Search

Bacterial enteropathogens acquired from contaminated food are the principal causes of travelers' diarrhea (TD). We evaluated desserts obtained from popular restaurants in the tourist city of Guadalajara, Mexico, and Houston, Texas, to determine coliform and Escherichia coli contamination levels and presence of diarrheagenic E. coli known to be important in TD. Contamination for all organisms was seen for desserts served in Guadalajara restaurants. Desserts should be considered as potentially risky foods for development of TD among international visitors to developing regions of the world.

Background & Aims: Antimotility agents provide rapid temporary relief of acute diarrhea, whereas antibiotics slowly cure the illness. Thus, the combination of an antimotility agent and an antibiotic may provide greater therapeutic benefit than either drug alone. This study evaluated the efficacy and safety of rifaximin-loperamide in the treatment of travelers' diarrhea., Methods: Consenting adults with acute diarrhea (> or =3 unformed stools in 24 hours with > or =1 symptom of enteric infection) were randomized to receive rifaximin 200 mg 3 times daily for 3 days; loperamide 4 mg initially followed by 2 mg after each unformed stool; or a combination of both drugs using the same dosing regimen. The primary end point was the median time from beginning therapy until passing the last unformed stool., Results: A total of 310 patients completed treatment with rifaximin (n = 102), loperamide (n = 104), or rifaximin-loperamide combination therapy (n = 104). The groups showed demographic similarity. Rifaximin and rifaximin-loperamide significantly reduced the median time until passage of the last unformed stool (32.5 +/- 4.14 h and 27.3 +/- 4.13 h, respectively) vs loperamide (69 +/- 4.11 h; P = .0019). The mean number of unformed stools passed during illness was lower with rifaximin-loperamide (3.99 +/- 4.28) compared with rifaximin (6.23 +/- 6.90; P = .004) or loperamide alone (6.72 +/- 6.93; P = .002). All treatments were well tolerated with a low incidence of adverse events., Conclusions: Rifaximin-loperamide therapy provided rapid symptomatic improvement and greater overall wellness compared with either agent alone.

The use of antibacterial drugs was first shown to effectively reduce the occurrence of traveler's diarrhea nearly 50 years ago. The approach was not encouraged for general use by a Consensus Development Conference in 1985 because of concerns about adverse effects of the drugs and the possible development of resistance against systemically absorbed drugs. When therapy with poorly absorbed rifaximin was shown to be as effective as therapy with systemically absorbed drugs in shortening the duration of traveler's diarrhea, without the development of resistant coliform flora, the use of rifaximin for the prevention of traveler's diarrhea was studied. In the present study, rifaximin provided 72% protection against the development of diarrhea and 77% protection against active or treated diarrhea during 2 weeks of drug administration to United States students in Mexico. Rifaximin offers a potentially useful approach for preventing traveler's diarrhea. Potential areas of future study include use of the drug to prevent diarrhea due to mucosally invasive bacteria, including ciprofloxacin-resistant Campylobacter species, and to reduce the occurrence of postinfectious irritable bowel syndrome.

Background: Travelers' diarrhea causes substantial morbidity and postinfectious irritable bowel syndrome., Objective: To evaluate nonabsorbable rifaximin for prevention of travelers' diarrhea., Design: Randomized, double-blind, placebo-controlled clinical trial., Setting: Guadalajara, Mexico., Participants: U.S. students., Intervention: On arrival in Guadalajara, Mexico, 210 U.S. adults received rifaximin (200 mg/d, 200 mg twice daily, or 200 mg 3 times daily) or placebo for 2 weeks., Measurements: Participants were followed daily for 3 weeks for enteric disease and symptoms and daily for 5 weeks for drug side effects. Changes in intestinal coliform flora were studied., Results: Travelers' diarrhea developed in 14.74% of participants taking rifaximin and 53.70% of those taking placebo (rate ratio, 0.27 [95% CI, 0.17 to 0.43]). Rifaximin provided 72% and 77% protection against travelers' diarrhea and antibiotic-treated travelers' diarrhea, respectively (P < 0.001 for both), and all rifaximin doses were superior to placebo. In the groups that did not report travelers' diarrhea, rifaximin significantly reduced the occurrence of mild diarrhea (P = 0.02) and moderate and severe intestinal problems (P = 0.009 for pain or cramps; P = 0.02 for excessive gas). Rates of adverse events were comparable in the rifaximin and placebo groups. Minimal changes in coliform flora were found during rifaximin therapy., Limitations: Rifaximin safely prevented travelers' diarrhea in Mexico, where most cases are caused by diarrhea-producing Escherichia coli. A study is needed in Asia to determine whether rifaximin can prevent diarrhea caused by invasive bacterial pathogens., Conclusions: Rifaximin prevents travelers' diarrhea with minimal changes in fecal flora, and more liberal chemoprophylaxis against this disease should be considered. Future studies should evaluate whether rifaximin is effective in preventing postinfectious irritable bowel syndrome.

