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.

——

#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.

___

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.

—–

Emergence and #spread of #ciprofloxacin-resistant Neisseria #gonorrhoeae in #NSW, #Australia: lessons from history (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Emergence and spread of ciprofloxacin-resistant Neisseria gonorrhoeae in New South Wales, Australia: lessons from history

Jane K Hanrahan, Tiffany R Hogan, Cameron Buckley, Ella Trembizki, Hazel Mitchell, Colleen L Lau, David M Whiley, Monica M Lahra

Journal of Antimicrobial Chemotherapy, dkz182, https://doi.org/10.1093/jac/dkz182

Published: 06 June 2019

 

Abstract

Objectives

Our aim was to investigate the emergence and spread of ciprofloxacin resistance in clinical Neisseria gonorrhoeae isolates in New South Wales, Australia, from the first reported case in 1991 until ciprofloxacin resistance was sustained at or above the WHO threshold for treatment change of 5% (1999), to inform future strategies for controlling gonococcal antimicrobial resistance.

Methods

The index isolate and all subsequent clinical isolates of ciprofloxacin-resistant N. gonorrhoeae in New South Wales from 1991 to 1999 were genotyped using a previously described method on the Agena MassARRAY iPLEX platform. Region of acquisition data, where available, were used to determine whether cases were travel associated.

Results

In New South Wales, of the 325 ciprofloxacin-resistant N. gonorrhoeae isolates reported from 1991 to 1999, 98% (320/325) were able to be recovered and 100% (320/320) were genotyped. There were 66 different genotypes, comprising 1–99 isolates each. Notably no single clone was found to account for ciprofloxacin resistance being sustained in the population, with considerable variability in genotype prevalence observed throughout the study period. A total of 65% (209/320) of genotyped isolates had information regarding the likely place of acquisition; of these, 44% (93/209) were associated with overseas travel or sexual contact with an overseas visitor. The first ciprofloxacin-resistant N. gonorrhoeae in New South Wales was associated with travel to Thailand. Index cases of each resistant genotype were significantly more likely to have been acquired overseas (51.5%), predominantly in Asia (45%, 30/66).

Conclusions

The continued importation of multiple genotypes, rather than the expansion of a single genotype, led to ciprofloxacin-resistant N. gonorrhoeae being established in New South Wales.

Topic: ciprofloxacin – gonococcal infection – asia – australia – drug resistance, microbial – genotype – neisseria gonorrhoeae – new south wales – thailand – travel – world health organization

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Ciprofloxacin; Neisseria gonorrhoeae; New South Wales; Australia.

——

Adjunctive #transferrin to reduce the emergence of #antibiotic #resistance in Gram-negative #bacteria (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Adjunctive transferrin to reduce the emergence of antibiotic resistance in Gram-negative bacteria

Brian M Luna, Ksenia Ershova, Jun Yan, Amber Ulhaq, Travis B Nielsen, Sarah Hsieh, Paul Pantapalangkoor, Brian Vanscoy, Paul Ambrose, Sue Rudin, Kristine Hujer, Robert A Bonomo, Luis Actis, Eric P Skaar, Brad Spellberg

Journal of Antimicrobial Chemotherapy, dkz225, https://doi.org/10.1093/jac/dkz225

Published: 06 June 2019

 

Abstract

Background

New strategies are needed to slow the emergence of antibiotic resistance among bacterial pathogens. In particular, society is experiencing a crisis of antibiotic-resistant infections caused by Gram-negative bacterial pathogens and novel therapeutics are desperately needed to combat such diseases. Acquisition of iron from the host is a nearly universal requirement for microbial pathogens—including Gram-negative bacteria—to cause infection. We have previously reported that apo-transferrin (lacking iron) can inhibit the growth of Staphylococcus aureus in culture and diminish emergence of resistance to rifampicin.

Objectives

To define the potential of apo-transferrin to inhibit in vitro growth of Klebsiella pneumoniae and Acinetobacter baumannii, key Gram-negative pathogens, and to reduce emergence of resistance to antibiotics.

