Double-blind, randomized, controlled clinical trial of norfloxacin for cholera

Abstract

In a double-blind, randomized clinical trial with 78 adults with acute watery diarrhea and severe dehydration, 37 subjects were positive for Vibrio cholerae. In conjunction with rehydration therapy, 13 patients received norfloxacin, 12 received trimethoprim-sulfamethoxazole (TMP-SMX), and 12 received a placebo. Norfloxacin was superior to TMP-SMX and to the placebo in reducing stool output, duration of diarrhea, fluid requirements, and vibrio excretion. TMP-SMX was no better than the placebo.Acute watery diarrhea caused by Vibrio cholerae is an important cause of hospitalization in Calcutta (6). Several drugs, namely tetracycline (2, 8), furazolidone (5), and trimethoprim-sulfamethoxazole (TMP-SMX) (3), have been found to be effective in reducing stool volume, duration of diarrhea, and vibrio excretion in patients with cholera. Recently, a wide range of bacterial enteropathogens including V. cholerae have been found to be highly susceptible to norfloxacin (4, 7), a 4-quinolone which is similar to nalidixic acid. In this report, we present the findings of a comparative evaluation of the use of norfloxacin, TMP-SMX, or placebo in the treatment of cholera accompanied by severe dehydration.Subjects included in the study were adult male (for ease of collection of stool and urine separately) patients, of more than 18 years of age, who had been admitted to the diarrhea ward of the Infectious Diseases Hospital, Calcutta, with acute watery diarrhea and severe dehydration (11) of less than 24-h duration. Those patients who had received any drug or intravenous fluid before admission or who had any systemic illness were excluded from the study. After enrollment, all patients were placed on cholera cots and were rehydrated with intravenous Ringer lactate and oral rehydration solution as recommended by the World Health Organization (11). A thorough history was taken, a physical examination was performed, and findings were recorded on a prepared form. The amounts of intravenous and oral fluid administered, volume of stool output, and duration of diarrhea were recorded. On admission, a fresh stool sample was collected by using a sterile rectal catheter and was immediately sent to the laboratory for screening of bacterial enteropathogens according to standard techniques (10). Thereafter, rectal swabs collected from all patients for 5 consecutive days were examined for isolation of V. cholerae. All of the V. cholerae isolates were tested for their susceptibility to drugs such as tetracycline, chloramphenicol, ampicillin, TMP-SMX, nalidixic acid, and norfloxacin by the KirbyBauer disk diffusion technique (1). Informed consent was obtained from all patients.Patients included in the study were randomly assigned to one of three treatment groups by using a random number table: group A (n = 26) received norfloxacin (400 mg) twice daily, group B (n = 25) received TMP (160 mg)-SMX (800 * Corresponding author. mg) twice daily, and group C (n = 27) received the placebo twice daily. The two drugs and the placebo were in the form of tablets ...

Incidence and Molecular Analysis of V. cholerae among Some Primitive Tribes in Odisha, India

“…Emergence of fluroquinolone resistant V. cholerae O1 and O139 have appeared as a great threat in therapeutic practice as ciprofloxacin and norfloxacin are broad-spectrum fluroquinolone and possess excellent activity against V. cholerae O1 and O139 serogroup . These drugs are effective in treatment of cholera among adults and children (Bhattacharya et al, 1990). Possibly selective pressure exerted by nalidixic acid, disproportionate use of fluoroquinolone and increase in the incidence of nalidixic acid resistant strains of O1 and O139 (due to single mutation in gyrA and other related gene) might be the leading cause of appearance of fluoroquinolone resistance (with two or more mutation at gyrA).…”

Emergence of Fluoroquinolone-Resistant Strains of Vibrio cholerae O1 Biotype El Tor among Hospitalized Patients with Cholera in Calcutta, India

“…Clinical studies have shown that these drugs are effective in treatment of cholera in adults and children (2)(3)(4). For the past 11 years, we have been monitoring the incidence of antibiotic susceptibility and genotypic changes in V. cholerae isolates from cholera patients admitted at the Infectious Diseases Hospital, Calcutta, India.…”

Role of Active Efflux in Association with Target Gene Mutations in Fluoroquinolone Resistance in Clinical Isolates of Vibrio cholerae

“…Quinolones possess excellent activity against Vibrio cholerae (2,5,17), the causative agent of cholera epidemics (15,16). However, quinolone resistance has been reported recently in clinical isolates from Calcutta, India (6; P. Garg, S. Sinha, R. Chakraborty, S. K. Bhattacharya, G. B. Nair, and T. Ramamurthy, Letter, Antimicrob.…”