Efficacy and safety of #tigecycline in #treatment of #pneumonia caused by #MDR Acinetobacter baumannii: a systematic review and meta-analysis (J Antimicrob Chemother., abstract)

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

Efficacy and safety of tigecycline in treatment of pneumonia caused by MDR Acinetobacter baumannii: a systematic review and meta-analysis

Hekun Mei, Tianli Yang, Jin Wang, Rui Wang, Yun Cai

Journal of Antimicrobial Chemotherapy, dkz337, https://doi.org/10.1093/jac/dkz337

Published: 03 August 2019

 

Abstract

Background

Use of tigecycline in treating MDR Acinetobacter baumannii (MDRAB) remains controversial.

Objectives

To comprehensively assess the safety and efficacy of tigecycline in pneumonia caused by Acinetobacter baumannii.

Methods

PubMed, Embase, Web of Science and Cochrane library databases were searched up to 12 March 2019. Studies were included if they compared tigecycline-based regimens with other antibiotic regimens for treating AB pulmonary infections and we pooled the clinical outcomes, microbiological response, adverse events or mortality.

Results

One prospective study and nine retrospective studies were included in this meta-analysis. The results showed similar clinical cure rates (OR = 1.04, 95% CI = 0.60–1.81; P = 0.89) and mortality rates (OR = 1.11, 95% CI = 0.65–1.89; P = 0.71) comparing tigecycline groups with the control groups. However, a significantly lower microbiological eradication rate was found in the tigecycline groups (OR = 0.43, 95% CI = 0.27–0.66; P = 0.0001). Incidence of nephrotoxicity in tigecycline-based regimens was significantly lower than in colistin-based regimens (OR = 0.34, 95% CI = 0.16–0.74, I2 = 35%, P = 0.006). There were no randomized controlled trials (RCTs) included; incomplete safety data and regional bias caused by the majority of the studies originating in China are the main limitations of this meta-analysis.

Conclusions

Tigecycline can be used for treating MDRAB pulmonary infections owing to efficacy similar to that of other antibiotics. Moreover, tigecycline did not show a higher risk of mortality. Considering the lower microbiological eradication rate for tigecycline, which is likely to induce antimicrobial resistance, well-designed RCTs for high-dose tigecycline in treating pneumonia caused by AB are still needed.

Topic: colistin – pneumonia – safety – mortality – acinetobacter baumannii – nephrotoxicity – tigecycline – adverse event

Issue Section: Systematic review

© 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; Tigecycline; Acinetobacter baumannii; Pneumonia.

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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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A #MDR #Plasmid pIMP26, Carrying blaIMP-26, fosA5, blaDHA-1, and qnrB4 in #Enterobacter cloacae (Sci Rep., abstract)

[Source: Scientific Reports, full page: (LINK). Abstract, edited.]

Article | OPEN | Published: 15 July 2019

A Multidrug Resistance Plasmid pIMP26, Carrying blaIMP-26, fosA5, blaDHA-1, and qnrB4 in Enterobacter cloacae

Su Wang,  Kaixin Zhou, Shuzhen Xiao, Lianyan Xie, Feifei Gu, Xinxin Li, Yuxing Ni, Jingyong Sun & Lizhong Han

Scientific Reports, volume 9, Article number: 10212 (2019)

 

Abstract

IMP-26 was a rare IMP variant with more carbapenem-hydrolyzing activities, which was increasingly reported now in China. This study characterized a transferable multidrug resistance plasmid harboring blaIMP-26 from one Enterobacter cloacae bloodstream isolate in Shanghai and investigated the genetic environment of resistance genes. The isolate was subjected to antimicrobial susceptibility testing and multilocus sequence typing using broth microdilution method, Etest and PCR. The plasmid was analyzed through conjugation experiments, S1-nuclease pulsed-field gel electrophoresis and hybridization. Whole genome sequencing and sequence analysis was conducted for further investigation of the plasmid. E. cloacae RJ702, belonging to ST528 and carrying blaIMP-26, blaDHA-1, qnrB4 and fosA5, was resistant to almost all β-lactams, but susceptible to quinolones and tigecycline. The transconjugant inherited the multidrug resistance. The resistance genes were located on a 329,420-bp IncHI2 conjugative plasmid pIMP26 (ST1 subtype), which contained trhK/trhV, tra, parA and stbA family operon. The blaIMP-26 was arranged following intI1. The blaDHA-1 and qnrB4cluster was the downstream of ISCR1, same as that in p505108-MDR. The fosA5 cassette was mediated by IS4. This was the first report on complete nucleotide of a blaIMP-26-carrying plasmid in E. cloacae in China. Plasmid pIMP26 hosted high phylogenetic mosaicism, transferability and plasticity.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Beta-lactams; Enterobacter cloacae; Shanghai; China; Quinolones; Tigecycline.