Methods

The efficacy of apo-transferrin alone or in combination with meropenem or ciprofloxacin against K. pneumoniae and A. baumannii clinical isolates was tested by MIC assay, time–kill assay and assays for the selection of resistant mutants.

Results

We confirmed that apo-transferrin had detectable MICs for all strains tested of both pathogens. Apo-transferrin mediated an additive antimicrobial effect for both antibiotics against multiple strains in time–kill assays. Finally, adding apo-transferrin to ciprofloxacin or meropenem reduced the emergence of resistant mutants during 20 day serial passaging of both species.

Conclusions

These results suggest that apo-transferrin may have promise to suppress the emergence of antibiotic-resistant mutants when treating infections caused by Gram-negative bacteria.

Topic: antibiotics – iron – antibiotic resistance, bacterial – ciprofloxacin – gram-negative bacteria – transferrin – meropenem – malnutrition-inflammation-cachexia syndrome

Issue Section: ORIGINAL RESEARCH

Keywords: Antibiotics; Drugs Resistance; Meropenem; Ciprofloxacin; Transferrin.

——

N-acetylcysteine blocks SOS induction and #mutagenesis produced by #fluoroquinolones in #Escherichia coli (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

N-acetylcysteine blocks SOS induction and mutagenesis produced by fluoroquinolones in Escherichia coli

Ana I Rodríguez-Rosado, Estela Ynés Valencia, Alexandro Rodríguez-Rojas, Coloma Costas, Rodrigo S Galhardo, Jerónimo Rodríguez-Beltrán, Jesús Blázquez

Journal of Antimicrobial Chemotherapy, dkz210, https://doi.org/10.1093/jac/dkz210

Published: 18 May 2019

 

Abstract

Background

Fluoroquinolones such as ciprofloxacin induce the mutagenic SOS response and increase the levels of intracellular reactive oxygen species (ROS). Both the SOS response and ROS increase bacterial mutagenesis, fuelling the emergence of resistant mutants during antibiotic treatment. Recently, there has been growing interest in developing new drugs able to diminish the mutagenic effect of antibiotics by modulating ROS production and the SOS response.

Objectives

To test whether physiological concentrations of N-acetylcysteine, a clinically safe antioxidant drug currently used in human therapy, is able to reduce ROS production, SOS induction and mutagenesis in ciprofloxacin-treated bacteria without affecting antibiotic activity.

Methods

The Escherichia coli strain IBDS1 and its isogenic mutant deprived of SOS mutagenesis (TLS−) were treated with different concentrations of ciprofloxacin, N-acetylcysteine or both drugs in combination. Relevant parameters such as MICs, growth rates, ROS production, SOS induction, filamentation and antibiotic-induced mutation rates were evaluated.

Results

Treatment with N-acetylcysteine reduced intracellular ROS levels (by ∼40%), as well as SOS induction (by up to 75%) and bacterial filamentation caused by subinhibitory concentrations of ciprofloxacin, without affecting ciprofloxacin antibacterial activity. Remarkably, N-acetylcysteine completely abolished SOS-mediated mutagenesis.

Conclusions

Collectively, our data strongly support the notion that ROS are a key factor in antibiotic-induced SOS mutagenesis and open the possibility of using N-acetylcysteine in combination with antibiotic therapy to hinder the development of antibiotic resistance.

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; E. Coli; Ciprofloxacin; Fluoroquinolones; N-Acetylcysteine.

——

Joint #modelling of #resistance to six #antimicrobials in #urinary #Escherichia coli isolates in #Quebec, #Canada (Antimicrob Agents Chemother., abstract)

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

Joint modelling of resistance to six antimicrobials in urinary Escherichia coliisolates in Quebec, Canada

Jean-Paul R. Soucy, Alexandra M. Schmidt, Charles Frenette, Patrick Dolcé, Alexandre A. Boudreault, David L. Buckeridge, Caroline Quach

DOI: 10.1128/AAC.02531-18

 

