Zhi Dong Jiang

Prevalence of enteric pathogens among international travelers with diarrhea acquired in Kenya (Mombasa), India (Goa), or Jamaica (Montego Bay)

Stools from tourists from Europe and North America who acquired diarrhea in Mombasa (Kenya), Goa (India), or Montego Bay (Jamaica) were examined for enteric pathogens. Enterotoxigenic Escherichia coli (ETEC) was the most common pathogen (25%) identified in the 3 locations. Isolation of Shigella species was more frequent in Goa and Mombasa than in Montego Bay (10%, 9%, and 0.3%, respectively; P <.005). Viruses (rotaviruses and enteric adenoviruses) were found in 9% of travelers to the 3 areas. Of 275 ETEC isolates in this study, 158 (57%) produced a defined colonization factor antigen (CFA). Coli surface 6 (CS6) was the most frequent and was found in 41%-52% of CFA/CS-positive ETEC isolates. The frequency of resistance among bacterial enteropathogens to traditional antimicrobial agents was particularly high throughout the study period in all 3 regions. Quinolones were active against the bacterial enteropathogens in the 3 sites.

Enteroaggregative Escherichia coli as a Major Etiologic Agent in Traveler's Diarrhea in 3 Regions of the World

Enteroaggregative Escherichia coli (EAEC) has been reported to cause travelers diarrhea and persistent diarrhea in children in developing countries and in immunocompromised patients. To clarify the prevalence of EAEC in travelers diarrhea, we studied 636 US, Canadian, or European travelers with diarrhea: 218 in Guadalajara, Mexico (June--August 1997 and 1998), 125 in Ocho Rios, Jamaica (September 1997--May 1998), and 293 in Goa, India (January 1997--April 1997 and October 1997--February 1998). Stool samples were tested for conventional enteropathogens. EAEC strains were identified by use of the HEp-2 assay. EAEC was isolated in 26% of cases of travelers diarrhea (ranging from 19% in Goa to 33% in Guadalajara) and was second only to enterotoxigenic E. coli as the most common enteropathogen in all areas. Identification of EAEC reduced the number of cases for which the pathogen was unknown from 327 (51%) to 237 (37%) and explained 28% of cases with unknown etiology. EAEC was a major cause of travelers diarrhea in 3 geographically distinct study areas.

Post-Diarrhea Chronic Intestinal Symptoms and Irritable Bowel Syndrome in North American Travelers to Mexico

OBJECTIVES:Irritable bowel syndrome (IBS) has been reported to complicate bacterial diarrhea. Because of the frequency of international travel and the common occurrence of bacterial diarrhea, we studied the occurrence of chronic gastrointestinal complaints and post-diarrhea IBS in North U.S. travelers to Mexico.METHODS:One hundred and sixty-nine healthy students were followed prospectively for 5 wk for the occurrence and etiology of diarrhea while studying for 5 wk in Mexico. Subjects recorded their symptoms during travel and completed a gastrointestinal symptom questionnaire 6 months after returning to the United States to determine the presence of IBS using the Rome II criteria.RESULTS:Ninety-seven (57%) subjects returned a completed questionnaire. Sixty-one (63%) developed diarrhea while in Mexico, mostly due to enterotoxigenic and enteroaggregative Escherichia coli. Six months after travel the following chronic symptoms were reported: loose stools, abdominal pain, and fecal urgency in 17 (18%), 17 (18%), and 9 (9%) respectively. Of the 60 patients surveyed who had acquired diarrhea in Mexico, 7 (11%) met the criteria for IBS 6 months later of which 6 (10%) were newly diagnosed. No identified pathogen in the initial illness was associated with the development of IBS.CONCLUSIONS:Chronic gastrointestinal complaints including IBS are common in returning travelers having experienced diarrhea. Postinfectious complications of travelers diarrhea require further study for etiology and strategy for prevention.

Rifaximin versus Ciprofloxacin for the Treatment of Traveler's Diarrhea: A Randomized, Double-Blind Clinical Trial

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 travelers diarrhea.

Genetic Susceptibility to Enteroaggregative Escherichia coli Diarrhea: Polymorphism in the Interleukin-8 Promotor Region

Enteroaggregative Escherichia coli (EAEC) infection can be identified in 26% of travelers with diarrhea and is associated with fecal interleukin (IL)-8 production. We hypothesized that single-nucleotide polymorphisms (SNPs) in the IL-8 gene are associated with EAEC-related symptoms. Fecal IL-8 production and IL-8 SNPs at 5 loci were identified in 69 US students who remained in Mexico for 5 weeks; 23 subjects had EAEC-associated diarrhea, 7 were asymptomatic EAEC carriers, 22 had nonspecific diarrhea, and 17 were asymptomatic without an enteropathogen. The chances of having EAEC-associated diarrhea were significantly increased among those with the AA genotype at the -251 position (odds ratio [OR], 208.51; 95% confidence interval [CI], 28.5-1525.36) and among those with AT genotype (OR, 14.3; 95% CI, 1.98-105.74), compared with those with the TT genotype at the -251 position. Among subjects with EAEC-associated diarrhea, the AA genotype at the -251 position produced greater concentrations of fecal IL-8 than those with the AT or TT genotype (P=.0053). In the present study, the AA genotype at the -251 position was associated with the occurrence of EAEC-associated diarrhea and increased levels of fecal IL-8.

