Paradoxical effect of 1-(1-naphthylmethyl)-piperazine on resistance to tetracyclines in multidrug-resistant Acinetobacter baumannii.
OBJECTIVE
The efflux inhibitor 1-(1-naphthylmethyl)-piperazine (NMP) has been demonstrated to reverse multidrug resistance in Acinetobacter baumannii. We investigated the interaction of NMP with tigecycline and three other tetracyclines on clinical isolates of A. baumannii.


METHODS
One hundred and four clinical isolates of Acinetobacter were tested for susceptibility to tigecycline, minocycline, doxycycline and tetracycline by disc diffusion, and tigecycline MICs were determined by Etest, both in the presence and absence of NMP. Tigecycline MICs and zones of inhibition were interpreted using the BSAC guidelines. An OXA carbapenemase multiplex PCR was also performed on each isolate.


RESULTS
Mean zones of inhibition for tetracycline, doxycycline and minocycline increased by 11.3%, 22.9% and 11.2%, respectively, in the presence of NMP. In contrast, tigecycline susceptibility was decreased in the presence of NMP, with mean zones of inhibition decreasing by 8.4%. Based on PCR results, all but six isolates belonged to the OXA-23 clone 1.


CONCLUSIONS
Susceptibility to tigecycline of the A. baumannii OXA-23 clone 1 prevalent in the UK is reduced (approximately 2-fold) by the presence of the efflux inhibitor NMP. NMP does not have the same effect on susceptibility to other tetracyclines.
Bean
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DC
Centre for Infectious Disease, Institute of Cell and Molecular Science, Barts and The London, Queen Mary's School of Medicine and Dentistry, London, UK.
Wareham
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DW
D000151:Acinetobacter Infections / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D010879:Piperazines / Q000494:pharmacology*; D013753:Tetracycline Resistance / Q000187:drug effects*; D013754:Tetracyclines / Q000494:pharmacology*; D006113:United Kingdom
C511391:1-(1-naphthylmethyl)piperazine; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D010879:Piperazines; D013754:Tetracyclines