#Decreasing and stabilising #trends of #antimicrobial #consumption and #resistance in #Escherichia coli and #Klebsiella pneumoniae in segmented regression analysis, #EU / #EEA, 2001 to 2018 (Euro Surveill., abstract)

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

Decreasing and stabilising trends of antimicrobial consumption and resistance in Escherichia coli and Klebsiella pneumoniae in segmented regression analysis, European Union/European Economic Area, 2001 to 2018

Germán Peñalva 1, Liselotte Diaz Högberg 2, Klaus Weist 2, Vera Vlahović-Palčevski 3, Ole Heuer 2, Dominique L Monnet 2, ESAC-Net study group 4, EARS-Net study group 5

Affiliations: 1 Department of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocio, CSIC, University of Seville, Spain; 2 European Centre for Disease Prevention and Control, Solna, Sweden; 3 Department of Clinical Pharmacology, University Hospital Rijeka / Medical Faculty and Faculty of Health Studies, University of Rijeka, Rijeka, Croatia; 4 ESAC-Net study group participants are listed at the end of the article; 5 EARS-Net study group participants are listed at the end of the article

Correspondence:  Liselotte Diaz Högberg

Citation style for this article: Peñalva Germán, Högberg Liselotte Diaz, Weist Klaus, Vlahović-Palčevski Vera, Heuer Ole, Monnet Dominique L, ESAC-Net study group, EARS-Net study group. Decreasing and stabilising trends of antimicrobial consumption and resistance in Escherichia coli and Klebsiella pneumoniae in segmented regression analysis, European Union/European Economic Area, 2001 to 2018. Euro Surveill. 2019;24(46):pii=1900656. https://doi.org/10.2807/1560-7917.ES.2019.24.46.1900656

Received: 29 Oct 2019;   Accepted: 13 Nov 2019

 

Abstract

Investments to reduce the spread of antimicrobial resistance (AMR) in the European Union have been made, including efforts to strengthen prudent antimicrobial use. Using segmented regression, we report decreasing and stabilising trends in data reported to the European Surveillance of Antimicrobial Consumption Network and stabilising trends in data reported to the European Antimicrobial Resistance Surveillance Network. Our results could be an early indication of the effect of prioritising AMR on the public health agenda.

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

Keywords: Antibiotics; Drugs Resistance; EU; European Region.

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Identification of AbaR4 #Acinetobacter baumannii #resistance island in clinical isolates of blaOXA-23-positive #Proteus mirabilis (J Antimicrob Chemother., abstract)

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

Identification of AbaR4 Acinetobacter baumannii resistance island in clinical isolates of blaOXA-23-positive Proteus mirabilis

Sophie Octavia, Weizhen Xu, Oon Tek Ng, Kalisvar Marimuthu, Indumathi Venkatachalam, Bernadette Cheng, Raymond T P Lin, Jeanette W P Teo

Journal of Antimicrobial Chemotherapy, dkz472, https://doi.org/10.1093/jac/dkz472

Published: 14 November 2019

 

Abstract

Objectives

blaOXA-23 is a class D carbapenemase-encoding gene typical of the Acinetobacter genus. However, its occurrence in the Enterobacteriaceae is uncommon. Here we provide the genome characterization of blaOXA-23-positive Proteus mirabilis.

Methods

In Singapore, a national surveillance of carbapenem non-susceptible clinical Enterobacteriaceae has enabled the collection of OXA-23 bearing isolates. Three clinical P. mirabilis were whole-genome sequenced using Oxford Nanopore MinION and Illumina platforms. The sequence accuracy of MinION long-read contigs was enhanced by polishing with Illumina-derived short-read data.

Results

In two P. mirabilis genomes, blaOXA-23 was detected as two copies, present on the chromosome and on a 60 018 bp plasmid. blaOXA-23 was associated with the classic Acinetobacter composite transposon Tn2006, bounded by two copies of ISAba1 bracketing the carbapenemase gene. The Tn2006 itself was embedded within an Acinetobacter baumannii AbaR4 resistance island. In the chromosome, the AbaR4 was found integrated into the comM gene, which is also the preferred ‘hotspot’ in A. baumannii. In the plasmid, AbaR4 integrated into a putative colicin gene.

Conclusions

Our description of an A. baumannii AbaR4 encoding blaOXA-23 in P. mirabilis is to our knowledge the first description of an Acinetobacter resistance island in Proteus and suggests that P. mirabilis may be a reservoir for this class D carbapenemase gene.

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; Carbapenem; Acinetobacter baumannii; Proteus mirabilis; Singapore.

