Mechanisms of Antimicrobial Resistance in Bacteria
Section snippets
Why is resistance a concern?
There are a number of reasons why bacterial resistance should be a concern for physicians. First, resistant bacteria, particularly staphylococci, enterococci, Klebsiella pneumoniae, and Pseudomonas spp,2, 3, 4, 5, 6, 7 are becoming commonplace in healthcare institutions. Bacterial resistance often results in treatment failure, which can have serious consequences, especially in critically ill patients. Inadequate empiric antibacterial therapy, defined as the initial use of an antibacterial agent
How do antibacterial agents work?
Most antimicrobial agents used for the treatment of bacterial infections may be categorized according to their principal mechanism of action. There are 4 major modes of action: (1) interference with cell wall synthesis, (2) inhibition of protein synthesis, (3) interference with nucleic acid synthesis, and (4) inhibition of a metabolic pathway (Table 1).17
Antibacterial drugs that work by inhibiting bacterial cell wall synthesis include the β-lactams, such as the penicillins, cephalosporins,
Mechanisms of resistance to antibacterial agents
Bacteria may manifest resistance to antibacterial drugs through a variety of mechanisms. Some species of bacteria are innately resistant to ≥1 class of antimicrobial agents. In such cases, all strains of that bacterial species are likewise resistant to all the members of those antibacterial classes. Of greater concern are cases of acquired resistance, where initially susceptible populations of bacteria become resistant to an antibacterial agent and proliferate and spread under the selective
E coli: Development of Resistance to Third-Generation Cephalosporins
E coli is a common cause of urinary tract infections and bacteremia in humans, and is frequently resistant to aminopenicillins, such as amoxicillin or ampicillin, and narrow-spectrum cephalosporins.24, 25, 26 Resistance is typically mediated by the acquisition of plasmid-encoded β-lactamases, such as TEM-1, TEM-2, or SHV-1, which hydrolyze and inactivate these drugs.27 Some E coli strains develop resistance to third-generation cephalosporins and monobactams (i.e., aztreonam) through the
Summary
It is clear that bacteria will continue to develop resistance to currently available antibacterial drugs by either new mutations or the exchange of genetic information, that is, putting old resistance genes into new hosts. In many healthcare facilities around the world, bacterial pathogens that express multiple resistance mechanisms are becoming the norm, complicating treatment and increasing both human morbidity and financial costs. Prudent use of antibacterial drugs—using the appropriate drug
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