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 traveler's diarrhea.

Native valve endocarditis due to Bartonella henselae in a middle-aged human immunodeficiency virus-negative woman.

We report the case of a human immunodeficiency virus-negative woman who developed native valve endocarditis of the aortic valve due to Bartonell henselae infection. The diagnosis was established using serology and PCR analysis of excised aortic valve tissue.

Successful treatment of vancomycin-resistant Enterococcus faecium meningitis with linezolid: case report and literature review.

Vancomycin-resistant enterococci (VRE) are a rare cause of meningitis, occurring primarily in patients who have undergone neurosurgical procedures. We describe the first reported case of VRE meningitis successfully treated with linezolid. A 56-y-old female with subarachnoid hemorrhage underwent ventriculostomy and embolization of cerebral aneurysms. Her postoperative course was complicated by multiple infections needing repeated antibiotic courses, culminating in the development of VRE meningitis. She was treated with 600 mg of i.v. linezolid (MIC < 0.75 microg/ml) every 12 h for 6 weeks. After the fourth dose, peak and trough linezolid concentrations were 11.45 and 0.14 microg/ml in serum and 3.19 and 2.39 microg/ml in cerebral spinal fluid (CSF). On Day 19 of linezolid therapy, serum and CSF trough concentrations were 1.53 and 2.98 microg/ml, respectively. Linezolid achieved sufficient CSF concentrations to bring about clinical and bacteriological cure. We conclude that i.v. linezolid may be a useful option for treating VRE meningitis. We also present findings of a literature review, which identified 11 cases of VRE meningitis treated with other pharmacologic agents with mixed success.

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 traveler's diarrhea and persistent diarrhea in children in developing countries and in immunocompromised patients. To clarify the prevalence of EAEC in traveler's 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 traveler's 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 traveler's diarrhea in 3 geographically distinct study areas.

Emergence of trimethoprim-resistant Escherichia coli in healthy persons in the absence of prophylactic or therapeutic antibiotics during travel to Guadalajara, Mexico.

Thirty-nine healthy US students without diarrheal disease and who had not received prophylactic or therapeutic antibiotics were monitored for emergence of trimethoprim-resistant gram-negative fecal flora for a 3-week period after arrival in Guadalajara, Mexico. During this time period, most students showed no change in total fecal gram-negative bacteria (p > 0.05) but showed an increasing level of trimethoprim (TMP) resistance (p < 0.01) among fecal coliforms. Escherichia coli was the TMP-resistant organism isolated in 18 of 39 (46%) healthy students. These 18 TMP-resistant E. coli were also resistant to ampicillin (44%), azithromycin (11%), chloramphenicol (39%), ciprofloxacin (11%), doxycycline (89%), erythromycin (100%), furazolidone (72%), levofloxacin (17%), trimethoprim-sulfamethoxazole (89%) and trovafloxacin (17%). In the absence of prophylactic and therapeutic antibiotics, increased acquisition of TMP-resistant gram-negative fecal flora in this developing country is probably due to poor sanitary conditions and the recurrent and heavy exposure to antimicrobial-resistant indigenous flora as a result of contaminated food and drink.

Empirical antimicrobial therapy for traveler's diarrhea.

Over 7 million cases of traveler's diarrhea, defined as the passage of > or = 3 unformed stools in a 24-h period, occur each year among visitors to developing countries. Bacterial enteric pathogens are the most common etiologic agents isolated. Preliminary clinical results for patients with diarrhea predominantly caused by Campylobacter species have shown that azithromycin may be an effective alternative to fluoroquinolones for the treatment of traveler's diarrhea.

Intestinal secretory immunoglobulin A response to enteroaggregative Escherichia coli in travelers with diarrhea.

We examined stool samples from travelers for secretory immunoglobulin A (sIgA) to enteroaggregative Escherichia coli (EAEC) during episodes of acute diarrhea. Ten paired samples from 10 patients with diarrhea caused by EAEC were examined for the presence of specific sIgA by dot blot and Western blot immunoassays. Five samples were positive by dot blotting, and two samples were positive by Western blotting.

Characterization of enterotoxigenic Escherichia coli strains in patients with travelers' diarrhea acquired in Guadalajara, Mexico, 1992-1997.

The relationship between enterotoxigenic Escherichia coli (ETEC) and travelers' diarrhea was examined in a high-risk area in 1992-1997. Toxin patterns, colonization-factor antigens (CFAs), and in vitro antimicrobial susceptibility were determined. In total, 928 US students with diarrhea acquired in Guadalajara, Mexico, were screened for enteric pathogens. Diagnosis of ETEC infection was done with oligonucleotide probes. ETEC was isolated in 19.9% of the travelers with diarrhea. CFAs were identified in 51% of the ETEC strains. The highest CFA frequency was observed among heat-stable isolates. Ampicillin, furazolidone, and sulfisoxazole resistance of ETEC increased during the study period. ETEC isolation rates and CFA patterns varied little during the 6 years of the study, which has implications for immunoprophylactic strategies. The finding that differences in the results of ribotyping and plasmid analysis change over time suggests that multiple strains of ETEC were responsible for the illness in the region studied.

Reactive arthritis associated with typhoid vaccination in travelers: report of two cases with negative HLA-B27.

As international travel to developing countries increases, more people seek medical advice concerning food and water-borne diseases, including typhoid fever. Prevention of typhoid fever in high-risk groups (travelers to endemic areas, laboratory workers and household contacts of typhoid carriers) should rely primarily on prevention of exposure. However, immunization is an important adjunct. The decision to immunize against typhoid fever should be individualized, taking into account the benefits versus the risk of possible adverse reactions. Cases of reactive arthritis have been associated with the heat-phenol inactivated 'whole cell' parenteral vaccine, but to our knowledge reactive arthritis has not been previously reported with the oral form (Ty21a). This is a report of HLA-B27 negative reactive arthritis occurring in two travelers after the administration of oral Ty21a typhoid vaccine.

