Antimicrobial activities of seven novel tetramethylpiperidine-substituted phenazines against multiple-drug-resistant Gram-positive bacteria.
BACKGROUND
A dramatic increase in multiple-drug-resistant (MDR) Gram-positive pathogens has occurred in recent times, leading to increased rates or morbidity and mortality and also associated with high costs for the treatment of these infections. It is clear that there is an urgent need for the development of effective antimicrobial agents. The anti-bacterial activity of seven 2,2,6,6-tetramethylpiperidine (TMP)-substituted phenazines, compared to clofazimine (B663), were tested against 70 clinical isolates of methicillin-resistant Staphylococcus aureus, MDR Streptococcus pneumoniae and resistant Enterococcus sp.


METHODS
Standard minimum inhibitory concentration agar dilution susceptibility tests were done on all isolates, including ATCC control strains.


RESULTS
All the TMP-substituted phenazines were more active than clofazimine against all isolates tested. Compound B4125 was the most active by inhibiting all growth of the organisms tested, including vancomycin-resistant Enterococcus faecium.


CONCLUSIONS
Clofazimine has been shown to have anti-staphylococcal activity. We demonstrate enhanced anti-bacterial activity of TMP-substituted phenazines against drug-resistant Gram-positive organisms compared to clofazimine.
Huygens
Flavia
F
Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, South Africa. f.huygens@qut.edu.au
O'Sullivan
John F
JF
van Rensburg
Constance E J
CE
D002991:Clofazimine / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D016983:Enterococcus / Q000187:drug effects*; D007917:Leprostatic Agents / Q000494:pharmacology; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D010619:Phenazines / Q000494:pharmacology*; D010880:Piperidines / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013296:Streptococcus pneumoniae / Q000187:drug effects*
D007917:Leprostatic Agents; D010619:Phenazines; D010880:Piperidines; D002991:Clofazimine