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Comparison of the inoculum size effects of #antibiotics on IMP-6 β-lactamase-producing #Enterobacteriaceae co-harboring #plasmid-mediated #quinolone #resistance genes (PLOS One, abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Comparison of the inoculum size effects of antibiotics on IMP-6 β-lactamase-producing Enterobacteriaceae co-harboring plasmid-mediated quinolone resistance genes

Yoshihiko Ogawa, Ryuichi Nakano , Kei Kasahara, Tomoki Mizuno, Nobuyasu Hirai, Akiyo Nakano, Yuki Suzuki, Naoki Kakuta, Takashi Masui, Hisakazu Yano, Keiichi Mikasa

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Published: November 13, 2019 / DOI: https://doi.org/10.1371/journal.pone.0225210

 

Abstract

Almost all cases of carbapenemase-producing Enterobacteriaceae infections in Japan are caused by blaIMP-positive Enterobacteriaceae (especially blaIMP-6) and infections caused by other types of carbapenemase-producing Enterobacteriaceae are quite rare. We examined drug resistance genes co-harboring with blaIMP-6 and their inoculum size effects. We screened β-lactamase genes, plasmid-mediated quinolone resistance (PMQR) genes, and aminoglycoside-modifying enzyme genes by PCR and performed sequencing for 14 blaIMP-6-positive Enterobacteriaceae. Further, all PMQR-positive isolates were submitted to conjugation and inoculum effect evaluation. Our data showed that 13 of the 14 isolates harbored CTX-M-2 and one co-harbored CTX-M-2 and CTX-M-1 as extended-spectrum β-lactamases. All isolates carried one or more PMQRs; aac(6’)-Ib-cr was the most prevalent (92.8%), and was followed by oqxA (64.3%), qnrS (50%), oqxAB (21.4%), and qnrB (14.3%). However, Klebsiella pneumoniae contains chromosomal OqxAB. Inoculum size effects were significant in all strains for meropenem, 13 strains for imipenem, 7 for levofloxacin, and 3 for amikacin. We observed that 11 of the experimental strains (100%), 8 strains (72.7%), and 1 strain showed inoculum size effects for meropenem, imipenem, and amikacin, respectively. However, four strains harbored qnr genes and two strains harbored qnr genes and QRDR mutations concurrently; no inoculum size effect was seen for levofloxacin. The blaIMP-6-positive Enterobacteriaceae that we studied was found to harbor at least one plasmid-mediated drug resistance gene. The inoculum size effect for carbapenems was thought to be mainly due to IMP-6-type metallo-β-lactamase; however qnrB and qnrS also had a minimal impact on the inoculum size effect for levofloxacin.

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Citation: Ogawa Y, Nakano R, Kasahara K, Mizuno T, Hirai N, Nakano A, et al. (2019) Comparison of the inoculum size effects of antibiotics on IMP-6 β-lactamase-producing Enterobacteriaceae co-harboring plasmid-mediated quinolone resistance genes. PLoS ONE 14(11): e0225210. https://doi.org/10.1371/journal.pone.0225210

Editor: Shampa Anupurba, Institute of Medical Sciences, Banaras Hindu University, INDIA

Received: July 22, 2019; Accepted: October 29, 2019; Published: November 13, 2019

Copyright: © 2019 Ogawa 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 relevant data are within the manuscript.

Funding: This study was supported by JSPS KAKENHI (grant number: 17K10027 and 16K09940).

Competing interests: The authors have declared that no competing interests exist.

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

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#Antibiotic use in #mandarin #production (Citrus reticulata Blanco) in major mandarin-producing areas in #Thailand: A survey assessment (PLOS One, abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Antibiotic use in mandarin production (Citrus reticulata Blanco) in major mandarin-producing areas in Thailand: A survey assessment

Sunicha Chanvatik , Siriporn Donnua , Angkana Lekagul , Wanwisa Kaewkhankhaeng , Vuthiphan Vongmongkol , Pornpimon Athipunyakom , Saenchai Khamlar , Maitree Prommintara , Viroj Tangcharoensathien

___

Published: November 13, 2019 / DOI: https://doi.org/10.1371/journal.pone.0225172

 

Abstract

Background

Antimicrobial resistance (AMR), one of the major global threats to human security, has serious negative consequences for both health and economies. Excessive and inappropriate uses of antibiotics are the main drivers of the emergence of resistant bacterial strains. In Thailand, antibiotics have been used in citrus production since 2012 to treat citrus greening disease or Huanglongbing disease, despite no antibiotics being registered for use in mandarin. This raises concerns about irrational use of antibiotics, which can cause AMR.

