In Vitro Antibacterial Activity of the Aminoglycoside Antibiotics

Abstract

The aminoglycosidic aminocyclitols are a diverse group of bactericidal antimicrobial agents that bind tightly to bacterial ribosomes and interfere with their protein synthesis. Bacteria may be resistant to these drugs because of alterations in the active transport process (which under normal conditions leads to intracellular accumulation of lethal concentrations of aminoglycosidic aminocyclitols), by the production of several types of aminoglycoside-modifying enzymes (acetyltransferases, adenylyltransferases, or phosphotransferases), or by mutations that alter ribosomal binding of these drugs. The aminoglycosides vary in their spectra of activity. Amikacin, because of its resistance to enzymatic modification, has the broadest spectrum of the clinically available aminoglycosidic aminocyclitols. A number of investigational aminoglycosides are currently being studied. Some of these, such as the fortimicins and verdamicin, are naturally occurring compounds that were discovered by standard screening techniques; others were produced by mutational biosynthesis. Chemical modification of naturally occurring or semisynthetic compounds resulted in a number of new agents with enhanced resistance to enzymatic modification by bacteria resistant to other agents.