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

1374 colonization or infection by any or all microorganisms
present in the environment of a patient often fails.
SECTION VII
CHEMOTHERAPY OF MICROBIAL DISEASES
Prophylaxis is used in immunosuppressed patients such as
those with HIV-AIDS or are post-transplantation and on antirejection
medications. The efficacy of prophylaxis in these patients
is based on excellent evidence (Anonymous, 2000; DHHS Panel on
Guidelines for the Prevention and Treatment of Opportunistic
Infections in HIV-Infected Adults and Adolescents, 2008). In these
groups of patients, specific antiparasitic, antibacterial, antiviral, and
antifungal therapy is administered based on the well-defined pattern
of pathogens that are major causes of morbidity during
immunosuppression. A risk-benefit analysis is used to determine
choice and duration of prophylaxis. Prophylaxis of opportunistic
infections in patients with AIDS is started when the CD4 count falls
below 200 cells per mm 3 . In post-transplant patients, prophylaxis
depends on time since the transplant procedure, which is related to
intensity of use and type of immunosuppressive therapy.
Prophylaxis should be discontinued in patients who are doing well
at certain time points, such as 1 year post-transplant. In AIDS
patients, prophylaxis is discontinued when the CD4 count climbs
above 200 cells/mm 3 . Infections for which prophylaxis is given
include Pneumocystis jiroveci, Mycobacterium avium-intracellulare,
Toxoplasma gondii, Candida species, Aspergillus species,
Cytomegalovirus, and other Herpesviridae. In general, lower doses
of prophylactic agent are given compared to when the same drug is
used for treatment.
Chemoprophylaxis is also used to prevent wound infections
after various surgical procedures. Wound infection results when a
critical number of bacteria are present in the wound at the time of
closure. Antimicrobial agents directed against the invading microorganisms
may reduce the number of viable bacteria below the critical
level and thus prevent infection. Several factors are important for
the effective and judicious use of antibiotics for surgical prophylaxis.
First, antimicrobial activity must be present at the wound site at the
time of its closure. Thus, infusion of the first antimicrobial dose
should begin within 60 minutes before surgical incision and should
be discontinued within 24 hours of the end of surgery (Bratzler and
Houck, 2004). Second, the antibiotic must be active against the most
likely contaminating microorganisms for that type of surgery. A
number of studies indicate that chemoprophylaxis can be justified
in dirty or contaminated surgical procedures (e.g., resection of the
colon), where the incidence of wound infections is high. These
include <10% of all surgical procedures. In clean surgical procedures,
which account for ~75% of the total, the expected incidence
of wound infection is <5%, and antibiotics should not be used routinely.
When the surgery involves insertion of a prosthetic implant
(e.g., prosthetic valve, vascular graft, prosthetic joint), cardiac surgery,
or neurosurgical procedures, the complications of infection are
so drastic that most authorities currently agree to chemoprophylaxis
for these indications.
Patients at the highest risk for infective endocarditis for
which prophylaxis is recommended fall into four groups (Wilson
et al., 2007):
• those with a prosthetic material used for heart valve repair or
replacement
• previous infective endocarditis
• congenital heart disease such as unrepaired cyanotic heart disease,
or within 6 months of repair of the heart disease with prosthetic
material, or those with residual defects adjacent to prosthetic
material
• postcardiac transplant patients with heart valve defects
Chemoprophylaxis is reasonable in these patients when undergoing
dental procedures if there is manipulation of gingival tissue or
periapical region of teeth, or perforation of oral mucosa, but not for
other dental procedures. Recommended therapy is a single dose of
oral amoxicillin 30 minutes to 1 hour before the procedure or intravenous
ampicillin or ceftriaxone in those unable to take oral medication.
A macrolide or clindamycin may be administered for patients
who are allergic to β-lactam agents. Therapy may be administered
no more than 2 hours after the procedure for patients who failed to
receive the prophylaxis prior to the procedure (Wilson et al., 2007).
Prophylaxis is also reasonable for procedures that will involve
infected skin and soft tissues as well as infected respiratory tract, but
not in routine genitourinary and GI tract procedures. If the organism
causing the infection is known, then the prophylactic antibiotic for
patients undergoing these procedures should be tailored toward that
particular organism.
Prophylaxis may be used to protect healthy persons from
acquisition of or invasion by specific microorganisms to which they
are exposed. This is termed post-exposure prophylaxis. Successful
examples of this practice include rifampin administration to prevent
meningococcal meningitis in people who are in close contact with a
case, prevention of gonorrhea or syphilis after contact with an
infected person, and macrolides after contact with confirmed cases
of pertussis. Post-exposure prophylaxis is recommended in those
patients inadvertently exposed to HIV infection. Currently, combination
therapy from one of the classes of antiretrovirals, nucleoside
reverse transcriptase inhibitors, nucleotide reverse transcriptase
inhibitors, non-nucleoside reverse transcriptase inhibitors, protease
inhibitors, and fusion inhibitors is administered for 4 weeks (Panlilio
et al., 2005). For influenza, the neuraminidase inhibitor oseltamivir
has been recommended for prevention of influenza A and B in
healthy adults and children with close contact of laboratoryconfirmed
cases (Hayden and Pavia, 2006).
Mother-to-child transmission of HIV and syphilis are important
public health problems for which specific chemotherapeutic regimens
have been devised, based on locality. Anti-retroviral therapy
is administered for HIV prophylaxis during the pregnancy and peripartum
periods. Prophylactic therapy for syphilis during pregnancy
is effective in reducing neonatal death and infant neurological, auditory,
and bone malformations.
Pre-emptive therapy. Pre-emptive therapy is used as a substitute for
universal prophylaxis and as early targeted therapy in high-risk
patients who already have a laboratory or other test indicating that
an asymptomatic patient has become infected. The principle is that
delivery of therapy prior to development of symptoms (presymptomatic)
aborts impending disease, and the therapy is for a short and
defined duration (Singh, 2001). This has been applied in the clinic
to therapy for cytomegalovirus (CMV) after both hematopoietic
stem cell transplants and after solid organ transplantation. It is
unclear whether this method is superior to keeping all at-risk
patients on ganciclovir. Recent evidence in liver transplant patients