Potential utility of a peptide deformylase inhibitor (NVP PDF-713) against oxazolidinone-resistant or streptogramin-resistant Gram-positive organism isolates.
OBJECTIVE
To evaluate the potency of a novel peptide deformylase inhibitor, NVP PDF-713, against Gram-positive organisms having resistances to linezolid or quinupristin/dalfopristin.


METHODS
A total of 45 strains from three genera (six species groups) were tested by reference broth microdilution methods. The mechanism of resistance to the oxazolidinone was determined by sequencing of the gene encoding the ribosomal target.


RESULTS
NVP PDF-713 retained activity against linezolid-resistant staphylococci (MIC range 0.25-2 mg/L), Streptococcus oralis (MIC 0.5 mg/L), Enterococcus faecalis (MIC range 2-4 mg/L) and Enterococcus faecium (MIC range 0.5-4 mg/L). Quinupristin/dalfopristin-resistant E. faecium (MIC range 1-2 mg/L) and staphylococci (MIC range 0.12-2 mg/L) were also inhibited by NVP PDF-713. Many (10 of 13 strains) of the linezolid-resistant enterococci were resistant to vancomycin and these clinical strains had a G2576U ribosomal target mutation.


CONCLUSIONS
NVP PDF-713 appears to be a promising clinical candidate among the peptide deformylase inhibitors for the treatment of infections caused by Gram-positive organisms that possess resistances to oxazolidinones or streptogramin combinations.
Jones
Ronald N
RN
The JONES Group/JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USA. ronald-jones@jmilabs.com
Moet
Gary J
GJ
Sader
Helio S
HS
Fritsche
Thomas R
TR
D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000235:genetics; D009154:Mutation / Q000235:genetics; D023303:Oxazolidinones / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D011786:Quality Control; D025361:Streptogramins / Q000494:pharmacology*; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; C487638:NVP PDF 713; D023303:Oxazolidinones; D010455:Peptides; D025361:Streptogramins; D014640:Vancomycin; D000581:Amidohydrolases; C084507:peptide deformylase