Objective

To assess the status of greening disease and the use of antibiotics in mandarin production.

Method

A face-to-face interview survey in 2017 with 221 mandarin growers in two major mandarin-producing areas.

Findings

Greening disease is one of the most serious diseases in mandarins and farmers in the two major mandarin-producing areas in Thailand used ampicillin, amoxicillin, tetracycline and penicillin to treat it. As no antibiotics are registered for use in plants, farmers used antibiotics (registered with the Thai Food and Drug Administration) for human use, either active pharmaceutical ingredients or finished products. They commonly purchased them from retail pharmacies or agrochemical suppliers. Farmers were influenced to use antibiotics by their orchard neighbours and advice from a few academics. The farmers injected antibiotics into the tree trunks approximately three to four times a year and stopped for more than two months before harvesting for in-season fruits.

Conclusion

Antibiotics registered for human use are being applied to control greening diseases. We recommend scaling up sustainable disease control measures and curtail the use of antibiotics through close and effective dialogue among ‘One Health’ partners.

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Citation: Chanvatik S, Donnua S, Lekagul A, Kaewkhankhaeng W, Vongmongkol V, Athipunyakom P, et al. (2019) Antibiotic use in mandarin production (Citrus reticulata Blanco) in major mandarin-producing areas in Thailand: A survey assessment. PLoS ONE 14(11): e0225172. https://doi.org/10.1371/journal.pone.0225172

Editor: Richard Mankin, US Department of Agriculture, UNITED STATES

Received: July 9, 2019; Accepted: October 30, 2019; Published: November 13, 2019

Copyright: © 2019 Chanvatik 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 relevant data are within the paper and its Supporting Information files.

Funding: This study was supported by funding from the Food and Agriculture Organization of the United Nations (Grant number: LOA/RAP/2017/17). The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of this manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Antibiotics; Drugs Resistance; Amoxicillin; Tetracyclines; Ampicillin; Penicillin; Plant diseases; Thailand.

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#Bedaquiline, #moxifloxacin, #pretomanid, and #pyrazinamide during the first 8 weeks of #treatment of patients with drug-susceptible or drug-resistant #pulmonary #TB:… (Lancet Resp Med., abstract)

[Source: The Lancet Respiratory Medicine, full page: (LINK). Abstract, edited.]

Bedaquiline, moxifloxacin, pretomanid, and pyrazinamide during the first 8 weeks of treatment of patients with drug-susceptible or drug-resistant pulmonary tuberculosis: a multicentre, open-label, partially randomised, phase 2b trial

Conor D Tweed, MD, Rodney Dawson, MD, Divan A Burger, PhD, Almari Conradie, MPharm, Angela M Crook, PhD, Carl M Mendel, MD, Francesca Conradie, MBBCh, Andreas H Diacon, MD, Nyanda E Ntinginya, PhD, Daniel E Everitt, MD, Frederick Haraka, MD, Mengchun Li, MD, Christo H van Niekerk, MD, Alphonse Okwera, PhD, Mohammed S Rassool, MBChB, Klaus Reither, PhD, Modulakgotla A Sebe, MBChB, Suzanne Staples, MPhil, Ebrahim Variava, MD, Melvin Spigelman, MD

Open Access / Published: November 12, 2019 / DOI: https://doi.org/10.1016/S2213-2600(19)30366-2

 

Summary

Background

New anti-tuberculosis regimens that are shorter, simpler, and less toxic than those that are currently available are needed as part of the global effort to address the tuberculosis epidemic. We aimed to investigate the bactericidal activity and safety profile of combinations of bedaquiline, pretomanid, moxifloxacin, and pyrazinamide in the first 8 weeks of treatment of pulmonary tuberculosis.

