Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Oral aztreonam was effective and well tolerated in treating travelers' diarrhea

ACP J Club. 1992 July-Aug;117:17. doi:10.7326/ACPJC-1992-117-1-017


Source Citation

DuPont HL, Ericsson CD, Mathewson JJ, de la Cabada FJ, Conrad DA. Oral aztreonam, a poorly absorbed yet effective therapy for bacterial diarrhea in US travelers to Mexico. JAMA. 1992 Apr 8;267:1932-5.


Abstract

Objective

To study the efficacy of oral aztreonam for treating acute diarrhea acquired in Mexico by adult travelers from the United States.

Design

Randomized, double-blind, placebo-controlled, 2-week trial.

Setting

University student health clinic in Mexico.

Patients

U.S. university students studying in Mexico (age range 18 to 60 y) were included if they had acute diarrhea defined as passage, over a period of ≥ 4 unformed stools in 24 hours or 3 unformed stools in 8 hours. Patients also needed to have at least one other symptom (abdominal pain, cramps, nausea, vomiting, or fever). Patients were excluded if they were pregnant or lactating, or had hypersensitivity to β-lactam antimicrobials, or hepatic dysfunction, achlorhydria, intestinal disease, or any serious underlying medical disorder. They were also excluded if they had received an antibiotic with activity against enteropathogens within 5 days. Follow-up was 92%.

Intervention

Patients were randomized to receive placebo (n = 93) or oral aztreonam (n = 98), 100 mg, 3 times per day for 5 days.

Main outcome measures

Time to clinical recovery, treatment failures, adverse effects, and microbiologic eradication of pathogen from stool were measured. Stool samples were collected and a complete blood count, serum chemistry profile, and urinalysis were done before and after the study. Patients kept symptom diaries and were seen daily in the school clinic during treatment and 2 to 4 days later.

Main results

Pretreatment stool samples contained enterotoxigenic Escherichia coli (39%), Shigella species (6%), Salmonella species (3%), Aeromonas species (2%), Edwardsiella tarda (1%), and Plesiomonas shigelloides (0.5%). After therapy, 92 patients (94%) taking aztreonam improved clinically compared with 68 (73%) in the placebo group (P < 0.01). {This absolute benefit increase of 21% means that 5 patients would need to be treated with aztreonam for 5 days (compared with placebo) to have 1 additional patient improve clinically, 95% CI 3 to 9; the relative benefit increase was 28%, CI 16% to 49%.}* Mean duration of diarrhea in patients taking aztreonam was 44 hours compared with 84 hours for those in the placebo group (P < 0.001). Compared with placebo, aztreonam was associated with a greater rate of enteropathogen eradication (95% vs 70%, P < 0.01). The group did not differ for the rate of side effects (aztreonam 18% vs placebo 13%).

Conclusion

Aztreonam, 100 mg, taken orally 3 times per day for 5 days, was effective and well tolerated in adult travelers to Mexico with travelers' diarrhea.

Sources of funding: National Institutes of Health and Bristol-Myers Squibb.

Address for article reprint: Dr. H.L. DuPont, 6431 Fannin, Room 1.729 JFB, University of Texas Medical School, Houston, TX 77030, USA.

*Numbers calculated from data in article.


Commentary

Acute diarrhea frequently occurs in travelers from the United States to Mexico and other less developed countries. Most travelers' diarrhea is self-limited and requires only oral rehydration and nonspecific therapy. In patients with severe diarrhea, especially if accompanied by fever and bloody stools, specific antimicrobial therapy is indicated. Antimicrobial agents such as sulfamethoxazole-trimethoprim (SMX-TMP), ciprofloxacin, and norfloxacin will shorten the duration of diarrhea. The development of bacterial resistance, however, may limit the effectiveness of these agents, and their use can be contraindicated in children and pregnant women or in patients with renal and hepatic dysfunction.

This report shows that oral aztreonam is effective in the treatment of travelers' diarrhea. All enteropathogens isolated from the patients' pretreatment stools were susceptible to this drug. Aztreonam reduced the duration of diarrhea caused by enterotoxigenic E. coli by more than 50% compared with placebo, a difference that is probably clinically important. The results are, however, less certain for other pathogens. Only a few patients had shigellosis and were in the subgroup of patients with fecal leukocytes. No significant difference existed in the duration of diarrhea for patients with shigellosis in the group receiving aztreonam compared with placebo.

Aztreonam has excellent in-vitro activity against the enteropathogens causing travelers' diarrhea and is potentially a useful alternative for the treatment of travelers' diarrhea, being poorly absorbed from the intestine and well tolerated. The oral form of aztreonam, however, is currently not licensed in North America. Until more data, including information on the use of aztreonam in salmonellosis and shigellosis, are available, SMX-TMP combined with loperamide is recommended for most patients with travelers' diarrhea requiring antimicrobial therapy (1).

Tom D.Y. Chin, MD, MPH
University of Kansas Medical CenterKansas City, Kansas, USA

Tom D.Y. Chin, MD, MPH
University of Kansas Medical Center
Kansas City, Kansas, USA


Reference

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