Randomised trial of single-dose ciprofloxacin for travellers' diarrhoea. Oral aztreonam, a poorly absorbed yet effective therapy for bacterial diarrhea in US travelers to Mexico. Antimicrobial therapy for travelers' diarrhea. Treatment of travellers' diarrhoea with pivmecillinam. Furazolidone versus ampicillin in the treatment of traveler's diarrhea. Short-term treatment of traveler's diarrhea with norfloxacin: a double-blind, placebo-controlled study during two seasons. Use of azithromycin for the treatment of Campylobacter enteritis in travelers to Thailand, an area where ciprofloxacin resistance is prevalent. Optimal dosing of trimethoprim-sulfamethoxazole when used with loperamide to treat traveler's diarrhea. Role of a novel antidiarrheal agent, BW942C, alone or in combination with trimethoprim-sulfamethoxazole in the treatment of traveler's diarrhea. Ciprofloxacin or trimethoprim-sulfamethoxazole as initial therapy for travelers' diarrhea. A placebo-controlled, randomized trial. Single Dose Ofloxacin plus Loperamide Compared with Single Dose or Three Days of Ofloxacin in the Treatment of Traveler's Diarrhea. Short-term self-treatment of travellers' diarrhoea with norfloxacin: a placebo-controlled study. Treatment of traveler's diarrhea with ciprofloxacin and loperamide. Treatment of traveler's diarrhea with sulfamethoxazole and trimethoprim and loperamide. Norfloxacin compared to trimethoprim/sulfamethoxazole for the treatment of travelers' diarrhea among U.S. military personnel deployed to South America and West Africa. Treatment of travelers' diarrhea: ciprofloxacin plus loperamide compared with ciprofloxacin alone. A placebo-controlled, randomized trial. Ecological effects of short-term ciprofloxacin treatment of travellers' diarrhoea.
Diarrhoea is the most common illness affecting travellers to developing countries. Our study was designed to compare the efficacy of a single 500 mg dose of ciprofloxacin with placebo for treatment of acute diarrhoea in travellers. British troops who were within their first 8 weeks of deployment in Belize and who presented within 24 h of the onset of diarrhoea, were randomized to receive either ciprofloxacin 500 mg or placebo. Every subject recorded the number and consistency of stools and presence of any other associated symptoms for 72 h or until recovery. Of 88 subjects enrolled, 83 were evaluable, of whom 45 received ciprofloxacin and 38 placebo. Groups did not differ with regard to duration or severity of diarrhoea at randomisation. Mean (SE) duration of diarrhoea, as assessed by time to the last liquid and last unformed stool, was reduced from 50.4 (4.5) h and 53.5 (4.4) h, respectively, in the placebo group to 20.9 (3.4) h and 24.8 (3.8) h in those receiving ciprofloxacin (p < 0.0001). Mean number of liquid stools was reduced from 11.4 (1.2) in the placebo group to 5.0 (0.7) in the ciprofloxacin-treated group (p < 0.0001). The cumulative percentages of subjects with no unformed stool after 24 h, 48 h, and 72 h were, respectively, 64%, 82%, and 93% in the ciprofloxacin group and 11%, 42%, and 79% in the placebo group (p < 0.0001, p < 0.001, and not significant, respectively). A single 500 mg dose of ciprofloxacin was an effective empirical treatment for reducing the duration and severity of diarrhoea in travellers. The regimen should maximise compliance and reduce the cost and duration of therapy. To evaluate a poorly absorbed antimicrobial with in vitro activity against all major bacterial enteropathogens in oral therapy for bacterial diarrhea.
                One hundred ninety-one US students with diarrhea acquired in Mexico received 100 mg of aztreonam or matching placebo three times a day for 5 days. Stools were cultured for bacterial enteropathogens before and after therapy.
                We studied US students who acquired diarrhea in Mexico (travelers' diarrhea) in view of the high frequency of bacterial agents in this setting.
                We examined time of clinical recovery, treatment failures, adverse experiences, and microbiologic eradication from stool of the etiologic agent in subjects randomized to receive aztreonam or placebo.
