Rifaximin: a nonabsorbed antimicrobial in the therapy of travelers' 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

Piperacillin/tazobactam in the treatment of hospitalized patients with urinary tract infections: an open non-comparative and multicentered trial.

The aim of this multicentered, prospective and open study was to determine the clinical and bacteriological efficacy and safety of piperacillin/tazobactam (4g/500 mg IV tid) in the treatment of 79 adult patients with complicated urinary tract infections (UTI) requiring hospitalization. Forty-seven women and 32 men (mean age 54.2 years, and range 21-91) from 4 Argentinean and 6 Mexican hospitals were enrolled. Sixty-one clinically and bacteriologically evaluable patients were treated for a mean of 9.1 days (range 5-15). A favorable clinical response was seen in 83.6% and 80% at early and late assessment, respectively. Bacteriological eradication was achieved in 85.3% and 80% at early and late estimation, respectively. Escherichia coli was isolated in 33 cases, Klebsiella pneumoniae in 8, Enterococcus spp. in 7, Proteus mirabilis in 6, Pseudomonas aeruginosa in 3, Enterobacter spp. and Morganella morganii in 2. While 21% of all the clinical isolates were resistant to piperacillin, none of them was initially resistant to piperacillin/tazobactam. However, one female patient with a persistent UTI caused by E. coli developed resistance to piperacillin/tazobactam during treatment. A 64-year-old man with frontal meningioma developed purulent meningitis due to Enterobacter cloacae after neurosurgery. He was initially treated with ciprofloxacin, rifampin and amikacin and because of persistence of fever, he was moved to piperacillin/tazobactam. After 5 days of therapy, he developed coma secondary to intracranial hemorrhage and died. By then, the platelet count was normal (220,000/microliters), but the prothrombin time (19.5 seconds) and the partial thromboplastin time (63 seconds) were significantly prolonged. Our data suggest that piperacillin/tazobactam is a reliable therapy for complicated, non-complicated, community or hospital-acquired UTI.

Proportional hazards analysis of diarrhea due to enterotoxigenic Escherichia coli and breast feeding in a cohort of urban Mexican children.

Ninety-eight women-infant pairs were followed for up to 50 weeks in the northern part of Guadalajara, Mexico, from August 1986 to July 1987 as part of a community-based, prospective study of the relation between infant feeding patterns and enterotoxigenic Escherichia coli producing heat-labile toxin (LT-ETEC) diarrheal disease. Strictly formula-fed children had an incidence of diarrhea over three times that of strictly breast-fed infants and twice that of breast-fed and supplementally fed children. Strictly formula-fed infants colonized by LT-ETEC were symptomatic for diarrhea nearly three times as often as strictly breast-fed infants and twice as often as infants receiving a mixed diet. The fitting of parametric hazard models to durations until LT-ETEC colonization revealed that the hazard for the first colonization was time invariant. The hazard of diarrhea increased by 400-500% during the rainy season or among children 3 months of age or older who received avena, a barley drink. The best-fitting hazard models to durations until symptomatic expression of LT-ETEC infection all increased through time. This hazard was inversely impacted by the overall amount of LT-ETEC-specific, immunoglobulin A antibodies the infant received via the mother's breast milk and by the provision of traditional medicinal teas.

Oral aztreonam, a poorly absorbed yet effective therapy for bacterial diarrhea in US travelers to Mexico.

OBJECTIVE: To evaluate a poorly absorbed antimicrobial with in vitro activity against all major bacterial enteropathogens in oral therapy for bacterial diarrhea. DESIGN: 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. SETTING: We studied US students who acquired diarrhea in Mexico (travelers' diarrhea) in view of the high frequency of bacterial agents in this setting. MAIN OUTCOME MEASURE: 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. RESULTS: 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. CONCLUSIONS: Oral aztreonam, which is poorly absorbed, was well tolerated and was an effective therapy for bacterial diarrhea in US adults in Mexico.

Antimicrobial therapy of bacterial diarrhea in adult residents of Mexico--lack of an effect.

