#Contact #precautions in single-bed or multiple-bed rooms for #patients with #ESBL-producing #Enterobacteriaceae in #Dutch #hospitals:… (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Contact precautions in single-bed or multiple-bed rooms for patients with extended-spectrum β-lactamase-producing Enterobacteriaceae in Dutch hospitals: a cluster-randomised, crossover, non-inferiority study

Marjolein F Q Kluytmans-van den Bergh, PhD, Patricia C J Bruijning-Verhagen, PhD, Prof Christina M J E Vandenbroucke-Grauls, PhD, Els I G B de Brauwer, PhD, Anton G M Buiting, PhD, Bram M Diederen, PhD, Erika P M van Elzakker, MD, Prof Alex W Friedrich, PhD, Joost Hopman, MD, Nashwan al Naiemi, PhD, Prof John W A Rossen, PhD, Gijs J H M Ruijs, PhD, Prof Paul H M Savelkoul, PhD, Carlo Verhulst, BASc, Prof Margreet C Vos, PhD, Prof Andreas Voss, PhD, Prof Marc J M Bonten, PhD, Prof Jan A J W Kluytmans, PhD, on behalf of theSoM Study Group †

Published: August 23, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30262-2




Use of single-bed rooms for control of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is under debate; the added value when applying contact precautions has not been shown. We aimed to assess whether an isolation strategy of contact precautions in a multiple-bed room was non-inferior to a strategy of contact precautions in a single-bed room for preventing transmission of ESBL-producing Enterobacteriaceae.


We did a cluster-randomised, crossover, non-inferiority study on medical and surgical wards of 16 Dutch hospitals. During two consecutive study periods, either contact precautions in a single-bed room or contact precautions in a multiple-bed room were applied as the preferred isolation strategy for patients with ESBL-producing Enterobacteriaceae cultured from a routine clinical sample (index patients). Eligible index patients were aged 18 years or older, had no strict indication for barrier precautions in a single-bed room, had a culture result reported within 7 days of culture and before discharge, and had no wardmate known to be colonised or infected with an ESBL-producing Enterobacteriaceae isolate of the same bacterial species with a similar antibiogram. Hospitals were randomly assigned in a 1:1 ratio by computer to one of two sequences of isolation strategies, stratified by university or non-university hospital. Allocation was masked for laboratory technicians who assessed the outcomes but not for patients, treating doctors, and infection-control practitioners enrolling index patients. The primary outcome was transmission of ESBL-producing Enterobacteriaceae to wardmates, which was defined as rectal carriage of an ESBL-producing Enterobacteriaceae isolate that was clonally related to the index patient’s isolate in at least one wardmate. The primary analysis was done in the per-protocol population, which included patients who were adherent to the assigned room type. A 10% non-inferiority margin for the risk difference was used to assess non-inferiority. This study is registered with Nederlands Trialregister, NTR2799.


16 hospitals were randomised, eight to each sequence of isolation strategies. All hospitals randomised to the sequence single-bed room then multiple-bed room and five of eight hospitals randomised to the sequence multiple-bed room then single-bed room completed both study periods and were analysed. From April 24, 2011, to Feb 27, 2014, 1652 index patients and 12 875 wardmates were assessed for eligibility. Of those, 693 index patients and 9527 wardmates were enrolled and 463 index patients and 7093 wardmates were included in the per-protocol population. Transmission of ESBL-producing Enterobacteriaceae to at least one wardmate was identified for 11 (4%) of 275 index patients during the single-bed room strategy period and for 14 (7%) of 188 index patients during the multiple-bed room strategy period (crude risk difference 3·4%, 90% CI −0·3 to 7·1).


For patients with ESBL-producing Enterobacteriaceae cultured from a routine clinical sample, an isolation strategy of contact precautions in a multiple-bed room was non-inferior to a strategy of contact precautions in a single-bed room for preventing transmission of ESBL-producing Enterobacteriaceae. Non-inferiority of the multiple-bed room strategy might change the current single-bed room preference for isolation of patients with ESBL-producing Enterobacteriaceae and, thus, broaden infection-control options for ESBL-producing Enterobacteriaceae in daily clinical practice.