                Aztreonam reduced the average duration of diarrhea compared with the placebo: for all cases, by 40 hours (P much less than .01); for those with enterotoxigenic Escherichia coli diarrhea, by 50 hours (P less than .01); for those with shigellosis, by 90 hours (P, not significant [small sample size]); for all bacterial agents, by 57 hours (P much less than .01). Clinical failures during the 5 days of therapy were seen in six patients (6%) receiving aztreonam and 25 (27%) receiving placebo (P less than .01). Pathogen eradication occurred in 95% of those receiving aztreonam and in 70% of those receiving the placebo (P less than .01). All bacterial enteropathogens were susceptible in vitro to aztreonam. The drug was well tolerated.
                Oral aztreonam, which is poorly absorbed, was well tolerated and was an effective therapy for bacterial diarrhea in US adults in Mexico. Three clinical trials were carried out to examine the efficacy of various antimicrobial agents in the treatment of travelers' diarrhea among students from the United States in Mexico. Thirty-seven subjects received twice daily for five days 160 mg of trimethoprim (TMP) and 800 mg of sulfamethoxazole (SMZ), 38 received 200 mg of TMP, and 35 received a placebo. Another group of students were given 100 mg of furazolidone (47 students) or ampicillin (47 students) four times a day for five days. In the third study, 500 mg of bicozamycin (72 students) or a placebo (68 students) was given four times a day for three days. Most students who received TMP-SMZ (78%), TMP (84%), or bicozamycin (85%) had recovered by 48 hr after initiation of treatment, as compared with 14% and 47% in the corresponding placebo groups and 55% in the furazolidone group. The agents had a positive effect for all etiologic categories, including diarrhea due to enterotoxigenic Escherichia coli and Shigella strains and illness without any established etiologic agents. Treatment failures were unusual with TMP-SMZ, TMP, and bicozamycin therapy (5% vs. 39% for the placebo-treated students). The drugs were well tolerated. The use of TMP-SMZ or TMP alone in the empiric treatment of moderate to severe travelers' diarrhea is advocated. nan Ninety-four U.S. students who acquired diarrhea in Mexico were treated with furazolidone (47 subjects) or ampicillin (47 subjects) on a double-blind random basis. Of 47 students, 26 (55%) who received furazolidone (100 mg four times daily for 5 days) recovered from illness within 48 h after initiation of therapy, in contrast to 15 of 47 (32%) who received ampicillin (500 mg four times daily for 5 days) (P less than 0.05). Altogether, 74% of students treated with furazolidone and 49% of those receiving ampicillin were well within 72 h (P less than 0.05). When furazolidone was compared with ampicillin, clinical illness was shortened on the average from 65 to 61 h for enterotoxigenic Escherichia coli diarrhea, from 83 to 58 h for shigellosis, from 82 to 51 h for diarrhea unassociated with a detectable agent, and from 72 to 57 h for all cases irrespective of etiology. Although not dramatically effective in the current trial, the broad spectrum of activity of furazolidone is of interest. Because of in vitro activity against Campylobacter strains and known effectiveness in treating giardiasis, furazolidone should be considered in therapy for diarrhea of unknown etiology in certain settings when laboratory processing of stools for etiological agent is not feasible. Clinical efficacy of norfloxacin for treatment of traveler's diarrhea in 106 Finnish tourists vacationing in Morocco was evaluated during two different seasons. When the criteria for diagnosis of traveler's diarrhea were fulfilled, norfloxacin (400 mg) or a placebo was given orally, twice daily for 3 days. All symptoms and signs subsided sooner in the norfloxacin group. The clearest difference was observed in the duration of diarrhea: 1.2 days in the norfloxacin group vs. 3.3 days in the placebo group (P < .001). The duration of diarrhea due to particular species was as follows for the two groups: in cases due to Salmonella enterica, 1.1 vs 4.1 days (P < .01); in cases due to Campylobacter jejuni, 1.8 vs. 5.0 days (P < .01); and in cases due to enterotoxigenic Escherichia coli, 1.0 day vs. 3.1 days (P < .01). The rate of full recovery during administration of norfloxacin or a placebo was also greater among the norfloxacin recipients: 84% vs. 47% (P < .001). No significant adverse effects were reported. Norfloxacin proved to be safe and effective in therapy for traveler's diarrhea. We evaluated the use of azithromycin (500 mg) or ciprofloxacin (500 mg) daily for 3 days for the treatment of acute diarrhea among United States military personnel in Thailand. Stool cultures were obtained and symptoms were recorded on study days 0, 1, 2, 3, and 10. Campylobacter species were the most common