A pilot study was performed to compare the effects of a restricted physiologic diet in 48 subjects with those of an unrestricted diet in 57 subjects on the duration and symptoms of acute travelers' diarrhea among US adults being treated with an antimicrobial agent in Mexico. Restricted physiologic diet was defined as the avoidance of certain foods during diarrheal illness, as specified in limited published literature. The mean duration of diarrhea (37 vs. 33 h) and clinical symptoms were similar between those practicing the restricted diet and those practicing unrestricted diets. These results suggest that restricting diet during treatment of travelers' diarrhea with an antimicrobial agent is not associated with improvement of clinical symptoms or with decreased duration of diarrhea. However, a much higher number of subjects would need to be studied to prove this point statistically.

Increased drug resistance among enteropathogens is an emergent problem in travelers' diarrhea. This randomized, double-blind trial was conducted in Guadalajara, Mexico, during the summers of 1999-2001 to compare azithromycin with levofloxacin for the treatment of travelers' diarrhea. A total of 217 US adults were randomized to receive a single oral dose of azithromycin (1000 mg; 108 persons) or levofloxacin (500 mg; 109 persons), with a follow-up period of 4 days. Three patients in each group dropped out of the study. The median time between initiation of therapy and passage of the last unformed stool (azithromycin group, 22.3 h; levofloxacin group, 21.5 h) and the number of unformed stools passed during the 4-day follow-up period (azithromycin group, 6.5; levofloxacin group, 5.5) were similar. Treatment failure occurred in 10 patients (9.5%) receiving azithromycin and 8 patients (7.5%) receiving levofloxacin. Possible minor, self-limiting adverse events occurred in 57 patients in each treatment group. Azithromycin was found to be a safe and effective alternative to levofloxacin for the treatment of acute travelers' diarrhea in US adult travelers to Mexico.

The natural history of enteroaggregative Escherichia coli (EAEC) and enterotoxigenic E. coli (ETEC) infection was studied among 40 US travelers who provided weekly stool samples for 4 weeks after arrival in Mexico. At enrollment, 5 subjects were colonized by EAEC and 3 by ETEC. During the first 2 weeks after enrollment, 12 developed EAEC diarrhea, 7 developed ETEC diarrhea (5 with mixed EAEC/ETEC diarrhea), 13 had EAEC colonization, and 7 had ETEC colonization. During the third and fourth weeks, 4 experienced EAEC diarrhea, 2 experienced ETEC diarrhea (1 with mixed EAEC/ETEC diarrhea), 31 had EAEC colonization, and none had ETEC colonization. Plasmid DNA analysis showed a high degree of heterogeneity among EAEC isolates. Symptomatic EAEC infection occurred early after arrival in Guadalajara, Mexico, and was as common as ETEC infection. Asymptomatic EAEC infection was recurrent.

Rifaximin is a poorly absorbed rifamycin derivative under investigation for treatment of infectious diarrhea. Adult students from the United States in Mexico and international tourists in Jamaica were randomized to receive either rifaximin (400 mg twice per day) or ciprofloxacin (500 mg twice per day) for 3 days, following a double-blinded model, from June 1997 to September 1998. A total of 187 subjects with diarrhea were studied. Time from initiation of therapy to passage of last unformed stool was comparable for those receiving rifaximin or ciprofloxacin (median, 25.7 hours versus 25.0 hours, respectively). There was no significant difference in the proportion of subjects in the 2 groups with respect to clinical improvement during the first 24 hours (P=.199), failure to respond to treatment (P=.411), or microbiological cure (P=.222). The incidence of adverse events was low and similar in each group. Rifaximin is a safe and effective alternative to ciprofloxacin in the treatment of traveler's diarrhea.