Netherlands Organisation for Health Research and Development.

Keywords: Antibiotics; Drugs Resistance; Beta-lactams; Enterobacteriaceae; Nosocomial outbreaks; Netherlands.



Towards #endemicity: large-scale #expansion of the #NDM-1-producing #Klebsiella pneumoniae ST11 lineage in #Poland, 2015–16 (J Antimicrob Chemother., abstract)

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

Towards endemicity: large-scale expansion of the NDM-1-producing Klebsiella pneumoniae ST11 lineage in Poland, 2015–16

A Baraniak, M Machulska, D Żabicka, E Literacka, R Izdebski, P Urbanowicz, K Bojarska,M Herda, A Kozińska, W Hryniewicz, M Gniadkowski, NDM-PL Study Group

Journal of Antimicrobial Chemotherapy, dkz315, https://doi.org/10.1093/jac/dkz315

Published: 13 August 2019




In 2015 and 2016 Poland recorded rapid proliferation of New Delhi MBL (NDM)-producing Enterobacterales, with at least 470 and 1780 cases, respectively. We addressed the roles of the Klebsiella pneumoniae ST11 NDM-1 outbreak genotype, already spreading in 2012–14, and of newly imported organisms in this increase.


The study included 2136 NDM-positive isolates identified between April 2015 and December 2016, following transfer of patients with K. pneumoniae ST147 NDM-1 from Tunisia to Warsaw in March 2015. The isolates were screened by PCR mapping for variants of blaNDM-carrying Tn125-like elements. Selected isolates were typed by PFGE and MLST. NDM-encoding plasmids were analysed by nuclease S1/hybridization, transfer assays, PCR-based replicon typing and PCR mapping.


The organisms were mainly K. pneumoniae containing the Tn125A variant of the ST11 epidemic lineage (n = 2094; ∼98%). Their representatives were of the outbreak pulsotype and ST11, and produced NDM-1, encoded by specific IncFII (pKPX-1/pB-3002cz)-like plasmids. The isolates were recovered in 145 healthcare centres in 13/16 administrative regions, predominantly the Warsaw area. The ‘Tunisian’ genotype K. pneumoniae ST147 NDM-1 Tn125F comprised 18 isolates (0.8%) from eight institutions. The remaining 24 isolates, mostly K. pneumoniae and Escherichia coli of diverse STs, produced NDM-1 or NDM-5 specified by various Tn125 derivatives and plasmids.


The K. pneumoniae ST11 NDM-1 outbreak has dramatically expanded in Poland since 2012, which may bring about a countrywide endemic situation in the near future. In addition, the so-far limited K. pneumoniae ST147 NDM-1 outbreak plus multiple NDM imports from different countries were observed in 2015–16.


© 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; Beta-lactams; NDM1; NDM5; Poland.


The #antimicrobial #peptide thanatin disrupts the bacterial outer membrane and inactivates the #NDM-1 metallo-β-lactamase (Nat Commun., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Nat Commun. 2019 Aug 6;10(1):3517. doi: 10.1038/s41467-019-11503-3.

The antimicrobial peptide thanatin disrupts the bacterial outer membrane and inactivates the NDM-1 metallo-β-lactamase.

Ma B1, Fang C1, Lu L2, Wang M1, Xue X1, Zhou Y1, Li M1, Hu Y1, Luo X3, Hou Z4.

Author information: 1 Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi’an, 710032, China. 2 Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710038, China. 3 Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi’an, 710032, China. xxluo3@fmmu.edu.cn. 4 Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi’an, 710032, China. hzh_0001@163.com.



New Delhi metallo-β-lactamase-1 (NDM-1) is the most prevalent type of metallo-β-lactamase and hydrolyzes almost all clinically used β-lactam antibiotics. Here we show that the antimicrobial peptide thanatin disrupts the outer membrane of NDM-1-producing bacteria by competitively displacing divalent cations on the outer membrane and inducing the release of lipopolysaccharides. In addition, thanatin inhibits the enzymatic activity of NDM-1 by displacing zinc ions from the active site, and reverses carbapenem resistance in NDM-1-producing bacteria in vitro and in vivo. Thus, thanatin’s dual mechanism of action may be useful for combating infections caused by NDM-1-producing pathogens.