pathogen isolated (44 isolates from 42 patients). All Campylobacter isolates were susceptible to azithromycin; 22 were resistant to ciprofloxacin. Among the 42 patients with campylobacter infection, there were 2 clinical and 6 bacteriologic treatment failures in the ciprofloxacin group and no treatment failures in the azithromycin group (P = .021 for bacteriologic failures). Overall, azithromycin was as effective as ciprofloxacin in decreasing the duration of illness (36.9 hours vs. 38.2 hours, respectively) and the number of stools (6.4 vs. 7.8, respectively). Among those not infected with Campylobacter species (n = 30), the duration of illness was 32.9 hours vs. 20.7 hours (P = .03) for the azithromycin and ciprofloxacin groups, respectively. Azithromycin is superior to ciprofloxacin in decreasing the excretion of Campylobacter species and as effective as ciprofloxacin in shortening the duration of illness. Azithromycin therapy may be an effective alternative to ciprofloxacin therapy in areas where ciprofloxacin-resistant Campylobacter species are prevalent. To explore the optimal dosing regimen for trimethoprim-sulfamethoxazole (TMP-SMX) when used in combination with loperamide to treat traveler's diarrhea, 190 U.S. adults with acute diarrhea were enrolled in a double-blind, randomized trial in Guadalajara, Mexico. All patients received loperamide (4-mg loading dose; 2 mg after each loose stool, not to exceed 16 mg/day for 3 days) and were randomized to receive a 3-day course of TMP-SMX (160:800 mg twice daily for six doses) (group A), a single large dose of TMP-SMX (320:1,600 mg) (group B), or a large loading dose (320:1,600 mg) followed by standard doses for 3 days (160:800 mg twice daily for five doses) (group C). Patients in group C responded best (P < 0.01), with 75% of subjects recovered from diarrhea in 12 h compared with 34 h (group A) and 33 h (group B). Similar differences in favor of group C were noted in the subset of patients who presented with moderate to severe diarrhea. On average, patients in group C took significantly (P < 0.05) less loperamide (1.2 mg) after the 4-mg loading dose compared with patients in group A (2.4 mg) or group B (2.0 mg). We conclude that the most efficacious treatment of traveler's diarrhea in the interior of Mexico is to take loperamide in usual doses to control symptoms in combination with a single large dose of TMP-SMX, which should then be continued for 3 days in standard doses. The efficacy of BW942C, a novel enkephalinlike pentapeptide antidiarrheal agent, was compared with the efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) and the combination of the two agents in a placebo-controlled trial of the 72-h treatment of acute diarrhea. Subjects with diarrhea but without bloody stools or fever greater than 102 degrees F (38.9 degrees C) were enrolled. Administered to 134 U.S. adults with diarrhea that developed shortly after their arrival in Guadalajara, Mexico, BW942C was more efficacious than TMP-SMX in relieving diarrhea and cramps in the first 12 h of therapy, especially among subjects with diarrhea caused by enterotoxigenic E. coli. In the BW942C treatment group, 25% of subjects eventually took additional therapy because their diarrhea did not respond to BW942C alone. Neurological side effects such as dizziness and light-headedness occurred more frequently among BW942C-treated subjects. Therapy for 3 days with TMP-SMX provided lasting relief comparable with previously reported 5-day therapy. Use of the combination of both agents provided the benefits of prompt relief afforded by BW942C and lasting relief afforded by TMP-SMX. BW942C might prove to be an agent suitable for the treatment of acute diarrhea, with TMP-SMX reserved for treatment of those who do not respond adequately. The empiric use of the combination of BW942C and TMP-SMX appears appropriate for the treatment of severe nondysenteric disease. The efficacy of ciprofloxacin was compared with that of trimethoprim-sulfamethoxazole in a placebo-controlled trial of the 5-day treatment of acute diarrhea among 181 adults recently arrived in Guadalajara, Mexico. Both antimicrobial agents were significantly (p less than 0.0001) more efficacious than placebo in the treatment of diarrhea, with the average duration of diarrhea being 29, 20, and 81 hours, respectively, in the ciprofloxacin, trimethoprim-sulfamethoxazole, and placebo treatment groups. The antimicrobial agents were also more efficacious than placebo in treating diarrhea caused by enterotoxigenic Escherichia coli, invasive enteropathogens, and unknown pathogens. Both antimicrobials were effective in treating mild-to-moderate and moderate-to-severe disease, and both were well tolerated. Ciprofloxacin appears to be a logical alternative to trimethoprim-sulfamethoxazole in the initial treatment of acute travelers' diarrhea. 