Updated #Prevalence of #mcr-like Genes among #Escherichia coli and #Klebsiella pneumoniae in SENTRY Program and Characterization of mcr-1.11 Variant (Antimicrob Agents Chemother., abstract)

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

Updated Prevalence of mcr-like Genes among Escherichia coli and Klebsiella pneumoniae in SENTRY Program and Characterization of mcr-1.11 Variant

Lalitagauri M. Deshpande, Cory Hubler, Andrew P. Davis, Mariana Castanheira

DOI: 10.1128/AAC.02450-18

 

ABSTRACT

Increased prevalence of infections caused by Gram-negative pathogens that are multidrug resistant has prompted the reconsideration of polymyxins as therapeutic options.…

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

Keywords: Antibiotics; Drugs Resistance; Polymyxins; MCR1.

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Novel #Polymyxin Combination with #Antiretroviral #Zidovudine Exerts Synergistic Killing against #NDM-producing #MDR #Klebsiella pneumoniae (Antimicrob Agents Chemother., abstract)

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

Novel Polymyxin Combination with Antiretroviral Zidovudine Exerts Synergistic Killing against NDM-producing MDR Klebsiella pneumoniae

Yu-Wei Lin, Nusaibah Abdul Rahim, Jinxin Zhao, Mei-Ling Han, Heidi H. Yu, Hasini Wickremasinghe, Ke Chen, Jiping Wang, David L. Paterson, Yan Zhu, Gauri G. Rao, Qi Tony Zhou,Alan Forrest, Tony Velkov, Jian Li

DOI: 10.1128/AAC.02176-18

 

ABSTRACT

Polymyxins are used as a last-line therapy against multidrug-resistant (MDR) New Delhi metallo-β-lactamase (NDM) producing Klebsiella pneumoniae. However, polymyxin resistance can emerge with monotherapy; therefore, novel strategies are urgently needed to minimize the resistance and maintain their clinical utility. This study aimed to investigate the pharmacodynamics of polymyxin B in combination with the antiretroviral drug zidovudine against K. pneumoniae. Three isolates were evaluated in static time-kill studies (0 – 64 mg/L) over 48 h. A one-compartment in vitro pharmacokinetic/pharmacodynamic (PK/PD) model (IVM) was used to simulate humanized dosage regimens of polymyxin B (4 mg/L as continuous infusion) and zidovudine (as bolus dose thrice daily to achieve Cmax = 6 mg/L) against K. pneumoniae BM1 over 72 h. The antimicrobial synergy of the combination was further evaluated in a murine thigh infection model against K. pneumoniae 02. In the static time-kill studies, polymyxin B monotherapy produced rapid and extensive killing against all three isolates followed by extensive regrowth, whereas zidovudine produced modest killing followed by significant regrowth at 24 h. Polymyxin B in combination with zidovudine significantly enhanced the antimicrobial activity (≥ 4 log10CFU/mL) and minimized bacterial regrowth. In the IVM, the combination was synergistic and the total bacterial loads were below the limit of detection for up to 72 h. In the murine thigh infection model, the bacterial burden at 24 h in the combination group was ≥ 3 log10CFU/thigh lower compared to each monotherapy against K. pneumoniae 02. Overall, polymyxin B-zidovudine combination demonstrates superior antimicrobial efficacy and minimized emergence of resistance to polymyxins.

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

Keywords: Antibiotics; Antivirals; Drugs Resistance; Polymyxins; AZT; Klebsiella pneumoniae.

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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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Emergence of a #MDR #hypervirulent #Klebsiella pneumoniae of ST23 with a rare #blaCTX-M-24-harboring virulence #plasmid (Antimicrob Agents Chemother., abstract)

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

Emergence of a multidrug-resistant hypervirulent Klebsiella pneumoniae of ST23 with a rare blaCTX-M-24-harboring virulence plasmid

Dingxia Shen, Guannan Ma, Cuidan Li, Xinmiao Jia, Chuan Qin, Tingting Yang, Lifeng Wang, Xiaoyuan Jiang, Nan Ding, Xiuli Zhang, Liya Yue, Zhe Yin, Lijun Zeng, Yongliang Zhao,Dongsheng Zhou, Fei Chen

