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Chemotherapy. 2010;56(2):153-7. doi: 10.1159/000313529. Epub 2010 Apr 21.

Extended spectrum of quinolone resistance, even to a potential latter third-generation agent, as a result of a minimum of two GrlA and two GyrA alterations in quinolone-resistant Staphylococcus aureus.

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1
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.

Abstract

BACKGROUND:

This study was performed to determine the extended spectrum of quinolone resistance caused by increased mutations within the target enzymes of quinolones.

METHODS:

The minimum inhibitory concentrations (MICs) for ciprofloxacin, sparfloxacin, trovafloxacin and DW286 were determined against 98 ciprofloxacin-resistant Staphylococcus aureus strains. Also, PCR-amplified grlA, grlB, gyrA and gyrB DNA fragments were sequenced and amino acid changes were analyzed.

RESULTS:

The MIC(50) values of quinolones decreased with later-generation compounds, i.e. >or=64 microg/ml for ciprofloxacin, 16 microg/ml for sparfloxacin, 2 microg/ml for trovafloxacin and 0.25 microg/ml for DW286. Combinations of amino acid changes within GrlA (Ser-80, Tyr-83 or Glu-84), GrlB (Pro-451, Pro-585 or Asp-432) and GyrA (Ser-84, Ser-85 or Glu-88) were constructed. The combination of Ser-80-->Phe within GrlA and Ser-84-->Leu within GyrA was the fundamental combination in alterations involved in ciprofloxacin resistance, and additional alterations extended quinolone resistance.

CONCLUSION:

A larger number of alterations within GrlA and GyrA further extended the spectrum of quinolone resistance.

PMID:
20407243
DOI:
10.1159/000313529
[Indexed for MEDLINE]

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