Antiamoebic drugs for treating amoebic colitis - The Cochrane Library

Metronidazole is considered as the drug of choice for treating
invasive amoebiasis (WHO 1994; Medical Letter 2004; WHO
2005; AAP 2006). The standard regimen of metronidazole for the
treatment of amoebic colitis is 500 to 750 mg given three times
daily in adults and 30 to 50 mg/kg/day in children given for five
to 10 days (WHO 1994; Medical Letter 2004; WHO 2005; AAP
2006). Although there are those who believe that this dose may
have sufficient activity against both trophozoites and cysts (Powell
1970; WHO 1994; Li 1996), others believe that metronidazole is
not reliably effective in eliminating cysts in the colonic lumen (
Powell 1966; Powell 1967a; Powell 1967b; Powell 1969a; Powell
1969). Thus, the general recommendation is that patients with invasive
amoebiasis should receive a luminal amoebicide after treatment
with a tissue amoebicide, in order to eliminate any surviving
organisms in the colon (WHO 1995; WHO 1997; Medical Letter
2004; AAP 2006). This recommendation is based on the assumption
that drugs acting on different protozoal processes may enhance
each other’s effect. However, the evidence to support combination
therapy has not been reviewed, and it is not known whether
drug combinations reduce clinical symptoms or eradicate parasites
more effectively compared with giving a tissue amoebicide alone.
Furthermore, the increased complexity of combination regimens,
additional drug costs, and possible increased adverse events, coupled
with the unavailability of luminal agents in the market, act
as major deterrents to compliance with this recommendation.
Adverse effects may occur even with conventional doses of metronidazole
and include headaches, loss of appetite, nausea, metallic
taste, and vomiting (WHO 1995; Tracy 2001). Individuals should
avoid alcoholic drinks during metronidazole therapy because of
vomiting, headache, flushing, and abdominal pain that may occur.
Dizziness, convulsions, poor co-ordination, and numbness
of the extremities are less common but more serious adverse effects
that warrant discontinuation of metronidazole (Tracy 2001).
Other nitroimidazole drugs with longer half lives, such as tinidazole,
ornidazole, and secnidazole, allow shorter periods of treatment
and appear to be better tolerated compared with metronidazole.
These drugs have been used successfully when administered
in shorter courses and have been recommended as alternative
antiamoebic drugs to metronidazole (Haque 2003; Stanley
2003; Medical Letter 2004; WHO 2005; AAP 2006). Treatment
failures have been reported with metronidazole with most failures
attributed to incorrect diagnosis, unsuitable choice of drug, or failure
to observe certain principles of treatment rather than drug resistance
(Knight 1980; Wassman 1999). However, the induction
of metronidazole-resistant E. histolytica strains in the laboratory
suggests that indiscriminate use of antiamoebic drugs can result
in an increased minimum inhibitory concentration against E. histolytica
(Samarawickrema 1997; Wassman 1999).
A systematic review summarized the effects of different drug treatments
for amoebic dysentery in endemic areas (Dans 2006). The
systematic review included 12 randomized controlled trials and
found that while ornidazole, secnidazole, and tinidazole were likely
to be beneficial for treating amoebic dysentery, metronidazole was
unlikely to be beneficial. The results of the trials were not combined,
and no formal statistical methods were performed to determine
summary measures of the effectiveness of the drugs.
Adequate therapy for amoebic colitis is necessary to reduce severity
of illness, prevent the development of complicated disease and extraintestinal
spread, and decrease infectiousness and transmission
to others. In developing countries, where amoebiasis is common
and most of the patients are treated in private practice or as hospital
outpatients, the aim of treatment should be towards an effective,
safe, and simple regimen that can be given on an outpatient basis.
A reliable summary of the evidence is needed to determine the best
treatment for amoebic colitis. The occurrence of treatment failures
and unpleasant adverse effects associated with metronidazole in
some patients and the possibility of overt clinical resistance of
E. histolytica to metronidazole make it imperative to investigate
alternative treatment. The benefits of using combination regimens
over monotherapy and single-dose regimens over longer regimens
have to be determined. Furthermore, the effectiveness of potential
new antiamoebic drugs has to be ascertained.
O B J E C T I V E S
To evaluate antiamoebic drugs for treating amoebic colitis. The
review particularly aims to compare:
1. single agent alternatives with metronidazole;
2. any antiamoebic drug with placebo;
3. combination regimens with monotherapy; and
4. single-dose regimens with longer regimens.
M E T H O D S
Criteria for considering studies for this review
Types of studies
Antiamoebic drugs for treating amoebic colitis (Review)
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Randomized controlled trials. We excluded quasi-randomized trials.
Types of participants
Adults and children with clinical symptoms of amoebic colitis (as
outlined in WHO 1997 and Haque 2003) and the demonstration
of E. histolytica cysts or trophozoites in a stool sample, or
E. histolytica trophozoites in a tissue biopsy or ulcer scraping by
5