Less severe disease can be treated with a variety of nonan-tibiotic agents (Table 10.3). Bismuth subsalicylate (BSS)-containing compounds decrease the number of unformed stools passed after beginning treatment by almost 50%. The antisecretory and antimotility agent, loperamide, is more efficacious than BSS. Neither is as effective as an antibiotic.
Some studies with antimotility agents such as diphenoxylate suggested that the agents might prolong the course of disease caused by invasive enteropathogens. In a small number of prisoners, shigellosis was treated with an antibiotic and diphenoxylate. Shedding of Shigella and fever where prolonged. Patients with bloody diarrhea treated with diphenoxylate alone had a longer course of disease than did placebo-treated subjects. The use of antimotility agents should be avoided in the treatment of Clostridium difficile disease. Conversely, current research indicates disease is not prolonged when patients are able to take an antibiotic when they feel they are not getting enough relief from loperamide. Also, cipro-floxacin plus loperamide treats Shigella dysentery more effectively than ciprofloxacin alone (Murphy et al., 1993).
Loperamide is absorbed rapidly and acts more quickly than BSS preparations, which take nearly 4h to begin having their effect. Loperamide is a safe drug that is available over the counter. It is approved for use in children as young as 3 years old.
The prescription product diphenoxylate plus atropine (Lomotil) is popular, but the drug is not as efficacious as loperamide in the treatment of diarrhea and has a relatively unfavorable side-effect profile. Elderly men can suffer urinary retention due to the atropine. Lomotil is habit forming and central nervous system side-effects are possible.
Other symptomatic drugs that have been advocated in
TRAVELERS' DIARRHEA Table 10.3 Symptomatic treatment of travelers' diarrhea
Bismuth subsalicylate preparations
Zaldaride maleate SP 303
3 g initially and after each loose stool for a total of 9g per day
30 ml (1 ounce) every half hour for a total of 240 ml (8 ounces)
4 mg loading dose, then 2 mg after each loose stool, not to exceed 16 mg per day
Rinse mouth carefully. Brush teeth and tongue after evening dose Over-the-counter directions limit total daily dose to 8 mg. Oral hydration does not add to symptomatic relief afforded by loperamide Not yet marketed. Calmodulin antagonist Mechanism of action not known. Not yet approved but alternatively available as a natural preparation the past include the anticholinergic agents, activated charcoal, Lactobacillus preparations, polycarbophil, methylcellulose, psyllium, and kaolin/pectin preparations (Petrucelli et al., 1997). All of these are not effective for the treatment of travelers' diarrhea with the exception of attapulgite (a hydrated aluminum silicate clay preparation), which performed well enough in trials to recommend it for mild diarrhea. Attapulgite is a safe product that can be recommended for use in pregnant women. It causes a more formed stool; however, net losses of water and electrolytes persist unabated.
Recent studies have shown that a new and novel calmodulin inhibitor, zaldaride, is useful in decreasing the duration of diarrhea from an average of 42 h in untreated subjects to an average of 20 h (DuPont et al., 1993; Ok-huysen et al., 1995). The drug worked both in ETEC disease as well as in other bacterial diseases, suggesting a common role for calmodulin for the pathogenesis of diarrhea. A loading dose will likely be necessary for optimal use. Zaldaride is not yet marketed worldwide. Still another agent, the antisecretory drug SP303, shows promise in the symptomatic relief of travelers' diarrhea.
The combination of an antibiotic and loperamide has been studied with the usual dose of each agent. In one study more than half of the patients passed no further unformed stools once combination therapy was begun. The average duration of diarrhea was only a few hours, even when patients had blood in stools at enrollment. This result was superior to treatment with either agent alone and was confirmed in subsequent studies (Ericsson et al., 1997). Some studies have not verified such remarkable results, either when Campylobacter was a common cause of disease or when disease among placebo controls was relatively mild.
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