Mechanisms of bacterial resistance to antimicrobial agents

Abstract

The mechanisms behind the development and spread of bacterial resistance to antimicrobial drugs are reviewed. The chief mechanisms by which antimicrobials act are interference with nucleic acid synthesis, binding to ribosomes, and inhibition of cell-wall synthesis and folate metabolism. Bacteria have evolved genetic and biochemical ways of resisting these antimicrobial actions. Genetic mechanisms include mutation and acquisition of new DNA. Bacteria resist antimicrobials biochemically by inactivating the drugs with beta-lactamases, acetylases, adenylases, and phosphorylases; reducing drug access sites of action by virtue of membrane characteristics; altering the drug target so that the antimicrobial no longer binds to it; bypassing the drug's metabolism; and developing tolerance. Enterococcal and staphylococcal resistance mechanisms are of particular importance clinically. There are three types of enterococcal resistance: (1) intrinsic resistance to aminoglycosides, aztreonam, cephalosporins, clindamycin, imipenem, penicillin, and trimethoprim-sulfamethoxazole, (2) tolerance to all cell-wall-active antimicrobials, and (3) acquired resistance to penicillin, aminoglycosides, chloramphenicol, erythromycin, tetracycline, and vancomycin. Staphylococcal resistance to penicillins is expressed as beta-lactamase production, secretion of novel beta-lactamases, expression of novel penicillin-binding proteins (PBPs) to which penicillins bind poorly, and increased production of or altered affinity to existing PBPs. Of great concern is whether newly described glycopeptide resistance can be transferred clinically from enterococci to staphylococci. Vancomycin use is discouraged to limit the spread of glycopeptide resistance. Many mechanisms are responsible for the development and spread of antimicrobial resistance.