Multidrug efflux inhibition in Acinetobacter baumannii: comparison between 1-(1-naphthylmethyl)-piperazine and phenyl-arginine-beta-naphthylamide.
OBJECTIVE
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-beta-naphthylamide (PAbetaN), 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. PAbetaN 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 PAbetaN. 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.


CONCLUSIONS
NMP can partially reverse MDR in A. baumannii and differs substantially in its activity from that of PAbetaN.
Center for Infectious Diseases and Travel Medicine, University Hospital, Freiburg, Germany.
Stefanie
S
Pannek
Paul G
PG
Higgins
Petra
P
Steinke
Daniel
D
Jonas
Murat
M
Akova
Jürgen A
JA
Bohnert
Harald
H
Seifert
Winfried V
WV
Kern
D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004151:Dipeptides / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D026901:Membrane Transport Proteins / Q000096:biosynthesis; D008826:Microbial Sensitivity Tests; D010879:Piperazines / Q000494:pharmacology*
C511391:1-(1-naphthylmethyl)piperazine; C492436:AdeA protein, Acinetobacter baumannii; C445684:AdeB protein, Acinetobacter baumannii; C492437:AdeC protein, Acinetobacter baumannii; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004151:Dipeptides; D026901:Membrane Transport Proteins; D010879:Piperazines; C419365:phenylalanine arginine beta-naphthylamide