Identification of Widespread Antibiotic Exposure in Patients With Cholera Correlates With Clinically Relevant Microbiota Changes

J Infect Dis. 2019 Oct 8;220(10):1655-1666. doi: 10.1093/infdis/jiz299.


Background: A first step to combating antimicrobial resistance in enteric pathogens is to establish an objective assessment of antibiotic exposure. Our goal was to develop and evaluate a liquid chromatography-ion trap mass spectrometry (LC/MS) method to determine antibiotic exposure in patients with cholera.

Methods: A priority list for targeted LC/MS was generated from medication-vendor surveys in Bangladesh. A study of patients with and those without cholera was conducted to collect and analyze paired urine and stool samples.

Results: Among 845 patients, 11% (90) were Vibrio cholerae positive; among these 90 patients, analysis of stool specimens revealed ≥1 antibiotic in 86% and ≥2 antibiotics in 52%. Among 44 patients with cholera and paired urine and stool specimens, ≥1 antibiotic was detected in 98% and ≥2 antibiotics were detected in 84%, despite 55% self-reporting medication use. Compared with LC/MS, a low-cost antimicrobial detection bioassay lacked a sufficient negative predictive value (10%; 95% confidence interval, 6%-16%). Detection of guideline-recommended antibiotics in stool specimens did (for azithromycin; P = .040) and did not (for ciprofloxacin) correlate with V. cholerae suppression. A nonrecommended antibiotic (metronidazole) was associated with decreases in anaerobes (ie, Prevotella organisms; P < .001).

Conclusion: These findings suggest that there may be no true negative control group when attempting to account for antibiotic exposure in settings like those in this study.

Keywords: Vibrio cholerae; AMR; Bangladesh; Diarrhoea; LC/MS; antimicrobial resistance; cholera; diarrhea; mass spectrometry.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / analysis*
  • Bangladesh
  • Child
  • Child, Preschool
  • Cholera / drug therapy*
  • Chromatography, Liquid
  • Drug Utilization*
  • Feces / chemistry*
  • Female
  • Humans
  • Infant
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Surveys and Questionnaires
  • Urine / chemistry*
  • Vibrio cholerae / isolation & purification*
  • Young Adult


  • Anti-Bacterial Agents