In Vitro Synergy and In Vivo Activity of Tigecycline-Ciprofloxacin Combination Therapy against Vibrio vulnificus Sepsis

doi:10.1128/AAC.00310-19

. 2019 Sep 23;63(10):e00310-19.

doi: 10.1128/AAC.00310-19. Print 2019 Oct.

In Vitro Synergy and In Vivo Activity of Tigecycline-Ciprofloxacin Combination Therapy against Vibrio vulnificus Sepsis

Seong Eun Kim^#¹, Hee Kyung Kim^#^{1

2}, Su-Mi Choi¹, Yohan Yu¹, Uh Jin Kim¹, Kalifa Sanneh Darboe^{1

2}, Seung-Ji Kang¹, Kyung-Hwa Park¹, Gaeun Kang³, Young Ran Kim⁴, Joon Haeng Rhee^{5

6}, Sook-In Jung⁷, Hee-Chang Jang⁷

Affiliations

¹ Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, Republic of Korea.
² Department of Biomedical Science, Chonnam National University Medical School, Gwangju, Republic of Korea.
³ Department of Clinical Pharmacology, Chonnam National University Hospital, Gwangju, Republic of Korea.
⁴ College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, Republic of Korea.
⁵ Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea.
⁶ Clinical R&D Center, Chonnam National University Medical School, Gwangju, Republic of Korea.
⁷ Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, Republic of Korea sijung@chonnam.ac.kr haroc153@naver.com.

^# Contributed equally.

PMID: 31332060
PMCID: PMC6761547
DOI: 10.1128/AAC.00310-19

In Vitro Synergy and In Vivo Activity of Tigecycline-Ciprofloxacin Combination Therapy against Vibrio vulnificus Sepsis

Seong Eun Kim et al. Antimicrob Agents Chemother. 2019.

. 2019 Sep 23;63(10):e00310-19.

doi: 10.1128/AAC.00310-19. Print 2019 Oct.

Authors

Affiliations

¹ Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, Republic of Korea.
² Department of Biomedical Science, Chonnam National University Medical School, Gwangju, Republic of Korea.
³ Department of Clinical Pharmacology, Chonnam National University Hospital, Gwangju, Republic of Korea.
⁴ College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, Republic of Korea.
⁵ Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea.
⁶ Clinical R&D Center, Chonnam National University Medical School, Gwangju, Republic of Korea.
⁷ Department of Infectious Diseases, Chonnam National University Medical School, Gwangju, Republic of Korea sijung@chonnam.ac.kr haroc153@naver.com.

^# Contributed equally.

PMID: 31332060
PMCID: PMC6761547
DOI: 10.1128/AAC.00310-19

Abstract

The mortality rate associated with Vibrio vulnificus sepsis remains high. An in vitro time-kill assay revealed synergism between tigecycline and ciprofloxacin. The survival rate was significantly higher in mice treated with tigecycline plus ciprofloxacin than in mice treated with cefotaxime plus minocycline. Thus, combination treatment with tigecycline-ciprofloxacin may be an effective novel antibiotic regimen for V. vulnificus sepsis.

Keywords: V. vulnificus; sepsis; tigecycline.

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Figures

**FIG 1**
Time-kill curves for V. vulnificus CMCP6 (a) and MO6-24/O (b) isolates after incubation with 3/4 MICs of single and multiple antibiotics.