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. In a randomized, double blind, placebo-controlled, multicentre trial, 447 travellers to Africa, Asia or Latin America started three days treatment with norfloxacin 400 mg bd or placebo within 24 h after the onset of travellers' diarrhoea. One hundred and four subjects developed diarrhoea and of those 94 (46 in the norfloxacin group and 48 in the placebo group) could be analysed for efficacy. By the last treatment day, 34 patients in the norfloxacin and 18 in the placebo group were cured (P = 0.0001), four and three improved and five and 19, respectively, were failures. Recurrences were seen in three patients on norfloxacin and eight on placebo. The mean time to cure was 3.2 days in the norfloxacin group and 4.4 days in the placebo group (P less than 0.005). The number of loose stools was significantly lower in the norfloxacin group. Nine adverse events were reported; seven in the placebo and two in the norfloxacin group. Pre- and post-travel faecal samples were studied in 19 patients treated with norfloxacin, 21 treated with placebo and 21 untreated subjects without diarrhoea. In treated subjects, increased frequencies of Escherichia coli resistant to ampicillin, co-trimoxazole, doxycycline and chloramphenicol were found in both groups, though more frequently in the placebo one. No subject had norfloxacin resistant Esch. coli pre- and post-travel. To determine the efficacy of loperamide given with long- and short-course quinolone therapy for treating traveler's diarrhea, 142 US military personnel were randomized to receive a single 750-mg dose of ciprofloxacin with placebo, 750 mg of ciprofloxacin with loperamide, or a 3-day course of 500 mg of ciprofloxacin twice daily with loperamide. Culture of pretreatment stool specimens revealed campylobacters (41%), salmonellae (18%), enterotoxigenic Escherichia coli (ETEC, 6%), and shigellae (4%). Of the participants, 87% completely recovered within 72 h of entry. Total duration of illness did not differ significantly among the three treatment groups, but patients in the 3-day ciprofloxacin plus loperamide group reported a lower cumulative number of liquid bowel movements at 48 and 72 h after enrollment compared with patients in the single-dose ciprofloxacin plus placebo group (1.8 vs. 3.6, P = .01; 2.0 vs. 3.9, P = .01). While not delivering a remarkable therapeutic advantage, loperamide appears to be safe for treatment of non-ETEC causes of traveler's diarrhea. Two of 54 patients with Campylobacter enteritis had a clinical relapse after treatment that was associated with development of ciprofloxacin resistance. In a randomized, double-blind, placebo-controlled trial, 227 US adults with acute diarrhea in Mexico received a single dose of sulfamethoxazole and trimethoprim (1600/320 mg) or 3 days of therapy with loperamide hydrochloride (4-mg loading dose, then 2 mg orally after each loose stool), sulfamethoxazole-trimethoprim (800/160 mg orally twice daily), or the combination of both. Subjects treated with the combination had the shortest average duration of diarrhea compared with the placebo group (1 hour vs 59 hours), took the least amount of loperamide after the loading dose (3.8 mg), and had the shortest duration of diarrhea associated with fecal leukocytes or blood-tinged stools (4.5 hours). A single dose of sulfamethoxazole-trimethoprim was also efficacious (28 vs 59 hours), but loperamide alone was significantly effective only when treatment failures were treated with antibiotics (33 vs 58 hours). The combination of sulfamethoxazole-trimethoprim plus loperamide can be highly recommended for the treatment of most patients with traveler's diarrhea. A randomized treatment trial of travelers' diarrhea was carried out among U.S. military personnel participating in routine exercises in several port cities in South America and West Africa. A 5-day, twice daily course of either norfloxacin (400 mg) or trimethoprim/sulfamethoxazole (TMP/SMX, 160/800 mg) was given to 142 volunteers. At the end of 5 days of treatment, diarrhea had resolved in 100% of 73 patients receiving norfloxacin and 97.1% (67/69) receiving TMP/SMX. A probable bacterial pathogen was determined in 44% of 142 subjects: 49% of the norfloxacin group and 39% of the TMP/SMX group. The most common pathogens detected were enterotoxigenic Escherichia coli in 20% of cases and rotavirus in 15%. Resistance to TMP/SMX was present in 20 (27%) bacterial isolates, while no resistance to norfloxacin was found. Eight of 10 patients in the TMP/SMX treatment group who had TMP/SMX-resistant bacterial enteropathogens improved clinically. Both norfloxacin and TMP/SMX were clinically effective in the treatment of travelers' diarrhea in this military population. To compare the safety and efficacy of loperamide used in combination with ciprofloxacin or ciprofloxacin alone for the treatment of travelers' diarrhea.
