Diverse #vectors and mechanisms #spread #NDM beta-lactamases among #carbapenem resistant #Enterobacteriaceae in the Greater #Boston area (Antimicrob Agents Chemother., abstract)

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

Diverse vectors and mechanisms spread NDM beta-lactamases among carbapenem resistant Enterobacteriaceae in the Greater Boston area

Nicole Pecora, Xiaomin Zhao, Kathleen Nudel, Maria Hoffmann, Ning Li, Andrew B. Onderdonk, Deborah Yokoe, Eric Brown, Marc Allard, Lynn Bry

DOI: 10.1128/AAC.02040-18



New Delhi metallo-beta-lactamases (NDMs) are an uncommon but emerging cause of carbapenem resistance in the United States. Genomic factors promoting their domestic spread remain poorly characterized. A prospective genomic surveillance program among Boston-area hospitals identified multiple new occurrences of NDM carrying strains of E. coli and E. cloacaecomplex in inpatient and outpatient settings, representing the first occurrences of NDM-mediated resistance since initiating genomic surveillance in 2011. Cases included domestic patients with no international exposures. PacBio sequencing of isolates identified strain characteristics, resistance genes, and the complement of mobile vectors mediating spread. Analyses revealed a common 3114-bp region containing the blaNDM gene, with carriage of this conserved region among unique strains by diverse transposon and plasmid backbones. Functional studies revealed broad capacity for blaNDM transmission by conjugation, transposition, and complex inter-plasmid recombination events. NDMs represent a rapidly spreading form of drug resistance that can occur in inpatient and outpatient settings and in patients without international exposures. In contrast to Tn4401-based spread of Klebsiella pneumoniae carbapenemases (KPCs), diverse transposable elements mobilize NDM enzymes, commonly with other resistance genes, enabling naïve strains to acquire multi- and extensively-drug resistance profiles with single transposition or plasmid conjugation events. Genomic surveillance provides effective means to rapidly identify these gene-level drivers of resistance and mobilization, to inform clinical decisions to prevent further spread.

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

Keywords: Antibiotics; Drugs Resistance; Carbapenem; NDM1; USA; Enterobacteriaceae.



#Spreading #patterns of #NDM-producing #Enterobacteriaceae in clinical and #environmental settings in #Yangon, #Myanmar (Antimicrob Agents Chemother., abstract)

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

Spreading patterns of NDM-producing Enterobacteriaceae in clinical and environmental settings in Yangon, Myanmar

Yo Sugawara, Yukihiro Akeda, Hideharu Hagiya, Noriko Sakamoto, Dan Takeuchi, Rathina Kumar Shanmugakani, Daisuke Motooka, Isao Nishi, Khwar Nyo Zin, Mya Mya Aye, Thuzar Myint,Kazunori Tomono, Shigeyuki Hamada

DOI: 10.1128/AAC.01924-18



The spread of carbapenemase-producing Enterobacteriaceae (CPE) has become a global concern, contributing to widespread carbapenem resistance. However, the specific dissemination patterns of carbapenemase genes have not been intensively investigated in developing countries, including Myanmar, where NDM-type carbapenemases are spreading in clinical settings. In the present study, we phenotypically and genetically characterized 91 CPE isolates obtained from clinical (n = 77) and environmental (n = 14) samples in Yangon, Myanmar. We determined the dissemination of plasmids harboring genes encoding NDM-1 and its variants using whole-genome sequencing and plasmid analysis. IncFII plasmids harboring blaNDM-5 and IncX3 plasmids harboring blaNDM-4 or blaNDM-7 were the most prevalent plasmid types identified among the isolates. The IncFII plasmids were predominantly carried by clinical isolates of Escherichia coli, and their clonal expansion was observed within the same ward of a hospital. By contrast, the IncX3 plasmids were found in phylogenetically divergent isolates from clinical and environmental samples classified into nine species, suggesting the widespread dissemination of plasmids via horizontal transfer. Half of the environmental isolates were found to possess IncX3 plasmids, and this type of plasmid was confirmed to transfer more effectively to recipient organisms at a relatively low temperature (25°C) compared to the IncFII plasmid. Moreover, various other plasmid types were identified harboring blaNDM-1, including IncFIB, IncFII, IncL/M, and IncA/C2, among clinical isolates of Klebsiella pneumoniae or Enterobacter cloacae complex. Overall, our results highlight three distinct patterns of the dissemination of blaNDM-harboring plasmids among CPE isolates in Myanmar, contributing to gaining a better understanding of their molecular epidemiology and dissemination in an endemic setting.

