Telavancin: mechanisms of action, in vitro activity, and mechanisms of resistance

Clin Infect Dis. 2015 Sep 15;61 Suppl 2:S58-68. doi: 10.1093/cid/civ534.

Abstract

Telavancin is a semisynthetic lipoglycopeptide derivative of vancomycin. Telavancin has a dual mechanism of antibacterial action, disrupting peptidoglycan synthesis and cell membrane function. In 2014, the Clinical and Laboratory Standards Institute (CLSI) revised the antimicrobial susceptibility testing method for telavancin, resulting in minimum inhibitory concentration (MIC) determinations that are more accurate and reproducible and demonstrate greater in vitro potency than shown with the previous testing method. The CLSI testing method changes coincided with revised telavancin MIC interpretive break point criteria for susceptibility approved by the US Food and Drug Administration for Staphylococcus aureus (≤0.12 µg/mL), Streptococcus pyogenes (≤0.12 µg/mL), Streptococcus agalactiae (≤0.12 µg/mL), Streptococcus anginosus group (≤0.06 µg/mL), and Enterococcus faecalis (vancomycin susceptible, ≤0.25 µg/mL). Telavancin is equally potent against methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA). It demonstrates activity against isolates of heterogeneous vancomycin-intermediate S. aureus and vancomycin-intermediate S. aureus but is poorly active against vancomycin-resistant S. aureus. It also demonstrates potent activity against Staphylococcus epidermidis and Streptococcus spp. (MIC90 ≤0.03 µg/mL). Thus far, it has not been possible to select for high-level telavancin resistance in the laboratory using serially passaged clinical isolates of MRSA and MSSA.

Keywords: drug resistance; mechanism of action; methicillin-resistant Staphylococcus aureus; revised MIC break point; telavancin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoglycosides / pharmacology*
  • Aminoglycosides / therapeutic use*
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use*
  • Drug Resistance, Bacterial* / genetics
  • Enterococcus / drug effects
  • Enterococcus / genetics
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacterial Infections / drug therapy
  • Gram-Positive Bacterial Infections / microbiology
  • Humans
  • Lipoglycopeptides
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Microbial Sensitivity Tests
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / microbiology
  • Staphylococcus / drug effects
  • Staphylococcus / genetics
  • Streptococcus / drug effects
  • Streptococcus / genetics

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Lipoglycopeptides
  • telavancin