Background/aims: Bacterial enteropathogens, the major cause of travelers' diarrhea, are customarily treated with antibacterial drugs. Rifaximin, a nonabsorbed antimicrobial was examined as treatment for travelers' diarrhea., Methods: A randomized, prospective, double-blind clinical trial was carried out in 72 US adults in Mexico. Patients with acute diarrhea received one of three doses of rifaximin (200, 400 and 600 mg t.i.d.) or trimethoprim/sulfamethoxazole (TMP/SMX, 160 mg/800 mg b.i.d.) for 5 days. Results were compared with data from 2 placebo-treated historical control populations., Results: The shortest duration of treated diarrhea was seen in the group receiving 200 mg rifaximin t. i.d (NS). Clinical failure to respond to treatment occurred in 6 of 55 (11%) rifaximin-treated subjects versus 5 of 17 (29%) of TMP/SMX-treated subjects (NS). Sixteen of twenty (80%) of the enteropathogens isolated from the rifaximin-treated subjects and 7 of 7 (100%) from the TMP/SMX group were eradicated by treatment (NS). Sixteen of twenty-four (67%) enteropathogens identified were susceptible to TMP and all 24 were inhibited by

In this double-blind study with 232 patients, 300 mg of ofloxacin given orally twice daily for 5 or 3 days was compared with placebo for the treatment of acute diarrhea in U.S. students visiting Guadalajara, Mexico. The 3-day regimen of ofloxacin was found to be as effective as the 5-day regimen in producing a clinical and microbiologic cure. Clinical cures for patients who received ofloxacin for 5 days occurred in 59 of 66 (89%) subjects, whereas clinical cure occurred in 77 of 81 (95%) of those who received ofloxacin for 3 days and in 56 of 79 (71%) of those who took placebo (P = 0.0001). When the duration of diarrhea after therapy was begun was compared in subgroups, a significant (P less than 0.05) shortening of posttreatment illness occurred in comparison with that in the placebo group for the following groups: for 5 days of ofloxacin, cases of shigellosis (32 versus 98 h); for 3 days of ofloxacin, all cases (28 versus 56 h), cases of enterotoxigenic Escherichia coli diarrhea (26 versus 66 h), cases of shigellosis (24 versus 98 h), all cases of illnesses associated with a bacterial enteropathogen (28 versus 69 h), and cases of illnesses in which numerous leukocytes were found in stool by microscopy (22 versus 49 h). Microbiologic eradication rates were 75 of 78 (96%) for patients who received ofloxacin and 37 of 46 (80%) for patients who received placebo (P = 0.009). There was no significant difference in the number of adverse events reported by patients in either of the treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

An open-label, parallel comparison of loperamide hydrochloride (Imodium A-D) and bismuth subsalicylate (Pepto-Bismol) was conducted using nonprescription dosages in adult students with acute diarrhea (three or more unformed stools in the preceding 24 hours plus at least one additional symptom of enteric infection). For the two-day study period, the daily dosage was limited to 8 mg (40 ml) for loperamide-treated subjects and to 4.9 g for bismuth subsalicylate-treated subjects. At these dosages, loperamide significantly reduced the average number of unformed bowel movements relative to bismuth subsalicylate. Following the initial dose of treatment, control of diarrhea was maintained significantly longer with loperamide than with bismuth subsalicylate. Time to last unformed stool was significantly shorter with loperamide than with bismuth subsalicylate. In providing overall subjective relief, subjects rated loperamide significantly better than bismuth subsalicylate at the end of the 24 hours. Both treatments were well tolerated, and none of the minor adverse effects reported resulted in discontinuation of therapy. It was concluded that loperamide is effective at a daily dosage limit of 8 mg (40 ml) for the treatment of acute nonspecific diarrhea and provides faster, more effective relief than bismuth subsalicylate.

The efficacy of nonprescription doses of loperamide hydrochloride (Imodium A-D) was compared with nonfibrous activated attapulgite (Diasorb) in a randomized, parallel, open-label study of adult patients with acute diarrhea. The results of the study showed loperamide to be more effective than attapulgite in the control of diarrhea. Loperamide significantly reduced stool frequency compared with attapulgite, particularly within the first 12-hour period following the start of therapy, and significantly shortened the mean time to last unformed stool (loperamide, 14.2 hours, versus attapulgite, 19.5 hours). Subjective evaluations of severity of enteric symptoms, overall relief following treatment, and overall relief after 48 hours of treatment were equivalent for both drugs. Both treatments were well tolerated, and there was no difference between treatments with respect to the proportion of patients reporting adverse experiences.

