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- Title
TR-700 in vitro activity against and resistance mutation frequencies among Gram-positive pathogens.
- Authors
Ronald N. Jones; Gary J. Moet; Helio S. Sader; Rodrigo E. Mendes; Mariana Castanheira
- Abstract
Background TR-700, the active component of the oxazolidinone prodrug TR-701, has demonstrated potent activity against numerous Gram-positive species. In this study, single-step mutation frequencies, passaging and the activity of TR-700 were tested against a worldwide collection of linezolid-non-susceptible organisms and matched controls. Methods One hundred and twenty linezolid-non-susceptible and 120 controls matched by genus/species, geographic origin, site of infection and time were susceptibility tested by reference broth microdilution methods. Species of isolates were: Enterococcus faecalis (16 linezolid non-susceptible/16 wild-type strains); Enterococcus faecium (55/55), Staphylococcus aureus (8/8); coagulase-negative staphylococci (at least 7 spp., 40/40) and viridans group streptococci (2 spp., 1/1). 23S rRNA target mutations or cfr genes were detected by PCR and sequencing. Results Among linezolid-non-susceptible strains, the resistance mechanisms were G2576T (109), cfr (4) and unknown (7), with strains originating from Europe, Far East and North and South America. Most strains were multidrug-resistant and cfr isolates exhibited co-resistance to phenicols, clindamycin, linezolid, pleuromutilins and streptogramin B. TR-700 MIC values, regardless of species, were 4–32-fold lower than those of linezolid. TR-700 MIC results were ≤4, ≤8 or ≤16 mg/L for 88%, 96% and >99% of linezolid-non-susceptible strains, respectively. Spontaneous single-step mutations were undetected ( Conclusions TR-700 exhibited enhanced activity against linezolid-non-susceptible and wild-type control strains of Gram-positive cocci. A significant number (nearly 90%) of linezolid-non-susceptible strains were inhibited by potentially achievable levels (≤4 mg/L) of TR-700. All strains with the emerging cfr-mediated resistance determinant had TR-700 MIC results at ≤8 mg/L.
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2009, Vol 63, Issue 4, p716
- ISSN
0305-7453
- Publication type
Academic Journal
- DOI
10.1093/jac/dkp021