Effect of 1-(1-naphthylmethyl)-piperazine, a novel putative efflux pump inhibitor, on antimicrobial drug susceptibility in clinical isolates of Enterobacteriaceae other than Escherichia coli.
OBJECTIVE
1-(1-Naphthylmethyl)-piperazine (NMP) has been shown to reverse multidrug resistance (MDR) in Escherichia coli overexpressing RND type efflux pumps, but there is no data on its activity in Enterobacteriaceae other than E. coli.


METHODS
The antimicrobial susceptibilities of laboratory strains and 167 clinical isolates of Enterobacteriaceae to a variety of antimicrobial agents were determined in the absence and presence of NMP and, for comparison, of Phe-Arg-beta-naphthylamide (PAbetaN), another putative efflux pump inhibitor (EPI). A 4-fold or greater reduction of the MIC after EPI addition was considered significant.


RESULTS
NMP consistently reduced the MIC of linezolid in Citrobacter freundii, Enterobacter aerogenes and Klebsiella pneumoniae clinical isolates. Significant effects of NMP addition in >50% of tested isolates were also seen for levofloxacin, tetracycline and chloramphenicol in E. aerogenes, and for levofloxacin and tetracycline in K. pneumoniae, whereas no or minor effects were observed in Serratia marcescens. MDR reversal by NMP was more likely in isolates with decreased susceptibility to fluoroquinolones. In most fluoroquinolone-resistant strains the activity was sufficient to render isolates drug-susceptible at clinically achievable concentrations. The activity of PAbetaN was different from that of NMP, suggesting different modes of action of the two putative EPIs.


CONCLUSIONS
NMP has moderate activity in reversing MDR in many but not all members of the Enterobacteriaceae family including clinical isolates. Its effects on resistance reversal depend on bacterial species and drug, and are different from those seen with PAbetaN.
Schumacher
Anja
A
Center for Infectious Diseases and Travel Medicine, Department of Medicine, University Hospital, Freiburg, Germany.
Steinke
Petra
P
Bohnert
Jürgen A
JA
Akova
Murat
M
Jonas
Daniel
D
Kern
Winfried V
WV
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003470:Culture Media; D004151:Dipeptides / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial; D004755:Enterobacteriaceae / Q000187:drug effects*; D004756:Enterobacteriaceae Infections / Q000382:microbiology*; D005456:Fluorescent Dyes; D026901:Membrane Transport Proteins / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D010879:Piperazines / Q000494:pharmacology*; D011754:Pyronine
C409484:1-(2-naphthylmethyl)-4-benzylpiperazine; D000900:Anti-Bacterial Agents; D003470:Culture Media; D004151:Dipeptides; D005456:Fluorescent Dyes; D026901:Membrane Transport Proteins; D010879:Piperazines; C419365:phenylalanine arginine beta-naphthylamide; D011754:Pyronine