Synergistic antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of Vibrio vulnificus infection
Shyh-Ren Chiang, Hung-Jen Tang, Ping-Chin Chang, Kuo-Chen Cheng, Wen-Chien Ko, Chung-Hua Chen, Yin-Ching Chuang
Departments of 1Medicine and Intensive Care Medicine, Chi-Mei Medical Center, Tainan; Department of Medicine, National Cheng Kung University, Medical College, Tainan; Department of Medicine, Ton-Yen General Hospital, Hsin-Chu; and Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan
Received: June 1, 2006 Revised: July 10, 2006 Accepted: July 17, 2006
Background and purpose:
Vibrio vulnificuscauses primary bacteremia and necrotizing wound infection, leading to high morbidity and mortality in humans. This study aimed to evaluate the antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of V. vulnificus infection.
We investigated the dynamics of proinflammatory cytokines and their modulation by antimicrobial agents using a murine model of V. vulnificus infection. The change in cytokine levels was followed over a time course to identify the antimicrobial activity of the drugs against V. vulnificus. BALB/c female mice were challenged with an intraperitoneal infection using a clinical invasive isolate of Vv05191, and their cytokine levels were assayed over various time points.
Serum levels of tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6 post-infection were found to be inoculum dose-dependent and positively correlated to the subsequent fatality rate in the infected mice. With an inoculum of 6.6 × 106 colony-forming units and intraperitoneal administration of cefotaxime, minocycline, or both, the serum and peritoneal fluid cytokine levels increased and then declined gradually. Comparison of the 3 antimicrobial regimens revealed that the magnitude of reduction in cytokine levels was greatest in mice treated with cefotaxime-minocycline combination. Moreover, the peritoneal fluid cytokine level in the combination group was significantly lower than that in the groups treated with minocycline or cefotaxime alone.
The current results support the superiority of the combination therapy in treating invasive V. vulnificus infections.
Antibacterial agents; Cytokines; Drug therapy, combination; Vibrio vulnificus
J Microbiol Immunol Infect. 2007;40:123-133.