TY - JOUR T1 - Molecular surveillance of rising fluoroquinolone resistance in non-invasive S. pneumoniae isolates in Belgium collected in a survey (1995-2014) JF - Plos One Y1 - 2015 A1 - Pieter-Jan Ceyssens A1 - F. Van Bambeke A1 - Sophie Bertrand A1 - Damee,S. A1 - Fux,F. A1 - Wesley Mattheus A1 - Nyssen,H.J. A1 - Van Bossuyt,E. A1 - Jan Verhaegen A1 - The Belgian Streptococcus pneumoniae study group A1 - Tulkens,P.M. A1 - R. Vanhoof KW - fluoroquinolone KW - longitudinal study KW - non-invasive infections KW - Pat A/B KW - Streptococcus pneumoniae AB -

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 MICCIP 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.

VL - 11 CP - 5 U1 -

37042

U2 - 14/12/2015;15/12/2015 M3 - 10.1371/journal.pone.0154816 ER -