In vitro and in vivo antibacterial activity of tigecycline against Vibrio vulnificus.
OBJECTIVE
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 × 105CFU/mL) inoculum, all infected mice survived with tigecycline alone, tigecycline plus cefotaxime, or minocycline plus cefotaxime on the 14thday. At the inoculum of 1.25 × 106CFU, the survival rate was 33.3% on the 14thday 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).


CONCLUSIONS
Our in vitro combination and animal studies indicate that tigecycline could be an option for the treatment of invasive V. vulnificus infections.
Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Health and Nutrition, Chia Nan University of Pharmacy & Science, Tainan, Taiwan.
Hung-Jen
HJ
Tang
Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.
Chi-Chung
CC
Chen
Department of Intensive Care Medicine, Chi Mei Medical Center, Liou Ying, Tainan, Taiwan.
Chih-Cheng
CC
Lai
Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan.
Chun-Cheng
CC
Zhang
Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan.
Tzu-Chieh
TC
Weng
Department of Medicine, Chi Mei Medical Center, Liou Ying, Tainan, Taiwan.
Yu-Hsin
YH
Chiu
Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan.
Han-Siong
HS
Toh
Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan.
Shyh-Ren
SR
Chiang
Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.
Wen-Liang
WL
Yu
Department of Medicine, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan. Electronic address: winston3415@gmail.com.
Wen-Chien
WC
Ko
Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; Department of Medicine, Chi Mei Medical Center, Liou Ying, Tainan, Taiwan. Electronic address: chuangkenneth@hotmail.com.
Yin-Ching
YC
Chuang
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002439:Cefotaxime / Q000494:pharmacology; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004338:Drug Combinations; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010538:Peritonitis / Q000188:drug therapy / Q000382:microbiology; D015996:Survival Rate; D013624:Taiwan; D000078304:Tigecycline; D013997:Time Factors; D014735:Vibrio Infections / Q000188:drug therapy*; D041261:Vibrio vulnificus / Q000187:drug effects* / Q000302:isolation & purification
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D000078304:Tigecycline; D008911:Minocycline; D002439:Cefotaxime
Vibrio vulnificus; killing effects; tigecycline