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The activity of some quinolones against Stenotrophomonas maltophilia and Pseudomonas aeruginosa clinical isolates in the presence of pump inhibitors

Abstract number: 902_p492

Laudy A.E.

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Objectives:

The most common cause of multidrug resistant strains is the efflux mechanism. The presence of such efflux systems was described for Pseudomonas aeruginosa and Stenotrophomonas maltophilia. In P. Aeruginosa, the presence of three efflux systems (MexAB-OprM, MexCD-OprJ and MexEF-OprN) responsible for quinolones resistance was described. These MDR pumps belonging to the RND family are inhibited by Phe-Arg-b-naphthylamide. On the contrary, reserpine does not inhibit RND pumps. The presence of similar efflux systems was shown also in S. maltophilia (MexAB-OprM and SmeDEF). Probably, S. maltophilia has also other efflux pumps.

Methods:

In our study, activity of some quinolones (nalidixic acid, ciprofloxacin) against S. maltophilia and P. aeruginosa clinical isolates in the presence and absence of pump inhibitors was determined. The following pump inhibitors in two concentrations (20 mg/L and 80 gm/L) were used: Phe-Arg-b-naphthylamide, reserpine and omeprazol. We also looked for a new inhibitors among newly synthesised compounds, 6-(adamant-1-yl)pyrimidines.

Results:

From the studied inhibitors only Phe-Arg-b-naphthylamide affected the susceptibility of tested strains to quinolones, first of all to nalidixic acid. Generally, the presence of higher concentration of inhibitor pump (80 mg/L) increased most effectively sensitivity to nalidixic acid both S. maltophilia and P. aeruginosa. In 90% of S. maltophilia and 80% of P. aeruginosa the MIC decreased from threefold to 20-fold in the presence of Phe-Arg-b-naphthylamide. On the contrary, this inhibitor affected the MIC of ciprofloxacin only for a few strains. Moreover, Phe-Arg-b-naphthylamide alone has shown the activity against three strains of P. aeruginosa (MIC 20, 40 and 160 mg/L). The other studied pump inhibitors did not change generally the MIC of both quinolones. Unlike the inhibitory activity of Phe-Arg-b-naphthylamide agents as reserpine and omeprazole increased slightly the MIC of tested quinolones for some strains of S. maltophilia.

Conclusions:

Our data confirm that opposed to reserpine the second tested agent Phe-Arg-b-naphthylamide inhibited efflux pumps not only on P. aeruginosa but also on S. maltophilia. Moreover, obtained results indicated that depending on the structure of antibiotics the quinolones are maybe transported with different effectiveness through the efflux pumps. Additionally, it is possible that in case of S. maltophilia reserpine act antagonistically to ciprofloxacin.

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Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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