In the studies reported, evidence has been presented that U.S. students traveling to Mexico represent a model for the study of travelers' diarrhea. The incidence of illness acquisition approximates that published in other studies of travelers. Natural immunity was shown to develop as students remained in Mexico presumably through repeated exposure to prevalent agents, particularly ETEC. ETEC, shigella strains and no detectable agent represented the largest groups when etiologic assessment was made. Food probably served as the important source of diarrhea particularly that due to ETEC and shigella strains. The level of bacteria isolated from food suggested that organism replication occurred due to improper temperature storage rather than to heavy initial contamination. The location of food consumption was related to degree of risk: self preparation was the safest, eating in Mexican homes the least safe and consumption of food in public restaurants was intermediate in risk. Water probably played a role in the transmission of viral infection. The risk of water contamination appeared to be highest during the rainy seasons. Finally, the antimicrobial agents TMP/SMX and TMP alone were shown to effectively prevent and treat this form of travelers' diarrhea.

Two trials were carried out to evaluate antimicrobial agents in the therapy of travellers' diarrhoea. In the first, 72 students were given 500 mg bicozamycin (BI), a poorly absorbable drug, q.i.d. for three days and 68 were given a placebo. In the second, 37 students were given trimethoprim/sulphamethoxazole (160 mg TMP-SMX 800 mg), 38 TMP (200 mg), and in 35 a placebo was given b.i.d. for five days. Diarrhoea lasted on average 28 hours in those receiving BI compared to 64 hours in the placebo group (p = 0.00009). Significant shortening of diarrhoea after taking BI was seen for all subjects with illness, as well as those with ETEC diarrhoea, shigellosis and for those with unknown causes of illness. A significant clinical response was also noted in all categories of diarrhoea for both TMP-SMX and TMP when compared to placebo group.

One hundred forty-seven students from the United States were given trimethoprim-sulfamethoxazole (TMP-SMZ; 160 mg of TMP and 800 mg of SMZ) twice daily for 21 days after their arrival in Mexico. They were watched for the development of diarrhea during the 21 days and for an additional eight days after the termination of TMP-SMZ therapy. Diarrheal illness occurred in 11 (16%) of 67 students taking TMP-SMZ and in 44 (55%) of 80 students receiving a placebo; the differences were significant (P less than 0.001). Milder symptoms not quite satisfying the criteria for illness were also less common in the group receiving the active drug: 23% vs. 69% (P less than 0.001). The drug appeared to prevent infection by fully virulent enterotoxigenic Escherichia coli (strains producing heat-stable toxin and those producing heat-labile toxin) and perhaps by shigella strains. During the eight days of follow-up after drug administration, 14 students (26%) who had taken TMP-SMZ and two (2.5%) who had taken the placebo experienced diarrhea (P less than 0.05). Twelve subjects (14%) in the TMP-SMZ group and one subject (1%) in the placebo group developed a generalized rash that necessitated discontinuance of the drug. The eruption occurred after 9-16 days of drug administration (mean, 10 days). This study shows that TMP-SMZ taken twice daily can prevent travelers' diarrhea for up to three weeks. Diarrhea will develop, however, if the drug is stopped while the risk remains.

Within 48 hours of arrival in Mexico, 182 US students participated in a study to compare the efficacy of two dosages of bismuth subsalicylate (262 mg per tablet) as a prophylactic agent against diarrhea. The students were randomly assigned to receive two tablets (high dose) or one tablet (low dose) of bismuth subsalicylate four times daily or a placebo four times daily during a three-week period. Among these completing the trial, diarrhea (four or more unformed stools in 24 hours or three in eight hours, plus one other symptom) occurred in seven (14%) of 51 receiving the high-dose regimen compared with 15 (24%) of 63 receiving the low-dose regimen and 23 (40%) of 58 in the placebo group. Protection rates were 65% for high-dose and 40% for low-dose bismuth subsalicylate. Diarrhea caused by enterotoxigenic Escherichia coli was found in one student receiving the high-dose regimen, in no students receiving the low-dose regimen, and in seven placebo-treated subjects. Bismuth subsalicylate was well tolerated; the most common side effects were blackening of tongues and stools. Bismuth subsalicylate use in both dosages was associated with tinnitus at a low, clinically insignificant frequency of 1.2 days per 100 days of treatment. The dosage of two tablets of bismuth subsalicylate four times daily (2.1 g/d) appears to be a safe and effective means of reducing the occurrence of travelers' diarrhea among persons at risk for periods up to three weeks.