JAC Advance Access originally published online on March 31, 2004
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Journal of Antimicrobial Chemotherapy (2004) 53, 804-807
© 2004 The British Society for Antimicrobial Chemotherapy
Potential utility of a peptide deformylase inhibitor (NVP PDF-713) against oxazolidinone-resistant or streptogramin-resistant Gram-positive organism isolates
1 The JONES Group/JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317; 2 Tufts University School of Medicine, Boston, MA, USA
Received 15 December 2003; returned 20 January 2004; revised 8 February 2004; accepted 13 February 2004
Objectives: To evaluate the potency of a novel peptide deformylase inhibitor, NVP PDF-713, against Gram-positive organisms having resistances to linezolid or quinupristin/dalfopristin.
Materials and 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.
Keywords: streptococci, enterococci, staphylococci, streptogramins, oxazolidinones
* Corresponding author. Tel: +1-319-665-3370; Fax: +1-319-665-3371; E-mail: ronald-jones{at}jmilabs.com
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