title: Surveillance for linezolid resistance via the Zyvox® Annual Appraisal of Potency and Spectrum (ZAAPS) programme (2014): evolving resistance mechanisms with stable susceptibility rates.
abstract: The objective of this study was to report the linezolid in vitro activity observed during the Zyvox(®) Annual Appraisal of Potency and Spectrum (ZAAPS) programme for 2014.
  
  
  
  In total, 7541 organisms causing documented infections were consecutively collected in 66 centres in 33 countries, excluding the USA. Susceptibility testing was performed by broth microdilution. Isolates displaying linezolid MIC results of ≥4 mg/L were molecularly characterized.
  
  
  
  Linezolid inhibited all Staphylococcus aureus at ≤2 mg/L, with MIC50 results of 1 mg/L, regardless of methicillin resistance. A similar linezolid MIC50 result (i.e. 0.5 mg/L) was observed against CoNS, with the vast majority of isolates (99.4%) also inhibited at ≤2 mg/L. Six CoNS that exhibited elevated linezolid MIC values were found to contain alterations in the 23S rRNA and/or L3 ribosomal protein. Linezolid exhibited consistent modal MIC and MIC50 results (1 mg/L) against enterococci, regardless of species or vancomycin resistance. Three Enterococcus faecalis from Galway and Dublin (Ireland) and Kelantan (Malaysia) showed MIC results of 4 to 8 mg/L and carried optrA. All Streptococcus pneumoniae, viridans-group streptococci and β-haemolytic streptococci were inhibited by linezolid at ≤2, ≤2 and ≤1 mg/L, respectively, with equivalent MIC90 results (1 mg/L for all groups).
  
  
  
  These results document the continued long-term and stable in vitro potency of linezolid and reveal a limited number of isolates with decreased susceptibility to linezolid (i.e. MIC ≥4 mg/L). The latter isolates primarily showed mutations in the 23S rRNA gene and/or L3 protein, but cfr was not detected. Moreover, this study shows that isolates carrying the newly described ABC transporter optrA are not restricted to China.
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA rodrigo-mendes@jmilabs.com.
authors.forename: Rodrigo E
authors.initials: RE
authors.lastname: Mendes
authors.affiliation: Pfizer Inc., New York, NY 10017, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Hogan
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA.
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Flamm
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D062665:Epidemiological Monitoring; D014943:Global Health; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D000069349:Linezolid / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins; D000069349:Linezolid