Optimal dosing of trimethoprim-sulfamethoxazole when used with loperamide to treat traveler's diarrhea

Abstract

To explore the optimal dosing regimen for trimethoprim-sulfamethoxazole (TMP-SMX) when used in combination with loperamide to treat traveler's diarrhea, 190 U.S. adults with acute diarrhea were enrolled in a double-blind, randomized trial in Guadalajara, Mexico. All patients received loperamide (4-mg loading dose; 2 mg after each loose stool, not to exceed 16 mg/day for 3 days) and were randomized to receive a 3-day course of TMP-SMX (160:800 mg twice daily for six doses) (group A), a single large dose of TMP-SMX (320:1,600 mg) (group B), or a large loading dose (320:1,600 mg) followed by standard doses for 3 days (160:800 mg twice daily for five doses) (group C). Patients in group C responded best (P < 0.01), with 75% of subjects recovered from diarrhea in 12 h compared with 34 h (group A) and 33 h (group B). Similar differences in favor of group C were noted in the subset of patients who presented with moderate to severe diarrhea. On average, patients in group C took significantly (P < 0.05) less loperamide (1.2 mg) after the 4-mg loading dose compared with patients in group A (2.4 mg) or group B (2.0 mg). We conclude that the most efficacious treatment of traveler's diarrhea in the interior of Mexico is to take loperamide in usual doses to control symptoms in combination with a single large dose of TMP-SMX, which should then be continued for 3 days in standard doses.

The Practice of Travel Medicine: Guidelines by the Infectious Diseases Society of America

“…A study of loperamide and TMP-SMX [15] demonstrated a 1-h median duration of diarrhea in the combination-treated group, compared with a 34-h median duration in those treated with TMP-SMX alone. Similar results were noted in a subsequent study of loperamide plus TMP-SMX [222], and the observation was extended to the combination of loperamide plus ofloxacin [191,192]. There was no significant benefit of the combination loperamide plus ciprofloxacin when the placebo-treated comparison arm experienced relatively mild disease [185].…”

“…Loperamide is more efficacious in controlling diarrhea than bismuth subsalicylate [178] and has an onset of action within the first 4 h after ingestion. When it is used in combination with an antibiotic, there may be rapid improvement of traveler's diarrhea [191,192,216,222]. It appears to be safe in most types of diarrhea, as long as it is not used above the recommended dose, although we do not recommend using it when there is gross blood in the stool or temperature 138.5ЊC (e.g., in cases of dysentery) or in young children [179,223,224].…”

“…Although many clinical trials have studied 3 or more days of therapy with an antibiotic for the treatment of traveler's diarrhea, a single dose has been shown to be effective [16,238], and in several head-to-head comparisons, has been shown to have equivalent efficacy to a 3-day course of antibiotics [15,191,192,222,239]. Concern has been raised, however, that severe diarrhea might be better treated with 3 days of therapy than with a single dose.…”

Antimotility Agents for the Treatment ofClostridium difficileDiarrhea and Colitis

“…The beneficial effects of loperamide use in conjunction with active antimicrobials for travelers' diarrhea are apparent even when the causative pathogens have included enteroinvasive E. coli, Shigella species, Salmonella species, or Campylobacter species [53,[56][57][58]. Similar results have been demonstrated in a relatively large study in which hospitalized adult patients with bacillary dysentery ( ) were treated with ciprofloxacin n p 42 and loperamide [59].…”

Diarrhea in the returned traveler

“…Studies comparing combination therapy with loperamide and either trimethoprim/sulfamethoxazole (TMP/SMX) or a quinolone antibiotic have found the combination to be superior to the use of an antibiotic alone [37]. Some studies have shown that more than half of the patients treated with combination therapy, even after only one dose, will not pass another loose stool, and that over 90% of the patients will be cured by 24 hours [40][41][42]. However, ETEC was the predominant pathogen in these studies, and other studies have not shown that combination therapy is any more effective than therapy with an antibiotic alone, especially if the predominant pathogen is Campylobacter or Shigella sp [43,44].…”