Chapter 54: Aminoglycosides

INTRODUCTION

The aminoglycoside group includes gentamicin, tobramycin, amikacin, netilmicin (not available in the U.S.), kanamycin, streptomycin, paromomycin, and neomycin. These drugs are used primarily to treat infections caused by aerobic gram-negative bacteria; streptomycin is an important agent for the treatment of tuberculosis, and paromomycin is used orally for intestinal amebiasis and in the management of hepatic coma. In contrast to most inhibitors of microbial protein synthesis, which are bacteriostatic, the aminoglycosides are bactericidal inhibitors of protein synthesis. Mutations affecting proteins in the bacterial ribosome, the target for these drugs, can confer marked resistance to their action. However, most commonly resistance is due to acquisition of plasmids or transposon-encoding genes for aminoglycoside-metabolizing enzymes or from impaired transport of drug into the cell. Thus, there can be cross-resistance between members of the class.

These agents contain amino sugars linked to an aminocyclitol ring by glycosidic bonds (Figure 54–1). They are polycations, and their polarity is responsible in part for pharmacokinetic properties shared by all members of the group. For example, none is absorbed adequately after oral administration, inadequate concentrations are found in cerebrospinal fluid (CSF), and all are excreted relatively rapidly by the normal kidney. Although aminoglycosides are widely used and important agents, serious toxicity limits their utility. All members of the group share the same spectrum of toxicity, most notably nephrotoxicity and ototoxicity, which can involve the auditory and vestibular functions of the eighth cranial nerve.