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

Gonococcal Infections. Gonococci gradually have become more
resistant to penicillin G, and penicillins are no longer the therapy of
choice, unless it is known that gonococcal strains in a particular geographic
area are susceptible. Uncomplicated gonococcal urethritis
is the most common infection, and a single intramuscular injection
of 250 mg ceftriaxone is the recommended treatment (Handsfield
and Sparling, 2005).
Gonococcal arthritis, disseminated gonococcal infections
with skin lesions, and gonococcemia should be treated with ceftriaxone
1 g daily given either intramuscularly or intravenously for
7-10 days. Ophthalmia neonatorum also should be treated with ceftriaxone
for 7-10 days (25-50 mg/kg per day intramuscularly or
intravenously).
Syphilis. Therapy of syphilis with penicillin G is highly effective.
Primary, secondary, and latent syphilis of <1-year duration may be
treated with penicillin G procaine (2.4 million units per day intramuscularly)
plus probenecid (1.0 g/day orally) for 10 days or with
1-3 weekly intramuscular doses of 2.4 million units of penicillin G
benzathine (three doses in patients with HIV infection). Patients with
late latent syphilis, neurosyphilis, or cardiovascular syphilis may be
treated with a variety of regimens. Because the latter two conditions
are potentially lethal and their progression can be halted (but not
reversed), intensive therapy with 20 million units of penicillin G
daily for 10 days is recommended. There are no proven alternatives
for treating syphilis in pregnant women, so penicillin-allergic individuals
must be acutely desensitized to prevent anaphylaxis (Centers
for Disease Control and Prevention, 2006).
Infants with congenital syphilis discovered at birth or during the
postnatal period should be treated for at least 10 days with 50,000 units/kg
daily of aqueous penicillin G in two divided doses or 50,000 units/kg of
procaine penicillin G in a single daily dose (Tramont, 2005).
Most patients (70-90%) with secondary syphilis develop the
Jarisch-Herxheimer reaction. This also may be seen in patients
with other forms of syphilis. Several hours after the first injection
of penicillin, chills, fever, headache, myalgias, and arthralgias may
develop. The syphilitic cutaneous lesions may become more prominent,
edematous, and brilliant in color. Manifestations usually persist
for a few hours, and the rash begins to fade within 48 hours. It
does not recur with the second or subsequent injections of penicillin.
This reaction is thought to be due to release of spirochetal
antigens with subsequent host reactions to the products. Aspirin
gives symptomatic relief, and therapy with penicillin should not
be discontinued.
Actinomycosis. Penicillin G is the agent of choice for the treatment of
all forms of actinomycosis. The dose should be 10-20 million units
of penicillin G intravenously per day for 6 weeks. Some physicians
continue therapy for 2-3 months with oral penicillin V (500 mg four
times daily). Surgical drainage or excision of the lesion may be necessary
before cure is accomplished.
Diphtheria. There is no evidence that penicillin or any other antibiotic
alters the incidence of complications or the outcome of diphtheria;
specific antitoxin is the only effective treatment. However,
penicillin G eliminates the carrier state. The parenteral administration
of 2-3 million units per day in divided doses for 10-12 days
eliminates the diphtheria bacilli from the pharynx and other sites in
practically 100% of patients. A single daily injection of penicillin G
procaine for the same period produces comparable results.
Anthrax. Strains of Bacillus anthracis resistant to penicillin have
been recovered from human infections. When penicillin G is used,
the dose should be 12-20 million units per day.
Clostridial Infections. Penicillin G is the agent of choice for gas gangrene;
the dose is in the range of 12-20 million units per day given
parenterally as an adjunct to the antitoxin. Adequate debridement of
the infected areas is essential. Antimicrobial drugs probably have no
effect on the ultimate outcome of tetanus. Débridement and administration
of human tetanus immune globulin may be indicated. Penicillin
is administered, however, to eradicate the vegetative forms of the bacteria
that may persist.
Fusospirochetal Infections. Gingivostomatitis, produced by the synergistic
action of Leptotrichia buccalis and spirochetes that are present
in the mouth, is readily treatable with penicillin. For simple
“trench mouth,” 500 mg penicillin V given every 6 hours for several
days is usually sufficient to clear the disease.
Rat-Bite Fever. The two microorganisms responsible for this infection,
Spirillum minor in the Far East and Streptobacillus moniliformis
in America and Europe, are sensitive to penicillin G, the therapeutic
agent of choice. Because most cases due to Streptobacillus are complicated
by bacteremia and, in many instances, by metastatic infections,
especially of the synovia and endocardium, the dose should
be large; a daily dose of 12-15 million units given parenterally for
3-4 weeks has been recommended.
Listeria Infections. Ampicillin (with gentamicin for immunosuppressed
patients with meningitis) and penicillin G are the drugs of
choice in the management of infections owing to L. monocytogenes.
The recommended dose of ampicillin is 1-2 g intravenously
every 4 hours. The recommended dose of penicillin G is 15-20 million
units parenterally per day for at least 2 weeks. When endocarditis
is the problem, the dose is the same, but the duration of treatment
should be no less than 4 weeks.
Lyme Disease. Although a tetracycline is the usual drug of choice for
early disease, amoxicillin is effective; the dose is 500 mg three times
daily for 21 days. Severe disease is treated with a third-generation
cephalosporin or up to 20 million units of intravenous penicillin G
daily for 10-14 days.
Erysipeloid. The causative agent of this disease, Erysipelothrix rhusiopathiae,
is sensitive to penicillin. The uncomplicated infection
responds well to a single injection of 1.2 million units of penicillin
G benzathine. When endocarditis is present, penicillin G, 12-20 million
units per day, has been found to be effective; therapy should be
continued for 4-6 weeks.
Pasteurella multocida. Pasteurella multocida is the cause of wound
infections after a cat or dog bite. It is uniformly susceptible to penicillin
G and ampicillin and resistant to penicillinase-resistant penicillins and
first-generation cephalosporins (Goldstein et al., 1988). When the
infection causes meningitis, a third-generation cephalosporin is preferred
because the MICs are slightly lower than for penicillin.
Prophylactic Uses of the Penicillins. The demonstrated effectiveness
of penicillin in eradicating microorganisms was followed quickly and
quite naturally by attempts to prove that it also was effective in preventing
infection in susceptible hosts. As a result, the antibiotic has
been administered in almost every situation in which a risk of bacterial
invasion has been present. As prophylaxis has been investigated
1485
CHAPTER 53
PENICILLINS, CEPHALOSPORINS, AND OTHER β-LACTAM ANTIBIOTICS