The treatment of bacterial infections is increasingly complicated by the ability of
bacteria to develop resistance to antimicrobial agents. Antimicrobial agents are often
categorized according to their principal mechanism of action. Mechanisms include interference
with cell wall synthesis (eg, β-lactams and glycopeptide agents), inhibition of protein
synthesis (macrolides and tetracyclines), interference with nucleic acid synthesis
(fluoroquinolones and rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole),
and disruption of bacterial membrane structure (polymyxins and daptomycin). Bacteria
may be intrinsically resistant to ≥1 class of antimicrobial agents, or may acquire
resistance by de novo mutation or via the acquisition of resistance genes from other
organisms. Acquired resistance genes may enable a bacterium to produce enzymes that
destroy the antibacterial drug, to express efflux systems that prevent the drug from
reaching its intracellular target, to modify the drug's target site, or to produce
an alternative metabolic pathway that bypasses the action of the drug. Acquisition
of new genetic material by antimicrobial-susceptible bacteria from resistant strains
of bacteria may occur through conjugation, transformation, or transduction, with transposons
often facilitating the incorporation of the multiple resistance genes into the host's
genome or plasmids. Use of antibacterial agents creates selective pressure for the
emergence of resistant strains. Herein 3 case histories—one involving Escherichia coli resistance to third-generation cephalosporins, another focusing on the emergence
of vancomycin-resistant Staphylococcus aureus, and a third detailing multidrug resistance in Pseudomonas aeruginosa—are reviewed to illustrate the varied ways in which resistant bacteria develop.
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© 2006 Association for Professionals in Infection Control and Epidemiology, Inc. and Elsevier, Inc. Published by Elsevier Inc. All rights reserved.
