DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

the infusion, which falls to ~20 μg/mL 30 minutes later. The concentration
12 hours after a 7.5 mg/kg dose typically is 5-10 μg/mL. A
15 mg/kg once-daily dose produces peak concentrations 50-60
μg/mL and a trough of <1 μg/mL. For treatment of mycobacterial
infections, thrice-weekly dosing schedules of amikacin are often
used, with doses up to 25 mg/kg.
Untoward Effects. As with the other aminoglycosides, amikacin
causes ototoxicity, hearing loss, and nephrotoxicity.
Netilmicin
Netilmicin is the latest of the aminoglycosides to be marketed.
It is similar to gentamicin and tobramycin in its
pharmacokinetic properties and dosage. Its antibacterial
activity is broad against aerobic gram-negative bacilli.
Like amikacin, it is not metabolized by most of the
aminoglycoside-inactivating enzymes, and it therefore
may be active against certain bacteria that are resistant to
gentamicin.
Therapeutic Uses. Netilmicin is useful for the treatment of serious
infections owing to susceptible Enterobacteriaceae and other aerobic
gram-negative bacilli. It is effective against certain gentamicin-resistant
pathogens, with the exception of enterococci (Panwalker et al.,
1978).
The recommended dose of netilmicin for complicated urinary
tract infections in adults is 1.5-2 mg/kg every 12 hours. For other
serious systemic infections, a total daily dose of 4-7 mg/kg is administered
as a single dose or two to three divided doses. Children
should receive 3-7 mg/kg per day in two to three divided doses;
neonates receive 3.5-5 mg/kg per day as a single daily dose (Gosden
et al., 2001). The distribution and elimination of netilmicin, gentamicin,
and tobramycin are very similar. The t 1/2
for elimination is usually
2–2.5 hours in adults and increases with renal insufficiency.
Untoward Effects. As with other aminoglycosides, netilmicin also
may produce ototoxicity and nephrotoxicity. Animal models suggest
that netilmicin may be less toxic than other aminoglycosides, but
this remains to be proven in humans (Tange et al., 1995).
Streptomycin
Streptomycin is used for the treatment of certain
unusual infections generally in combination with other
antimicrobial agents. Because it generally is less active
than other members of the class against aerobic gramnegative
rods, it is rarely used.
Therapeutic Uses. Bacterial Endocarditis. Streptomycin and penicillin
in combination are synergistically bactericidal in vitro and in
animal models of infection against strains of enterococci, group D
streptococci, and the various oral streptococci of the viridans group.
The combination of penicillin G, which by itself is only bacteriostatic
against enterococci, and streptomycin is effective as bactericidal therapy
for enterococcal endocarditis. Gentamicin is generally preferred for
its lesser toxicity; also, gentamicin should be used when the strain of
enterococcus is resistant to streptomycin (MIC >2 mg/mL).
Streptomycin should be used instead of gentamicin when the strain
is resistant to the latter and susceptibility has been demonstrated to
streptomycin, which may occur because the enzymes that inactivate
these two aminoglycosides are different.
Streptomycin may be administered by deep intramuscular
injection or intravenously. Intramuscular injection may be painful,
with a hot tender mass developing at the site of injection. The dose of
streptomycin is 15 mg/kg per day for patients with creatinine clearances
>80 mL/minute. It typically is administered as a 1000-mg single
daily dose for tuberculosis or 500 mg twice daily, resulting in peak
serum concentrations of ~50-60 and 15-30 μg/mL and trough concentrations
of <1 and 5-10 μg/mL, respectively. The total daily dose
should be reduced in direct proportion to the reduction in creatinine
clearance for creatinine clearances >30 mL/minute (Table 54–2).
Tularemia. Streptomycin (or gentamicin) is the drug of choice for
the treatment of tularemia. Most cases respond to the administration
of 1-2 g (15-25 mg/kg) streptomycin per day (in divided doses) for
10-14 days. Fluoroquinolones and tetracyclines also are effective,
although the failure rate may be higher with tetracyclines.
Plague. Streptomycin is effective agent for the treatment of all forms
of plague. The recommended dose is 2 g/day in two divided doses for
10 days. Gentamicin is probably as efficacious (Boulanger et al.,
2004).
Tuberculosis. Streptomycin is a second-line agent for the treatment of
active tuberculosis, and streptomycin always should be used in combination
with at least one or two other drugs to which the causative
strain is susceptible. The dose for patients with normal renal function
is 15 mg/kg per day as a single intramuscular injection for 2-3
months and then two or three times a week thereafter.
Untoward Effects. Streptomycin has been replaced by gentamicin
for most indications because the toxicity of gentamicin is primarily
renal and reversible, whereas that of streptomycin is vestibular and
irreversible. The administration of streptomycin may produce dysfunction
of the optic nerve, including scotomas, presenting as
enlargement of the blind spot. Among the less common toxic reactions
to streptomycin is peripheral neuritis. This may be due either
to accidental injection of a nerve during the course of parenteral
therapy or to toxicity involving nerves remote from the site of
antibiotic administration.
Kanamycin
The use of kanamycin has declined markedly because
its spectrum of activity is limited compared with other
aminoglycosides, and it is among the most toxic aminoglycosides.
Kanamycin sulfate is available for injection
and oral use. The parenteral dose for adults is 15 mg/kg
per day (2-4 equally divided and spaced doses), with a
maximum of 1.5 g/day. Children may be given up to
15 mg/kg per day.
Therapeutic Uses. Kanamycin is all but obsolete, and there are few
indications for its use. Kanamycin has been employed to treat tuberculosis
in combination with other effective drugs. It has no therapeutic
advantage over streptomycin or amikacin and probably is
more toxic; either should be used instead, depending on susceptibility
of the isolate.
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CHAPTER 54
AMINOGLYCOSIDES