Antimicrobial Therapy

Kean first demonstrated the successful prevention of travelers' diarrhea with antimicrobial agents in 1963.

Many studies have verified the efficacy of antimicrobial agents in both the prevention and the treatment of the syndrome. Antibiotics can limit the course of diarrhea to approximately 1 day. Untreated diarrhea lasts over 3 days. The benefits of antibiotic therapy include significant reductions in the total duration of diarrhea, earlier relief of accompanying symptoms like cramps, and a decrease in the amounts of time spent in bed and missing or altering planned activities. Some experts still consider that antibiotics have little role in the empiric treatment of travelers' diarrhea (Petrucelli et al., 1997). While it is true that travelers' diarrhea is a self-limited disease, in the authors' opinion the considerable relief afforded by antibiotic treatment argues against therapeutic nihilism.

A number of antibiotics have been shown to be useful in the treatment of travelers' diarrhea. For years trimethoprim-sulfamethoxazole (TMP-SMX) was an excellent choice for treatment of travelers' diarrhea, and trimethoprim alone could be substituted for patients who were allergic to sulfa preparations. TMP-SMX resistance around the world has increased so much that it is no longer a preferred empiric treatment choice.

Currently, the most readily available of the active antibiotics for treatment are fluoroquinolones such as nor-floxacin, ciprofloxacin, ofloxacin, enoxacin, fleroxacin and others (Table 10.2). All appear to be highly effective, so the choice of one should probably be based solely on the price.

Nonabsorbed antibiotics (e.g. bicozamycin, aztreonam, and rifaximin) were predicted to be less effective for the treatment of diarrhea because antibiotic absorption and high mucosal levels were thought to be necessary. However, these agents have been proven to be efficacious in treating diarrhea due to the full range of causal bacterial agents, including those like Salmonella that cause in-tracellular infection. The theoretic reason for preferring nonabsorbed agents is that they should engender fewer side-effects and should be safer to use in children and pregnant women, in whom the currently preferred quinolones are contraindicated. With the exception of rifaximin, which is available in some countries but not worldwide, companies have been slow to develop such agents further, presumably because the market is not large enough to satisfy their economic motivations.

Erythromycin is effective in Campylobacter disease and has been shown to be effective in the prevention of travelers' diarrhea, probably owing to its activity against Gram-negative enteric organisms in the alkaline milieu of the gut. Erythromycin, however, has not been studied for the treatment of travelers' diarrhea. The azalide, azi-thromycin, has been studied in Campylobacter disease, and it is also efficacious (Kuschner et al., 1995). In vitro studies predict that azithromycin should be active in treating travelers' diarrhea.

Certain antibiotics are available over the counter in many developing countries and local physicians might recommend them. These include ampicillin, which is simply not active enough around the world to be an effective choice. Furazolidone is active not only against bacterial causes of travelers' diarrhea but also against Giardia. This feature can be a benefit in some regions of the world like Russia, where the risk of acquisition of Giardia appears to be exceptionally high. The problem is that furazolidone is only about one-half as effective as the preferred quinolones in the treatment of the common bacterial causes of travelers' diarrhea.

Increasing resistance around the world has limited the usefulness of doxycycline. Chloramphenicol is cheap and readily available over the counter in many countries, but its rare but devastating bone marrow toxicity limits its widespread recommendation. Clioquinol was studied many years ago with variable results. It was taken off the market in many countries because of serious ophthal-mologic adverse effects. Doxycycline, chloramphenicol and clioquinol cannot be recommended.

The duration of treatment with antibiotics has steadily decreased with ongoing study. Now a single dose of antibiotic can be recommended for most patients (DuPont and Ericsson, 1993; Ericsson and Rey, 1997). The invasive pathogens and severe disease are the causes and clinical state that might require lengthier therapy than a single dose. As a rule Shigella responds to single dose therapy, but disease caused by S. dysenteriae appears best treated with a 3-day course of antibiotic. Fortunately, S. dysenteriae is an uncommon cause of travelers' diarrhea. More study is needed before single-dose therapy can be recommended confidently for Campylobacter disease. In areas of the world where C. jejuni is especially prevalent (e.g. Southeast Asia), at least a 3 day course of antibiotic is recommended. Probably 3 day therapy should be preferred over single-dose therapy to treat winter-time diarrhea, because Campylobacter is a relatively more common cause of winter-time diarrhea in regions where it is otherwise not a common cause of travelers' diarrhea during peak summer-time travel (e.g. Morocco and Mexico).

Antibiotic resistance has developed during treatment of Campylobacter disease with the quinolones. Symptoms have relapsed despite having responded initially. When quinolones are used as agents of choice for self-therapy in areas where Campylobacter are common causes of travelers' diarrhea, the patient might need to be armed with a course of azithromycin to take in the event that quinolone-treated disease relapses. Alternatively, rifaximin could be prescribed in place of a fluoroquinolone if it is available. Azithromycin needs more study before it can be advocated as front-line therapy.

We provide clients with 3 day courses of a quinolone for self-therapy. We ask them to re-evaluate themselves when the next dose of antibiotic would be due. If they are still passing unformed stools, or fever or passage of bloody stools was a feature of their disease, we recommend that they finish the full 3 days of antibiotic. Otherwise, we feel that single-dose antibiotic therapy usually suffices.

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