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

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Myanmar; Enterobacteriaceae.


#Azidothymidine [#AZT] produces synergistic #activity in combination with #colistin against #antibiotic-resistant #Enterobacteriaceae (Antimicrob Agents Chemother., abstract)

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

Azidothymidine produces synergistic activity in combination with colistin against antibiotic-resistant Enterobacteriaceae

Yanmin Hu, Yingjun Liu, Anthony Coates

DOI: 10.1128/AAC.01630-18



Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, antibiotic-resistant Enterobacteriaceae is prevalent and extremely difficult to treat. Reusing existing drugs and rejuvenating the therapeutic potential of existing antibiotics represent an attractive novel strategy. Azidothymidine (AZT) is an antiretroviral drug which is used in combination with other antivirals to prevent and to treat HIV/AIDS. AZT is also active against Gram-negative bacteria but has not been developed for that purpose. Here we investigated in vitro and in vivo efficacy of AZT in combination with colistin against antibiotic-resistant Enterobacteriaceae including extended-spectrum beta-lactamase (ESBL), New Delhi metallo-beta-lactamase 1 (NDM) or the mobilized colistin resistance (mcr-1) producing strains. Minimum inhibitory concentration was determined using the broth microdilution method. The combinatory effect of AZT and colistin was examined using the checkerboard method and time-kill analysis. A murine peritoneal infection model was used to test the therapeutic effect of the combination of AZT and colistin. Fractional inhibitory concentration index from checkerboard assay demonstrated that AZT synergized with colistin against 61% and 87% of ESBL-producing Escherichia coli and Klebsiella pneumoniae, respectively, 100% of NDM-1-producing strains and 92% of mcr-1 producing E. coli. Time-kill analysis demonstrated significant synergistic activities when AZT was combined with colistin. In the murine peritoneal infection model, AZT in combination with colistin showed augmented activities of both drugs in the treatment of NDM-1 K. pneumoniae and mcr-1 E. coli infections. AZT and colistin combination poses a potential to be used coherently to treat antibiotic-resistant Enterobacteriaceae infections.

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

Keywords: Antivirals; Antibiotics; Drugs Resistance; Colistin; AZT; MCR1; Enterobacteriaceae.


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



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.


CG258 #Klebsiella pneumoniae isolates without β-lactam #resistance at the onset of the #carbapenem-resistant #Enterobacteriaceae #epidemic in #NYC (J Antimicrob Chemother., abstract)

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

CG258 Klebsiella pneumoniae isolates without β-lactam resistance at the onset of the carbapenem-resistant Enterobacteriaceae epidemic in New York City

Brandon Eilertson, Liang Chen, Audrey Li, Kalyan D Chavda, Bhakti Chavda, Barry N Kreiswirth

Journal of Antimicrobial Chemotherapy, dky394, https://doi.org/10.1093/jac/dky394

Published: 01 October 2018




To examine the epidemiology of β-lactam resistance in ‘clonal group 258’ (CG258), a successful KPC clonal group, over 14 years.


Isolates were collected from 1999 to 2013 for a study of antibiotic resistance in Enterobacteriaceae in New York City; 515 bloodstream isolates had antibiotic susceptibility data available and 436 were available for a CG258 PCR assay. The 56 resulting CG258 isolates were characterized by MLST, capsular type and ESBL and KPC carriage. KPC-positive isolates were assessed for common KPC plasmid types, KPC subtype and Tn4401 isoform.


