Susceptibility & Resistance
Some bacteria are not susceptible to penicillin, why?
Penicillin can not get to the site of action Gram-negative bacteria
Cell wall has a different architecture Mycoplasma, Archaea
It is actively exported from the site of action
It is inactivated and/or decomposed
-Lactamase also called penicillinase
It is a branched tricyclic, glycosylated, nonribosomal peptide produced by the Fermentation of
•Vancomycin acts by inhibiting proper cell wall synthesis in Gram-positive bacteria.
Effective against Gram-positive bacteria, such as Streptomyces, Corynebacteria, Listeria,
•Specifically, vancomycin prevents incorporation of N-acetylmuramic acid (NAM)- and N-
acetylglucosamine (NAG)-peptide subunits into the peptidoglycan matrix; which forms
the major structural component of Gram-positive cell walls.
•The large hydrophilic molecule is able to form hydrogen bond interactions with the
terminal D-alanyl-D-alanine moieties of the NAM/NAG-peptides.
•Normally this is a five-point interaction. This binding of vancomycin to the D-Ala- D-Ala
prevents the incorporation of the NAM/NAG-peptide subunits into the peptidoglycan
•Microbial resistance to vancomycin is a growing problem, particularly within health care
facilities such as hospitals.
•With vancomycin being the last-line antibiotic for serious Gram-positive infections there
is the growing prospect that resistance will result in a return to the days when fatal
bacterial infections were common.
•Vancomycin-resistant enterococci (VRE) emerged in 1987. Vancomycin-resistance
emerged in more common pathogenic organisms during the 1990s and 2000s, including
vancomycin-intermediate Staphylococcus aureus (VISA), vancomycinresistant
Staphylococcus aureus (VRSA), and vancomycin-resistant Clostridium difficile.