PMID: 31388008 DOI: 10.1038/s41467-019-11503-3

Keywords: Antibiotics; Drugs Resistance; NDM1; Beta-lactams.


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)



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.


Optical #DNA #Mapping Combined with #Cas9-Targeted #Resistance #Gene #Identification for Rapid #Tracking of Resistance #Plasmids in a #NICU #Outbreak (mBio, abstract)

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

Optical DNA Mapping Combined with Cas9-Targeted Resistance Gene Identification for Rapid Tracking of Resistance Plasmids in a Neonatal Intensive Care Unit Outbreak

Santosh K. Bikkarolla, Viveka Nordberg, Fredrika Rajer, Vilhelm Müller, Muhammad Humaun Kabir, Sriram KK, Albertas Dvirnas, Tobias Ambjörnsson, Christian G. Giske, Lars Navér,Linus Sandegren, Fredrik Westerlund

Spyros Pournaras, Invited Editor, Karen Bush, Editor

DOI: 10.1128/mBio.00347-19



The global spread of antibiotic resistance among Enterobacteriaceae is largely due to multidrug resistance plasmids that can transfer between different bacterial strains and species. Horizontal gene transfer of resistance plasmids can complicate hospital outbreaks and cause problems in epidemiological tracing, since tracing is usually based on bacterial clonality. We have developed a method, based on optical DNA mapping combined with Cas9-assisted identification of resistance genes, which is used here to characterize plasmids during an extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae outbreak at a Swedish neonatal intensive care unit. The outbreak included 17 neonates initially colonized with ESBL-producing Klebsiella pneumoniae (ESBL-KP), some of which were found to carry additional ESBL-producing Escherichia coli (ESBL-EC) in follow-up samples. We demonstrate that all ESBL-KP isolates contained two plasmids with the blaCTX-M-15 gene located on the smaller one (~80 kbp). The same ESBL-KP clone was present in follow-up samples for up to 2 years in some patients, and the plasmid carrying the blaCTX-M-15 gene was stable throughout this time period. However, extensive genetic rearrangements within the second plasmid were observed in the optical DNA maps for several of the ESBL-KP isolates. Optical mapping also demonstrated that even though other bacterial clones and species carrying blaCTX-M group 1 genes were found in some neonates, no transfer of resistance plasmids had occurred. The data instead pointed toward unrelated acquisition of ESBL-producing Enterobacteriaceae (EPE). In addition to revealing important information about the specific outbreak, the method presented is a promising tool for surveillance and infection control in clinical settings.


This study presents how a novel method, based on visualizing single plasmids using sequence-specific fluorescent labeling, could be used to analyze the genetic dynamics of an outbreak of resistant bacteria in a neonatal intensive care unit at a Swedish hospital. Plasmids are a central reason for the rapid global spread of bacterial resistance to antibiotics. In a single experimental procedure, this method replaces many traditional plasmid analysis techniques that together provide limited details and are slow to perform. The method is much faster than long-read whole-genome sequencing and offers direct genetic comparison of patient samples. We could conclude that no transfer of resistance plasmids had occurred between different bacteria during the outbreak and that secondary cases of ESBL-producing Enterobacteriaceae carriage were instead likely due to influx of new strains. We believe that the method offers potential in improving surveillance and infection control of resistant bacteria in hospitals.

Keywords: Antibiotics; Drugs Resistance; Enterobacteriaceae; Beta-lactams; Nosocomial Outbreaks; Diagnostic tests.


Available #evidence of #antibiotic #resistance from #ESBL-producing #Enterobacteriaceae in #paediatric patients in 20 countries: a systematic review and meta-analysis (Bull World Health Organ., abstract)

[Source: Bulletin of the World Health Organization, full page: (LINK). Abstract, edited.]

