McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 9  Antibiotics

AMINOGLYCOSIDES The aminoglycosides (Table 9.1) are a group of powerful antibiotics used to treat serious infections caused by gram-negative aerobic bacilli. Because most of these drugs have potentially serious adverse effects, newer, less toxic drugs have replaced aminoglycosides in the treatment of less serious infections. Aminoglycosides include amikacin ( Amikin ), gentamicin, neomycin and tobramycin ( Tobra-Day ). Therapeutic actions and indications The aminoglycosides are bactericidal. They inhibit protein synthesis in susceptible strains of gram-negative bacteria. They irreversibly bind to a unit of the bacteria ribosomes, leading to misreading of the genetic code and cell death (Figure 9.1). These drugs are used to treat serious infections caused by susceptible strains of gram-negative bacteria, including Pseudomonas aeruginosa , E. coli , Proteus species, the Klebsiella– Enterobacter–Serratia group, Citrobacter species, and Staphylococcus species such as S. aureus. Aminoglyco- sides are indicated for the treatment of serious infections that are susceptible to penicillin when penicillin is con- traindicated, and they can be used in severe infections before culture and sensitivity tests have been completed. See Table 9.1 for usual indications for each of these drugs. Pharmacokinetics The aminoglycosides are poorly absorbed from the GI tract but rapidly absorbed after intramuscular (IM) injec- tion, reaching peak levels within 1 hour. These drugs have an average half-life of 2 to 3 hours. They are widely distributed throughout the body, cross the placenta and

enter breast milk, and are excreted unchanged in the urine (see contraindications and cautions). Amikacin is available for short-term IM or intra­ venous (IV) use. Gentamicin is available in many forms: ophthalmic, topical, IV, intrathecal, impregnated beads on surgical wire and liposomal injection. Neomycin is available in topical and oral forms. Tobramycin is used for short-term IM or IV treatment. Contraindications and cautions Aminoglycosides are contraindicated in the following conditions: known allergy to any of the aminoglyco- sides; renal or hepatic disease that could be exacerbated by toxic aminoglycoside effects and that could interfere with drug metabolism and excretion, leading to higher toxicity ; pre-existing hearing loss, which could be intensified by toxic drug effects on the auditory nerve ; active infection with herpes or mycobacterial infections that could be worsened by the effects of an aminoglyco- side on normal defence mechanisms ; myasthenia gravis or parkinsonism, which are often exacerbated by the effects of a particular aminoglycoside on the nervous system ; and breastfeeding, because aminoglycosides are excreted in breast milk and potentially could cause serious effects in the infant. Caution is necessary when these agents are admin- istered during pregnancy because aminoglycosides are used to treat only severe infections, and the benefits of the drug must be carefully weighed against potential adverse effects on the fetus. It is necessary to test urine function frequently when these drugs are used because they depend on the kidney for excretion and are toxic to the kidney.

TABLE 9.1

DRUGS IN FOCUS Aminoglycosides

Drug name

Dosage/route

Usual indications

amikacin (generic)

15 mg/kg/day IM or IV divided into two or three equal doses; reduce dose in renal failure Ear: 2–3 drops into the ear t.d.s. or q.i.d. Eye: 2 drops q 1–2 hours initially, then b.d or t.d.s. Adult: 3 mg/kg/day IM or IV in three equal doses q 8 hours; reduce dose in renal failure Paediatric: 2–2.5 mg/kg/day q 8 hours IV or IM Adult: 4–12 g/day in divided doses PO for 5–6 days Paediatric: 50–100 mg/kg/day in divided doses PO for hepatic coma Adult: 3 mg/kg/day in three equal doses IM or IV q 8 hours; reduce dose in renal failure Paediatric: 300 mg b.d. by nebuliser

Treatment of serious gram-negative infections Treatment of ear and eye infections

framycetin (Soframycin)

Treatment of Pseudomonas infections and a wide variety of gram-negative infections Suppression of GI normal flora preoperatively; treatment of hepatic coma; topical treatment of skin wounds

gentamicin (generic)

neomycin (Kenacomb, Neosulf)

tobramycin (Tobi, Tobrex)

Short-term IV or IM treatment of serious infections; ocular infections caused by susceptible bacteria