Two clinical trials in adults in Mexico are reported. In the first trial, long-term residents of Mexico with acute fecal leukocyte-positive diarrhea were randomized to receive trimethoprim/sulfamethoxazole (TMP/SMX), clioquinol or a placebo. Neither antimicrobial shortened the illness for all cases or for those with shigellosis or enterotoxigenic Escherichia coli diarrhea. In a second study, US and Mexican students received enoxacin, TMP/SMX or a placebo on a blind random basis. While the placebo-treated subjects with bacterial diarrhea tended to be more ill after treatment than other groups, no statistical differences were seen in treatment groups. These studies cast doubts on the value of antimicrobial drugs for 'invasive' and other forms of bacterial diarrhea in adults living in endemic areas and indicate the importance of a placebo control group when conducting clinical trials in these populations.

Use of bismuth subsalicylate for the prevention of travelers' diarrhea.

During the months of July 1977 and July 1985, students from the United States participated in a double-blind, placebo-controlled trial examining the effectiveness of liquid bismuth subsalicylate (BSS) (1977) and two dosages of the tablet formulation of BSS (1985) in preventing diarrhea while in Guadalajara, Mexico. In the first study, 62 subjects received BSS for 3 weeks at a dosage of 60 mL four times daily (4.2 g of BSS/d) compared with 66 students receiving an oral placebo at a similar dosage schedule. In the second study, 51 students took two tablets four times daily (2.1 g of BSS/d), 63 took one tablet four times daily (1.05 g of BSS/d), and 58 took a placebo (two tablets taken four times daily), each for 3 weeks. In the initial study, 14 (23%) BSS-treated subjects developed diarrhea compared with 40 (61%) placebo-tested persons (P less than .0001). In the second trial, seven (14%) subjects taking two tablets of BSS four times daily, 15 (24%) taking one tablet of BSS four times daily, and 23 (40%) receiving placebo tablets experienced diarrhea (P less than .001 for the higher dose). The percent protection provided by BSS was 62% for the group that received 4.2 g/d, 65% for 2.1 g/d, and 40% for 1.05 g/d, when compared with the corresponding placebo group. In cases in which stools were analyzed, seven (24%) of 29 BSS-treated subjects who had diarrhea had a detectable enteric pathogen, compared with 35 (59%) of 59 of those randomized to receive a placebo. BSS was well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Test-of-cure stool cultures for traveler's diarrhea.

Whether enteropathogens were eradicated or persisted in test-of-cure stool cultures from 251 patients with traveler's diarrhea, the durations of diarrhea were similar within the antimicrobial agent-treated (32 versus 33 h) and placebo-treated (82 versus 96 h) groups. Routine test-of-cure stool cultures can be useful for evaluating treatment failures and for assessing asymptomatic carriage of enteropathogens after treatment, but they are not mandated in the design of placebo-controlled antimicrobial treatment trials in traveler's diarrhea when the focus of the trial is clinical efficacy.

Prevention of travelers' diarrhea by the tablet formulation of bismuth subsalicylate.

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.

Ciprofloxacin or trimethoprim-sulfamethoxazole as initial therapy for travelers' diarrhea. A placebo-controlled, randomized trial.

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.

Correlation between intestinal immune response to colonization factor antigen/I and acquired resistance to enterotoxigenic Escherichia coli diarrhea in an adult rabbit model.

Immunoprotection against diarrhea caused by colonization factor antigen/I (CFA/I)-positive, human-associated, enterotoxigenic Escherichia coli was investigated using the adult rabbit intestinal temporary ligation technique. An oral dose of 1 X 10(8) viable cells of enterotoxigenic Escherichia coli strain H-10407 (078:H11:CFA/I) produced diarrhea in all animals challenged. Rabbits allowed to survive this challenge dose were re-challenged approximately six weeks later with the result that four of seven (57%) did not develop diarrhea. Peroral immunization of rabbits with purified CFA/I elicited protection against challenge with strain H-10407; this protection was dose-related and CFA/I-specific. Immunoprotection did not correlate with a systemic antibody response. CFA/I produced a relatively poor immune response in terms of the number of IgM- and IgG-producing cells in the lamina propria of the animals but did elicit a vigorous increase in the number of intestinal IgA- and anti-CFA/I-producing cells. There was a highly significant inverse relationship between the number of IgA- and anti-CFA/I-producing cells in the lamina propria of the rabbits and the diarrhea response to the challenge strain H-10407 (correlation coefficients of -0.616 and -0.678 respectively). It is concluded that anti-CFA/I antibody, probably of the IgA class, is the major immune response to orally administered CFA/I and that this response is highly immunoprotective.