gram positive cocci - enterococci

• enterococci

  • used to be classified as group D streptococci
  • part of the normal enteric (GI/GU) microbiota --> opportunistic pathogens w/ low virulence, rarely cause infection in healthy adults
  • infections largely seen in hospitalized pts
  • 2 most important (but not only) species are Enterococcus faecalis and Enterococcus faecium
  • intrinsically resistant to many commonly used antibiotics
  • ability to acquire additional antibiotic resistance
  • in general, E. faecium has more antibiotic resistance than E. faecalis
  • enterococci are intrinsically resistant to cephalosporins!
• enterococcal infections

  • hospital-acquired infections
  • catheter-associated bacteremia
  • UTIs
  • wound infections
  • endocarditis
  • diagnosis: culture
  • drug of choice: IV vancomycin
• threat level - serious

  • most VRE are caused by E. faecium
  • vancomycin-resistant enterococci (VRE) are a common and difficult-to-treat cause of hospital-acquired infection
• • resistance is mediated by acquisition of plasmid-mediated gene clusters called van genes
  • the mechanism described below is vanA-associated resistant (most common type)
  • resistance is mediated by substituting the D-Ala-D-Ala peptide on NAM subunits w/ D-Ala-D-Lac which have significantly lower binding affinity to vancomycin
• example of enterococcal mechanisms of resistance

  1. vancomycin resistance

  • substitution of D-Ala-D-Ala peptide on peptidoglycan precursors w/ D-Ala-D-Lac --> significantly lower binding affinity to vancomycin

  2. beta-lactam resistance

  • most E. faecium are resistant to penicillin and ampicillin due to production of PBP 5, which has low affinity for beta lactams
• example of enterococcal mechanisms of resistance (cont.)

  3. aminoglycoside resistance

  • AGs inhibt ribosomal protein synthesis
  • enterococci are intrinsically resistant to AG monotherapy but when combined w/ a second cell wall active antibiotic (ampicillin, vancomycin, etc.), they can work synergistically and allow AGs to reach their site of action
  • some enterococci can overcome AGs even when used in combination w/ a second cell wall active antibiotic
  • this is called high level resistance due to production of enzymes that inactivate AGs