Publications
| Moxifloxacin and gatifloxacin preferentially target GyrA in Streptococcus pneumoniae. |
Authors: L. Kilburn, K. Salim, J. Downar, B. Tong, D.E. Low, D.J. Bast, J.C.S. deAzavedo.
Background: Topoisomerase IV mutations are important for resistance to fluoroquinolones (FQ's) such as ciprofloxacin and levofloxacin which initially target ParC. Preferential binding sites and subsequent mutations selected for by newer FQ's have not been well characterized.
Method: A clinical strain of Sp containing no mutations in the quinolone-resistance determining region (QRDR) of either ParC or GyrA was sequentially subcultured in increasing concentrations of gatifloxacin (MIC 0.25-128 µg/ml), moxifloxacin (MIC 0.125-128 µg/ml), or ciprofloxacin (1-256 µg/ml) over 23 consecutive days. NCCLS guidelines were used to confirm MIC values for every increase in MIC for which the QRDR regions of ParC and GyrA were amplified and sequenced.
Results: Sequential mutations in response to increasing concentrations of moxifloxacin, gatifloxacin and ciprofloxacin are shown below:
Conclusions: Results suggest that GyrA is the preferential target site of both moxifloxacin and gatifloxacin. Gatifloxacin selected for the same substitutions in ParC and GyrA as has been found with ciprofloxacin whereas moxifloxacin selected for novel ParC substitutions.
Presented At:
40th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto, Ontario, 9/17/2000.
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1999 Microbiology Department, Mount Sinai Hospital, Toronto, ON, Canada.
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