Streptomycin

MECHANISM OF ACTION The aminoglycoside antibiotics are rapidly bactericidal. Bacterial killing is concentration-dependent, but residual bactericidal activity persists even after the serum concentration has fallen below the minimum inhibitory concentration. These properties account for the efficacy of once-daily dosing regimens.

Driven by the membrane electrical potential (interior negative), aminoglycosides diffuse through aqueous channels formed by porin proteins in the outer membrane of gram-negative bacteria and enter the periplasmic space. This rate-limiting process (and thus the antimicrobial efficacy of aminoglycosides) can be blocked or inhibited by a reduction in pH or anaerobic conditions, as in an abscess. Once inside the cell, aminoglycosides bind to polysomes and interfere with protein synthesis by causing misreading and premature termination of mRNA translation (Figure 45-2). The resulting aberrant proteins may be inserted into the cell membrane, altering permeability and further stimulating aminoglycoside transport.

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