Antimotility agent

Abstract: Background Travelers' diarrhea is the most common travel-related malady. It affects millions of international travelers to developing countries annually and can significantly disrupt travel plans. Objective To provide an update on the evaluation, diagnosis, treatment, and prevention of traveler's diarrhea. Methods A PubMed search was completed in Clinical Queries using the key term "traveler's diarrhea". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to English literature. Patents were searched using the key term "traveler's diarrhea" from www.freepatentsonline.com. Results Between 10% and 40% of travelers develop diarrhea. The attack rate is highest for travelers from a developed country who visit a developing country. Children are at particular risk. Travelers' diarrhea is usually acquired through ingestion of food and water contaminated by feces. Most cases are due to a bacterial pathogen, commonly, Escherichia coli, and occur within the first few days after arrival in a foreign country. Dehydration is the most common complication. Pretravel education on hygiene and on the safe selection of food items is important in minimizing episodes. For mild travelers' diarrhea, the use of antibiotic is not recommended. The use of bismuth subsalicylate or loperamide may be considered. For moderate travelers' diarrhea, antibiotics such as fluoroquinolones, azithromycin, and rifaximin may be used. Loperamide may be considered as monotherapy or adjunctive therapy. For severe travelers' diarrhea, antibiotics such as azithromycin, fluoroquinolones, and rifaximin should be used. Azithromycin can be used even for the treatment of dysentery whereas fluoroquinolones and rifaximin cannot be used for such purpose. Recent patents related to the management of travelers' diarrhea are discussed. Conclusion Although travelers' diarrhea is usually self-limited, many travelers prefer expedient relief of diarrhea, especially when they are traveling for extended periods by air or ground. Judicious use of an antimotility agent and antimicrobial therapy reduces the duration and severity of diarrhea.

Abstract: Antimotility agent use for the treatment of Clostridium difficile infection (CDI) is discouraged. We reviewed the literature and unpublished postmarketing surveillance reports regarding antimotility treatment of CDI. Twenty reports met inclusion criteria, describing 55 patients with CDI who were exposed to antimotility agents. All studies were case reports or series, with the exception of 1 retrospective review. Nineteen patients (35%) improved, with clinical resolution. Nine patients (16%) died, and 27 patients (49%) had unknown outcomes. Seventeen patients (31%) with CDI developed colonic dilation; 5 of these patients with severe CDI died. However, all patients who experienced complications or died were given antimotility agents alone initially, without an appropriate antibiotic. Twenty-three patients who received metronidazole or vancomycin coadministered with the antimotility agent experienced no complications. Evidence supporting the hypothesis that worsened outcomes are associated with antimotility therapy of CDI is lacking. Further study of the role of antimotility agents in providing symptomatic relief and reducing environmental contamination with infectious stool may be warranted.

Abstract: Background: Although the use of the antimicrobial, trimethoprim-sulfamethoxazole, in combination with the antisecretory and antimotility agent, loperamide, has been shown to be efficacious in the treatment of traveler's diarrhea, the use of fluoroquinolone antimicrobials in combination with loperamide has less support in the literature. The present study was designed to compare the efficacy of ofloxacin versus ofloxacin plus loperamide in the treatment of acute traveler's diarrhea. Method: This prospective, randomized, evaluator-blinded treatment trial was conducted in Guadalajara, Mexico, during the summers of 1992-1994. Adults newly arrived in Mexico from the United States who developed acute diarrhea of less than 2 weeks' duration were randomized to receive orally either: A) ofloxacin, 400 mg once; B) ofloxacin, 200 mg twice a day for six doses; or C) ofloxacin, 400 mg once, plus loperamide, 4 mg once followed by 2 mg after each loose stool, not to exceed 16 mg per day, for 3 days. The duration of illness was the number of hours elapsed from the beginning of therapy to the passage of the last unformed stool. Results: Ofloxacin and loperamide were well tolerated. Combination therapy with single dose ofloxacin plus loperamide was significantly more efficacious in reducing the duration of diarrhea than single dose ofloxacin or ofloxacin given for 3 days (p <.00001). Furthermore, combination therapy was more efficacious when enterotoxigenic Escherichia coli (ETEC) was the pathogen (p <.01) or when no pathogen was isolated (p <.001). Sixty-three percent of subjects passed no further unformed stools after the initial doses of combination therapy, and 91% were well by the end of the first 24 hours. Conclusions: The combined use of a single dose of ofloxacin with loperamide is safe and more efficacious in the treatment of traveler's diarrhea than use of ofloxacin alone.

Abstract: Although Campylobacter jejuni is now recognized as a common cause of gastroenteritis, fatalities associated with this infection in the United States have not been previously reported. Two fatalities associated with C jejuni infections occurred over a two-year period in the Denver metropolitan area. The first case was in a previously healthy 26-year-old woman who died following a two-day diarrheal illness. The second case was in a 69-year-old diabetic woman who died 19 hours after developing a gastrointestinal tract illness one day following hospital discharge for an orthopedic procedure. Both patients had taken an antimotility agent. During this same two-year period there were 24.4 reported cases of C jejuni infections per 100,000 population. The death rate per reported case was 2.4 per 1,000, and the overall death rate in the entire five-county population was 0.059 per 100,000 population. The exact causes of death for the two patients are not clear; however, hypokalemia may be a contributing factor, especially since there was no evidence of profound volume depletion in the one patient for whom laboratory data were available. Prompt hospitalization and withholding of antimotility agents may have prevented these deaths. ( JAMA 1985;253:2873-2875)