ZAAPS Program results for 2015: an activity and spectrum analysis of linezolid using clinical isolates from medical centres in 32 countries

J Antimicrob Chemother. 2017 Nov 1;72(11):3093-3099. doi: 10.1093/jac/dkx251.

Abstract

Objectives: To report the linezolid in vitro activity obtained during the 2015 ZAAPS Program.

Methods: In total, 7587 organisms causing documented infections were consecutively collected in 65 centres in 32 ex-USA countries. Broth microdilution susceptibility testing was performed. Isolates displaying linezolid MIC results of ≥ 4 mg/L were molecularly characterized.

Results: Linezolid inhibited >99.9% of Staphylococcus aureus at ≤ 2 mg/L, with MIC50 results of 1 mg/L, regardless of methicillin resistance. A similar linezolid MIC50 result (0.5 mg/L) was observed for CoNS, with the vast majority of isolates (99.7%) also inhibited at ≤ 2 mg/L. Three CoNS (linezolid MIC, 16-64 mg/L) from Italy were found to contain alterations in the 23S rRNA and/or L3/L4 ribosomal proteins. One isolate also harboured cfr. Linezolid exhibited consistent modal MIC and MIC50 results (1 mg/L) for enterococci regardless of species or vancomycin resistance. One Enterococcus faecalis (linezolid MIC, 8 mg/L) from Galway, Ireland, carried optrA. One Enterococcus faecium (linezolid MIC, 16 mg/L) from Italy contained a G2576T mutation in the 23S rRNA. 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).

Conclusions: These results document the continued long-term and stable in vitro potency of linezolid and a limited number of isolates with decreased susceptibility to linezolid (MIC, ≥4 mg/L). The latter isolates showed primarily mutations in the 23S rRNA gene and/or L3/L4 proteins, with plasmid-mediated resistance (cfr and optrA) also present, albeit at a low prevalence.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Asia / epidemiology
  • Canada / epidemiology
  • Drug Resistance, Bacterial / genetics
  • Enterococcus faecalis / drug effects
  • Enterococcus faecalis / genetics
  • Enterococcus faecalis / isolation & purification
  • Epidemiological Monitoring*
  • Europe / epidemiology
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacteria / genetics
  • Gram-Positive Bacteria / isolation & purification*
  • Gram-Positive Bacterial Infections / drug therapy
  • Gram-Positive Bacterial Infections / epidemiology
  • Hospitals
  • Humans
  • Internationality
  • Intersectoral Collaboration
  • Linezolid / pharmacology*
  • Microbial Sensitivity Tests
  • Plasmids
  • RNA, Ribosomal, 23S / genetics
  • South America / epidemiology
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / isolation & purification
  • Streptococcus pneumoniae / drug effects
  • Streptococcus pneumoniae / genetics
  • Streptococcus pneumoniae / isolation & purification

Substances

  • Anti-Bacterial Agents
  • RNA, Ribosomal, 23S
  • Linezolid