Do I treat a patient with a stool study result negative for Shigella but positive for Shigella toxin who is still symptomatic with azithromycin?

Management of Stool Study Positive for Shigella Toxin but Negative for Shigella

Azithromycin should not be used to treat a patient with a stool study that is negative for Shigella but positive for Shigella toxin who remains symptomatic, as treatment should be based on confirmed bacterial isolation rather than toxin detection alone. 1

Understanding the Clinical Scenario

• A positive Shigella toxin test without bacterial isolation suggests several possibilities:
  • Previous Shigella infection with ongoing symptoms but cleared organism 1
  • False positive toxin test 1
  • Cross-reactivity with other organisms producing similar toxins 1

Diagnostic Considerations

• Reevaluation is indicated for patients who don't respond to initial therapy or have persistent symptoms 1
• Consider non-infectious causes for persistent symptoms, including:
  • Lactose intolerance 1
  • Inflammatory bowel disease (IBD) 1
  • Irritable bowel syndrome (IBS) 1
• These conditions should especially be considered if symptoms have lasted 14 or more days 1

Treatment Algorithm

1. For confirmed Shigella infection (culture positive):

   • Treatment with azithromycin is recommended for 3-7 days 1
   • Fluoroquinolones are an alternative depending on susceptibility patterns 1, 2

2. For toxin-positive, culture-negative cases:

   • Do not initiate antimicrobial therapy based solely on toxin detection 1
   • Reassess fluid and electrolyte balance 1
   • Evaluate nutritional status 1
   • Consider non-infectious etiologies 1

3. For persistent symptoms:

   • Clinical and laboratory reevaluation is indicated 1
   • Consider stool culture using different media or molecular methods to confirm or rule out Shigella 1
   • Evaluate for other enteric pathogens 1

Evidence Analysis

• The 2017 IDSA guidelines clearly state that antimicrobial treatment should be modified or discontinued when a clinically plausible organism is identified 1
• In this case, the absence of isolated Shigella organisms despite toxin positivity does not support antimicrobial treatment 1
• Recent evidence shows increasing resistance to azithromycin in Shigella species, further supporting judicious use of antibiotics only when clearly indicated 3
• Treatment of shigellosis is recommended to shorten illness duration and prevent spread, but requires confirmed bacterial infection 1, 2

Important Caveats

• Empiric treatment is only recommended in specific scenarios:
  • Infants <3 months with suspected bacterial etiology 1, 4
  • Immunocompetent patients with documented fever, abdominal pain, bloody diarrhea, and bacillary dysentery presumptively due to Shigella 1, 4
  • Recent international travelers with fever ≥38.5°C and/or signs of sepsis 1, 4
  • Immunocompromised patients with severe illness and bloody diarrhea 1, 4
• False positive toxin tests can occur with multiplex PCR assays that may detect colonization rather than active infection 5
• Primary treatment for most infectious diarrhea should focus on adequate rehydration with oral rehydration solution 4