In vitro activity of older and newer fluoroquinolones against efflux-mediated high-level ciprofloxacin-resistant Streptococcus pneumoniae
The effect of high-level efflux activity on the MICs of fluoroquinolones against Streptococcus pneumoniae in the absence of topoisomerase mutations leading to fluoroquinolones resistance was investigated. A S. pneumoniae ATCC 46619-derived strain with high-level efflux activity was obtained (SP-25A)...
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Published in | International journal of antimicrobial agents Vol. 24; no. 2; pp. 185 - 187 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
London
Elsevier B.V
01.08.2004
Amsterdam Elsevier New York, NY |
Subjects | |
Online Access | Get full text |
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Summary: | The effect of high-level efflux activity on the MICs of fluoroquinolones against
Streptococcus pneumoniae in the absence of topoisomerase mutations leading to fluoroquinolones resistance was investigated. A
S. pneumoniae ATCC 46619-derived strain with high-level efflux activity was obtained (SP-25A). Both the parent and obtained strains were tested against efflux substrates acriflavine (Acr) and ethidium bromide (EtBr), and against norfloxacin (NFX), ciprofloxacin (CFX), levofloxacin (LFX), moxifloxacin (MFX), trovafloxacin (TVX) and sitafloxacin (SFX), in presence and absence of the efflux pump inhibitor reserpine.
gyrA,
gyrB,
parC and
parE QRDR genes were amplified by PCR and sequenced. MICs of NFX and CFX against SP-25A were 64-fold higher than parent strain MICs (256
mg/L versus 4
mg/L and 64
mg/L versus 1
mg/L, respectively). MIC of LFX increased from 1 to 4
mg/L and MICs of MFX, TVX and SFX remained virtually unchanged (0.1–0.2
mg/L). MICs of Acr and EtBr against SP-25A were 8- and 16-fold higher than against parent strains. In both cases, reserpine reverted MICs to the parent strain values (1 and 0.2
mg/L). Only
parE showed two mutations leading to a Pro
454→Ser and a Glu
443→Lys changes, which have previously been shown not to lead to significant fluoroquinolones MIC increases. SP-25A showed a significant increase of MICs of the hydrophilic fluoroquinolones, apparently derived only from efflux activity. Efflux activity, at these high levels, can lead to high-level resistance to older hydrophilic fluoroquinolones, but does affect newer fluoroquinolones such as moxifloxacin, trovafloxacin and sitafloxacin. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0924-8579 1872-7913 |
DOI: | 10.1016/j.ijantimicag.2004.01.012 |