RT–PCR revealed 56 isolates were CG258. Seventeen of the 56 CG258 isolates were phenotypically susceptible to all carbapenems (all KPC negative). Five out of 17 susceptible isolates were of the cps-2 (wzi154) capsule type; none was cps-1 (wzi29). Nineteen out of 28 KPC-2 isolates were cps-1 (wzi29) and 8/10 KPC-3 isolates carried cps-2 (wzi154); however, cps-2 (wzi154) predominated among KPC-2-positive isolates in 2003 and 2004. KPC-2 was first detected in 2003 and KPC-3 was first detected in 2006. KPC-harbouring plasmids pKpQIL (all Tn4401a) and pBK30683 (all Tn4401d) were detected in 16/38 and 6/38 carbapenem-resistant isolates, respectively.


CG258-lineage Klebsiella pneumoniae isolates were completely absent in 1999, but common in 2003. Twenty-one percent of CG258 isolates were susceptible to carbapenems in addition to lacking both common ESBL and blaKPC-mediated resistance. The cps-2 (wzi154) capsule type was common in both these susceptible isolates and in early KPC-2-harbouring isolates, suggesting it was the initial capsule type in CG258. Carbapenem-resistant isolates carried common KPC-harbouring plasmids with the same KPC and Tn4401 isoforms, suggesting frequent clonal spread.

Topic: polymerase chain reaction – plasmids – antibiotic resistance, bacterial – carbapenem – epidemiology – disease transmission – enterobacteriaceae – klebsiella pneumoniae – lactams – new york city – protein isoforms – reverse transcriptase  polymerase chain reaction – epidemics – antimicrobial susceptibility – multi-antibiotic resistance – extended-spectrum beta lactamases – bacterial carbapenemase resistance blakpc gene – carbapenem resistance – carbapenem-resistant enterobacteriaceae


© 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; Carbapenem; Beta-lactams; Enterobacteriaceae; NYC; USA; Klebsiella pneumoniae.


Treatment of extended spectrum βlactamase producing #Enterobacteriaceae (#ESBLs) #infections: what have we learned until now (F1000Res., abstract)

[Source: F1000 Research, full page: (LINK). Abstract, edited.]

Treatment of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBLs) infections: what have we learned until now? [version 1; referees: 2 approved]

Zoi Dorothea Pana1, Theoklis Zaoutis 2

Author details: 1 Infectious Diseases Department, 3rd Department of Pediatrics, Hippokration General Hospital Aristotle University, Thessaloniki, Greece; 2 Infectious Diseases Department, The Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA



The spread of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-PE) has dramatically increased worldwide, and this “evolving crisis” is currently regarded as one of the most important public health threats. The growing problem of ESBL-PE antimicrobial resistance seems to have a dual face between “Scylla and Charybdis”: on one hand the potential for rapid spread and dissemination of resistance mechanisms and on the other hand the injudicious overuse of antimicrobial agents and the inadequate infection control measures, especially in the health-care setting. Given the World Health Organization’s warning against a “post antibiotic era”, health-care providers are at a critical standpoint to find a “balance” between safe and effective ESBL-PE treatment and avoidance of inducing further resistance mechanisms. The aim of the review is to summarize the updated published knowledge in an attempt to answer basic everyday clinical questions on how to proceed to effective and the best ESBL-PE treatment options based on the existing published data.


