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


Therapeutics

Norfloxacin cured acute diarrheal disease especially in patients who were culture positive or severely ill

ACP J Club. 1992 Nov-Dec;117:71. doi:10.7326/ACPJC-1992-117-3-071


Source Citation

Wiström J, Jertborn M, Ekwall E, et al. Empiric treatment of acute diarrheal disease with norfloxacin. A randomized, placebo-controlled study. Ann Intern Med. 1992 Aug 1;117:202-8.


Abstract

Objective

To evaluate the efficacy and safety of norfloxacin for the treatment of acute diarrhea.

Design

Randomized, double-blind, placebo-controlled, multicenter trial.

Setting

Departments of infectious disease at 6 Swedish hospitals.

Patients

Patients were ≥ 12 years old (mean age, 37 y), with a history of diarrhea for ≥ 4 loose stools per day or ≥ 2 loose stools per day plus fever ≥ 38.0 °C, vomiting, or abdominal cramps during the previous 24 hours. Exclusion criteria were quinolone hypersensitivity; recent antibiotic treatment; renal failure; diarrhea of noninfectious, viral, or parasitic etiology; Clostridium difficile infection; food poisoning; severe vomiting or septicemia; or human immunodeficiency virus infection. 3377 patients were screened, 598 (18%) were eligible and randomized, and 511 (85%) were evaluable for efficacy.

Intervention

Patients received either norfloxacin (n = 301), 400 mg, or placebo (n = 297) twice daily for 5 days.

Main outcome measures

Patients were classified as cured (≤ 1 loose stool per 24 hours without additional symptoms), improved (2 loose stools per 24 hours without additional symptoms or 1 loose stool per 24 hours with accompanying symptoms), or failed.

Main results

70% of enrolled patients had a history of recent travel. 63% of patients who took norfloxacin were cured compared with 51% of those who took placebo (P = 0.003). {This absolute benefit increase (ABI) of 12% means that 9 patients would need to be treated (NNT) with norfloxacin (compared with placebo) for 5 days to produce 1 additional cure, 95% CI 5 to 35; the relative benefit increase (RBI) was 22%, CI 5% to 43%.}* Norfloxacin was more effective in culture-positive patients (cured 53% vs 39%, P = 0.008); {ABI 14%; NNT 7, CI 4 to 45; RBI 37%, CI 5% to 80%}* and severely ill patients (cured 45% vs 19%, P = 0.04); {ABI 26%; NNT 4, CI 2 to 29; RBI 132%, CI 11% to 403%}*. The median time to cure was 3 days for the norfloxacin group compared with 4 days for placebo (P = 0.02). All evaluable as well as culture-positive (but not culture-negative) patients taking norfloxacin had a lower mean number of loose stools on days 2 through 6 compared with patients taking placebo (P < 0.01). Norfloxacin was less effective than placebo in eliminating Salmonella species on days 12 to 17 (18% vs 49%, P = 0.006), whereas the opposite was true for Campylobacter species (69% vs 50%, P = 0.03).

Conclusions

Norfloxacin was effective for curing acute diarrhea in patients who were culture-positive or severely ill. The usefulness of this treatment was limited by the observation that norfloxacin delayed the elimination of Salmonella.

Source of funding: Astra Arcus AB, Södertälje, Sweden.

For article reprint: Dr. J. Wiström, Department of Infectious Diseases, University of Umeå, Regional Hospital of Umeå, S-901 85 Umeå, Sweden.

*Numbers calculated from data in article.


Commentary

When confronted with a patient with acute diarrhea, conventional clinical wisdom is to avoid treatment with antibiotics unless the patient is severely ill, because most cases are self-limited and treatment may prolong the presence of the infective agent. Indeed, clinical cures (i.e., a decrease in stool frequency to normal and resolution of accompanying symptoms) can be achieved without obligatory elimination of the causative agent (1). Acute diarrhea can be incapacitating, however, and several agents can shorten its course, including sulfamethoxazole-trimethoprim with loperamide, ciprofloxacin, and, more recently, aztreonam. Unfortunately, none of the available compounds is effective against all the important pathogens. In addition, increasing resistance rates and difficulty of use in children and pregnant women limit their usefulness.

The study by Wiström and colleagues shows that norfloxacin, when given within 5 days of the onset of diarrhea, has an overall favorable effect. The treatment effects were largely limited to culture-positive patients, patients who were severely ill, and patients with salmonellosis (although norfloxacin increased the elimination time of the Salmonella). It is noteworthy that 70% of enrolled patients had a history of recent travel with symptoms occurring soon after returning home (average < 3 d). This is a likely explanation for the high rate of positive bacterial cultures (50%) despite the fact that enterotoxigenic Escherichia coli was not assessed. Such a high rate of positive cultures may not be present in all clinical settings. Of concern was the detection of a fourfold increase in resistance to norfloxacin in 6 of 9 patients in whom Campylobacter species was isolated after treatment. Because norfloxacin had only a modest therapeutic effect, its routine use should be avoided.

Sander J. Veldhuyzen van Zanten, MD
Dalhousie UniversityHalifax, Nova Scotia, Canada

Sander J. Veldhuyzen van Zanten, MD
Dalhousie University
Halifax, Nova Scotia, Canada


Reference

1. Ericsson CD, DuPont HL, Mathewson JJ, et al. Test-of-cure stool cultures for traveler's diarrhea. J Clin Microbiol. 1988;26:1047-9.