In Vitro Activity and Fecal Concentration of Rifaximin after Oral Administration

ABSTRACT Rifaximin showed moderately high MICs (the MIC at which 90% of the isolates tested were inhibited = 50 μg/ml) for 145 bacterial enteropathogens from patients with travelers diarrhea acquired in Mexico during the summers of 1997 and 1998. Rifaximin concentrations in stool the day after oral administration (800 mg daily for 3 days) were high (average, 7,961 μg/g), proving the value of the drug.

Therapy of travelers’ diarrhea with rifaximin on various continents

OBJECTIVE:Our aim was to compare the efficacy and safety of rifaximin, a virtually nonabsorbed antibiotic, 600 and 1200 mg per day, with placebo in patients with travelers’ diarrhea.METHODS:This was a multicenter, 1:1:1 randomized, parallel-group, double-blind study, conducted in Antigua, Guatemala; Guadalajara and Morelia, Mexico; and the coast of Kenya north and south of Mombasa. Adult patients with acute travelers’ diarrhea were recruited; exclusion criteria included primarily medication that could influence the outcome. Subjects were treated for 3 days, three times daily; follow-up lasted 5 days. For each 24-h period, the subjects completed a diary card. Pre- and posttreatment stool, blood, and urine samples were assessed.RESULTS:Among the 380 volunteers, median time to the last unformed stool was 32.5 and 32.9 h in both rifaximin groups, compared with 60.0 h with placebo (p = 0.0001). Also, secondary clinical outcome measures were favorably influenced by the active agent. No relevant side effects were reported.CONCLUSION:Rifaximin is efficacious and safe for treatment of travelers’ diarrhea at daily doses of 600 mg or higher.

In Vitro Antimicrobial Susceptibility Testing of Bacterial Enteropathogens Causing Traveler's Diarrhea in Four Geographic Regions

ABSTRACT The emergence of resistant enteropathogens has been reported worldwide. Few data are available on the contemporary in vitro activities of commonly used antimicrobial agents against enteropathogens causing travelers diarrhea (TD). The susceptibility patterns of antimicrobial agents currently available or under evaluation against pathogens causing TD in four different areas of the world were evaluated. Pathogens were identified in stool samples from U.S., Canadian, or European adults (18 years of age or older) with TD during 1997, visiting India, Mexico, Jamaica, or Kenya. MICs of 11different antimicrobials were determined against 284 bacterial enteropathogens by the agar dilution method. Ciprofloxacin, levofloxacin, ceftriaxone, and azithromycin were highly active in vitro against the enteropathogens, while traditional antimicrobials such as ampicillin, trimethoprim, and trimethoprim/sulfamethoxazole showed high levels and high frequencies of resistance. Rifaximin, a promising and poorly absorbable drug, had an MIC at which 90% of the strains tested were inhibited of 32 μg/ml, 250 times lower than the concentration of this drug in the stools. Amdinocillin, nalidixic acid, and doxycycline showed moderate activity. Fluoroquinolones are still the drugs of choice for TD in most regions of the world, although our study has a limitation due to the lack of Escherichia coli samples from Kenya and possible bias in selection of the patients for evaluation. Azithromycin and rifaximin should be considered as promising new agents. The widespread in vitro resistance of the traditional antimicrobial agents reported since the 1980s and the new finding of resistance to fluoroquinolones in Southeast Asia are the main reasons for monitoring carefully the antimicrobial susceptibility patterns worldwide and for developing and evaluating new antimicrobial agents for the treatment of TD.

Rifaximin: In vitro and in vivo antibacterial activity - A review

In vitro inhibitory activity of rifaximin is directed against Gram-positive and Gram-negative, aerobic and anaerobic bacteria. It is effective in the treatment of gastrointestinal infections when given orally because of the high concentration of the drug remaining in the gut lumen. Laboratory investigations have been carried out to assess the in vitro activity of rifaximin on different bacterial strains isolated from both human and domestic animals. The objective of this project is to review the in vitro and in vivo activity of rifaximin against bacterial infection with Gram-negative rods, Gram-positive rods and Gram-positive cocci and their resistance to rifaximin. The available data suggest that rifaximin is active in vitro and in vivo in the treatment of bacterial infection of adults and children.

Markers of Inflammation in Bacterial Diarrhea among Travelers, with a Focus on Enteroaggregative Escherichia coli Pathogenicity

The intestinal inflammatory response of travelers diarrhea acquired in Goa, India, and Guadalajara, Mexico, was studied. Fecal lactoferrin was found in stool samples in which enteroaggregative Escherichia coli (EAEC), enterotoxigenic E. coli, or Salmonella or Shigella species were isolated, with Shigella-positive cases showing the highest level. Samples from cases of Shigella-associated diarrhea had the highest concentrations of fecal cytokines. Travelers to India who had EAEC-associated diarrhea showed elevated levels of interleukin (IL)-8 (median, 341.15 pg/mL) and IL-1beta (median, 749.90 pg/mL). Although 15 travelers to Mexico who had EAEC-associated diarrhea had a median concentration of 0 pg/mL for both IL-8 and IL-1beta, 2 had high levels of IL-8 (1853 and 11,786 pg/mL), and 5 showed elevated levels of IL-1beta (1-1240 pg/mL). Samples from patients in India who had pathogen-negative diarrhea or from patients in Mexico who had asymptomatic EAEC infection were negative for cytokines. Bacterial pathogens causing travelers diarrhea commonly produce intestinal inflammation, although a subset of patients with EAEC-associated diarrhea fail to develop an inflammatory response.