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Molecular Analysis of Rising Fluoroquinolone Resistance in Belgian Non-Invasive Streptococcus pneumoniae Isolates (1995-2014)

We present the results of a longitudinal surveillance study (1995–2014) on fluoroquinolone resistance (FQ-R) among Belgian non-invasive Streptococcus pneumoniae isolates (n = 5,602). For many years, the switch to respiratory fluoroquinolones for the treatment of (a)typical pneumonia had no impact on...

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Autores principales: Ceyssens, Pieter-Jan, Van Bambeke, Françoise, Mattheus, Wesley, Bertrand, Sophie, Fux, Frédéric, Van Bossuyt, Eddie, Damée, Sabrina, Nyssen, Henry-Jean, De Craeye, Stéphane, Verhaegen, Jan, Tulkens, Paul M., Vanhoof, Raymond
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881901/
https://www.ncbi.nlm.nih.gov/pubmed/27227336
http://dx.doi.org/10.1371/journal.pone.0154816
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author Ceyssens, Pieter-Jan
Van Bambeke, Françoise
Mattheus, Wesley
Bertrand, Sophie
Fux, Frédéric
Van Bossuyt, Eddie
Damée, Sabrina
Nyssen, Henry-Jean
De Craeye, Stéphane
Verhaegen, Jan
Tulkens, Paul M.
Vanhoof, Raymond
author_facet Ceyssens, Pieter-Jan
Van Bambeke, Françoise
Mattheus, Wesley
Bertrand, Sophie
Fux, Frédéric
Van Bossuyt, Eddie
Damée, Sabrina
Nyssen, Henry-Jean
De Craeye, Stéphane
Verhaegen, Jan
Tulkens, Paul M.
Vanhoof, Raymond
author_sort Ceyssens, Pieter-Jan
collection PubMed
description We present the results of a longitudinal surveillance study (1995–2014) on fluoroquinolone resistance (FQ-R) among Belgian non-invasive Streptococcus pneumoniae isolates (n = 5,602). For many years, the switch to respiratory fluoroquinolones for the treatment of (a)typical pneumonia had no impact on FQ-R levels. However, since 2011 we observed a significant decrease in susceptibility towards ciprofloxacin, ofloxacin and levofloxacin with peaks of 9.0%, 6.6% and 3.1% resistant isolates, respectively. Resistance to moxifloxacin arised sporadically, and remained <1% throughout the entire study period. We observed classical topoisomerase mutations in gyrA (n = 25), parC (n = 46) and parE (n = 3) in varying combinations, arguing against clonal expansion of FQ-R. The impact of recombination with co-habiting commensal streptococci on FQ-R remains marginal (10.4%). Notably, we observed that a rare combination of DNA Gyrase mutations (GyrA_S81L/GyrB_P454S) suffices for high-level moxifloxacin resistance, contrasting current model. Interestingly, 85/422 pneumococcal strains display MIC(CIP) values which were lowered by at least four dilutions by reserpine, pointing at involvement of efflux pumps in FQ-R. In contrast to susceptible strains, isolates resistant to ciprofloxacin significantly overexpressed the ABC pump PatAB in comparison to reference strain S. pneumoniae ATCC 49619, but this could only be linked to disruptive terminator mutations in a fraction of these. Conversely, no difference in expression of the Major Facilitator PmrA, unaffected by reserpine, was noted between susceptible and resistant S. pneumoniae strains. Finally, we observed that four isolates displayed intermediate to high-level ciprofloxacin resistance without any known molecular resistance mechanism. Focusing future molecular studies on these isolates, which are also commonly found in other studies, might greatly assist in the battle against rising pneumococcal drug resistance.
