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

of acute exacerbations of chronic bronchitis and sinusitis have been
rescinded, leaving only its indication for community-acquired pneumonia.
Because of the substantial risk of serious hepatotoxicity,
telithromycin should be used only in circumstances where it provides
a substantial advantage over less toxic therapies.
Skin and Soft-Tissue Infections. Macrolides are alternatives for treatment
of erysipelas and cellulitis among patients who have a serious
allergy to penicillin. Unfortunately, macrolide-resistant strains of
staphylococci and streptococci are increasingly encountered.
Erythromycin has been an alternative agent for the treatment of
relatively minor skin and soft-tissue infections caused by either
penicillin-sensitive or penicillin-resistant S. aureus. However, many
strains of S. aureus are resistant to macrolides, and they no longer
can be relied on unless in vitro susceptibility has been documented.
Chlamydial Infections. Chlamydial infections can be treated effectively
with any of the macrolides. A single 1-g dose of azithromycin
is recommended for patients with uncomplicated urethral, endocervical,
rectal, or epididymal infections because of the ease of compliance.
During pregnancy, erythromycin base, 500 mg four times daily
for 7 days, is recommended as first-line therapy for chlamydial urogenital
infections. Azithromycin, 1 g orally as a single dose, is a suitable
alternative. Erythromycin base is preferred for chlamydial
pneumonia of infancy and ophthalmia neonatorum (50 mg/kg per
day in four divided doses for 10-14 days). Azithromycin, 1 g/week
for 3 weeks, may be effective for lymphogranuloma venereum.
Diphtheria. Erythromycin, 250 mg four times daily for 7 days, is
very effective for acute infections or for eradicating the carrier
state. The other macrolides also are likely to be effective; because
clinical experience with them is lacking, they are not FDAapproved
for this indication. The presence of an antibiotic does
not alter the course of an acute infection with the diphtheria bacillus
or the risk of complications. Antitoxin is indicated in the treatment
of acute infection.
Pertussis. Erythromycin is the drug of choice for treating persons
with B. pertussis disease and for postexposure prophylaxis of household
members and close contacts. A 7-day regimen of erythromycin
estolate (40 mg/kg per day; maximum: 1 g/day; not available in U.S)
is as effective as the 14-day regimens traditionally recommended
(Halperin et al., 1997). Clarithromycin and azithromycin also are
effective (Bace et al., 1999). If administered early in the course of
whooping cough, erythromycin may shorten the duration of illness;
it has little influence on the disease once the paroxysmal stage is
reached, although it may eliminate the microorganisms from the
nasopharynx. Nasopharyngeal cultures should be obtained from people
with pertussis who do not improve with erythromycin therapy
because resistance has been reported.
Campylobacter Infections. The treatment of gastroenteritis caused by
C. jejuni with erythromycin (250-500 mg orally four times a day for
7 days) hastens eradication of the microorganism from the stools and
reduces the duration of symptoms. Availability of fluoroquinolones,
which are highly active against Campylobacter species and other
enteric pathogens, largely has replaced the use of erythromycin for
this disease in adults. Erythromycin remains useful for treatment of
Campylobacter gastroenteritis in children.
Helicobacter pylori Infection. Clarithromycin, 500 mg, in combination
with omeprazole, 20 mg, and amoxicillin, 1 g (PREVPAC), each
administered twice daily for 10-14 days, is effective for treatment
of peptic ulcer disease caused by H. pylori (Peterson et al., 2000).
Numerous other regimens, some effective as 7-day treatments, have
been studied and also are effective. The more effective regimens generally
include three agents, one of which usually is clarithromycin
(Chapter 45).
Mycobacterial Infections. Clarithromycin or azithromycin is recommended
as first-line therapy for prophylaxis and treatment of disseminated
infection caused by M. avium-intracellulare in AIDS patients
and for treatment of pulmonary disease in patients not infected with
HIV (Kovacs and Masur, 2000). Azithromycin (1.2 g once weekly) or
clarithromycin (500 mg twice daily) is recommended for primary prevention
for AIDS patients with <50 CD4 cells/mm 3 . Single-agent
therapy should not be used for treatment of active disease or for secondary
prevention in AIDS patients. Clarithromycin (500 mg twice
daily) plus ethambutol (15 mg/kg once daily) with or without rifabutin
is an effective combination regimen. Azithromycin (500 mg once
daily) may be used instead of clarithromycin, but clarithromycin
appears to be slightly more efficacious (Ward et al., 1998).
Clarithromycin also has been used with minocycline for the treatment
of Mycobacterium leprae in lepromatous leprosy.
Prophylactic Uses. Penicillin is the drug of choice for the prophylaxis
of recurrences of rheumatic fever. Erythromycin is an effective alternative
for individuals who are allergic to penicillin. Clarithromycin or
azithromycin (or clindamycin) are recommended alternatives for the
prevention of bacterial endocarditis in patients undergoing dental procedures
who are at high risk for endocarditis (Wilson et al., 2007).
Untoward Effects.
Hepatoxicity. Cholestatic hepatitis is the most striking side effect.
It is caused primarily by erythromycin estolate and rarely by the ethylsuccinate
or the stearate. The illness starts after 10-20 days of treatment
and is characterized initially by nausea, vomiting, and
abdominal cramps. The pain often mimics that of acute cholecystitis.
These symptoms are followed shortly thereafter by jaundice,
which may be accompanied by fever, leukocytosis, eosinophilia, and
elevated transaminases in plasma. Biopsy of the liver reveals
cholestasis, periportal infiltration by neutrophils, lymphocytes, and
eosinophils, and occasionally, necrosis of neighboring parenchymal
cells. Findings usually resolve within a few days after cessation of
drug therapy and rarely are prolonged. The syndrome may represent
a hypersensitivity reaction to the estolate ester.
Hepatotoxicity has also been observed with clarithromycin
and azithromycin, although at a lower rate than with erythromycin.
After its regulatory approval and widespread use, a number of postmarketing
reports of severe telithromycin-induced hepatotoxicity
emerged. These cases tended to have a short latency between drug
initiation and manifestation of hepatotoxicity, with some leading to
death or liver transplantation (Brinker et al., 2009). Because of this
toxicity, telithromycin should only be used in circumstances where
it represents a clear advantage over alternative agents.
GI Toxicity. Oral administration of erythromycin, especially of
large doses, frequently is accompanied by epigastric distress, which
may be quite severe. Intravenous administration of erythromycin
may cause similar symptoms, with abdominal cramps, nausea, vomiting,
and diarrhea. Erythromycin stimulates GI motility by acting
on motilin receptors. Because of this property, erythromycin is used
postoperatively to promote peristalsis; it has been exploited to speed
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CHAPTER 55
PROTEIN SYNTHESIS INHIBITORS AND MISCELLANEOUS ANTIBACTERIAL AGENTS