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

1532 failure. No dose has been established for patients in whom creatinine
clearance is <30 mL/minute, although a reduction in dosage
probably is advisable (Shi et al., 2004).
SECTION VII
CHEMOTHERAPY OF MICROBIAL DISEASES
Therapeutic Uses and Dosage. Depending on the nature
and severity of the infection, the usual oral dose of erythromycin
(erythromycin base) for adults ranges from
1-2 g per day, in equally divided and spaced amounts,
usually given every 6 hours. Erythromycin base is available
as immediate release (film-coated) and delayedrelease
(enteric-coated) tablets. Daily doses of
erythromycin as large as 8 g orally, given for 3 months,
have been well tolerated. Food should not be taken concurrently,
if possible, with erythromycin base or the
stearate formulations, but this is not necessary with erythromycin
estolate. The oral dose of erythromycin for children
is 30-50 mg/kg per day, divided into four portions;
this dose may be doubled for severe infections.
Intramuscular administration of erythromycin is not recommended
because of pain upon injection. Intravenous
administration is generally reserved for the therapy of
severe infections, such as legionellosis. The usual dose is
0.5-1 g every 6 hours; 1 g of erythromycin gluceptate (not
available in the U.S.) has been given intravenously
every 6 hours for as long as 4 weeks with no adverse
effects except for thrombophlebitis at the site of injection.
Erythromycin lactobionate is available for intravenous
injection. The combination of erythromycin and
sulfisoxazole appears to have synergistic antibacterial
activity; it is available as a suspension used primarily
for treatment of otitis media in children.
Clarithromycin (BIAXIN, others) usually is given
twice daily at a dose of 250 mg for children >12 years
and adults with mild to moderate infection. Larger
doses (e.g., 500 mg twice daily) are indicated for
more severe infection such as pneumonia or when
infection is caused by more resistant organisms such
as H. influenzae. Children <12 years old have
received 7.5 mg/kg twice daily in clinical studies. The
500-mg extended-release formulation is given as two
tablets once daily. Clarithromycin (500 mg) is also
packaged with lansoprazole (30 mg) and amoxicillin
(1 g) as a combination regimen (PREVPAC) that is
administered twice daily for 10 or 14 days to eradicate
H. pylori and to reduce the associated risk of
duodenal ulcer recurrence (Chapter 45).
Azithromycin (ZITHROMAX, other) should be given
1 hour before or 2 hours after meals when administered
orally. For outpatient therapy of community-acquired
pneumonia, pharyngitis, or skin and skin-structure infections,
a loading dose of 500 mg is given on the first day,
and then 250 mg per day is given for days 2 through 5.
A single 2-g dose of extended-release microspheres is an
alternative regimen for treatment of community-acquired
pneumonia or acute exacerbations of chronic bronchitis.
Treatment or prophylaxis of M. avium-intracellulare
infection in AIDS patients requires higher doses: 600 mg
daily in combination with one or more other agents for
treatment, or 1200 mg once weekly for primary prevention
(Kovacs and Masur, 2000). Azithromycin is useful in
treatment of sexually transmitted diseases, especially
during pregnancy when tetracyclines are contraindicated.
The treatment of uncomplicated nongonococcal urethritis
presumed to be caused by C. trachomatis consists of
a single 1-g dose of azithromycin. This dose also is
effective for chancroid. Azithromycin (1 g per week for
3 weeks) is an alternative regimen for treatment of granuloma
inguinale or lymphogranuloma venereum.
In children, the recommended dose of azithromycin
oral suspension for acute otitis media and pneumonia is
10 mg/kg on the first day (maximum: 500 mg) and
5 mg/kg (maximum: 250 mg per day) on days 2 through
5. A single 30 mg/kg dose is approved as an alternative
for otitis media. The dose for tonsillitis or pharyngitis is
12 mg/kg per day, up to 500 mg total, for 5 days.
Respiratory Tract Infections. Macrolides and ketolides are suitable
drugs for the treatment of a number of respiratory tract infections
due to their activity against Streptococcus pneumoniae, Haemophilus
influenzae, and atypical pathogens (Mycoplasma, Chlamydophilia,
Legionella). Azithromycin and clarithromycin are suitable choices
for treatment of mild to moderate community-acquired pneumonia
among ambulatory patients. In hospitalized patients, a macrolide is
commonly added to a cephalosporin for coverage of atypical respiratory
pathogens. Macrolides, fluoroquinolones, and tetracyclines
are drugs of choice for treatment of pneumonia caused by Chlamydia
pneumoniae or Mycoplasma pneumoniae. Erythromycin has been
considered as the drug of choice for treatment of pneumonia caused
by L. pneumophila, L. micdadei, or other Legionella spp. Because of
excellent in vitro activity, superior tissue concentration, the ease of
administration as a single daily dose, and better tolerability compared
to erythromycin, azithromycin (or a fluoroquinolone) has supplanted
erythromycin as the first-line agent for treatment of
legionellosis (Garey and Amsden, 1999). The recommended dose is
500 mg daily, intravenously or orally, for a total of 10-14 days.
Macrolides are also appropriate alternative agents for the
treatment of acute exacerbations of chronic bronchitis, acute otitis
media, acute streptococcal pharyngitis, and acute bacterial sinusitis.
Azithromycin or clarithromycin are generally preferred to erythromycin
for these indications due to their broader spectrum and superior
tolerability.
Telithromycin has shown to be effective in the treatment of
community-acquired pneumonia, acute exacerbations of chronic
bronchitis, and acute bacterial sinusitis, and has a potential advantage
over macrolides in regions where macrolide-resistant strains are
common. However, due to a number of cases of severe hepatotoxicity
due to telithromycin, telithromycin’s U.S. FDA approval for treatment