#Pneumococcal susceptibility to #antibiotics in #carriage: a 17 year time series analysis of the adaptive #evolution of non-vaccine emerging #serotypes to a new selective pressure environment (J Antimicrob Chemother., abstract)

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

Pneumococcal susceptibility to antibiotics in carriage: a 17 year time series analysis of the adaptive evolution of non-vaccine emerging serotypes to a new selective pressure environment

Naim Ouldali, Robert Cohen, Corinne Levy, Nathalie Gelbert-Baudino, Elisa Seror. François Corrard, François Vie Le Sage, Anne-Sylvestre Michot, Olivier Romain, Stéphane Bechet, Stéphane Bonacorsi, François Angoulvant, Emmanuelle Varon

Journal of Antimicrobial Chemotherapy, dkz281, https://doi.org/10.1093/jac/dkz281

Published: 06 July 2019

 

Abstract

Background

Pneumococcal conjugate vaccine (PCV) implementations led to major changes in serotype distribution and antibiotic resistance in carriage, accompanied by changes in antibiotic consumption.

Objectives

To assess the dynamic patterns of antimicrobial non-susceptibility across non-PCV13 serotypes following PCV implementations.

Methods

We conducted a quasi-experimental interrupted time series analysis based on a 17 year French nationwide prospective cohort. From 2001 to 2018, 121 paediatricians obtained nasopharyngeal swabs from children with acute otitis media who were aged 6 months to 2 years. The main outcome was the rate of penicillin-non-susceptible pneumococci (PNSP), analysed by segmented regression.

Results

We enrolled 10 204 children. After PCV13 implementation, the PNSP rate decreased (−0.5% per month; 95% CI −0.9 to −0.1), then, after 2014, the rate slightly increased (+0.7% per month; 95% CI +0.2 to +1.2). Global antibiotic use within the previous 3 months decreased over the study period (−22.2%; 95% CI −33.0 to −11.3), but aminopenicillin use remained high. Among the main non-PCV13 serotypes, four dynamic patterns of penicillin susceptibility evolution were observed, including unexpected patterns of serotypes emerging while remaining or even becoming penicillin susceptible. In contrast to PNSP strains, for these latter patterns, the rate of co-colonization with Haemophilus influenzae increased concomitant with their emergence.

Conclusions

In a context of continuing high antibiotic selective pressure, a progressive increase in PNSP rate was observed after 2014. However, we highlighted an unexpected variability in dynamic patterns of penicillin susceptibility among emerging non-PCV13 serotypes. Antibiotic resistance may not be the only adaptive mechanism to antimicrobial selective pressure, and co-colonization with H. influenzae may be involved.

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; Penicillin; Streptococcus pneumoniae; Vaccines; Haemophilus Influenzae.

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The #history, #genome and #biology of NCTC 30: a non-pandemic #Vibrio cholerae isolate from #WW1 (Proc Roy Soc Biosci., abstract)

[Source: Proceedings of the Royal Society, Biological Sciences, full page: (LINK). Abstract, edited.]

The history, genome and biology of NCTC 30: a non-pandemic Vibrio cholerae isolate from World War One

Matthew J. Dorman, Leanne Kane, Daryl Domman, Jake D. Turnbull, Claire Cormie,Mohammed-Abbas Fazal, David A. Goulding, Julie E. Russell, Sarah Alexander
and Nicholas R. Thomson

Published: 10 April 2019 / DOI: https://doi.org/10.1098/rspb.2018.2025

 

Abstract

The sixth global cholera pandemic lasted from 1899 to 1923. However, despite widespread fear of the disease and of its negative effects on troop morale, very few soldiers in the British Expeditionary Forces contracted cholera between 1914 and 1918. Here, we have revived and sequenced the genome of NCTC 30, a 102-year-old Vibrio cholerae isolate, which we believe is the oldest publicly available live V. cholerae strain in existence. NCTC 30 was isolated in 1916 from a British soldier convalescent in Egypt. We found that this strain does not encode cholera toxin, thought to be necessary to cause cholera, and is not part of V. cholerae lineages responsible for the pandemic disease. We also show that NCTC 30, which predates the introduction of penicillin-based antibiotics, harbours a functional β-lactamase antibiotic resistance gene. Our data corroborate and provide molecular explanations for previous phenotypic studies of NCTC 30 and provide a new high-quality genome sequence for historical, non-pandemic V. cholerae.