Keywords; lactamase producers, ESBL treatment, Enterobacteriaceae

Corresponding author: Theoklis Zaoutis

Competing interests: No competing interests were disclosed.Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright:  © 2018 Pana ZD and Zaoutis T. This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Pana ZD and Zaoutis T. Treatment of extended-spectrum β-lactamase-producing Enterobacteriaceae(ESBLs) infections: what have we learned until now? [version 1; referees: 2 approved]. F1000Research 2018, 7(F1000 Faculty Rev):1347 (doi: 10.12688/f1000research.14822.1)

First published: 29 Aug 2018, 7(F1000 Faculty Rev):1347 (doi: 10.12688/f1000research.14822.1)

Latest published: 29 Aug 2018, 7(F1000 Faculty Rev):1347 (doi: 10.12688/f1000research.14822.1)

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


Emergence of #Carbapenemase-Producing #Enterobacteriaceae, South-Central #Ontario, #Canada (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), full page: (LINK). Abstract, edited.]

Volume 24, Number 9—September 2018 / Research

Emergence of Carbapenemase-Producing Enterobacteriaceae, South-Central Ontario, Canada

Philipp P. Kohler2  , Roberto G. Melano, Samir N. Patel, Shumona Shafinaz, Amna Faheem, Brenda L. Coleman, Karen Green, Irene Armstrong, Huda Almohri, Sergio Borgia, Emily Borgundvaag, Jennie Johnstone, Kevin Katz, Freda Lam, Matthew P. Muller, Jeff Powis, Susan M. Poutanen, David Richardson, Anu Rebbapragada, Alicia Sarabia, Andrew Simor, Allison McGeer, and for the Toronto Invasive Bacterial Diseases Network (TIBDN)

Author affiliations: Sinai Health System, Toronto, Ontario, Canada (P.P. Kohler, S. Shafinaz, A. Faheem, B.L. Coleman, K. Green, E. Borgundvaag, S.M. Poutanen, A. McGeer); Public Health Ontario Laboratories, Toronto (R.G. Melano, S.N. Patel); University of Toronto, Toronto (R.G. Melano, S.N. Patel, B.L. Coleman, I. Armstrong, J. Johnstone, K. Katz, M.P. Muller, J. Powis, S.M. Poutanen, A. Sarabia, A. Simor, A. McGeer); Toronto Public Health, Toronto (I. Armstrong); LifeLabs, Toronto (H. Almohri); McMaster University, Hamilton, Ontario, Canada (S. Borgia); William Osler Health System, Brampton, Ontario, Canada (S. Borgia, D. Richardson); St. Joseph’s Health Centre, Toronto (J. Johnstone); Public Health Ontario, Toronto (J. Johnstone, K. Katz, F. Lam); North York General Hospital, Toronto (K. Katz); St. Michael’s Hospital, Toronto (M.P. Muller); Toronto East Health Network, Toronto (J. Powis); University Health Network, Toronto (S.M. Poutanen); Dynacare, Brampton (A. Rebbapragada); Trillium Health Partners, Toronto and Mississauga, Ontario, Canada (A. Sarabia); Sunnybrook Health Sciences Centre, Toronto (A. Simor)



We analyzed population-based surveillance data from the Toronto Invasive Bacterial Diseases Network to describe carbapenemase-producing Enterobacteriaceae (CPE) infections during 2007–2015 in south-central Ontario, Canada. We reviewed patients’ medical records and travel histories, analyzed microbiologic and clinical characteristics of CPE infections, and calculated incidence. Among 291 cases identified, New Delhi metallo-β-lactamase was the predominant carbapenemase (51%). The proportion of CPE-positive patients with prior admission to a hospital in Canada who had not received healthcare abroad or traveled to high-risk areas was 13% for patients with oxacillinase-48, 24% for patients with New Delhi metallo-β-lactamase, 55% for patients with Klebsiella pneumoniae carbapenemase, and 67% for patients with Verona integron-encoded metallo-β-lactamase. Incidence of CPE infection increased, reaching 0.33 cases/100,000 population in 2015. For a substantial proportion of patients, no healthcare abroad or high-risk travel could be established, suggesting CPE acquisition in Canada. Policy and practice changes are needed to mitigate nosocomial CPE transmission in hospitals in Canada.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Enterobacteriaceae; Ontario; Canada; Nosocomial Outbreaks.