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Detection of #plasmid-mediated #tigecycline-resistant gene tet(X4) in #Escherichia coli from #pork, #Sichuan and #Shandong Provinces, #China, February 2019 (Euro Surveill., abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Detection of plasmid-mediated tigecycline-resistant gene tet(X4) in Escherichia coli from pork, Sichuan and Shandong Provinces, China, February 2019

Li Bai1,2,3, Pengcheng Du3,4, Yinju Du5, Honghu Sun1,2,6, Pei Zhang1,2, Yuping Wan6, Qi Lin6, Séamus Fanning1,2,7, Shenghui Cui8, Yongning Wu1,2

Affiliations: 1 Key Laboratory of Food Safety Risk Assessment, National Health Commission of the People’s Republic of China, Beijing, People’s Republic of China; 2 Food Safety Research Unit of Chinese Academy of Medical Sciences, China National Center for Food Safety Risk Assessment, Beijing, People’s Republic of China; 3 These authors contributed equally to this work; 4 Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, People’s Republic of China; 5 Center for disease control and prevention of Liaocheng city, Liaocheng, People’s Republic of China; 6 Chengdu institute for Food and Drug Control, Chengdu, People’s Republic of China; 7 UCD-Centre for Food Safety, School of Public Health, Physiotherapy and Sports Science, University College Dublin, Belfield, Dublin, Ireland; 8 Department of Food Science, National Institutes for Food and Drug Control, Beijing, People’s Republic of China

Correspondence:  Yongning Wu

Citation style for this article: Bai Li, Du Pengcheng, Du Yinju, Sun Honghu, Zhang Pei, Wan Yuping, Lin Qi, Fanning Séamus, Cui Shenghui, Wu Yongning. Detection of plasmid-mediated tigecycline-resistant gene tet(X4) in Escherichia coli from pork, Sichuan and Shandong Provinces, China, February 2019. Euro Surveill.2019;24(25):pii=1900340. https://doi.org/10.2807/1560-7917.ES.2019.24.25.1900340

Received: 29 May 2019;   Accepted: 20 Jun 2019

 

Abstract

The plasmid-mediated high-level tigecycline resistance gene, tet(X4), was detected in seven Escherichia coli isolates from pork in two Chinese provinces. Two isolates belonged to the epidemic spreading sequence type ST101. Tet(X4) was adjacent to ISVsa3 and concurrent with floR in all seven isolates. In addition to IncFIB, the replicon IncFII was found to be linked to tet(X4). This report follows a recent detection of tet(X3)/(X4) in E. coli from animals and humans in China.

©  This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords: Antibiotics; Drugs Resistance; Tigecycline; Plasmids; Pigs; E. Coli; Food Safety; China; Sichuan; Shandong.

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The #application of #CRISPR/Cas9-based genome editing in studying the #mechanism of #pandrug #resistance in #Klebsiella pneumoniae (Antimicrob Agents Chemother., abstract)

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

The application of CRISPR/Cas9-based genome editing in studying the mechanism of pandrug resistance in Klebsiella pneumoniae

Qiaoling Sun, Yu Wang, Ning Dong, Lingwei Shen, Hongwei Zhou, Yan-yan Hu, Danxia Gu, Sheng Chen, Rong Zhang, Quanjiang Ji

DOI: 10.1128/AAC.00113-19

 

ABSTRACT

In this study, a CRISPR/Cas9-mediated genome editing method was used to study the functions of genes mgrB, tetA and ramR in mediating colistin and tigecycline resistance in carbapenem-resistant Klebsiella pneumoniae. Inactivation of the tetA, ramR, or mgrB genes by CRISPR/Cas9 affected bacterial susceptibility to tigecycline or colistin, respectively. This study proved that the CRISPR/Cas9-based genome editing method could be effectively applied to K. pneumoniae and should be further utilized for genetic characterization.

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

Keywords: Antibiotics; Drugs Resistance; Colistin; Tigecycline; CRISPR.