Enteroaggregative Escherichia coli as a cause of traveler's diarrhea: clinical response to ciprofloxacin.

The purpose of this study was to determine the role of enteroaggregative Escherichia coli (EAEC) in the development of traveler's diarrhea and the clinical response of patients with EAEC diarrhea following treatment with ciprofloxacin. Sixty-four travelers with diarrhea and no other recognized enteropathogen were enrolled in treatment studies in Jamaica and Mexico from July 1997 to July 1998. EAEC was isolated from 29 travelers (45.3%). There was a significant reduction in the duration of posttreatment diarrhea in the 16 patients treated with ciprofloxacin, as compared with that in the 13 patients who received placebo (mean of 35.3 versus 55.5 hours; P = .049). There was a nonsignificant reduction in the mean number of unformed stools passed during the 72 hours after enrollment in the ciprofloxacin-treated group (5.6), as compared with that in the placebo group (7.5) (P = .128). This study provides additional evidence that EAEC should be considered as a cause of antibiotic-responsive traveler's diarrhea.

Oral rehydration therapy plus loperamide versus loperamide alone in the treatment of traveler's diarrhea.

Eighty United States students in Mexico received either loperamide (an initial dose of 4 mg, followed by 2 mg after passage of each unformed stool, up to 8 mg/d; 40 patients) or loperamide (at the same dosage schedule) plus an oral rehydration therapy (ORT) preparation (500 mL initially, followed by 250 mL after each subsequently passed unformed stool, up to 1,000 mL per 24 hours; 40 patients). The ORT preparation was a modification of the World Health Organization-recommended solution, adjusted to a sodium concentration of 60 mEq/L. All treatments were given for 48 hours. The study demonstrated equivalent clinical responses with regard to diminishment of diarrhea or subjective findings such as abdominal pain/cramps, headache, dry mouth, dizziness, or thirst. Stool number (by form) and specific gravity of urine postenrollment were similar in the groups. Administration of loperamide plus ORT for the management of traveler's diarrhea, in cases in which subjects were encouraged to drink ad libitum, offered no benefit over administration of loperamide alone.

Prevention and empiric treatment of traveler's diarrhea.

Diarrheal illness has plagued travelers for centuries, and to this day it remains the most common medical problem affecting travelers from industrialized nations to areas of the world where substandard hygiene conditions and sanitation prevail. This article discusses the cause of diarrheal illness in travelers, as well as epidemiology, prevention, treatment, and a general approach to self-treatment.

Bacterial gut infections.

Infections of the bowel as a result of bacterial enteropathogens are one of the most common medical problems. The use of novel molecular biology techniques and the recent development of new antimicrobial drugs and vaccines are helping us to identify, understand, treat and prevent these infections.

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

Travelers' diarrhea. Epidemiology, prevention, and self-treatment.

Risk factors for travelers' diarrhea include adventurous behavior, consumption of unclean water or food, and special hosts like those taking long acting H2 blockers. Approaches to prevention include education about risk factors, which often fails to lead to modification of risky behavior, and chemoprophylaxis with bismuth subsalicylate-containing compounds or antimicrobial agents. Chemoprophylaxis is generally discouraged except in special circumstances and in high-risk hosts. Self-treatment of travelers' diarrhea is successful in limiting the course of diarrhea and minimizing losses of vacation and business time. Current therapeutic options, in order of increasing effectiveness, include attapulgite, BSS-containing compounds, loperamide, antimicrobial agents such as the fluoroquinolones, and the combination of loperamide and an antimicrobial agent. Under study are a nonabsorbed antimicrobial agent, rifaximin, and a novel calmodulin inhibitor, zaldaride. Development and evaluation of vaccines against enterotoxigenic Escherichia coli and Shigella are proceeding apace but are not yet available for routine use.

Occult blood versus fecal leukocytes in the diagnosis of bacterial diarrhea: a study of U.S. travelers to Mexico and Mexican children.

A study was done to test the effectiveness of fecal occult blood as a screening test for invasive bacterial pathogens and as a substitute for the fecal leukocyte examination in adult and pediatric cases of acute diarrhea. United States citizens studying in Mexico and Mexican children, both with acute diarrhea had their stools cultured, examined for fecal leukocytes, and tested for occult blood. Using culture results as the criterion standard for detection of bacterial agents, and fecal leukocytes for diarrhea associated with diffuse colonic inflammation, occult blood was tested for its sensitivity, specificity, and predictive value using 2 x 2 tables. Analysis of the data found that occult blood negative samples were reliable indicators of a lack of invasive bacteria in both adult and pediatric patients (negative predictive values of 87% and 96%, respectively). Positive results for either test were not reliably predictive as indicators of invasive bacteria among adults. A positive occult blood test result was significantly more sensitive than a positive fecal leukocyte test result (79% versus 42%) in detecting invasive bacteria in the pediatric patients; however, the positive predictive value was only 24%. The fecal occult blood test is an uncomplicated, low-cost test that was reliable when giving a negative result in detecting a lack of invasive bacteria in adult and pediatric patients with diarrhea. In children, a positive result on a fecal occult blood test is sensitive but not specific in detecting invasive bacterial enteropathogens. These data also indicate that a commercially available test for occult blood represents a suitable alternative to microscopic examination of fecal samples for leukocytes obtained from patients with acute diarrhea.