In vitro #synergy and in vivo activity of #tigecycline plus #ciprofloxacin combination #therapy against #Vibrio vulnificus #sepsis (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

In vitro synergy and in vivo activity of tigecycline plus ciprofloxacin combination therapy against Vibrio vulnificus sepsis

Seong Eun Kim, Hee Kyung Kim, Su-Mi Choi, Yohan Yu, Uh Jin Kim, Kalifa Sanneh Darboe, Seung-Ji Kang, Kyung-Hwa Park, Gaeun Kang, Young Ran Kim, Joon Haeng Rhee, Sook-In Jung,Hee-Chang Jang

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 plus ciprofloxacin can be an effective novel antibiotic regimen for V. vulnificus sepsis.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Vibrio vulnificus; Sepsis; Ciprofloxacin; Tigecycline.

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#Outcomes of Third-Generation #Cephalosporin Plus #Ciprofloxacin or #Doxycycline Therapy in Patients with #Vibrio vulnificus #Septicemia: A Propensity Score-Matched Analysis (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Outcomes of Third-Generation Cephalosporin Plus Ciprofloxacin or Doxycycline Therapy in Patients with Vibrio vulnificus Septicemia: A Propensity Score-Matched Analysis

Seong Eun Kim, Sung Un Shin, Tae Hoon Oh, Uh Jin Kim, Kalifa Sanneh Darboe, Seung-Ji Kang, Hee-Chang Jang, Sook-In Jung, Hee-Young Shin, Kyung-Hwa Park

Published: June 12, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007478 / This is an uncorrected proof.

 

Abstract

Background

Combination therapy with a third-generation cephalosporin (TGC) and a tetracycline analogue is recommended for Vibrio vulnificus infection. The combination of a TGC and ciprofloxacin has synergistic in vitro bactericidal activity against V. vulnificus. No clinical study has compared the standard regimen with TGC plus ciprofloxacin therapy for V. vulnificus infection.

Methods

Patients with a confirmed V. vulnificus infection at two medical centers in Korea from 1991 to 2016 were enrolled in this study. The patients were grouped according to the type of antibiotic administered. A retrospective propensity-score-matched case-control study of patients treated with TGC plus doxycycline or TGC plus ciprofloxacin was performed. The clinical characteristics and outcomes of the patients were analyzed.

Results

A total of 218 patients were confirmed to have V. vulnificus septicemia during the study, and the 30-day survival rate was 39% (85/218). The patients were classified into the following six treatment groups: TGC monotherapy (n = 82), TGC plus doxycycline therapy (n = 42), TGC plus ciprofloxacin therapy (n = 39), ciprofloxacin monotherapy (n = 14), other β-lactam monotherapy (n = 10), and other (n = 31). The survival rates of these groups were as follows: TGC monotherapy (35%), TGC plus doxycycline (38%), TGC plus ciprofloxacin (54%), ciprofloxacin monotherapy (29%), other β-lactam (20%), and other (39%). The 30-day survival rate showed no significant difference between the TGC plus doxycycline and TGC plus ciprofloxacin groups (log-rank test, P = 0.18). Among the 81 patients treated with TGC plus doxycycline or TGC plus ciprofloxacin, 12 per treatment group were selected by propensity-score matching. There was no significant difference in the baseline characteristics or the frequency of fasciotomy between the two groups. The 30-day survival rate showed no significant difference between the TGC plus doxycycline (50%) and TGC plus ciprofloxacin (67%) groups (log-rank test, P = 0.46).

Conclusion

Our data suggest that the outcome of TGC plus ciprofloxacin therapy was comparable to that of TGC plus doxycycline therapy in patients with V. vulnificus septicemia.

 

Author summary

The combination of a third-generation cephalosporin (TGC) and ciprofloxacin has synergy in vitro bactericidal activity against V. vulnificus. No clinical study has compared the standard regimen with TGC plus ciprofloxacin therapy for V. vulnificus infection. A total of 218 patients were enrolled who are confirmed to have V. vulnificus septicemia in two medical centers in Korea from 1991 to 2016. The 30-day survival rate was 39% (85/218) for all patients, 38% (16/42) for TGC plus doxycycline and 54% (21/39) for TGC plus ciprofloxacin (log rank test, P = 0.18). A propensity score-matched analysis was performed and 12 per treatment groups were selected. The 30-day survival rate showed no significant difference between the TGC plus doxycycline (50%, 6/12) and TGC plus ciprofloxacin (67%, 4/12) groups (log-rank test, P = 0.46). The outcome of TGC plus ciprofloxacin therapy was comparable to that of TGC plus doxycycline therapy in patients with V. vulnificus septicemia.

