Aminoglycosides: Mechanisms of Action and Resistance
The binding site of the aminoglycoside seems to be anionic structures such as the polar heads of phospholipids contained in the cytoplasmic membrane. Energy-dependent phase II is characterized by a much faster accumulation of aminoglycosides intracellularly. L. E. Bryan and H. M. Van den Elzen suggest that the interaction of the membrane-bound aminoglycosides with the ribosomal binding sites induces a change in the state of membrane energy, which facilitates entry of the antibiotics. Aminoglycosides are often combined with other antimicrobial agents in the therapy of infections, with the hope that the antibacterial effect of the combination will be greater than the expected summation of effects of the component drugs. The mechanism of synergism in enterococci appears to consist of cell wall injury induced by penicillin, which allows increased uptake of aminoglycoside by the bacterial cell. Aminoglycosides have also been combined with penicillinase-resistant penicillins in the therapy of serious S. aureus infections, such as endocarditis.