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Mechanisms of Bacterial Resistance to Antibiotics
Laura A. Dever, RPh;
Terence S. Dermody, MD
Arch Intern Med. 1991;151(5):886-895.
Abstract
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The three fundamental mechanisms of antimicrobial resistance are (1) enzymatic degradation of antibacterial drugs, (2) alteration of bacterial proteins that are antimicrobial targets, and (3) changes in membrane permeability to antibiotics. Antibiotic resistance can be either plasmid mediated or maintained on the bacterial chromosome. The most important mechanism of resistance to the penicillins and cephalosporins is antibiotic hydrolysis mediated by the bacterial enzyme β-lactamase. The expression of chromosomal β-lactamase can either be induced or stably derepressed by exposure to β-lactam drugs. Methods to overcome resistance to β-lactam antibiotics include the development of new antibiotics that are stable to β-lactamase attack and the coadministration of β-lactamase inhibitors with β-lactam drugs. Resistance to methicillin, which is stable to gram-positive β-lactamase, occurs through the alteration of an antibiotic target protein, penicillin-binding protein 2. Production of antibioticmodifying enzymes and synthesis of antibiotic-insensitive bacterial targets are the primary resistance mechanisms for the other classes of antibiotics, including trimethoprim, the sulfonamides, the aminoglycosides, chloramphenicol, and the quinolone drugs. Reduced antibiotic penetration is also a resistance mechanism for several classes of antibiotics, including the β-lactam drugs, the aminoglycosides, chloramphenicol, and the quinolones.
(Arch Intern Med. 1991;151:886-895)
Author Affiliations
From the Pharmacy Department, New England Medical Center (Ms Dever); Department of Microbiology and Molecular Genetics, Harvard Medical School (Dr Dermody); and Department of Medicine, Brigham and Women's Hospital (Dr Dermody), Boston, Mass. Dr Dermody is now with the Department of Pediatric Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tenn.
Footnotes
Accepted for publication October 16, 1990.
Reprint requests to Department of Pediatric Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN 37232 (Dr Dermody).
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