Synergistic antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of Vibrio vulnificus infection.
OBJECTIVE
Vibrio vulnificus causes 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.


METHODS
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.


RESULTS
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 x 10(6) 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.


CONCLUSIONS
The current results support the superiority of the combination therapy in treating invasive V. vulnificus infections.
Chiang
Shyh Ren
SR
Department of Medicine, Chi-Mei Medical Center, Tainan, Taiwan.
Tang
Hung Jen
HJ
Chang
Ping Chin
PC
Cheng
Kuo Chen
KC
Ko
Wen Chien
WC
Chen
Chung Hua
CH
Chuang
Yin Ching
YC
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001202:Ascitic Fluid / Q000276:immunology; D002439:Cefotaxime / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000032:analysis / Q000097:blood*; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008911:Minocycline / Q000494:pharmacology* / Q000627:therapeutic use; D016019:Survival Analysis; D014735:Vibrio Infections / Q000188:drug therapy* / Q000276:immunology* / Q000382:microbiology; D041261:Vibrio vulnificus / Q000187:drug effects* / Q000276:immunology
D000900:Anti-Bacterial Agents; D016207:Cytokines; D008911:Minocycline; D002439:Cefotaxime