ABSTRACT

Empirical treatment of urinary tract infections should be based on susceptibility profiles specific to the locale and patient population. Additionally, these susceptibility profiles should account for correlations between resistance to different types of antimicrobials. We used hierarchical logistic regression models to investigate geographic, temporal, and demographic trends in resistance to six antimicrobials in community-acquired and nosocomial urinary E. coli isolates from three communities in the province of Quebec, Canada procured between April 2010 and December 2017. A total of 74,986 community-acquired (age ≥ 18) and 4,384 nosocomial isolates (age ≥ 65) were analyzed. In both community-acquired and nosocomial isolates, we found geographic variation in the prevalence of resistance. Male sex (community-acquired hierarchical mean OR = 1.24, 95% credible interval: 1.02–1.50; nosocomial hierarchical mean OR = 1.16, 95% CI: 0.92–1.41) and recent hospitalization (community-acquired hierarchical mean OR = 1.49, 95% CI: 1.33–1.66; nosocomial hierarchical mean OR = 1.31, 95% CI: 0.99–1.78) were associated with a higher risk of resistance to most types of antimicrobials. We found distinct seasonal trends in both community-acquired and nosocomial isolates, but only community-acquired isolates showed a consistent annual pattern. Ciprofloxacin resistance increased sharply with patient age. We found clinically relevant differences in antimicrobial resistance in urinary E. coli isolates between locales and patient populations in the province of Quebec. These results could help inform empirical treatment decisions for urinary tract infections. In the future, similar models integrating local, provincial, and national resistance data could be incorporated into decision-support systems for clinicians.

Copyright © 2019 Soucy et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Antibiotics; Drugs Resistance; E. Coli; Ciprofloxacin; Canada; UTI.

——

#Fluoroquinolone #resistance in #carbapenem-resistant #Elizabethkingia anophelis: phenotypic and genotypic characteristics of clinical isolates … (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Fluoroquinolone resistance in carbapenem-resistant Elizabethkingia anophelis: phenotypic and genotypic characteristics of clinical isolates with topoisomerase mutations and comparative genomic analysis

Ming-Jr Jian, Yun-Hsiang Cheng, Hsing-Yi Chung, Yu-Hsuan Cheng, Hung-Yi Yang, Chih-Sin Hsu, Cherng-Lih Perng, Hung-Sheng Shang

Journal of Antimicrobial Chemotherapy, dkz045, https://doi.org/10.1093/jac/dkz045

Published: 04 March 2019

 

Abstract

Background

MDR Elizabethkingia anophelis strains are implicated in an increasing number of healthcare-associated infections worldwide, including a recent cluster of E. anophelis infections in the Midwestern USA associated with significant morbidity and mortality. However, there is minimal information on the antimicrobial susceptibilities of E. anophelis strains or their antimicrobial resistance to carbapenems and fluoroquinolones.

Objectives

Our aim was to examine the susceptibilities and genetic profiles of clinical isolates of E. anophelis from our hospital, characterize their carbapenemase genes and production of MBLs, and determine the mechanism of fluoroquinolone resistance.

Methods

A total of 115 non-duplicated isolates of E. anophelis were examined. MICs of antimicrobial agents were determined using the Sensititre 96-well broth microdilution panel method. QRDR mutations and MBL genes were identified using PCR. MBL production was screened for using a combined disc test.

Results

All E. anophelis isolates harboured the blaGOB and blaB genes with resistance to carbapenems. Antibiotic susceptibility testing indicated different resistance patterns to ciprofloxacin and levofloxacin in most isolates. Sequencing analysis confirmed that a concurrent GyrA amino acid substitution (Ser83Ile or Ser83Arg) in the hotspots of respective QRDRs was primarily responsible for high-level ciprofloxacin/levofloxacin resistance. Only one isolate had no mutation but a high fluoroquinolone MIC.

Conclusions

Our study identified a strong correlation between antibiotic susceptibility profiles and mechanisms of fluoroquinolone resistance among carbapenem-resistant E. anophelis isolates, providing an important foundation for continued surveillance and epidemiological analyses of emerging E. anophelis opportunistic infections. Minocycline or ciprofloxacin has the potential for treatment of severe E. anophelis infections.

Issue Section: ORIGINAL RESEARCH

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Elizabethkingia anophelis; Minocycline; Ciprofloxacin.

——