Keywords: Antibiotics; Drugs Resistance; Penicillin; Beta-lactams; Vibrio cholerae.

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#WGS #analysis of #MDR #serotype 15A #Streptococcus pneumoniae in #Japan and the emergence of a highly resistant serotype 15A-ST9084 clone (Antimicrob Agents Chemother., abstract)

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

Whole-genome sequencing analysis of multidrug-resistant serotype 15A Streptococcus pneumoniae in Japan and the emergence of a highly resistant serotype 15A-ST9084 clone

Satoshi Nakano, Takao Fujisawa, Yutaka Ito, Bin Chang, Yasufumi Matsumura, Masaki Yamamoto, Shigeru Suga, Makoto Ohnishi, Miki Nagao

DOI: 10.1128/AAC.02579-18

 

ABSTRACT

Since the introduction of pneumococcal conjugate vaccines, an increase in the incidence of disease attributable to serotype 15A-ST63 pneumococci has been observed in many regions worldwide. We conducted a nationwide pediatric pneumococcal infection surveillance study between 2012 and 2014 in Japan. In the surveillance study, we detected multidrug-resistant serotype 15A-CC63 strains (resistant to macrolides, penicillin, cefotaxime and meropenem); in this study, we analyzed these resistant isolates to determine the dynamics and mechanism of resistance using whole-genome sequencing. In most of the penicillin-, cefotaxime- and meropenem-resistant strains, recombination occurred in the pbp2x region resulting in the acquisition of additional cefotaxime resistance to penicillin and meropenem. In the multidrug-resistant serotype 15A-CC63 strains, we identified a specific clone with ST9084, and all of the isolates were recovered from Yamaguchi prefecture in Japan. All of the serotype 15A-ST9084 isolates had a novel pbp2x-43 that was inserted by recombination events. The conserved amino acid motif profiles of pbp1a, pbp2b and pbp2x of the strains were identical to those in serotype 19A-ST320. A Bayesian analysis-based date estimation suggested that this clone emerged in approximately 2002 before the introduction of PCV in Japan. This clone should be monitored because serotype 15A is not contained in the currently used PCV13 and it was resistance to beta-lactams, which are often use in a clinical setting.

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

Keywords: Antibiotics; Drugs Resistance; Beta-lactams; Penicillin; Cefotaxime; Meropenem; S. pneumoniae; Japan.

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Y229W substitution in #NDM-1/L209F variant restores the hydrolytic activity of the enzyme towards #penicillins, #cephalosporins and #carbapenems: kinetic profile and molecular dynamic studies (Antimicrob Agents Chemother., abstract)

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

Y229W substitution in NDM-1/L209F variant restores the hydrolytic activity of the enzyme towards penicillins, cephalosporins and carbapenems: kinetic profile and molecular dynamic studies

Alessandra Piccirilli, Fabrizia Brisdelli, Massimiliano Aschi, Giuseppe Celenza, Gianfranco Amicosante, Mariagrazia Perilli

DOI: 10.1128/AAC.02270-18

 

ABSTRACT

NDM-1 enzyme is the most common metallo-β-lactamase identified in many Gram-negative bacteria causing severe nosocomial infections. The aim of this study was to focus the attention on non-active site residues, L209 and Y229, of NDM-1 and to investigate their role in the catalytic mechanism. Specifically, the effect of Y229W substitution in L209F variant was evaluated by antimicrobial susceptibility testing, kinetic and molecular dynamic (MD) studies. The Y229W single mutant and L209F/Y229W double mutant were generated by site-directed mutagenesis. The Km, kcat and kcat/Km kinetic constants, calculated for the two mutants, were compared with those of NDM-1 and L209F variants. Compared to L209F single mutant, L209F/Y229W mutant showed a remarkable increase of kcat values of 100-, 240-, 250- and 420-fold for imipenem, meropenem, benzylpenicillin and cefepime, respectively. In L209F/Y229W enzyme we observed a remarkable increase of kcat/Km of 370-, 140- and 80-fold for cefepime, meropenem and cefazolin, respectively. The same behavior was stated by antimicrobial susceptibility test. MD simulations were carried out on both L209F and L209F/Y229W enzymes complexed with benzylpenicillin focusing the attention on the overall mechanical features and on the differences between the two systems. With respect to L209F variant, the L209F/Y229W double mutant showed a mechanical stabilization of Loop 10 and N-terminal region but a destabilization of C-terminal and 149-154 regions. The epistatic effect of Y229W mutation jointly with stabilization of Loop 10 lead to a better catalytic efficiency of β-lactams. NDM numbering is used in order to facilitate the comparison with other NDM-1 studies.

