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Therapeutics

Ciprofloxacin plus loperamide was not a better treatment than ciprofloxacin alone for travelers' diarrhea

ACP J Club. 1991 Sept-Oct;115:38. doi:10.7326/ACPJC-1991-115-2-038


Source Citation

Taylor DN, Sanchez JL, Candler W, et al. Treatment of travelers' diarrhea: ciprofloxacin plus loperamide compared with ciprofloxacin alone. Ann Intern Med. 1991 May 1;114:731-4. [PubMed ID: 2012354]


Abstract

Objective

To determine if treatment with ciprofloxacin plus loperamide compared with ciprofloxacin alone decreases the duration of travelers' diarrhea.

Design

Randomized, double-blind, placebo-controlled trial of 3 days' duration.

Setting

A United States military camp treatment facility near Cairo, Egypt.

Patients

Soldiers were enrolled if they had ≥ 3 liquid stools in 24 hours or 1 to 2 liquid stools accompanied by abdominal cramps or vomiting. Patients were excluded if they had a fever higher than 38.3°C, grossly bloody diarrhea, or diarrhea for longer than 60 hours. Patients who had previously received antidiarrheal medication or were noncompliant were excluded from the final analysis. 104 of 123 completed the study.

Intervention

Patients were randomly assigned to receive either ciprofloxacin, 500 mg twice daily for 3 days and loperamide, 4 mg, plus 2 mg after each unformed stool (no more than 16 mg per day) (n = 50) or ciprofloxacin and placebo (n = 54). Patients received the first dose under observation and self-administered subsequent doses.

Main outcome measures

The detection of Salmonella or Shigella species or enterotoxigenic Escherichia coli and improvement in symptoms defined as 50% decrease in the daily number of stools compared with the previous 24 hours.

Main results

After 24 hours, 41 of 50 patients (82%) in the group receiving ciprofloxacin and loperamide had improved or recovered compared with 36 of 54 patients (67%) in the group receiving ciprofloxacin and placebo (P = 0.08). 90% of the patients in the study group and 89% in the control group had improved or fully recovered after 48 hours (P > 0.2) {absolute risk difference 1%, CI -12% to 14%}.* The mean number of liquid stools was somewhat less for the ciprofloxacin and loperamide group after 24 hours (1.9 ± 0.2 vs 2.6 ± 0.2, P = 0.19) and after 48 hours (3.1 ± 0.3 vs 4.0 ± 0.3, P = 0.19). Detection of isolated pathogens in patients infected with enterotoxigenic E. coli showed that no difference existed in improvement between those who used ciprofloxacin and loperamide (78% after 24 h) and those who used ciprofloxicin and placebo (69% after 24h) (P > 0.2). No differences were detectable between treatment groups for patients infected with Salmonella or Shigella (n = 6).

Conclusion

Ciprofloxacin plus loperamide was not a better treatment than ciprofloxacin alone for travelers' diarrhea.

Source of funding: Not stated.

Address for article reprint: Dr. D.N. Taylor, Enteric Infections Branch, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.

*Numbers calculated from data in article.


Commentary

In this well-designed trial, loperamide appears to add to the benefit of ciprofloxacin for travelers' diarrhea (P = 0.08). Unfortunately, as the authors indicate, the power to detect a difference between the 2 treatment groups was low.

Loperamide has previously been shown to augment the action of trimethoprim-sulfamethoxazole in travelers' diarrhea (1). However, resistance of enterotoxigenic Escherichia coli (the most common pathogen isolated in travelers' diarrhea) to trimethoprim-sulfamethoxazole is of increasing concern (2), so the use of the quinolone antibiotics is becoming more widespread.

In persons who travel to developing countries, the average risk for diarrhea ranges from 20% to 50% (3). It is therefore not recommended that all travelers take antibiotics daily to try to prevent diarrhea. Instead, travelers should carry a treatment dose of antibiotics such as ciprofloxacin (500 mg twice daily for 3 days) to take if symptoms occur.

The study found that loperamide was safe and that the average patient took only 4 to 5 doses. Because loperamide is now available in an over-the-counter preparation and because even 24 additional hours of diarrhea may significantly inconvenience travelers, it might be appropriate for travelers to carry a supply of loperamide in addition to ciprofloxacin, pending a more definitive evaluation.

Mary D. Nettleman, MD
The University of Iowa College of MedicineIowa City, Iowa, USA


References

1. Ericsson CD, DuPont HL, Mathewson JJ, et al. Treatment of traveler's diarrhea with sulfamethoxazole and trimethoprim and loperamide. JAMA. 1990;263:257-61.

2. Murray BE, Mathewson JJ, DuPont H, Ericsson CD, Reves RR. Emergence of resistant fecal Escherichia coli in travelers not taking prophylactic antimicrobial agents. Antimicrob Agents Chemother. 1990;34:515-8.

3. Steffen R. Epidemiologic studies of travelers' diarrhea, severe gastrointestinal infections, and cholera. Rev Infect Dis. 1986;8(Suppl 2):S122-30.