头孢噻肟加米诺环素组（35%；7/20）和单独使用头孢噻肟组（0%；0/20）（两者P<0.05）。治疗后24小时和48小时，头孢噻肟加环丙沙星组肝脏和脾脏中的细菌计数相对于其他组显著降低。在亚抑制浓度下，环丙沙星比米诺环素或头孢噻肟更有效地抑制rtxA1转录和哺乳动物细胞毒性（两者P<0.05）。
环丙沙星在降低rtxA1转录和随后的细胞毒性方面比米诺环素或头孢噻肟更有效，并且环丙沙星和头孢噻肟联合用药在体内清除创伤弧菌方面比先前使用的方案更有效。这些数据表明环丙沙星和头孢噻肟联合用药是治疗人类创伤弧菌败血症的有效选择。
