C H A P T E R 9
Antibiotics
95
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
Treatment of serious gram-negative
infections
framycetin (Soframycin)
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.
Treatment of ear and eye infections
gentamicin (generic)
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
Treatment of Pseudomonas infections
and a wide variety of gram-negative
infections
neomycin (Kenacomb,
Neosulf)
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
Suppression of GI normal flora
preoperatively; treatment of hepatic
coma; topical treatment of skin wounds
tobramycin (Tobi, Tobrex)
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
Short-term IV or IM treatment of serious
infections; ocular infections caused by
susceptible bacteria
