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Multi-year characterization of the resistance mechanisms and activity of ABT-492 against ciprofloxacin-resistant Streptococcus pneumoniae



Multi-year characterization of the resistance mechanisms and activity of ABT-492 against ciprofloxacin-resistant Streptococcus pneumoniae



Abstracts of the Interscience Conference on Antimicrobial Agents & Chemotherapy 43: 224



Background: Various resistance mechanisms, including quinolone-resistance determining region (QRDR) mutations and active efflux, have lead to the emergence of CR SPN (MIC to ciprofloxacin gtoreq4ug/ml). The aim of this study was to evaluate the new respiratory fluoroquinolones, such as ABT-492 (ABT), against CR SPN and characterize the mechanisms by which these isolates have acquired resistance. Methods: 109 CR SPN were collected over a seven year period (1997-current) from 9 of 10 Canadian provinces as a component of an ongoing national respiratory organism surveillance study, and tested for their susceptibility to ABT, ciprofloxacin (cipro), gatifloxacin (gati), gemifloxacin (gemi), levofloxacin (levo), and moxifloxacin (moxi). The QRDRs of GyrA and ParC were sequenced, and active efflux was evaluated via reserpine studies for all isolates. Results: The order of activity of the fluoroquinolones, based on MIC50 and MIC90 (ug/ml), was ABT (0.25)>gemi (0.5)>moxi (4)>gati (8)>levo (16)>cipro (32). QRDR mutations were detected in 99/109 (91%) and 54/109 (50%) of the isolates for ParC and GyrA, respectively. Reserpine-sensitive efflux (fourfold or greater reduction in MIC in the presence of reserpine) of ciprofloxacin was observed in 37/109 (34%) of the isolates. Conclusion: Of the 109 CR SPN, 91% and 50% had QRDR mutations in ParC and GyrA, respectively and 34% were ciprofloxacin efflux positive. ABT was the most active fluoroquinolone evaluated against the CR SPN isolates.

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Accession: 035349663

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