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spelling pubmed-48819012016-06-10 Molecular Analysis of Rising Fluoroquinolone Resistance in Belgian Non-Invasive Streptococcus pneumoniae Isolates (1995-2014) Ceyssens, Pieter-Jan Van Bambeke, Françoise Mattheus, Wesley Bertrand, Sophie Fux, Frédéric Van Bossuyt, Eddie Damée, Sabrina Nyssen, Henry-Jean De Craeye, Stéphane Verhaegen, Jan Tulkens, Paul M. Vanhoof, Raymond PLoS One Research Article We present the results of a longitudinal surveillance study (1995–2014) on fluoroquinolone resistance (FQ-R) among Belgian non-invasive Streptococcus pneumoniae isolates (n = 5,602). For many years, the switch to respiratory fluoroquinolones for the treatment of (a)typical pneumonia had no impact on FQ-R levels. However, since 2011 we observed a significant decrease in susceptibility towards ciprofloxacin, ofloxacin and levofloxacin with peaks of 9.0%, 6.6% and 3.1% resistant isolates, respectively. Resistance to moxifloxacin arised sporadically, and remained <1% throughout the entire study period. We observed classical topoisomerase mutations in gyrA (n = 25), parC (n = 46) and parE (n = 3) in varying combinations, arguing against clonal expansion of FQ-R. The impact of recombination with co-habiting commensal streptococci on FQ-R remains marginal (10.4%). Notably, we observed that a rare combination of DNA Gyrase mutations (GyrA_S81L/GyrB_P454S) suffices for high-level moxifloxacin resistance, contrasting current model. Interestingly, 85/422 pneumococcal strains display MIC(CIP) values which were lowered by at least four dilutions by reserpine, pointing at involvement of efflux pumps in FQ-R. In contrast to susceptible strains, isolates resistant to ciprofloxacin significantly overexpressed the ABC pump PatAB in comparison to reference strain S. pneumoniae ATCC 49619, but this could only be linked to disruptive terminator mutations in a fraction of these. Conversely, no difference in expression of the Major Facilitator PmrA, unaffected by reserpine, was noted between susceptible and resistant S. pneumoniae strains. Finally, we observed that four isolates displayed intermediate to high-level ciprofloxacin resistance without any known molecular resistance mechanism. Focusing future molecular studies on these isolates, which are also commonly found in other studies, might greatly assist in the battle against rising pneumococcal drug resistance. Public Library of Science 2016-05-26 /pmc/articles/PMC4881901/ /pubmed/27227336 http://dx.doi.org/10.1371/journal.pone.0154816 Text en © 2016 Ceyssens et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ceyssens, Pieter-Jan
Van Bambeke, Françoise
Mattheus, Wesley
Bertrand, Sophie
Fux, Frédéric
Van Bossuyt, Eddie
Damée, Sabrina
Nyssen, Henry-Jean
De Craeye, Stéphane
Verhaegen, Jan
Tulkens, Paul M.
Vanhoof, Raymond
Molecular Analysis of Rising Fluoroquinolone Resistance in Belgian Non-Invasive Streptococcus pneumoniae Isolates (1995-2014)
title Molecular Analysis of Rising Fluoroquinolone Resistance in Belgian Non-Invasive Streptococcus pneumoniae Isolates (1995-2014)
title_full Molecular Analysis of Rising Fluoroquinolone Resistance in Belgian Non-Invasive Streptococcus pneumoniae Isolates (1995-2014)
title_fullStr Molecular Analysis of Rising Fluoroquinolone Resistance in Belgian Non-Invasive Streptococcus pneumoniae Isolates (1995-2014)
title_full_unstemmed Molecular Analysis of Rising Fluoroquinolone Resistance in Belgian Non-Invasive Streptococcus pneumoniae Isolates (1995-2014)
title_short Molecular Analysis of Rising Fluoroquinolone Resistance in Belgian Non-Invasive Streptococcus pneumoniae Isolates (1995-2014)
title_sort molecular analysis of rising fluoroquinolone resistance in belgian non-invasive streptococcus pneumoniae isolates (1995-2014)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881901/
https://www.ncbi.nlm.nih.gov/pubmed/27227336
http://dx.doi.org/10.1371/journal.pone.0154816
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