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Dose-dependent Synergistic Interactions of #Colistin with #Rifampicin, #Meropenem and #Tigecycline against #Carbapenem-resistant #Klebsiella pneumoniae #Biofilms (Antimicrob Agents Chemother., abstract)

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

Dose-dependent Synergistic Interactions of Colistin with Rifampicin, Meropenem and Tigecycline against Carbapenem-resistant Klebsiella pneumoniae Biofilms

Anastasia Geladari, Maria Simitsopoulou, Charalampos Antachopoulos, Emmanuel Roilides

DOI: 10.1128/AAC.02357-18

 

ABSTRACT

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) can cause biofilm-related bloodstream infections associated with significant morbidity and mortality worldwide. We investigated the bactericidal activities of colistin (CST), rifampicin (RIF), meropenem (MEM), gentamicin (GEN) and tigecycline (TGC) alone and that of CST in combination with RIF, MEM, GEN or TGC against CR-Kp mature biofilms. Twenty CR-Kp blood isolates were derived from equal number of bloodstream infections in adult patients. Biofilm formation was assessed by staining with 0.4% crystal violet and measuring optical density spectrophotometrically at 545 nm. Biofilm damage was measured as % reduction of metabolic activity by XTT assay. MIC50 for biofilms was determined as the minimum concentration that caused ≥50% bacterial damage compared to that for untreated controls. Antibacterial drug interactions were analyzed by the Bliss independence model. Four of the twenty CR-Kp isolates were biofilm producers. Biofilm MIC50’s of CST, RIF, MEM, GEN and TGC for these isolates were 64, 8, >256, 128 and 8 mg/L, respectively. Synergistic interactions were observed at 32-64 mg/L of CST combined with 0.25-4 mg/L of RIF, at 32 mg/L of CST combined with 0.007-0.25 mg/L of MEM, and at 16-32 mg/L of CST combined with 16-64 mg/L of TGC. The synergy was highest for CST+RIF, with %ΔE±SE 49.87±9.22 compared to 29.52±4.97 for CST+MEM (p<0.001) and 32.44±6.49 for CST+TGC (p<0.001). Indifferent results were exhibited by CST+GEN. None of the combinations exhibited antagonism. These drug interactive findings, especially that of CST with RIF, may be of importance in the treatment of biofilm-related CR-Kp infections.

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

Keywords: Antibiotics; Drugs Resistance; Carbapene; Klebsiella pneumoniae; Colistin; Gentamicin; Tigecycline; Meropenem; Rifampicin.

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Impact of Combination #Therapy vs Monotherapy on #Mortality from #Carbapenem-Resistant #Enterobacteriaceae #Bacteremia: A Retrospective Observational Study from a Chinese Network (Antimicrob Agents Chemother., abstract)

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

Impact of Combination Therapy vs Monotherapy on Mortality from Carbapenem-Resistant Enterobacteriaceae Bacteremia: A Retrospective Observational Study from a Chinese Network

Xiaojuan Wang, Qi Wang, Bin Cao, Shijun Sun, Yawei Zhang, Bing Gu, Binbin Li, Kang Liao, Feng Zhao, Liang Jin, Chunmei Jin, Chunxia Yang, Fengyan Pei, Zhijie Zhang, Hui Wang

DOI: 10.1128/AAC.01511-18

 

ABSTRACT

A total of 164 bloodstream infection cases due to carbapenem-resistant Enterobacteriaceae (CRE) in 2013-2017 were retrospectively collected from 36 tertiary hospitals in 19 provinces in China to evaluate outcomes and risk factors for mortality by univariable and multivariable analysis. The most frequent infected species was Klebsiella pneumoniae (69.5%, 114/164). The overall in-hospital and 14-day mortality were 32.9% (54/164) and 31.1% (42/135), respectively. Multivariable analysis revealed that septic shock (adjusted odds ratio [aOR] 6.339, 95% confidence interval [CI] 1.586-25.332, P = 0.009), Pitt bacteremia score (aOR 1.300, 95% CI 1.009-1.676, P = 0.042), and Charlson comorbidity index (aOR 1.392, 95% CI 1.104-1.755, P = 0.005) were independently associated with hazard effect on mortality. Combination therapy, especially tigecycline-based combination therapy had the lowest in-hospital mortality and rates of bacterial clearance. Survival analysis revealed that appropriate therapy was associated with lower 14-day mortality than inappropriate therapy (including non-active therapy, P = 0.022); combination therapy was superior to monotherapy (P = 0.036); metallo-β-lactamase producers resulted in lower 14-day mortality than strains without carbapenemases or KPC-2 producers (P= 0.009); strains with minimum inhibitory concentrations (MICs) > 8 mg/L for meropenem were associated with higher 14-day mortality than that with MICs ≤ 8 mg/L (P = 0.037). Collectively, severity of illness, meropenem MICs > 8 mg/L, carbapenemase-producing types are associated with clinical outcome. Early detection of carbapenemase type and initiating appropriate combination therapy within 96 h might be helpful for improving survival.

Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Tigecycline; Enterobacteriaceae; China.

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