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

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Beta-lactams; NDM1; Imipenem; Meropenem; Penicillins.

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Quantitative and qualitative analysis of #antimicrobial usage at #farm and #flock level on 181 #broiler farms in nine #European countries (J Antimicrob Chemother., abstract)

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

Quantitative and qualitative analysis of antimicrobial usage at farm and flock level on 181 broiler farms in nine European countries

Philip Joosten, Steven Sarrazin, Liese Van Gompel, Roosmarijn E C Luiken, Dik J Mevius, Jaap A Wagenaar, Dick J J Heederik, Jeroen Dewulf, EFFORT consortium

Journal of Antimicrobial Chemotherapy, dky498, https://doi.org/10.1093/jac/dky498

Published: 10 January 2019

 

Abstract

Objectives

To control the emerging threat of antimicrobial resistance, international policy appeals for appropriate monitoring of antimicrobial usage (AMU) at supranational, species and farm level. The aim of this study was to quantify AMU in broilers at farm and flock level in nine European countries.

Methods

Antimicrobial treatment data of one flock and purchased antimicrobials over one year were collected at 181 European broiler farms. Afterwards AMU was quantified using treatment incidence (TI) per 100 days based on Defined Daily Dose (DDDvet), Defined Course Dose (DCDvet) or Used Daily Dose (UDDvet) values. Total AMU at flock level was obtained by summing the TIDDDvet of all treatments in the sampled flock (TIDDDvetFl*).

Results

The median TIDDDvetFl* was 9.0 (95% CI 5.5–10.8), meaning that broilers were treated with antimicrobials during 9% of their rearing period. TIDDDvetFl* varied considerably within and between countries. However, in every country at least one untreated flock was present. Average TIDDDvetFl* at country level ranged from 3.3 to 36.7. Polymyxins, extended-spectrum aminopenicillins and fluoroquinolones were the most used antimicrobials, accounting for 26%, 26% and 18% of total AMU, respectively. Twenty-six percent of the farms started a treatment on day 1 of production, and 49% of overall AMU was administered within the first week.

Conclusions

Results show that rearing broilers without AMU is feasible. However, a huge variation in AMU in terms of amount, moment of administration and antimicrobial classes was observed. This shows that there is still ground to be covered when it comes to AMU on broiler farms.

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; Poultry; Polymyxins; Penicillin; Fluoroquinolones; European Region.

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Impact of #PCVs introduction on #antibiotic #resistance of #Streptococcus pneumoniae #meningitis in #children aged 5 years or younger, #Israel, 2004 to 2016 (Euro Surveill., abstract)

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

Impact of pneumococcal conjugate vaccines introduction on antibiotic resistance of Streptococcus pneumoniae meningitis in children aged 5 years or younger, Israel, 2004 to 2016

Shalom Ben-Shimol1,2, Noga Givon-Lavi1,2, David Greenberg1,2, Michal Stein3, Orli Megged4, Avihu Bar-Yochai5, Shahar Negari1,2, Ron Dagan2,on behalf of the Israel Bacteremia and Meningitis Active Surveillance Group6

Affiliations: 1 The Pediatric Infectious Disease Unit, Soroka University Medical Center, Beer-Sheva, Israel; 2 The Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; 3 Infectious Diseases and Infection Control Unit, Hillel Yaffe Medical Center, Hadera, Israel and Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel; 4 Pediatric Infectious Diseases Unit, Shaare Zedek Medical Center, affiliated with Hebrew University-Hadassah School of Medicine, Jerusalem, Israel; 5 Infectious Disease Unit, Assaf Harofe Medical Center, Zerifin, Israel; 6 Members of the Israel Bacteraemia and Meningitis Active Surveillance Group have been acknowledged at the end of the article

