In vitro and in vivo antibacterial activity of tigecycline against Vibrio vulnificus

J Microbiol Immunol Infect. 2018 Feb;51(1):76-81. doi: 10.1016/j.jmii.2016.04.009. Epub 2016 May 13.

Abstract

Background/purpose: The aim of this study is to investigate the role of tigecycline in Vibrio vulnificus infection.

Methods: Eight randomly selected clinical V. vulnificus isolates were studied to obtain the minimal inhibitory concentrations (MICs) of minocycline, cefotaxime, and tigecycline, and the time-kill curves of tigecycline alone or in combination with other drugs. A peritonitis mouse model was used for the evaluation of the therapeutic efficacy of tigecycline alone or cefotaxime in combination with minocycline or tigecycline.

Results: The MIC of minocycline, cefotaxime, and tigecycline for eight clinical V. vulnificus isolates was 0.06-0.12 μg/mL, 0.03-0.06 μg/mL, and 0.03-0.06 μg/mL, respectively. In time-killing studies, at the concentration of 1 × MIC, the inhibitory effect of tigecycline persisted for 24 hours in five of eight isolates. With 2 × MIC and trough level, the inhibitory effect was noted in all isolates for 24 hours. With the combination of minocycline plus cefotaxime and tigecycline plus cefotaxime at 1/2 × MIC, the bactericidal effect was noted in 25% and 62.5% of eight isolates and synergism in 50% and 75% of isolates. With a low (1.25 × 105 CFU/mL) inoculum, all infected mice survived with tigecycline alone, tigecycline plus cefotaxime, or minocycline plus cefotaxime on the 14th day. At the inoculum of 1.25 × 106 CFU, the survival rate was 33.3% on the 14th day in the tigecycline plus cefotaxime-treated group, but none of the mice treated by tigecycline alone or minocycline plus cefotaxime survived (33.3% vs. 0%, p = 0.01 by Fisher's exact test).

Conclusion: Our in vitro combination and animal studies indicate that tigecycline could be an option for the treatment of invasive V. vulnificus infections.

Keywords: Vibrio vulnificus; killing effects; tigecycline.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use*
  • Cefotaxime / pharmacology
  • Colony Count, Microbial
  • Disease Models, Animal
  • Drug Combinations
  • Drug Synergism
  • Drug Therapy, Combination
  • Humans
  • Mice
  • Microbial Sensitivity Tests
  • Minocycline / analogs & derivatives*
  • Minocycline / pharmacology
  • Minocycline / therapeutic use
  • Peritonitis / drug therapy
  • Peritonitis / microbiology
  • Survival Rate
  • Taiwan
  • Tigecycline
  • Time Factors
  • Vibrio Infections / drug therapy*
  • Vibrio vulnificus / drug effects*
  • Vibrio vulnificus / isolation & purification

Substances

  • Anti-Bacterial Agents
  • Drug Combinations
  • Tigecycline
  • Minocycline
  • Cefotaxime

Supplementary concepts

  • Vibrio vulnificus infection