Methods

In this multicentre, open-label, partially randomised, phase 2b trial, we prospectively recruited patients with drug-susceptible or rifampicin-resistant pulmonary tuberculosis from seven sites in South Africa, two in Tanzania, and one in Uganda. Patients aged 18 years or older with sputum smear grade 1+ or higher were eligible for enrolment, and a molecular assay (GeneXpert or MTBDRplus) was used to confirm the diagnosis of tuberculosis and to distinguish between drug-susceptible and rifampicin-resistant tuberculosis. Patients who were HIV positive with a baseline CD4 cell count of less than 100 cells per uL were excluded. Patients with drug-susceptible tuberculosis were randomly assigned (1:1:1) using numbered treatment packs with sequential allocation by the pharmacist to receive 56 days of treatment with standard tuberculosis therapy (oral isoniazid, rifampicin, pyrazinamide, and ethambutol; HRZE), or pretomanid (oral 200 mg daily) and pyrazinamide (oral 1500 mg daily) with either oral bedaquiline 400 mg daily on days 1–14 then 200 mg three times per week (BloadPaZ) or oral bedaquiline 200 mg daily (B200PaZ). Patients with rifampicin-resistant tuberculosis received 56 days of the B200PaZ regimen plus moxifloxacin 400 mg daily (BPaMZ). All treatment groups were open label, and randomisation was not stratified. Patients, trial investigators and staff, pharmacists or dispensers, laboratory staff (with the exception of the mycobacteriology laboratory staff), sponsor staff, and applicable contract research organisations were not masked. The primary efficacy outcome was daily percentage change in time to sputum culture positivity (TTP) in liquid medium over days 0–56 in the drug-susceptible tuberculosis population, based on non-linear mixed-effects regression modelling of log10 (TTP) over time. The efficacy analysis population contained patients who received at least one dose of medication and who had efficacy data available and had no major protocol violations. The safety population contained patients who received at least one dose of medication. This study is registered with ClinicalTrials.gov, NCT02193776, and all patients have completed follow-up.

Findings

Between Oct 24, 2014, and Dec 15, 2015, we enrolled 180 patients with drug-susceptible tuberculosis (59 were randomly assigned to BloadPaZ, 60 to B200PaZ, and 61 to HRZE) and 60 patients with rifampicin-resistant tuberculosis. 57 patients in the BloadPaZ group, 56 in the B200PaZ group, and 59 in the HRZE group were included in the primary analysis. B200PaZ produced the highest daily percentage change in TTP (5·17% [95% Bayesian credibility interval 4·61–5·77]), followed by BloadPaZ (4·87% [4·31–5·47]) and HRZE group (4·04% [3·67–4·42]). The bactericidal activity in B200PaZ and BloadPaZ groups versus that in the HRZE group was significantly different. Higher proportions of patients in the BloadPaZ (six [10%] of 59) and B200PaZ (five [8%] of 60) groups discontinued the study drug than in the HRZE group (two [3%] of 61) because of adverse events. Liver enzyme elevations were the most common grade 3 or 4 adverse events and resulted in the withdrawal of ten patients (five [8%] in the BloadPaZ group, three [5%] in the B200PaZ group, and two [3%] in the HRZE group). Serious treatment-related adverse events affected two (3%) patients in the BloadPaZ group and one (2%) patient in the HRZE group. Seven (4%) patients with drug-susceptible tuberculosis died and four (7%) patients with rifampicin-resistant tuberculosis died. None of the deaths were considered to be related to treatment.

Interpretation

B200PaZ is a promising regimen to treat patients with drug-susceptible tuberculosis. The bactericidal activity of both these regimens suggests that they have the potential to shorten treatment, and the simplified dosing schedule of B200PaZ could improve treatment adherence in the field. However, these findings must be investigated further in a phase 3 trial assessing treatment outcomes.

Funding

TB Alliance, UK Department for International Development, Bill & Melinda Gates Foundation, US Agency for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, and the Federal Ministry for Education and Research of Germany.

Keywords: Tuberculosis; Antibiotics; Drugs Resistance; Bedaquiline; Moxifloxacin; Pretomanid; Pyrazinamide.

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High- #Risk #International #Clones of #Carbapenem-Nonsusceptible #Pseudomonas aeruginosa Endemic to #Indonesian #ICUs: Impact of a Multifaceted Infection Control Intervention Analyzed at the Genomic Level (MBio, abstract)

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

High-Risk International Clones of Carbapenem-Nonsusceptible Pseudomonas aeruginosa Endemic to Indonesian Intensive Care Units: Impact of a Multifaceted Infection Control Intervention Analyzed at the Genomic Level

Andreu Coello Pelegrin, Yulia Rosa Saharman, Aurélien Griffon, Mattia Palmieri, Caroline Mirande, Anis Karuniawati, Rudyanto Sedono, Dita Aditianingsih, Wil H. F. Goessens, Alex van Belkum, Henri A. Verbrugh, Corné H. W. Klaassen, Juliëtte A. Severin

Peter Gilligan, Editor

DOI: 10.1128/mBio.02384-19

 