Available evidence of antibiotic resistance from extended-spectrum β-lactamase-producing Enterobacteriaceae in paediatric patients in 20 countries: a systematic review and meta-analysis

Yanhong Jessika Hu,a, Anju Ogyu,a, Benjamin J Cowling,a, Keiji Fukuda a & Herbert H Pang a

{a} School of Public Health, Patrick Manson Building (North Wing), 7 Sassoon Road, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special
Administrative Region, China.

Correspondence to Yanhong Jessika Hu (email: huhubest@gmail.com).

Submitted: 20 October 2018 – Revised version received: 8 April 2019 – Accepted: 9 April 2019 – Published online: 14 May 2019

Bull World Health Organ 2019;97:486–501B | doi: http://dx.doi.org/10.2471/BLT.18.225698




To make a systematic review of risk factors, outcomes and prevalence of extended-spectrum β-lactamase-associated infection in children and young adults in South-East Asia and the Western Pacific.


Up to June 2018 we searched online databases for published studies of infection with extended-spectrum β-lactamase-producing Enterobacteriaceae in individuals aged 0–21 years. We included case–control, cohort, cross-sectional and observational studies reporting patients positive and negative for these organisms. For the meta-analysis we used random-effects modelling of risk factors and outcomes for infection, and meta-regression for analysis of subgroups. We mapped the prevalence of these infections in 20 countries and areas using available surveillance data.


Of 6665 articles scanned, we included 40 studies from 11 countries and areas in the meta-analysis. The pooled studies included 2411 samples testing positive and 2874 negative. A higher risk of infectionwith extended-spectrum β-lactamase-producing bacteria was associated with previous hospital care, notably intensive care unit stays (pooled odds ratio, OR: 6.5; 95% confidence interval, CI: 3.04 to 13.73); antibiotic exposure (OR: 4.8; 95% CI: 2.25 to 10.27); and certain co-existing conditions. Empirical antibiotic therapy was protective against infection (OR: 0.29; 95% CI: 0.11 to 0.79). Infected patients had longer hospital stays (26 days; 95% CI: 12.81 to 38.89) and higher risk of death (OR: 3.2; 95% CI: 1.82 to 5.80). The population prevalence of infection was high in these regions and surveillance data for children were scarce.


Antibiotic stewardship policies to prevent infection and encourage appropriate treatment are needed in South-East Asia and the Western Pacific

Keywords: Antibiotics; Drugs Resistance; Pediatrics; Asia Region.


Emergence of #carbapenem resistant #Pseudomonas asiatica producing #NDM-1 and #VIM-2 metallo-β-lactamases in #Myanmar (Antimicrob Agents Chemother., abstract)

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

Emergence of carbapenem-resistant Pseudomonas asiatica producing NDM-1 and VIM-2 metallo-β-lactamases in Myanmar

Mari Tohya, Tatsuya Tada, Shin Watanabe, Kyoko Kuwahara-Arai, Khwar Nyo Zin, Ni Ni Zaw, May Yee Aung, San Mya, Khin Nyein Zan, Teruo Kirikae, Htay Htay Tin

DOI: 10.1128/AAC.00475-19



Pseudomonas asiatica is recently proposed species of the genus Pseudomonas. This study describes eight isolates of carbapenem-resistant P. asiatica harboring blaNDM-1 and blaVIM-2, genes encoding metallo-β-lactamase (MBL). These isolates were obtained from urine samples of patients hospitalized in Myanmar. These isolates were resistant to carbapenems but susceptible to colistin. All eight isolates were positive for a carbapenemase inactivation method, CIMTrisII, and seven were positive on an immunochromatographic assay for NDM-type MBL. One isolate was highly resistant to aminoglycosides. Whole genome sequencing showed that seven isolates harbored blaNDM-1 and one harbored blaVIM-2, with these genes located on the chromosome. One isolate harbored blaNDM-1 and rmtC, a gene encoding 16S rRNA methylase. Five types of genomic environments surrounding blaNDM-1 and blaVIM-2 were detected in these eight isolates, with four isolates having the same type. These data indicate that P. asiatica harboring genes encoding carbapenemases, including blaNDM-1 and blaVIM-2, are spreading in medical settings in Myanmar.

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

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Beta-lactams; Aminoglycosides; Pseudomonas asiatica; Myanmar.