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

1518 Prophylactic Uses. Kanamycin can be administered orally as
adjunctive therapy in cases of hepatic encephalopathy. The dose is 4-
6 g/day for 36-72 hours; quantities as large as 12 g/day (in divided
doses) have been given.
Untoward Effects. Kanamycin is ototoxic and nephrotoxic. Like
neomycin, its oral administration can cause malabsorption and
superinfection. The untoward effects of the oral administration of
aminoglycosides are considered in the section on neomycin.
Neomycin
Neomycin is a broad-spectrum antibiotic. Susceptible
microorganisms usually are inhibited by concentrations
of ≤10 μg/mL. Gram-negative species that are highly
sensitive are E. coli, Enterobacter aerogenes, Klebsiella
pneumoniae, and Proteus vulgaris. Gram-positive
microorganisms that are inhibited include S. aureus and
E. faecalis. M. tuberculosis also is sensitive to
neomycin. Strains of P. aeruginosa are resistant to
neomycin. Neomycin sulfate is available for topical and
oral administration. Neomycin currently is available in
many brands of creams, ointments, and other products
alone and in combination with polymyxin, bacitracin,
other antibiotics, and a variety of corticosteroids. There
is no evidence that these topical preparations shorten
the time required for healing of wounds or that those
containing a steroid are more effective.
SECTION VII
CHEMOTHERAPY OF MICROBIAL DISEASES
Therapeutic Uses. Neomycin has been used widely for topical application
in a variety of infections of the skin and mucous membranes
caused by microorganisms susceptible to the drug. These include infections
associated with burns, wounds, ulcers, and infected dermatoses.
However, such treatment does not eradicate bacteria from the lesions.
The oral administration of neomycin (usually in combination
with erythromycin base) has been employed primarily for “preparation”
of the bowel for surgery. For therapy of hepatic encephalopathy,
an oral daily dose of 4-12 g (in divided doses) is given, provided
that renal function is normal. Because renal insufficiency is a complication
of hepatic failure and neomycin is nephrotoxic, it is used
rarely for this indication.
Neomycin and polymyxin B have been used for irrigation of
the bladder. For this purpose, 1 mL of a preparation (NEOSPORIN G.U.
IRRIGANT) containing 40 mg neomycin and 200,000 units polymyxin
B per milliliter is diluted in 1 L of 0.9% sodium chloride solution and
is used for continuous irrigation of the urinary bladder through
appropriate catheter systems. The goal is to prevent bacteriuria and
bacteremia associated with indwelling catheters. The bladder is irrigated
at the rate of 1 L every 24 hours.
Absorption and Excretion. Neomycin is poorly absorbed from the
GI tract and is excreted by the kidney, as are the other aminoglycosides.
An oral dose of 3 g produces a peak plasma concentration of
1-4 μg/mL; a total daily intake of 10 g for 3 days yields a blood concentration
below that associated with systemic toxicity if renal function
is normal. Patients with renal insufficiency may accumulate the
drug. About 97% of an oral dose of neomycin is not absorbed and is
eliminated unchanged in the feces.
Untoward Effects. Hypersensitivity reactions, primarily skin rashes,
occur in 6-8% of patients when neomycin is applied topically.
Individuals sensitive to this agent may develop cross-reactions when
exposed to other aminoglycosides. The most important toxic effects
of neomycin are renal damage and nerve deafness; as a consequence,
the drug is no longer available for parenteral administration. Toxicity
has been reported in patients with normal renal function after topical
application or irrigation of wounds with 0.5% neomycin solution.
Neuromuscular blockade with respiratory paralysis also has occurred
after irrigation of wounds or serosal cavities. Individuals treated with
4-6 g/day of the drug by mouth sometimes develop a sprue-like syndrome
with diarrhea, steatorrhea, and azotorrhea. Overgrowth of
yeasts in the intestine also may occur; this is not associated with
diarrhea or other symptoms in most cases.
CLINICAL SUMMARY
The role of aminoglycosides in the treatment of bacterial
infections has diminished steadily as alternative
drugs have become available. The aminoglycosides are
narrow-spectrum agents, with their activity limited
mainly to gram-negative aerobes. Compared with other
antibacterials, aminoglycosides are among the most
toxic, particularly if used for prolonged periods of time;
serum concentrations must be monitored to avoid drug
accumulation. These agents are first-line therapy for
only a limited number of very specific, often historically
prominent infections, such as plague, tularemia,
and tuberculosis. Gentamicin or amikacin may have a
role as a backup agent in the treatment of nosocomial
infections caused by multidrug-resistant gram-negative
pathogens such as Pseudomonas or Acinetobacter.
Gentamicin also may be useful for the treatment of serious
urinary tract infections caused by enteric organisms
that have acquired resistance to sulfa drugs, penicillins,
cephalosporins, and fluoroquinolones. Although gentamicin
has been recommended for use in combination
with vancomycin or a β-lactam to enhance bactericidal
effect (i.e., synergism), the clinical benefit of such combinations
is unproven for most infections. Because
more effective and less toxic alternatives usually are
available, aminoglycosides should be used sparingly
and reserved for specific indications. If an aminoglycoside
must be used, the duration of therapy should be
kept to a minimum to avoid toxicity, and serum concentrations
should be monitored.
BIBLIOGRAPHY
American Thoracic Society. Guidelines for the management of
adults with hospital-acquired, ventilator-associated, and
healthcare-associated pneumonia. Am J Resp Crit Care Med,
2005, 171:388–416.