DOI: 10.1128/AAC.02273-18

 

ABSTRACT

We reported a MDR-HvKP strain of ST23 with a rare hybrid plasmid harboring virulence genes and blaCTX-M-24, and analyzed the genetic basis for relationship between genotypes and “MDR-hypervirulence” phenotypes. Further analysis indicates that the hybrid plasmid is formed by the IS903D-mediated intermolecular transposition of blaCTX-M-24 gene into the virulent plasmid. The emergence of MDR-HvKP strains, especially drug-resistant virulent plasmids poses unprecedented threats/challenges to public health. This is a dangerous tendency and should be closely monitored.

Copyright © 2019 Shen 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; Klebsiella pneumoniae.

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Complete #genome #analysis of a #Siphoviridae #phage TSK1 showing #biofilm removal potential against #Klebsiella pneumoniae (Sci Rep., abstract)

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

Complete genome analysis of a Siphoviridae phage TSK1 showing biofilm removal potential against Klebsiella pneumoniae

Rabia Tabassum, Muafia Shafique, Komal Amer Khawaja, Iqbal Ahmed Alvi, Yasir Rehman, Cody S. Sheik, Zaigham Abbas & Shafiq ur Rehman

Scientific Reports, volume 8, Article number: 17904 (2018)

 

Abstract

Multidrug-resistant Klebsiella pneumoniae is a nosocomial pathogen, produces septicemia, pneumonia and UTI. Excessive use of antibiotics contributes towards emergence of multidrug-resistance. Bacteriophage-therapy is a potential substitute of antibiotics with many advantages. In this investigation, microbiological and genome characterization of TSK1 bacteriophage and its biofilm elimination capability are presented. TSK1 showed narrow host range and highest stability at pH 7 and 37 °C. TSK1 reduced the growth of K. pneumoniaeduring the initial 14 hours of infection. Post-treatment with TSK1 against different age K. pneumoniae biofilms reduced 85–100% biomass. Pre-treatment of TSK1 bacteriophage against the biofilm of Klebsiella pneumoniae reduced > 99% biomass in initial 24 hr of incubation. The genome of TSK1 phage comprised 49,836 base pairs with GC composition of 50.44%. Total seventy-five open reading frames (ORFs) were predicted, 25 showed homology with known functional proteins, while 50 were called hypothetical, as no homologs with proved function exists in the genome databases. Blast and phylogenetic analysis put it in the Kp36 virus genus of family Siphoviridae. Proposed packaging strategy of TSK1 bacteriophage genome is headful packaging using the pac sites. The potential of TSK1 bacteriophage could be used to reduce the bacterial load and biofilm in clinical and non-clinical settings.

Keywords: Antibiotics; Drugs Resistance; Klebsiella pneumoniae; Bacteriophages; Siphoviridae.

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#Klebsiella pneumoniae causing #UTIs in companion #animals and #humans: population structure, antimicrobial resistance and virulence genes (J Antimicrob Chemother., abstract)

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

Klebsiella pneumoniae causing urinary tract infections in companion animals and humans: population structure, antimicrobial resistance and virulence genes

Cátia Marques, Juliana Menezes, Adriana Belas, Catarina Aboim, Patrícia Cavaco-Silva, Graça Trigueiro, Luís Telo Gama, Constança Pomba

Journal of Antimicrobial Chemotherapy, dky499, https://doi.org/10.1093/jac/dky499

Published: 10 December 2018

 

Abstract

Objectives

To characterize the population structure, antimicrobial resistance and virulence genes of Klebsiella spp. isolated from dogs, cats and humans with urinary tract infections (UTIs).

Methods

Klebsiella spp. from companion animals (n = 27) and humans (n = 77) with UTI were tested by the disc diffusion method against 29 antimicrobials. Resistant/intermediate isolates were tested by PCR for 16 resistance genes. Seven virulence genes were screened for by PCR. All Klebsiella pneumoniae from companion animals and third-generation cephalosporin (3GC)-resistant isolates from humans were typed by MLST. All Klebsiella spp. were compared after PFGE XbaI macro-restriction using Dice/UPGMA with 1.5% tolerance.

