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

1420 The organisms can be differentiated by antigen-detection
enzyme-linked immunosorbent assays or by polymerase chain reaction
(PCR)–based diagnostics. Humans are the only known hosts for
these protozoa, which are transmitted almost exclusively by the
fecal-oral route. Ingested E. histolytica cysts from contaminated food
or water survive acid gastric contents and transform into trophozoites
that reside in the large intestine. The outcome of E. histolytica infection
is variable. Many individuals remain asymptomatic but excrete
the infectious cyst form, making them a source for further infections.
In other individuals, E. histolytica trophozoites invade into the
colonic mucosa with resulting colitis and bloody diarrhea (amebic
dysentery). In a smaller proportion of patients, E. histolytica trophozoites
invade through the colonic mucosa, reach the portal circulation,
and travel to the liver, where they establish an amebic liver
abscess.
SECTION VII
CHEMOTHERAPY OF MICROBIAL DISEASES
The cornerstone of therapy for amebiasis is the
nitroimidazole compound metronidazole or its analogs
tinidazole and ornidazole. Metronidazole and tinidazole
are the only nitroimidazoles available in the U.S. and
are the drugs of choice for the treatment of amebic colitis,
amebic liver abscess, and any other extraintestinal
form of amebiasis. Because metronidazole is so well
absorbed in the gut, levels may not be therapeutic in the
colonic lumen, and the drug is less effective against
cysts. Hence patients with amebiasis (amebic colitis or
amebic liver abscess) also should receive a luminal
agent to eradicate any E. histolytica trophozoites residing
within the gut lumen. Luminal agents are also used
to treat asymptomatic individuals found to be infected
with E. histolytica. The nonabsorbed aminoglycoside
paromomycin and the 8-hydroxyquinoline compound
iodoquinol are two effective luminal agents. Diloxanide
furoate, previously considered the luminal agent of
choice for amebiasis, is no longer available in the U.S.
Nitazoxanide (ALINIA), a drug approved in the U.S. for
the treatment of cryptosporidiosis and giardiasis, is also
active against E. histolytica.
Giardiasis. Giardiasis, caused by the flagellated protozoan
Giardia intestinalis, is prevalent worldwide and is the
most commonly reported intestinal protozoal infection in
the U.S. (Hlavsa et al., 2005). Infection results from
ingestion of the cyst form of the parasite, which is found
in fecally contaminated water or food. Giardia is a zoonosis,
and cysts shed from animals or from infected humans
can contaminate recreational and drinking water supplies.
Human-to-human transmission via the fecal-oral route is
especially common among children in day-care centers
and nurseries, as well as among institutionalized individuals
and male homosexuals.
Infection with Giardia results in one of three syndromes: an
asymptomatic carrier state, acute self-limited diarrhea, or chronic
diarrhea. Asymptomatic infection is most common; these individuals
excrete Giardia cysts and serve as a source for new infections.
Most adults with symptomatic infection develop an acute self-limited
illness with watery, foul-smelling stools, abdominal distension, and
flatus. However, a significant proportion of these individuals go on
to develop a chronic diarrhea syndrome (>2 weeks of illness) with
signs of malabsorption (steatorrhea) and weight loss.
The diagnosis of giardiasis is made by identification
of cysts or trophozoites in fecal specimens or of
trophozoites in duodenal contents. Chemotherapy with
a 5-day course of metronidazole usually is successful,
although therapy may have to be repeated or prolonged
in some instances. A single dose of tinidazole (TINDAMAX,
others) probably is superior to metronidazole for the
treatment of giardiasis. Paromomycin (HUMATIN, others)
has been used to treat pregnant women to avoid any
possible mutagenic effects of the other drugs.
Nitazoxanide (ALINIA), N-(nitrothiazolyl) salicylamide,
and tinidazole were approved recently for the treatment
of giardiasis in immune-competent children <12 years
of age. Furazolidone, previously used for the treatment
of giardiasis, has been discontinued in the U.S.
Trichomoniasis. Trichomoniasis is caused by the flagellated
protozoan Trichomonas vaginalis. This organism
inhabits the genitourinary tract of the human host,
where it causes vaginitis in women and, uncommonly,
urethritis in men. Trichomoniasis is a sexually transmitted
disease, with >200 million people infected
worldwide and at least 3 million women infected in the
U.S. annually. Infection with Trichomonas has been
associated with an increased risk of acquiring HIV
infection. Only trophozoite forms of T. vaginalis have
been identified in infected secretions.
Metronidazole remains the drug of choice for the
treatment of trichomoniasis. However, treatment failures
owing to metronidazole-resistant organisms are
becoming more frequent (Dunne et al., 2003).
Tinidazole, another nitroimidazole that was approved
recently by the FDA, appears to be better tolerated than
metronidazole and has been used successfully at higher
doses to treat metronidazole-resistant T. vaginalis
(Sobel et al., 2001). Nitazoxanide shows activity
against T. vaginalis in vitro but has not undergone clinical
trials and is not licensed for the treatment of trichomoniasis.
Toxoplasmosis. Toxoplasmosis is a cosmopolitan
zoonotic infection caused by the obligate intracellular
protozoan Toxoplasma gondii (Montoya and Liesenfeld,
2004). Although cats and other feline species are the
natural hosts, tissue cysts (bradyzoites) have been