Antiamoebic drugs for treating amoebic colitis - The Cochrane Library

those who are asymptomatic (WHO 1997; Medical Letter 2004;
AAP 2006). Therefore, unless the diagnosis of E. histolytica infection
is uncertain in an asymptomatic individual, the use of placebo
as a comparison drug, particularly in cases with symptoms of invasive
disease, may not be justifiable nor ethical.
Combination regimen versus metronidazole alone
For all forms of invasive disease, including amoebic colitis, the
standard recommendation is to give a tissue amoebicide followed
by a luminal amoebicide to eliminate surviving cysts in the bowel
lumen (WHO 1995; WHO 1997; Medical Letter 2004; AAP
2006). The risk for parasitological failure was reduced by about
one-third in those given combination therapy compared with
metronidazole alone. The greater risk for failure with metronidazole
when administered alone may result from its inconsistent effect
in eliminating cysts in the bowel lumen and its failure to reach
adequate therapeutic concentrations in the large intestines (Reed
1992; Petri 1999; Haque 2003; Stanley 2003). The advantage of
combination therapy is attributed to the distinct activities of the
different drugs against the cysts and trophozoites found at the different
sites (WHO 1995; Tracy 2001; Medical Letter 2004).
Adverse events were incompletely reported, and it is not known
whether combination therapy would lead to increased adverse
events. Uncertainty also remains over which luminal agent is preferred
in combination with metronidazole or another nitroimidazole
to achieve eradication of cysts in the stools and to prevent
relapse, since none of the trials were of sufficient size to determine
this.
Comparison with other reviews
An earlier systematic review on amoebic dysentery concluded that
metronidazole was “unlikely to be beneficial” since some ineffectiveness
or associated harm was demonstrated in some trials
and that ornidazole, secnidazole, and tinidazole were “likely to be
beneficial”, since effectiveness for these drugs, with no increased
harms, was demonstrated in other trials (Dans 2006). In this current
review, we concluded that although tinidazole may be more
effective than metronidazole in reducing clinical failure, and was
probably associated with fewer adverse effects, it did not show any
significant advantage over metronidazole in reducing parasitological
failure. For ornidazole and secnidazole, there was insufficient
data to be able to draw any definite conclusions. The difference in
conclusions could be due to important differences in methodology.
The systematic review on amoebic dysentery used the Clinical
Evidence search strategy (Dans 2006) and included 12 randomized
controlled trials, defined therapeutic failure as persistence of
symptoms or persistence of parasites or both, analysed outcomes
reported at different time points together, and did not pool data
to generate an overall summary measure.
Antiamoebic drugs for treating amoebic colitis (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Applicability of results
This review was limited only to symptomatic individuals with
uncomplicated amoebic colitis. We did not study the effect of
antiamoebic drugs on those with severe amoebic colitis, complicated
disease, or extraintestinal amoebiasis. The potential effect
of malnutrition, immune suppression, or AIDS on treatment is
not known. Although asymptomatic infection with E. histolytica
is more common than symptomatic disease, treatment of these
individuals remains controversial because most will clear their infection
within one year and only about 3% to 10% will manifest
invasive disease (Gathiram 1987; Haque 2001; Blessman 2003b;
Haque 2002).
The limited availability of many antiamoebic drugs must be addressed
in the light of reports that newer nitroimidazole drugs may
be as effective as, and better tolerated than, metronidazole and
that there may be fewer clinical and parasitological failures when
luminal agents are given in conjunction with tissue amoebicides.
Metronidazole is widely used and may be the only available antiamoebic
drug in many countries. Tinidazole and the other nitroimidazole
drugs, such as ornidazole and secnidazole, and luminal
agents such as diloxanide furoate, iodoquinol, and paromomycin,
are not widely available and may only be purchased
from certain pharmaceutical companies or requested from government
agencies. Although tinidazole was shown to be probably
more effective and better tolerated than metronidazole in this review,
the limitations of the currently available evidence, and the
limited availability of tinidazole in many regions, would make a
widespread recommendation for its use impractical. Similarly, the
evidence to recommend combination therapy is inadequate, and
the limited availability of luminal agents in the market is a major
deterrent to compliance with the general recommendation for
combination therapy.
Limitations of the review
Limitations in study quality, the imprecise or sparse data in some
outcomes, important inconsistencies across the trials, and a high
probability of reporting or publication bias decrease the quality of
evidence. Therefore the conclusions of the review should be interpreted
with caution. Inaccurate diagnosis of E. histolytica infection
by stool microscopy, absence of standardized classification of the
various categories of amoebic colitis (particularly nondysenteric
amoebic colitis), and variable timing and definition of outcome
measurements would all lead to inaccuracy in assessing treatment
effects. In areas highly endemic for amoebiasis, true treatment failures
or relapse would be difficult to differentiate from reinfection
without the benefit of finger typing or genotyping. Incomplete
reporting of adverse events may lead to an inaccurate assessment
of adverse events.
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