**FIG 2**
Survival curve of mice infected with 1 × 10⁸ CFU V. vulnificus CMCP6. *, P < 0.05.

See this image and copyright information in PMC

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References

1. Oliver JD. 2015. The biology of Vibrio vulnificus. Microbiol Spectr 3. doi:10.1128/microbiolspec.VE-0001-2014. - DOI - PubMed
1. Hlady WG, Klontz KC. 1996. The epidemiology of Vibrio infections in Florida, 1981-1993. J Infect Dis 173:1176–1183. doi:10.1093/infdis/173.5.1176. - DOI - PubMed
1. Chuang YC, Liu JW, Ko WC, Lin KY, Wu JJ, Huang KY. 1997. In vitro synergism between cefotaxime and minocycline against Vibrio vulnificus. Antimicrob Agents Chemother 41:2214–2217. doi:10.1128/AAC.41.10.2214. - DOI - PMC - PubMed
1. Tang HJ, Chang MC, Ko WC, Huang KY, Lee CL, Chuang YC. 2002. In vitro and in vivo activities of newer fluoroquinolones against Vibrio vulnificus. Antimicrob Agents Chemother 46:3580–3584. doi:10.1128/aac.46.11.3580-3584.2002. - DOI - PMC - PubMed
1. Chuang YC, Ko WC, Wang ST, Liu JW, Kuo CF, Wu JJ, Huang KY. 1998. Minocycline and cefotaxime in the treatment of experimental murine Vibrio vulnificus infection. Antimicrob Agents Chemother 42:1319–1322. doi:10.1128/AAC.42.6.1319. - DOI - PMC - PubMed

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[1] Oliver JD. 2015. The biology of Vibrio vulnificus. Microbiol Spectr 3. doi:10.1128/microbiolspec.VE-0001-2014. - DOI - PubMed

[2] Oliver JD. 2015. The biology of Vibrio vulnificus. Microbiol Spectr 3. doi:10.1128/microbiolspec.VE-0001-2014. - DOI - PubMed

[3] Hlady WG, Klontz KC. 1996. The epidemiology of Vibrio infections in Florida, 1981-1993. J Infect Dis 173:1176–1183. doi:10.1093/infdis/173.5.1176. - DOI - PubMed

[4] Hlady WG, Klontz KC. 1996. The epidemiology of Vibrio infections in Florida, 1981-1993. J Infect Dis 173:1176–1183. doi:10.1093/infdis/173.5.1176. - DOI - PubMed

[5] Chuang YC, Liu JW, Ko WC, Lin KY, Wu JJ, Huang KY. 1997. In vitro synergism between cefotaxime and minocycline against Vibrio vulnificus. Antimicrob Agents Chemother 41:2214–2217. doi:10.1128/AAC.41.10.2214. - DOI - PMC - PubMed

[6] Chuang YC, Liu JW, Ko WC, Lin KY, Wu JJ, Huang KY. 1997. In vitro synergism between cefotaxime and minocycline against Vibrio vulnificus. Antimicrob Agents Chemother 41:2214–2217. doi:10.1128/AAC.41.10.2214. - DOI - PMC - PubMed

[7] Tang HJ, Chang MC, Ko WC, Huang KY, Lee CL, Chuang YC. 2002. In vitro and in vivo activities of newer fluoroquinolones against Vibrio vulnificus. Antimicrob Agents Chemother 46:3580–3584. doi:10.1128/aac.46.11.3580-3584.2002. - DOI - PMC - PubMed

[8] Tang HJ, Chang MC, Ko WC, Huang KY, Lee CL, Chuang YC. 2002. In vitro and in vivo activities of newer fluoroquinolones against Vibrio vulnificus. Antimicrob Agents Chemother 46:3580–3584. doi:10.1128/aac.46.11.3580-3584.2002. - DOI - PMC - PubMed

[9] Chuang YC, Ko WC, Wang ST, Liu JW, Kuo CF, Wu JJ, Huang KY. 1998. Minocycline and cefotaxime in the treatment of experimental murine Vibrio vulnificus infection. Antimicrob Agents Chemother 42:1319–1322. doi:10.1128/AAC.42.6.1319. - DOI - PMC - PubMed

[10] Chuang YC, Ko WC, Wang ST, Liu JW, Kuo CF, Wu JJ, Huang KY. 1998. Minocycline and cefotaxime in the treatment of experimental murine Vibrio vulnificus infection. Antimicrob Agents Chemother 42:1319–1322. doi:10.1128/AAC.42.6.1319. - DOI - PMC - PubMed

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In Vitro Synergy and In Vivo Activity of Tigecycline-Ciprofloxacin Combination Therapy against Vibrio vulnificus Sepsis

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In Vitro Synergy and In Vivo Activity of Tigecycline-Ciprofloxacin Combination Therapy against Vibrio vulnificus Sepsis

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