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

1484 1.5 million units every 8-12 hours. The dose of the drug must be readjusted
during dialysis and the period of progressive recovery of renal
function. If, in addition to renal failure, hepatic insufficiency also is
present, the t 1/2
will be prolonged even further.
SECTION VII
CHEMOTHERAPY OF MICROBIAL DISEASES
Therapeutic Uses
Pneumococcal Infections. Penicillin G remains the agent of choice
for the management of infections caused by sensitive strains of
S. pneumoniae. However, strains of pneumococci resistant to usual
doses of penicillin G are being isolated more frequently in several
countries, including the U.S. (Fiore et al., 2000).
Pneumococcal Pneumonia. Until it is highly likely or established that
the infecting isolate of pneumococcus is penicillin-sensitive, pneumococcal
pneumonia should be treated with a third-generation
cephalosporin or with 20-24 million units of penicillin G daily by
constant intravenous infusion. If the organism is sensitive to penicillin,
then the dose can be reduced (Medical Letter, 2007). For parenteral
therapy of sensitive isolates of pneumococci, penicillin G is
favored. Although oral treatment with 500 mg penicillin V given
every 6 hours for treatment of pneumonia owing to penicillin-sensitive
isolates has been used with success in this disease, it cannot be
recommended for routine initial use because of the existence of
resistance. Therapy should be continued for 7-10 days, including
3-5 days after the patient’s temperature has returned to normal.
Pneumococcal Meningitis. Until it is established that the infecting pneumococcus
is sensitive to penicillin, pneumococcal meningitis should
be treated with a combination of vancomycin and a third-generation
cephalosporin (Catalan et al., 1994; John, 1994). Dexamethasone
given at the same time as antibiotics was associated with an improved
outcome (de Gans and van de Beek, 2002). Prior to the appearance of
penicillin resistance, penicillin treatment reduced the death rate in
this disease from nearly 100% to ~25%. The recommended therapy is
20-24 million units of penicillin G daily by constant intravenous infusion
or divided into boluses given every 2-3 hours. The usual duration
of therapy is 14 days.
Streptococcal Infections. Streptococcal Pharyngitis (Including Scarlet
Fever). This is the most common disease produced by S. pyogenes
(group A β-hemolytic streptococcus). Penicillin-resistant isolates have
yet to be observed for S. pyogenes. The preferred oral therapy is with
penicillin V, 500 mg every 6 hours for 10 days. Penicillin therapy of
streptococcal pharyngitis reduces the risk of subsequent acute rheumatic
fever; however, current evidence suggests that the incidence of
glomerulonephritis that follows streptococcal infections is not reduced
to a significant degree by treatment with penicillin.
Streptococcal Toxic Shock and Necrotizing Fascitis. These are lifethreatening
infections associated with toxin production and are
treated optimally with penicillin plus clindamycin (to decrease toxin
synthesis) (Bisno and Stevens, 1996; Brown, 2004).
Streptococcal Pneumonia, Arthritis, Meningitis, and Endocarditis.
Although uncommon, these conditions should be treated with penicillin
G when they are caused by S. pyogenes; daily doses of 12-20
million units are administered intravenously for 2-4 weeks. Such
treatment of endocarditis should be continued for a full 4 weeks.
Infections Caused by Other Streptococci. The viridans group of
streptococci are the most common cause of infectious endocarditis.
These are nongroupable α-hemolytic microorganisms that are
increasingly resistant to penicillin G (minimum inhibitory concentration
[MIC] >0.1 μg/mL). Because enterococci also may be
α-hemolytic, and certain other α-hemolytic strains may be relatively
resistant to penicillin, it is important to determine quantitative microbial
sensitivities to penicillin G in patients with endocarditis. Patients
with penicillin-sensitive VIRIDANS group streptococcal endocarditis
can be treated successfully with daily doses of 12-20 million units of
intravenous penicillin G for 2 weeks in combination with gentamicin
1 mg/kg every 8 hours. Some physicians prefer a 4-week course of
treatment with penicillin G alone.
Enterococcal endocarditis is one of the few diseases treated
optimally with two antibiotics. The recommended therapy for penicillin-
and aminoglycoside-sensitive enterococcal endocarditis is
20 million units of penicillin G or 12 g ampicillin daily administered
intravenously in combination with a low dose of gentamicin. Therapy
usually should be continued for 6 weeks, but selected patients with a
short duration of illness (<3 months) have been treated successfully
in 4 weeks (Wilson et al., 1984).
Infections with Anaerobes. Many anaerobic infections are caused by
mixtures of microorganisms. Most are sensitive to penicillin G. An
exception is the B. fragilis group, in which up to 75% of strains may
be resistant to high concentrations of this antibiotic. Pulmonary and
periodontal infections (with the exception of β-lactamase-producing
Prevotella melaninogenica) usually respond well to penicillin
G, although a multicenter study indicated that clindamycin is more
effective than penicillin for therapy of lung abscess (Levison et al.,
1983). Mild-to-moderate infections at these sites may be treated with
oral medication (either penicillin G or penicillin V 400,000 units
[250 mg] four times daily). More severe infections should be treated
with 12-20 million units of penicillin G intravenously. Brain
abscesses also frequently contain several species of anaerobes, and
most authorities prefer to treat such disease with high doses of penicillin
G (20 million units per day) plus metronidazole or chloramphenicol.
Some physicians add a third-generation cephalosporin for
activity against aerobic gram-negative bacilli.
Staphylococcal Infections. The vast majority of staphylococcal
infections are caused by microorganisms that produce penicillinase
(Swartz, 2004). Hospital-acquired methicillin-resistant staphylococci
are resistant to penicillin G, all the penicillinase-resistant penicillins,
and the cephalosporins. Isolates occasionally may appear to
be sensitive to various cephalosporins in vitro, but resistant populations
arise during therapy and lead to failure. Vancomycin, linezolid,
quinupristin-dalfopristin, and daptomycin are active for
infections caused by these bacteria, although reduced susceptibility
to vancomycin has been observed. Community-acquired methicillin-resistant
S. aureus (MRSA) in many cases retains susceptibility
to trimethoprim-sulfamethoxazole, doxycycline, and
clindamycin (Medical Letter, 2007).
Meningococcal Infections. Penicillin G remains the drug of choice
for meningococcal disease. Patients should be treated with high
doses of penicillin given intravenously, as described for pneumococcal
meningitis. Penicillin-resistant strains of N. meningitides have
been reported in Britain and Spain but are infrequent at present. The
occurrence of penicillin-resistant strains should be considered in
patients who are slow to respond to treatment. Penicillin G does not
eliminate the meningococcal carrier state, and its administration thus
is ineffective as a prophylactic measure.