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Citation: Kim SE, Shin SU, Oh TH, Kim UJ, Darboe KS, Kang S-J, et al. (2019) Outcomes of Third-Generation Cephalosporin Plus Ciprofloxacin or Doxycycline Therapy in Patients with Vibrio vulnificus Septicemia: A Propensity Score-Matched Analysis. PLoS Negl Trop Dis 13(6): e0007478. https://doi.org/10.1371/journal.pntd.0007478

Editor: Husain Poonawala, Lowell General Hospital, UNITED STATES

Received: February 18, 2019; Accepted: May 20, 2019; Published: June 12, 2019

Copyright: © 2019 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All data files are available from the Harvard dataverse database (DOIs https://doi.org/10.7910/DVN/3AZYIP)

Funding: KH Park received funding from CNUH Research Fund, grant number CRI17021-1 (https://www.cnuh.com/main.cs). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Vibrio vulnificus; Septicemia; Antibiotics; Cephalosporins; Ciprofloxacin; Doxycyline.

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Efficacy of #Ceftriaxone, Cefepime, #Doxycycline, #Ciprofloxacin, and Combination #Therapy for #Vibrio vulnificus #Foodborne #Septicemia (AAC, abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Efficacy of Ceftriaxone, Cefepime, Doxycycline, Ciprofloxacin, and Combination Therapy for Vibrio vulnificus Foodborne Septicemia

Sonya A. Trinh a, Hannah E. Gavin b and Karla J. F. Satchell b*

Author Affiliations: a Northwestern University Feinberg School of Medicine, Department of Medicine, Division of Infectious Diseases, 645 North Michigan Avenue, Suite 900, Chicago, Illinois, 60611, USA; b Northwestern University Feinberg School of Medicine, Department of Microbiology-Immunology, 303 East Chicago Avenue, Ward 6-225, Chicago, Illinois, 60611, USA

 

ABSTRACT

Vibrio vulnificus foodborne infections have higher rates of sepsis and mortality compared to wound infections; however, antibiotic efficacy studies have not been performed in foodborne infection models. The efficacy of ceftriaxone, cefepime, doxycycline, ciprofloxacin, and combination therapy was assessed in a V. vulnificus intestinal infection in mice to model foodborne infections. Consistent with prior studies of cefotaxime, cefepime was synergistic with doxycycline and ciprofloxacin in vitro; combination therapy significantly decreased bacterial growth by ≥2log10 compared to antibiotic monotherapy (p<0.01). In vivo, survival in the ceftriaxone (50%), doxycycline (79%), and ciprofloxacin (80%) groups were significantly higher than the control group (0%) (p<0.0001). Survival with ceftriaxone-doxycycline (91%) and ceftriaxone-ciprofloxacin (100%) therapy was significantly higher than with ceftriaxone (50%) (p≤0.05). Survival with cefepime-doxycycline (96%) and cefepime-ciprofloxacin (90%) therapy was significantly higher than with cefepime (20%) (p<0.001). There was no difference in survival between the combination therapy groups. Thus, we conclude that combination therapy was the most effective treatment for V. vulnificus foodborne septicemia. In a septic patient with a recent ingestion of raw seafood, cefepime in combination with doxycycline or ciprofloxacin should be initiated for coverage of resistant Gram-negative organisms and V. vulnificus while awaiting a microbiological diagnosis. Once a diagnosis of V. vulnificus foodborne septicemia is established, treatment can be safely transitioned to ceftriaxone in combination with doxycycline or ciprofloxacin.

 

FOOTNOTES

*Corresponding Author: Karla J. F. Satchell, Northwestern University Feinberg School of Medicine, Department of Microbiology-Immunology, 303 East Chicago Avenue, Ward 6-205, Chicago, Illinois, 60611, USA, k-satchell@northwestern.edu

Copyright © 2017 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Vibrio Vulnificus; Ceftriaxone; Ciprofloxacin; Cefepime; Doxycycline.

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