Randomised controlled comparison of single-dose ciprofloxacin and doxycycline for cholera caused by Vibrio cholerae O1 or O139

Background Effective antimicrobial therapy can reduce the duration and volume of cholera diarrhoea by half. However, such treatment is currently limited by Vibrio cholerae resistance to the drugs commonly prescribed for cholera, and by the difficulties involved in the administration of multi-drug doses under field conditions. Because of its favourable pharmacokinetics we thought it likely that single-dose ciprofloxacin would be effective in the treatment of cholera. Methods In this double-blind study treatment was either a single 1 g oral dose of ciprofloxacin plus doxycycline placebo, or a single 300 mg oral dose of doxycycline plus ciprofloxacine placebo. 130 moderately or severely dehydrated men infected with V cholerae O1 and 130 infected with V cholerae O139 were randomly assigned treatment. Patients stayed in hospital for 5 days. We measured fluid intake and stool volume every 6 h, and a sample of stool for culture was obtained daily. The primary outcome measures were clinical success-the cessation of watery stool within 48 h; and bacteriological success-absence of V cholerae from cultures of stool after study day 2. Findings Among patients infected with V cholerae O1, treatment was clinically successful in 62 (94%) of 66 patients who received ciprofloxacin and in 47 (73%) of 64 who receive doxycycline (difference 21% [95% CI 8–33]); the corresponding proportions with bacteriological success were 63 (95%) and 44 (69%) (27% [14–39]). Among patients infected with V cholerae O139, treatment was clinically successful in 54 (92%) of 59 patients who received ciprofloxacin and in 65 (92%) of 71 who received doxycycline (<1% [−9 to 9]), and bacteriologically successful in 58 (98%) and 56 (79%), respectively (19% [9–30]). Total volume of watery stool did not differ significantly between ciprofloxacin-group and doxycycline-group patients infected with either V cholerae O1 or O139. All but one of the V cholerae O1 and all of the O139 isolates were susceptible in vitro to doxycycline, whereas 48 (37%) of the V cholerae O1 isolates and none of the O139 isolates were resistant to tetracycline. Treatment clinically failed in 14 (52%) of 27 doxycycline-treated patients infected with a tetracycline-resistant V cholerae O1 strain, compared with three (8%) of 37 patients infected with a tetracycline-susceptible strain (44% [23–65]). Interpretation Single-dose ciprofloxacin is effective in the treatment of cholera caused by V cholerae O1 or O139 and is better than single-dose doxycycline in the eradication of V cholerae from stool. Single-dose ciprofloxacin may also be the preferred treatment in areas where tetracycline-resistant V cholerae are common. In V cholerae, in-vitro doxycycline susceptibilities are not a useful indicator of the in-vivo efficacy of the drug.