Efficacy of Ciprofloxacin for Treatment of Cholera Associated with Diminished Susceptibility to Ciprofloxacin to Vibrio cholerae O1.
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 161 patients 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 MIC90 to ciprofloxacin increased from 0.010 in 1994 to 0.475 μgm/ml in 2012. Isolates became frankly resistant to nalidixic with the MIC90 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 (10th-90th 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.
icddr, b: International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
Wasif Ali
WA
Khan
icddr, b: International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh; Centre for International Health, Department of Preventive and Social Medicine, School of Medicine, University of Otago, Dunedin, New Zealand.
Debasish
D
Saha
icddr, b: International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
Sabeena
S
Ahmed
icddr, b: International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
Mohammed Abdus
MA
Salam
Mpilonhle, Mtubatuba, South Africa.
Michael Louis
ML
Bennish
D001459:Bangladesh; D002771:Cholera / Q000188:drug therapy*; D002939:Ciprofloxacin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D009268:Nalidixic Acid / Q000494:pharmacology; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D014734:Vibrio cholerae / Q000254:growth & development* / Q000302:isolation & purification
D009268:Nalidixic Acid; D002939:Ciprofloxacin