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QRDR mutations and efflux activity of 87 clinical S. pneumoniae isolates collected during the MOTIV Study (2004–2005)

Abstract number: 1734_13

Knezevic I., Weskott G., Doerlemann S., Surdakowski P., Operschall E., Arvis P., Choudhri S.H., Ehlert K., Ambler J.

Objectives: This study explored the mutation pattern of 87 S. pneumoniae isolates collected during the MOTIV study before antibiotic therapy was started. Hospitalised patients with CAP (PSI classes, III, IV or V) received 400 mg IV/PO moxifloxacin (MXF) q.d. or high dose ceftriaxone (CTX) 2 g q.d. and IV/PO levofloxacin (LFX) 500 mg b.i.d. for 7–14 days. MICs were determined for MXF, LFX, CFX, clarithromycin (CLAR) and penicillin (PEN). Quinolone resistance determining regions (QRDRs) of topoisomerase II and IV and efflux of MXF, LFX and CFX were analysed.

Methods: MICs were determined by broth microdilution method (CLSI methods). The QRDRs were amplified and sequenced. Strains were tested for active efflux by the broth microdilution method with or without 10 mg/mL reserpine. Strains for which there was ≥4-fold decrease in MIC in the presence of reserpine were considered positive for reserpine-inhibited efflux.

Results: All S. pneumoniae isolates were susceptible to MXF, LFX and CFX. MXF showed the lowest MIC90 (0.25 mg/L). 15% of isolates were resistant to CLAR and 17% were intermediate or resistant to PEN. No S. pneumoniae isolate possessed a first-step mutation in Ser79 of parC or Ser81 of gyrA. New mutations were found in gyrA (Asn137Ile) and gyrB (Arg571Cys, Tyr525His and Val355Ile). Mutations were found most frequently in parE (Ile460Val) and parC (Lys137Asn). 20 (23%) strains were observed to have efflux activity; 17 of these were active on CFX, of which 4 were also active on LFX and/or MXF. 2 strains had efflux that was active on LFX but not on CFX, and one strain had efflux with activity on LFX and MXF but not on CFX. All but one isolate with efflux had the Ile460Val substitution in the parE gene.

Conclusion: No fluoroquinolone resistance or Ser79/Ser81 substitutions in parC/gyrA could be detected among 87 S. pneumoniae isolates collected during the international MOTIV study. However, 4 new mutations were found in the QRDR of gyrA and gyrB but these mutations did not influence susceptibility to fluoroquinolones. Efflux pump activity was most prominent for CXF.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Subject:
Location: ICC, Munich, Germany
Presentation type:
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