Travelers’ diarrhea treatment

Bismuth subsahcylate [14882-18-9] Pepto-Bismol, is a basic salt of varying composition, corresponding approximately to i9-H0CgH4C02(Bi0). Like a number of other insoluble bismuth preparations, it is not currentiy approved in the United States for the treatment of peptic ulcer disease but is under active investigation for this purpose (180). It does appear to be effective for the rehef of mild diarrhea and for the prevention of travelers diarrhea (181). The ready availabiUty of this dmg, however, may lead to its ovemse and result in toxic effects caused by both the saUcylate and bismuth components. It has been suggested that bismuth subsahcylate is somewhat effective in the symptomatic treatment of isosporiasis, a disease caused by the intracellular parasite Isospora belli (182). 

Okhuysen PC. Current concepts in travelers diarrhea Epidemiology, antimicrobial resistance and treatment. Curr Opin Infect Dis 2005 18 522-526. 

Ericsson CD Travelers diarrhea. Epidemiology, prevention, and self-treatment. Infect Dis Clin North Am 1998 12 285-303. 

DuPont HL, Jiang ZD, Ericsson CD, Mathew-son JJ, Adachi J, Palazzini E, Riopel LM, Ashley D, Martinez-Sandoval F Rifaximin for the treatment of travelers diarrhea A randomized, double-blind clinical trial versus ciprofloxacin. Clin Infect Dis, submitted. 

DuPont HL, Reves R, Galindo R, Sullivan P, Wood L, Mendiola J Treatment of travelers diarrhea with trimethoprim/sulfamethoxazole and with trimethoprim alone. N Engl J Med 1982 307 841-844. 

Rifaximin Diarrhea Treatment - Infectious diarrhea Bacterial diarrhea - Travelers diarrhea... 

Fig. 1. Comparative effectiveness of treatment of patients with travelers diarrhea. Percentage of subjects who continued to have diarrhea by hour after treatment in subjects receiving one of three doses of rifaximin compared with two similar placebo-treated groups studied earlier using identical study methods (from DuPont et al. [13]).

Fig. 2. Mean number of unformed stools passed per day of study by subjects with travelers diarrhea taking rifaximin (400 mg twice a day) or ciprofloxain (500 mg twice a day). The mean values for the two treatment groups were comparable for each day of the study (from DuPont et al. [6]).

Despite such limitations, the data are uniformly favorable and generally indicate that treatment with rifaximin successfully limits the course of bacterial and travelers diarrhea to 1-2 days (fig. 1). In the case of travelers diarrhea, for which bacterial causes are well known, when treatment with rifaximin was compared to treatment with either trimethoprim-sulfamethoxazole or ciprofloxacin... 

Rifaximin appeared to be effective and safe in both adults and children. Not only do these data support the efficacy of a nonabsorbable antibiotic in the treatment of diarrhea, the lack of absorption and degree of safety reported to date support the likelihood that rifaximin will be safe to use in pregnant women. Currently, the drugs of choice for the treatment of bacterial diarrhea, especially travelers diarrhea, are the fluoroquinolones, which are contraindicated in pregnancy. While rifaximin will likely never be adequately studied in pregnancy, it should be safe. 

DuPont HL, Ericsson CD Prevention and treatment of travelers diarrhea. N Engl J Med 1993 328 1821-1827. 

Ericsson CD Rifaximin A new approach to the treatment of travelers diarrhea. Introduction. J Travel Med 2001 8(suppl 2) S25. 

Indications IV Infusion Prophylaxis and treatment of Pneumocystis car/n/ pneumonia Shigellosis Severe or complicated urinary tract infections Tablets Prophylaxis and treatment of Pneumocystis carinii pneumonia Acute exacerbation of chronic bronchitis Urinary tract infections Travelers diarrhea in adults Shigellosis Acute otitis media ... 

Ciprofloxacin and ofloxacin have broader spectra of activity that includes some gram-positive organisms so they have been used for a broad range of infections. Oral ciprofloxacin or ofloxacin is indicated for the treatment of complicated urinary tract infections and prostatitis. Ofloxacin is an effective therapy for chlamydial urethritis/ cervicitis and acute pelvic inflammatory disease. Oral ciprofloxacin or ofloxacin is effective in the treatment of acute diarrhea caused by enterotoxic E. coli (e.g., travelers diarrhea). Salmonella, Shigella, and Campylobacter... 

Recently, the U.S. Food and Drug Administration (U.S. FDA) has approved the release of rifaximin, a rifamycin antibiotic, for the treatment of travelers diarrhea (TD) caused by enterotoxigenic Escherichia coli. Although the drug is not intended for the treatment of TD, there are indications that the drug may be effective as a prophylactic agent. 

Diarrhea—Bacteria, viruses, or parasites can cause diarrhea, which depletes the body of nutrients and fluids. Loose watery stools are accompanied by nausea, abdominal cramps, and vomiting. Oral rehydration treatment acts to replenish fluid loss and rectify electrolyte imbalances. Different types of diarrhea include travelers diarrhea, normally caused by Escherichia coli bacterial dysentery (shigellosis), an acute bacterial infection of the large intestine amoebic dysentery, where cysts of infecting organisms are transmitted through food and water and giardiasis, caused by parasites that infect the small intestine. 

Rifaximin is available in Europe for the treatment of acute intestinal bacterial infections, hepatic encephalopathy, bacterial overgrowth syndrome, diverticular disease of the colon, and for the prevention of infections after colorectal surgery [3, 4]. Rifaximin is also licensed in Mexico, Asia and Northern Africa and has recently been approved in USA for the treatment of traveler s diarrhea. 

After the submission of this paper several publications have appeared in the literature that reinforce the role of rifaximin in the treatment of infectious diarrhea [1]. An entire issue of the Journal of Travel Medicine devoted to the use of this antibiotic in the treatment of traveler s diarrhea (TD) has been published [2-5], In addition, a recent paper from our laboratory [6] confirmed the rifaximin efficacy also in enteroaggregative Escherichia coli-mediated TD. Furthermore, in a randomized, double-blind, placebo-con-trolled study [7] even once daily administration of the antibiotic proved to be capable of preventing TD. Finally, Lawler and Wallace [8] recently reviewed the treatment options for bacterial diarrhea and considered rifaximin a useful addition to our therapeutic armamentarium. 

Diarrhea is a well-known complication of antibiotic therapy. Rates of antibiotic-associated diarrhea (AAD) vary from 5 to 25%. Some antibiotics are more likely to cause diarrhea than others, specifically, those that are broad spectrum and those that target anaerobic flora. This paper reviews the effects of antibiotics on the fecal flora as well as host factors which contribute to AAD. Clinical features and treatment of AAD are also described. Prevention of AAD rests on wise antibiotic policies, the use of probiotics and prevention of acquisition in the hospital setting. Data from clinical trials suggest that poorly absorbed antimicrobials might have a decreased risk of causing AAD and Clostridium difficile-associated disease, as concluded from studies of antibiotics used for preoperative bowel decontamination and poorly absorbed antibiotics used for traveler s diarrhea. Controlled trials would prove this but are not yet available. Probiotics may be a good adjunct to poorly absorbed antibiotics to minimize the risk of diarrhea associated with antibiotics. 

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