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Key drug.
Aminoglycosides generally are reserved for the treatment of patients with serious gram-negative infections that are resistant to other antibiotics. They normally are not used in primary care, but they are important antibiotics, and all providers should be familiar with their use. They are more potent than other antibiotics and are used systemically for serious infections. Aminoglycosides have a narrow therapeutic window, so careful dosing based on the pharmacokinetics of the drug is required. These agents are associated with significant nephrotoxicity (10% to 20%), ototoxicity (3% to 14%), and neuromuscular blockade (extremely rare). Aminoglycosides interact with β-lactam antibiotics, destroying the β-lactam ring, an amino group that renders both antibiotics inactive. They are excreted renally, so patients with impaired renal function are at increased risk for toxicity. Their use in treatment of infection is either IV or IM. Oral aminoglycosides are not absorbed; their only use is for suppression of intestinal bacteria in GI preoperative surgical preparation. Table 64-1 provides a summary of indications for each product. Aminoglycosides are used extensively in topical preparations. Topical aminoglycosides are discussed in Chapters 13 and 14 for localized treatment of the eye, skin, ear, and so forth. Nine aminoglycosides are available in the United States. Aminoglycosides were derived from a soil actinomycetes bacterium that had been systematically screened for antimicrobials. Gentamicin is a mixture of three closely related constituents.
TABLE 64-1
Indications for Aminoglycoside Agents
∗Aminoglycosides are not first-line drugs and are used only in patients with life-threatening infection.
Therapeutic Overview
Allergic reactions are rare but may include anaphylaxis, toxic epidermal necrolysis, erythema multiforme, and Stevens-Johnson syndrome.
Resistance
Resistance is rare but can occur through enzymatic inactivation. As is described in Chapter 57, mutations can result in resistance, such as resistance of Mycobacterium tuberculosis to streptomycin. A mutation has allowed many E. coli to become resistant. Resistance also may result from decreased drug uptake or efflux pump activity.
Mechanism of Action
Aminoglycosides have a six-membered ring with amino group substituents. The term aminoglycoside refers to the glycosidic bonds between the ring and amino-containing sugars. Aminoglycosides are bactericidal antibiotics that strongly and irreversibly bind to the 30S subunit of bacterial ribosomes, blocking the recognition step in protein synthesis and causing misreading of the genetic code. The ribosomes separate from messenger RNA; cell death ensues.
Treatment Principles
Aminoglycosides are used for suppression of GI bacterial flora and in the treatment of patients with hepatic coma.
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