                Double-blind, placebo-controlled, randomized clinical trial.
                United States Army hospital in Egypt.
                United States military personnel with travelers' diarrhea (n = 104) during a military exercise in November 1989. Persons who were noncompliant, had bloody diarrhea, or had received antidiarrheal medications before entry into the study were excluded.
                All participants with travelers' diarrhea were treated with ciprofloxacin, 500 mg twice daily for 3 days. Fifty of these patients were randomly assigned to receive loperamide, a 4-mg first dose and 2 mg for every loose stool (as much as 16 mg/d), and 54 were randomly assigned to receive placebo.
                Enterotoxigenic Escherichia coli was isolated from 57% of patients; Shigella and Salmonella, seen in 4% and 2% of patients, respectively, were not common.
                After 24 hours, the symptoms of 82% of patients in the ciprofloxacin and loperamide group compared with 67% in the ciprofloxacin and placebo group had improved or fully recovered (odds ratio, 2.3; 95% CI, 0.8 to 6.3; P = 0.08). After 48 hours, the symptoms of 90% of both groups had improved or fully recovered. The mean number of stools for those receiving loperamide was not much lower than those who did not receive loperamide after 24 hours (1.9 +/- 0.2 [SE] compared with 2.6 +/- 0.2) or 48 hours (3.1 +/- 0.3 compared with 4.0 +/- 0.3) of treatment (P = 0.19).
                In a region where enterotoxigenic E. coli was the predominant cause of travelers' diarrhea, loperamide combined with ciprofloxacin was not better than treatment with ciprofloxacin alone. Loperamide appeared to have some benefit in the first 24 hours of treatment in patients infected with enterotoxigenic E. coli. Both regimens were safe. Forty-two subjects travelling to Mexico for 11 days were enrolled in a randomized, double-blind, placebo-controlled trial comparing ciprofloxacin 250 mg twice daily for three days or placebo for treatment of travellers' diarrhoea. Seventeen (41%) subjects were randomized to treatment. By the last treatment day, all seven evaluable subjects in the ciprofloxacin group, and three of eight evaluable subjects in the placebo group were cured (P = 0.04). The mean time to cure was 26 h for ciprofloxacin and 60 h for placebo-treated patients (P = 0.03). Faecal specimen were collected pre-travel, after four days in Mexico, 48 h post-travel and four weeks post-travel. Potentially pathogenic Escherichia coli strains carrying diarrhoeagenic virulence genes were detected by DNA hybridization tests, during or after travel, in 41% of treated and 31% of asymptomatic travellers. Travel, irrespective of diarrhoea and type of treatment, had a minor impact on the aerobic and anaerobic microflora. In travellers with ongoing diarrhoea, a suppression of the numbers of anaerobic bacteria was found, but the microflora was otherwise virtually unaffected. Significantly increased frequencies of E. coli resistant to ampicillin, doxycycline, chloramphenicol and co-trimoxazole were found during and after travel in all categories of travellers, though more frequently in subjects who experienced diarrhoea. The susceptibility of Bacteroides spp. remained unchanged. The sensitivity of E. coli to ciprofloxacin was not affected by travel, except in four ciprofloxacin-treated subjects who acquired multiresistant E. coli with ciprofloxacin MICs of > or = 0.125 mg/L post-travel. Bacteroides strains with MICs of > or = 64 mg/L were isolated post-travel from four ciprofloxacin-treated patients, and from one of the other 34 travellers not treated with ciprofloxacin.
Antibiotic treatment is associated with shorter duration of diarrhoea but higher incidence of side-effects. Trials generally do not report duration of post-treatment diarrhoea using time-to-event analyses, and should do.