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Objective  We identified a poor clinical response to treatment of cholera with a single 1 g dose of ciprofloxacin, a standard treatment for cholera.    Methods  To determine reasons for the poor response and better therapeutic approaches we examined the minimal inhibitor concentration (MIC, n = 275) and disc-diffusion zone sizes (n = 205) for ciprofloxacin and nalidixic acid of  V .  cholerae  O1 strains isolated in Bangladesh from 1994 to 2012, and reexamined data from 161patients infected with  Vibrio cholerae  O1 recruited in four clinical trials who received single- or multiple-dose ciprofloxacin  for  treatment of cholera and compared their clinical response to the  V .  cholerae  O1 susceptibility.    Results  Although all 275 isolates of  V .  cholerae  O1 remained susceptible to ciprofloxacin using standard MIC and disc-diffusion thresholds, the MIC 90  to ciprofloxacin increased from 0.010 in 1994 to 0.475 μgm/ml in 2012. Isolates became frankly resistant to nalidixic with the MIC 90  increasing from 21 μgm/ml in 1994 to >256 μgm/ml and 166 of 205 isolates from 1994 to 2005 being frankly resistant using disc-diffusion testing. Isolates resistant to nalidixic acid by disc-diffusion testing had a median ciprofloxacin MIC of 0.190 μgm/ml (10 th -90 th  centiles 0.022 to 0.380); nalidixic acid-susceptible isolates had a median ciprofloxacin MIC of 0.002 (0.002 to 0.012).The rate of clinical success with single-dose ciprofloxacin treatment for nalidixic acid-susceptible strains was 94% (61 of 65 patients) and bacteriologic success 97% (63/65) compared to 18% (12/67) and 8% (5/67) respectively with nalidixic acid-resistant strains (P<0.001 for both comparisons). Multiple-dose treatment with ciprofloxacin had 86% and 100% clinical and bacteriologic success rates respectively in patients infected with nalidixic acid-susceptible strains of  V .  cholerae  O1 compared to clinical success 67% and bacteriologic success 60% with nalidixic acid-resistant strains.    Conclusions  Single-dose ciprofloxacin is not effective for treating cholera caused by  V .  cholerae  O1 with diminished susceptibility to ciprofloxacin, and nalidixic acid disc-diffusion testing effectively screens for such isolates.

Efficacy of Ciprofloxacin for Treatment of Cholera Associated with Diminished Susceptibility to Ciprofloxacin to Vibrio cholerae O1