October 29, 2008 (Washington, DC) — Patients with established traveler's diarrhea who received treatment with once-daily prulifloxacin, a fluoroquinolone prodrug, experienced a cure within about 24 hours, according to results from a randomized double-blind placebo-controlled phase 3 trial.

The results were presented in a late-breaking session here at the 48th Annual ICAAC/IDSA 46th Annual Meeting, a joint meeting of the American Society for Microbiology and the Infectious Diseases Society of America.

"We gave approximately 200 patients with traveler's diarrhea the antibiotic or placebo in a double-blind randomized assignment," explained coauthor Herbert L. DuPont, MD, from St. Luke's Episcopal Hospital and University of Texas–Houston School of Public Health and Medical School. "The average duration of continuing diarrhea after patients took their first pill was about 1 day." More than half the patients who received placebo were still sick 5 days later, he said.

A total of 282 patients were randomly assigned to receive oral prulifloxacin 600 mg once daily (n = 187) or placebo (n = 95). Patients recorded the time of passage, the consistency of the stool, and symptoms up to the "test of cure" visit (24 to 72 hours after the last dose) in daily diaries. The investigators collected stool samples for microbiologic examination before and after treatment.

The study's primary end point was time to last unformed stool (TLUS). TLUS was defined as the time from ingestion of the first dose to "passage of the last unformed stool after wellness was achieved." TLUS was also confirmed by patient diaries. Secondary end points included microbiologic eradication rates.

Patients receiving prulifloxacin experienced diarrhea cure at a median of 24.2 hours after starting treatment in both the microbiologically evaluable group and a modified intent-to-treat analysis, which included patients whose pathogen could not be identified. More than half the control group did not achieve wellness by the test-of-cure visit or were declared clinical failures. In microbiologically evaluable patients, pathogens were eradicated in 80.9% of the patients receiving prulifloxacin, compared with 52.7% of patients in the placebo group. Enterotoxigenic Escherichia coli (the most common pathogen found), enteroaggregative E coli, Campylobacter, Salmonella, and Shigella were all eradicated by the study drug.

As calculated using a Kaplan–Meier log-rank test in analyzing the microbiologically evaluable patients, prulifloxacin was found to be significantly superior to placebo ( < .0001). For the patients in the modified intent-to-treat analysis, prulifloxacin was also more effective than placebo (P < .0001). Safety analyses showed that the drug was well tolerated, with a safety profile similar to placebo.

Each year an estimated 10 million travelers, mainly to developing countries, develop traveler's diarrhea. The illness can be caused by a known pathogen, or the pathogen might never be identified. In 5% to 10% of cases, the illness progresses to irritable bowel syndrome that can last from weeks, to months, to years, and even to decades, according to Dr. DuPont. "More than half of these people are still sick as many as 6 years later."

Several antibiotic treatments are available for the treatment of traveler's diarrhea. But shortcomings of available therapies, such as inadequate bacterial coverage, increasing bacterial resistance, and problems with patient compliance, highlight a need for alternatives. "We believe this drug shortens the duration of the illness significantly," Dr. DuPont told Medscape Infectious Diseases. The drug's once-daily, 3-day regimen is patient-friendly, he said.

"Clearly, traveler's diarrhea is a major issue," commented Sheldon L. Kaplan, MD, chief ofthe Infectious Disease Service at Texas Children's Hospital, in Houston. Dr. Kaplan was not involved with the study. "You have a once-a-day quinolone that was clearly was effective in decreasing the duration of diarrhea."

The study was funded by Optimer Pharmaceuticals, Inc, the makers of prulifloxacin. Dr. DuPont is a consultant for Optimer. Dr. Kaplan has disclosed no relevant financial relationships.

48th Annual ICAAC/IDSA 46th Annual Meeting: A Joint Meeting of the American Society for Microbiology and the Infectious Diseases Society of America: Abstract L-4134a. Presented October 28, 2008.

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