Correspondence:  Ron Dagan

Citation style for this article: Ben-Shimol Shalom, Givon-Lavi Noga, Greenberg David, Stein Michal, Megged Orli, Bar-Yochai Avihu, Negari Shahar, Dagan Ron,on behalf of the Israel Bacteremia and Meningitis Active Surveillance Group. Impact of pneumococcal conjugate vaccines introduction on antibiotic resistance of Streptococcus pneumoniae meningitis in children aged 5 years or younger, Israel, 2004 to 2016. Euro Surveill. 2018;23(47):pii=1800081. https://doi.org/10.2807/1560-7917.ES.2018.23.47.1800081

Received: 21 Feb 2018;   Accepted: 09 Jul 2018

 

Abstract

Background

Empiric treatment of pneumococcal meningitis includes ceftriaxone with vancomycin to overcome ceftriaxone resistant disease. The addition of vancomycin bears a risk of adverse events, including increased antibiotic resistance. We assessed antibiotic resistance rates in pneumococcal meningitis before and after pneumococcal conjugate vaccine (PCV) implementation.

Methods

All pneumococcal meningitis episodes in children aged 5 years and younger, from 2004 to 2016, were extracted from the nationwide bacteremia and meningitis surveillance database. For comparison purposes, we defined pre-PCV period as 2004–2008 and PCV13 period as 2014–2016. Minimal inhibitory concentration (MIC) > 0.06 and > 0.5 μg/mL were defined as penicillin and ceftriaxone resistance, respectively.

Results

Overall, 325 episodes were identified. Pneumococcal meningitis incidence rates declined non-significantly by 17%, comparing PCV13 and pre-PCV periods. Throughout the study, 90% of isolates were tested for antibiotic susceptibility, with 26.6%, 2.1% and 0% of isolates resistant to penicillin, ceftriaxone and vancomycin, respectively. Mean proportions (± SD) of meningitis caused by penicillin-resistant pneumococci were 40.5% ± 8.0% and 9.6% ± 7.4% in the pre-PCV and the PCV13 periods, respectively, resulting in an overall 83.9% reduction (odd ratio:0.161; 95% confidence interval: 0.059–0.441) in penicillin resistance rates. The proportions of meningitis caused by ceftriaxone resistant pneumococci were 5.0% ± 0.8% in the pre-PCV period, but no ceftriaxone resistant isolates were identified since 2010.

Conclusions

PCV7/PCV13 sequential introduction resulted in > 80% reduction of penicillin- resistant pneumococcal meningitis and complete disappearance of ceftriaxone resistant disease. These trends should be considered by the treating physician when choosing an empiric treatment for pneumococcal meningitis.

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

Keywords: S. Pneumoniae; Pneumococcal meningitis; Vaccines; Israel; Antibiotics; Drugs Resistance; Ceftriaxone; Penicillins.

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Beyond #penicillin – rapid desensitization for specific #flucloxacillin hypersensitivity (Antimicrob Agents Chemother., abstract)

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

Beyond penicillin – rapid desensitization for specific flucloxacillin hypersensitivity

J. C. Kwong, K Urbancic, J. A. Trubiano

DOI: 10.1128/AAC.01371-18

 

ABSTRACT

Beta-lactam therapy for severe staphylococcal infections is associated with superior outcomes when compared to non-beta-lactam therapy. In patients with immediate hypersensitivity to beta-lactams, desensitization has been widely employed to allow beta-lactam therapy, but published protocols for anti-staphylococcal beta-lactams such as flucloxacillin are lacking. Here, we report a case and the desensitization protocol successfully used for a patient with isolated flucloxacillin immediate hypersensitivity, where a penicillin desensitization protocol would likely have resulted in an adverse drug reaction.

© Crown copyright 2018.

The government of Australia, Canada, or the UK (“the Crown”) owns the copyright interests of authors who are government employees. The Crown Copyright is not transferable.

Keywords: Antibiotics; Staphylococcus aureus; Beta-lactams; Penicillin; Flucloxacillin.

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