Linezolid Surveillance Results for the United States (LEADER Surveillance Program 2014)

Antimicrob Agents Chemother. 2016 Mar 25;60(4):2273-80. doi: 10.1128/AAC.02803-15. Print 2016 Apr.

Abstract

Thelinezolidexperience andaccuratedetermination ofresistance (LEADER) surveillance program has monitored linezolid activity, spectrum, and resistance since 2004. In 2014, a total of 6,865 Gram-positive pathogens from 60 medical centers from 36 states were submitted. The organism groups evaluated wereStaphylococcus aureus(3,106), coagulase-negative staphylococci (CoNS; 797), enterococci (855),Streptococcus pneumoniae(874), viridans group streptococci (359), and beta-hemolytic streptococci (874). Susceptibility testing was performed by reference broth microdilution at the monitoring laboratory. Linezolid-resistant isolates were confirmed by repeat testing. PCR and sequencing were performed to detect mutations in 23S rRNA, L3, L4, and L22 proteins and acquired genes (cfrandoptrA). The MIC50/90forStaphylococcus aureuswas 1/1 μg/ml, with 47.2% of isolates being methicillin-resistantStaphylococcus aureus Linezolid was active against allStreptococcus pneumoniaestrains and beta-hemolytic streptococci with a MIC50/90of 1/1 μg/ml and against viridans group streptococci with a MIC50/90of 0.5/1 μg/ml. Among the linezolid-nonsusceptible MRSA strains, one strain harboredcfronly (MIC, 4 μg/ml), one harbored G2576T (MIC, 8 μg/ml), and one containedcfrand G2576T with L3 changes (MIC, ≥8 μg/ml). Among CoNS, 0.75% (six isolates) of all strains demonstrated linezolid MIC results of ≥4 μg/ml. Five of these were identified asStaphylococcus epidermidis, four of which containedcfrin addition to the presence of mutations in the ribosomal proteins L3 and L4, alone or in combination with 23S rRNA (G2576T) mutations. Six enterococci (0.7%) were linezolid nonsusceptible (≥4 μg/ml; five with G2576T mutations, including one with an additionalcfrgene, and one strain withoptrAonly). Linezolid demonstrated excellent activity and a sustained susceptibility rate of 99.78% overall.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / therapeutic use*
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Drug Resistance, Bacterial / genetics
  • Enterococcus / drug effects*
  • Enterococcus / genetics
  • Enterococcus / growth & development
  • Enterococcus / metabolism
  • Gene Expression
  • Humans
  • Linezolid / therapeutic use*
  • Microbial Sensitivity Tests
  • Mutation
  • Public Health Surveillance*
  • RNA, Ribosomal, 23S / genetics
  • RNA, Ribosomal, 23S / metabolism
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / epidemiology
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / growth & development
  • Staphylococcus aureus / metabolism
  • Streptococcal Infections / drug therapy
  • Streptococcal Infections / epidemiology
  • Streptococcal Infections / microbiology
  • Streptococcus pneumoniae / drug effects*
  • Streptococcus pneumoniae / genetics
  • Streptococcus pneumoniae / growth & development
  • Streptococcus pneumoniae / metabolism
  • United States / epidemiology

Substances

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