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

1486 under controlled conditions, it has become clear that penicillin is
highly effective in some situations, useless and potentially dangerous
in others, and of questionable value in still others (Chapter 48).
SECTION VII
CHEMOTHERAPY OF MICROBIAL DISEASES
Streptococcal Infections. The administration of penicillin to individuals
exposed to S. pyogenes affords protection from infection.
The oral ingestion of 200,000 units of penicillin G or penicillin V
twice a day or a single injection of 1.2 million units of penicillin G
benzathine is effective. Indications for this type of prophylaxis
include outbreaks of streptococcal disease in closed populations,
such as boarding schools or military bases. Patients with extensive
deep burns are at high risk of severe wound infections with S. pyogenes;
“low-dose” prophylaxis for several days appears to be effective
in reducing the incidence of this complication.
Recurrences of Rheumatic Fever. The oral administration of 200,000
units of penicillin G or penicillin V every 12 hours produces a striking
decrease in the incidence of recurrences of rheumatic fever in susceptible
individuals. Because of the difficulties of compliance,
parenteral administration is preferable, especially in children. The
intramuscular injection of 1.2 million units of penicillin G benzathine
once a month yields excellent results. In cases of hypersensitivity to
penicillin, sulfisoxazole or sulfadiazine, 1 g twice a day for adults,
also is effective; for children weighing <27 kg, the dose is halved.
Prophylaxis must be continued throughout the year. The duration of
such treatment is an unsettled question. It has been suggested that
prophylaxis should be continued for life because instances of acute
rheumatic fever have been observed in the fifth and sixth decades.
However, the necessity for such prolonged prophylaxis has not been
established and may be unnecessary for young adults judged to be at
low risk for recurrence (Berrios et al., 1993).
Syphilis. Prophylaxis for a contact with syphilis consists of a
course of therapy as described for primary syphilis. A serological
test for syphilis should be performed at monthly intervals for at least
4 months thereafter.
Surgical Procedures in Patients with Valvular Heart Disease. About
25% of cases of subacute bacterial endocarditis follow dental extractions.
This observation, together with the fact that up to 80% of persons
who have teeth removed experience a transient bacteremia,
emphasizes the potential importance of chemoprophylaxis for those
who have congenital or acquired valvular heart disease of any type
and need to undergo dental procedures. Since transient bacterial
invasion of the bloodstream occurs occasionally after surgical procedures
(e.g., tonsillectomy and genitourinary and GI procedures)
and during childbirth, these, too, are indications for prophylaxis in
patients with valvular heart disease. Whether the incidence of bacterial
endocarditis actually is altered by this type of chemoprophylaxis
remains to be determined.
Detailed recommendations for adults and children with
valvular heart disease have been formulated (Wilson et al., 2007).
The Penicillinase-Resistant Penicillins
The penicillins described in this section are resistant to
hydrolysis by staphylococcal penicillinase. Their appropriate
use should be restricted to the treatment of infections
that are known or suspected to be caused by
staphylococci that elaborate the enzyme, which now
includes the vast majority of strains of this bacterium
that are encountered clinically. These drugs are much
less active than penicillin G against other penicillinsensitive
microorganisms, including non-penicillinaseproducing
staphylococci.
The role of the penicillinase-resistant penicillins
as the agents of choice for most staphylococcal disease
is changing with the increasing incidence of isolates of
so-called methicillin-resistant microorganisms. As commonly
used, this term denotes resistance of these bacteria
to all the penicillinase-resistant penicillins and
cephalosporins. Hospital-acquired strains usually are
resistant to the aminoglycosides, tetracyclines, erythromycin,
and clindamycin as well. Vancomycin is considered
the drug of choice for such infections, although
intermediate-level resistance is emerging (Centers for
Disease Control and Prevention, 2004). Some physicians
use a combination of vancomycin and rifampin,
especially for life-threatening infections and those involving
foreign bodies. Community-acquired methicillinresistant
strains are less likely to be resistant to other
classes of antibiotics with the exception of macrolides
(Okuma et al., 2002). MRSA contains an additional
high-molecular-weight PBP with a very low affinity
for β-lactam antibiotics (Spratt, 1994). From 40-60% of
strains of S. epidermidis also are resistant to the penicillinase-resistant
penicillins by the same mechanism.
As with MRSA, these strains may appear to be susceptible
to cephalosporins on disk-sensitivity testing, but
there usually is a significant population of microbes that
is resistant to cephalosporins and emerges during such
therapy. Vancomycin also is the drug of choice for serious
infection caused by methicillin-resistant S. epidermidis;
rifampin is given concurrently when a foreign
body is involved.
The Isoxazolyl Penicillins: Oxacillin, Cloxacillin, and
Dicloxacillin. These three congeneric semisynthetic penicillins
are similar pharmacologically and thus conveniently
are considered together. Their structural formulas
are shown in Table 53–1. All are relatively stable in an
acidic medium and absorbed adequately after oral administration.
All are markedly resistant to cleavage by penicillinase.
These drugs are not substitutes for penicillin G
in the treatment of diseases amenable to it, and they are
not active against enterococci or Listeria. Furthermore,
because of variability in intestinal absorption, oral administration
is not a substitute for the parenteral route in the
treatment of serious staphylococcal infections that require
a penicillin unaffected by penicillinase.
Pharmacological Properties. The isoxazolyl penicillins are potent
inhibitors of the growth of most penicillinase-producing staphylococci.