Symposium on antimicrobial therapyMechanisms of Resistance and Clinical Relevance of Resistance to β-Lactams, Glycopeptides, and Fluoroquinolones
Section snippets
Defining Resistance
Antimicrobial resistance and susceptibility in the clinical setting take many forms that are not predictable by in vitro susceptibility testing. For example, susceptible bacteria deep inside an abscess may not be accessible to antibiotics and therefore behave as if they are resistant. A fully susceptible organism may also act resistant if present in a biofilm attached to a foreign body. Conversely, species often considered resistant to specific antibiotics (eg, Pseudomonas aeruginosa and
Resistance to β-Lactams
β-Lactam antibiotics act by binding to cell wall synthesis enzymes known as penicillin-binding proteins (PBPs), thereby inhibiting peptidoglycan synthesis.9 Inhibition of PBPs weakens the cell wall, resulting in inhibition of cell growth and frequently in cell death. The 3 mechanisms of β-lactam resistance are reduced access to the PBPs, reduced PBP binding affinity, and destruction of the antibiotic through the expression of β-lactamase (enzymes that bind and hydrolyze β-lactams) (Table).10 In
Conclusion
Although the emergence of antimicrobial resistance is invariably associated with antimicrobial use, the multiple mechanisms of resistance, the frequency of gene exchange in the natural environment, and the nonspecific nature of many resistance mechanisms make developing resistance-specific strategies to reduce individual resistance phenotypes complicated and fraught with potential deleterious unintended consequences. Efforts to reduce overall antimicrobial exposure, for example, through
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