JAC Advance Access originally published online on March 10, 2006
Journal of Antimicrobial Chemotherapy 2006 57(5):970-974; doi:10.1093/jac/dkl081
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Multidrug efflux inhibition in Acinetobacter baumannii: comparison between 1-(1-naphthylmethyl)-piperazine and phenyl-arginine-ß-naphthylamide
1 Center for Infectious Diseases and Travel Medicine, University Hospital, Freiburg, Germany; 2 Institute of Medical Microbiology, Immunology and Hygiene, University Hospital, Köln, Germany; 3 Institute of Environmental Medicine and Hospital Epidemiology, University Hospital, Freiburg, Germany; 4 Section of Infectious Diseases, Hacettepe University, Ankara, Turkey
Received 6 December 2005; returned 8 January 2006; revised 7 February 2006; accepted 22 February 2006
* Correspondence address: Medizinische Universitätsklinik, Hugstetter Strasse 55, D-79106 Freiburg, Germany. Tel: +49-761-270-1819; Fax: +49-761-270-1820; E-mail: kern{at}if-freiburg.de
Objectives: 1-(1-Naphthylmethyl)-piperazine (NMP) has been shown to reverse multidrug resistance (MDR) in Escherichia coli overexpressing RND-type efflux pumps but there are no data on its activity in non-fermenters like Acinetobacter.
Methods: Antimicrobial susceptibility in the absence and presence of NMP and, for comparison, phenyl-arginine-ß-naphthylamide (PAßN), another putative efflux pump inhibitor (EPI), was tested in laboratory and mutant strains with differing intracellular dye accumulation and expression of adeB, and in clinical isolates of Acinetobacter baumannii.
Results: Based on a 4-fold or greater MIC reduction, the effects of both EPIs at low concentrations (25 mg/L) were limited. PAßN had a highly selective action on the reduction in the MIC of rifampicin and clarithromycin. At a higher concentration of the putative EPIs (100 mg/L), NMP was more active than PAßN. This effect was not limited to strains with adeB overexpression, but affected the susceptibility to linezolid, chloramphenicol and tetracycline most, and was enhanced in clinical isolates with reduced fluoroquinolone susceptibility.
Conclusion: NMP can partially reverse MDR in A. baumannii and differs substantially in its activity from that of PAßN.
Keywords: multidrug resistance , fluoroquinolones , nosocomial pathogens
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