ABSTRACT

Infection control effectiveness evaluations require detailed epidemiological and microbiological data. We analyzed the genomic profiles of carbapenem-nonsusceptible Pseudomonas aeruginosa (CNPA) strains collected from two intensive care units (ICUs) in the national referral hospital in Jakarta, Indonesia, where a multifaceted infection control intervention was applied. We used clinical data combined with whole-genome sequencing (WGS) of systematically collected CNPA to infer the transmission dynamics of CNPA strains and to characterize their resistome. We found that the number of CNPA transmissions and acquisitions by patients was highly variable over time but that, overall, the rates were not significantly reduced by the intervention. Environmental sources were involved in these transmissions and acquisitions. Four high-risk international CNPA clones (ST235, ST823, ST375, and ST446) dominated, but the distribution of these clones changed significantly after the intervention was implemented. Using resistome analysis, carbapenem resistance was explained by the presence of various carbapenemase-encoding genes (blaGES-5, blaVIM-2-8, and blaIMP-1-7-43) and by mutations within the porin OprD. Our results reveal for the first time the dynamics of P. aeruginosa antimicrobial resistance (AMR) profiles in Indonesia and additionally show the utility of WGS in combination with clinical data to evaluate the impact of an infection control intervention. (This study has been registered at www.trialregister.nl under registration no. NTR5541).

 

IMPORTANCE

In low-to-middle-income countries such as Indonesia, work in intensive care units (ICUs) can be hampered by lack of resources. Conducting large epidemiological studies in such settings using genomic tools is rather challenging. Still, we were able to systematically study the transmissions of carbapenem-nonsusceptible strains of P. aeruginosa (CNPA) within and between ICUs, before and after an infection control intervention. Our data show the importance of the broad dissemination of the internationally recognized CNPA clones, the relevance of environmental reservoirs, and the mixed effects of the implemented intervention; it led to a profound change in the clonal make-up of CNPA, but it did not reduce the patients’ risk of CNPA acquisitions. Thus, CNPA epidemiology in Indonesian ICUs is part of a global expansion of multiple CNPA clones that remains difficult to control by infection prevention measures.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Pseudomonas aeruginosa; ICU; Nosocomial outbreaks; Indonesia.

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#Evolution of #hypervirulence in #carbapenem-resistant #Klebsiella pneumoniae in #China: a multicentre, molecular epidemiological analysis (J Antimicrob Chemother., abstract)

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

Evolution of hypervirulence in carbapenem-resistant Klebsiella pneumoniae in China: a multicentre, molecular epidemiological analysis

Yawei Zhang, Longyang Jin, Pengwen Ouyang, Qi Wang, Ruobing Wang, Juan Wang, Hua Gao, Xiaojuan Wang, Hui Wang on behalf of the China Carbapenem-Resistant Enterobacteriaceae (CRE) Network

Journal of Antimicrobial Chemotherapy, dkz446, https://doi.org/10.1093/jac/dkz446

Published: 12 November 2019

 

Abstract

Objectives

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) have been increasingly reported in China. Here, a multicentre, longitudinal surveillance study on CR-hvKP is described.

Methods

We retrospectively investigated carbapenem-resistant K. pneumoniae (CRKP) in 56 centres across China during 2015–17 and screened the virulence genes (iucA, iroN, rmpA and rmpA2) for the presence of virulence plasmids. Hypermucoviscosity, serum killing and Galleria mellonella lethality experiments were conducted to identify CR-hvKP among strains with all four virulence genes. Capsule typing, fitness and plasmid features of CR-hvKP were also investigated.

Results

A total of 1052 CRKP were collected. Among these, 34.2% (360/1052) carried virulence genes and 72 of them had all four of the virulence genes tested. Fifty-five (76.4%) were considered to be CR-hvKP using the G. mellonella infection model, with KPC-2-producing K64-ST11 being the most common type (80%, 44/55). Prevalence of CR-hvKP differed greatly between regions, with the highest in Henan (25.4%, 17/67) and Shandong (25.8%, 25/97). A significant increase in CR-hvKP among KPC-2-producing ST11 strains was observed, from 2.1% (3/141) in 2015 to 7.0% (23/329) in 2017 (P = 0.045). Alarmingly, compared with classic CRKP, no difference in growth was found among CR-hvKP (P = 0.7028), suggesting a potential risk for dissemination. The hybrid virulence and resistance-encoding plasmid evolved from pLVPK and the resistance plasmid harbouring blaKPC-2, indicating evolution existed between the hypervirulence and hyper-resistance plasmid.

Conclusions

CR-hvKP were more frequently detected than previously assumed, especially among KPC-2-producing ST11. Dissemination of hypervirulence could be extremely rapid due to limited fitness cost. Also, the evolution of resistance genes into hypervirulence plasmids was identified, presenting significant challenges for public health and infection control.

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; Carbapenem; Klebsiella pneumoniae; Plasmids; China.

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