Azithromycin and Ciprofloxacin Treatment Outcomes During an Outbreak of Multidrug-Resistant Shigella sonnei Infections in a Retirement Community-Vermont, 2018

Clin Infect Dis. 2022 Feb 11;74(3):455-460. doi: 10.1093/cid/ciab450.


Background: In 2018, the Centers for Disease Control and Prevention and the Vermont Department of Health investigated an outbreak of multidrug-resistant Shigella sonnei infections in a retirement community that offered a continuum of care from independent living through skilled nursing care. The investigation identified 24 culture-confirmed cases. Isolates were resistant to trimethoprim-sulfamethoxazole, ampicillin, and ceftriaxone, and had decreased susceptibility to azithromycin and ciprofloxacin.

Methods: To evaluate clinical and microbiologic response, we reviewed inpatient and outpatient medical records for treatment outcomes among the 24 patients with culture-confirmed S. sonnei infection. We defined clinical failure as diarrhea (≥3 loose stools per day) for ≥1 day after treatment finished, and microbiologic failure as a stool culture that yielded S. sonnei after treatment finished. We used broth microdilution to perform antimicrobial susceptibility testing, and whole genome sequencing to identify resistance mechanisms.

Results: Isolates contained macrolide resistance genes mph(A) and erm(B) and had azithromycin minimum inhibitory concentrations above the Clinical and Laboratory Standards Institute epidemiological cutoff value of ≤16 µg/mL. Among 24 patients with culture-confirmed Shigella infection, 4 were treated with azithromycin; all had clinical treatment failure and 2 also had microbiologic treatment failure. Isolates were susceptible to ciprofloxacin but contained a gyrA mutation; 2 patients failed treatment with ciprofloxacin.

Conclusions: These azithromycin treatment failures demonstrate the importance of clinical breakpoints to aid clinicians in identifying alternative treatment options for resistant strains. Additionally, these treatment failures highlight a need for comprehensive susceptibility testing and systematic outcome studies, particularly given the emergence of multidrug-resistant Shigella among an expanding range of patient populations.

Keywords: Shigella sonnei; antibiotic treatment failure; azithromycin; ciprofloxacin; multidrug resistance.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Azithromycin / pharmacology
  • Azithromycin / therapeutic use
  • Ciprofloxacin / pharmacology
  • Ciprofloxacin / therapeutic use
  • Disease Outbreaks
  • Drug Resistance, Bacterial / genetics
  • Dysentery, Bacillary* / drug therapy
  • Dysentery, Bacillary* / epidemiology
  • Humans
  • Macrolides / therapeutic use
  • Microbial Sensitivity Tests
  • Retirement
  • Shigella sonnei / genetics
  • Shigella*
  • Treatment Outcome
  • Vermont


  • Anti-Bacterial Agents
  • Macrolides
  • Ciprofloxacin
  • Azithromycin