Results

blaCTX-M-15 was detected in >80% of 3GC-resistant strains. K. pneumoniaehigh-risk clonal lineage ST15 predominated in companion animal isolates (60%, n = 15/25). Most companion animal ST15 K. pneumoniae belonged to two PFGE clusters (C4, C5) that also included human strains. Companion animal and human ST15-CTX-M-15 K. pneumoniae shared a fimH-1/mrkD/entB/ycfM/kfu virulence profile, with a few (n = 4) also harbouring the yersiniabactin siderophore-encoding genes. The hospital-adapted ST11 K. pneumoniae clonal lineage was detected in a cat (n = 1) and a human (n = 1); both were MDR, had 81.1% Dice/UPGMA similarity and shared several virulence and resistance genes. Two 3GC-resistant ST348 strains with 86.7% Dice/UPGMA similarity were isolated from a cat and a human.

Conclusions

Companion animals with UTI become infected with high-risk K. pneumoniaeclonal lineages harbouring resistance and virulence genes similar to those detected in strains from humans. The ST15-CTX-M-15 K. pneumoniae clonal lineage was disseminated in companion animals with UTI. Caution must be applied by companion animal caretakers to avoid the spread of K. pneumoniaehigh-risk clonal lineages.

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2018. 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; Cephalosporins; Klebsiella pneumoniae; Cats; Human.

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#Octapeptin C4 and #polymyxin #resistance occur via distinct pathways in an epidemic #XDR #Klebsiella pneumoniae ST258 isolate (J Antimicrob Chemother., abstract)

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

Octapeptin C4 and polymyxin resistance occur via distinct pathways in an epidemic XDR Klebsiella pneumoniae ST258 isolate

Miranda E Pitt, Minh Duc Cao, Mark S Butler, Soumya Ramu, Devika Ganesamoorthy, Mark A T Blaskovich, Lachlan J M Coin, Matthew A Cooper

Journal of Antimicrobial Chemotherapy, dky458, https://doi.org/10.1093/jac/dky458

Published: 14 November 2018

 

Abstract

Background

Polymyxin B and E (colistin) have been pivotal in the treatment of XDR Gram-negative bacterial infections; however, resistance has emerged. A structurally related lipopeptide, octapeptin C4, has shown significant potency against XDR bacteria, including polymyxin-resistant strains, but its mode of action remains undefined.

Objectives

We sought to compare and contrast the acquisition of resistance in an XDR Klebsiella pneumoniae (ST258) clinical isolate in vitro with all three lipopeptides to potentially unveil variations in their mode of action.

Methods

The isolate was exposed to increasing concentrations of polymyxins and octapeptin C4 over 20 days. Day 20 strains underwent WGS, complementation assays, antimicrobial susceptibility testing and lipid A analysis.

Results

Twenty days of exposure to the polymyxins resulted in a 1000-fold increase in the MIC, whereas for octapeptin C4 a 4-fold increase was observed. There was no cross-resistance observed between the polymyxin- and octapeptin-resistant strains. Sequencing of polymyxin-resistant isolates revealed mutations in previously known resistance-associated genes, including crrB, mgrB, pmrB, phoPQ and yciM, along with novel mutations in qseC. Octapeptin C4-resistant isolates had mutations in mlaDF and pqiB, genes related to phospholipid transport. These genetic variations were reflected in distinct phenotypic changes to lipid A. Polymyxin-resistant isolates increased 4-amino-4-deoxyarabinose fortification of lipid A phosphate groups, whereas the lipid A of octapeptin C4-resistant strains harboured a higher abundance of hydroxymyristate and palmitoylate.

Conclusions

Octapeptin C4 has a distinct mode of action compared with the polymyxins, highlighting its potential as a future therapeutic agent to combat the increasing threat of XDR bacteria.

Topic: mutation – colistin – genes – klebsiella pneumoniae – lipid a – polymyxins – polymyxin b – epidemics – antimicrobial susceptibility test – gene complementation –

Issue Section: ORIGINAL RESEARCH

Keywords: Antibiotics; Drugs Resistance; Colistin; Polymyxins; Octapentin; K. pneumoniae.

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