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This chapter will be most useful after having a basic understanding of the material in Chapter 54, Aminoglycosides in Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12th Edition. In addition to the material presented here, the 12th Edition contains:

  • Figure 54-1 which shows the sites of activity of various plasmid-mediated enzymes capable of inactivating aminoglycosides

  • Table 54-1 which provides the minimal inhibitory concentrations of aminoglycosides that will inhibit 90% (MIC90) of clinical isolates for several bacterial species

  • Table 54-2 which provides an algorithm for dose reduction of aminoglycosides based on creatinine clearance


  • Understand aminoglycoside mechanisms of action and resistance.

  • Describe the advantages and disadvantages of multiple daily dosing versus once daily extended-interval dosing regimens for aminoglycosides.

  • Describe the rationale and the methods of plasma concentration monitoring of aminoglycoside therapy.

  • Describe the causes and clinical signs of aminoglycoside ototoxicity and nephrotoxicity and the best means of monitoring therapy to avoid these serious toxicities.

  • Understand the unique clinical differences among the aminoglycosides.


  • Amikacin

  • Gentamicin (GARAMYCIN, others)

  • Kanamycin

  • Neomycin

  • Netilmicin (NETROMYCIN)

  • Streptomycin

  • Tobramycin (TOBREX, others)


  • The aminoglycosides are rapidly bactericidal and their bacterial killing is concentration-dependent

  • Aminoglycosides exhibit a postantibiotic effect, that is, the bactericidal activity persists after serum concentration falls below the MIC

  • Duration of postantibiotic effect is also concentration-dependent

  • Inside the bacterial cell, the aminoglycosides bind to polysomes and interfere with protein synthesis by causing misreading and premature termination of mRNA translation (see Figure 40-1)


Effects of aminoglycosides on protein synthesis. A. Aminoglycoside (represented by dark grey circles) binds to the 30S ribosomal subunit and interferes with initiation of protein synthesis by fixing the 30S to 50S ribosomal complex at the start codon (AUG) of mRNA. As 30S to 50S complexes downstream complete translation of mRNA and detach, the abnormal initiation complexes, the so-called streptomycin monosomes, accumulate, blocking further translation of the message. Aminoglycoside binding to the 30S subunit also causes misreading of mRNA, leading to B, premature termination of translation with detachment of the ribosomal complex and incompletely synthesized protein or C, incorporation of incorrect amino acids (indicated by the grey X), resulting in the production of abnormal or nonfunctional proteins.


  • Failure of the aminoglycoside to penetrate the bacteria cell

  • Inactivation of the aminoglycoside by microbial enzymes

  • Low affinity of the aminoglycoside for the bacterial ribosome

The mechanisms of action and resistance of the aminoglycosides are shown in the side bars MECHANISMS OF ACTION OF AMINOGLYCOSIDE and MECHANISMS OF AMINOGLYCOSIDE RESISTANCE, respectively.

CASE 40-1

A 56-year-old woman is in hospital for the treatment of pneumonia. Her case is complicated because she acquired ...

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