Treatment of Yersinia pestis Infection
For Yersinia pestis infection (plague), dual therapy with two distinct classes of antimicrobials is strongly recommended for pneumonic or septicemic plague, while monotherapy can be used for uncomplicated bubonic plague. 1
First-Line Treatment Options by Clinical Presentation
Pneumonic or Septicemic Plague (Adults)
Requires dual therapy with two distinct antimicrobial classes
First-line combinations (choose one from each category):
Category 1:
- Ciprofloxacin: 400 mg IV every 8 hours or 500 mg PO every 8 hours
- Levofloxacin: 750 mg IV or PO every 24 hours
- Moxifloxacin: 400 mg IV or PO every 24 hours
Category 2:
- Gentamicin: 5 mg/kg IV or IM every 24 hours
- Streptomycin: 1 g IM every 12 hours
- Doxycycline: 200 mg IV loading dose, then 100 mg IV or PO every 12 hours
Bubonic or Pharyngeal Plague (Adults)
Monotherapy is generally sufficient for naturally occurring infections
First-line options:
- Ciprofloxacin: 400 mg IV every 8-12 hours or 500-750 mg PO every 12 hours
- Levofloxacin: 750 mg IV or PO every 24 hours
- Doxycycline: 200 mg loading dose, then 100 mg every 12 hours IV or PO
- Gentamicin: 5 mg/kg IV or IM every 24 hours
- Streptomycin: 1 g IM every 12 hours
Treatment Duration
- 10-14 days for all forms of plague 1
Special Populations
Children
For pneumonic or septicemic plague:
- Ciprofloxacin: 10 mg/kg IV every 8-12 hours or 15 mg/kg PO every 8-12 hours (max 400 mg/dose IV, 500 mg/dose PO every 8 hours)
- Levofloxacin: For weight <50 kg: 8 mg/kg every 12 hours; For weight ≥50 kg: 500-750 mg every 24 hours
- Doxycycline: For weight <45 kg: 4.4 mg/kg loading dose, then 2.2 mg/kg every 12 hours; For weight ≥45 kg: 200 mg loading dose, then 100 mg every 12 hours
Pregnant Women
Dual therapy is recommended with:
- Ciprofloxacin: 400 mg IV every 8 hours or 500 mg PO every 8 hours
- Gentamicin: 5 mg/kg IV or IM every 24 hours
Neonates
- Ciprofloxacin: 15 mg/kg every 12 hours PO
- Levofloxacin: 10 mg/kg every 12 hours PO
- Doxycycline: 2.2 mg/kg every 12 hours PO
Post-Exposure Prophylaxis
For individuals exposed to Y. pestis:
- Adults: Ciprofloxacin 500-750 mg PO every 12 hours or Doxycycline 100 mg PO every 12 hours for 7 days
- Children: Ciprofloxacin 15 mg/kg PO every 12 hours (max 750 mg/dose) or Doxycycline (weight-based dosing) for 7 days
Clinical Considerations and Pitfalls
Antimicrobial Selection Rationale
- Fluoroquinolones (ciprofloxacin, levofloxacin) have demonstrated excellent efficacy against Y. pestis both in vitro and in vivo 2, 3
- Ciprofloxacin has comparable efficacy against both intracellular and extracellular Y. pestis, making it particularly effective for early infection stages 2
- Levofloxacin has been shown to be superior to streptomycin in experimental models, with less resistance development 4
Important Cautions
- Avoid beta-lactams for pneumonic plague with bacteremia - studies have shown accelerated mortality with beta-lactams when used for late treatment of pneumonic plague 3
- Aminoglycoside monitoring - therapeutic drug monitoring is recommended when using gentamicin or streptomycin
- Tetracycline use in children - doxycycline should only be used in children <8 years when other options are exhausted due to risk of permanent tooth discoloration
- Delayed treatment risks - mortality increases significantly with delayed treatment, especially in pneumonic plague
Resistance Considerations
- Fluoroquinolones appear to have a lower risk of resistance development compared to streptomycin 4
- Moxifloxacin at standard doses (400 mg daily) has been shown to effectively prevent resistance emergence 5
Conclusion
Early administration of appropriate antimicrobials is critical for plague treatment success. For pneumonic or septicemic plague, dual therapy with a fluoroquinolone plus an aminoglycoside or doxycycline offers the best outcomes based on current evidence. Treatment should be initiated immediately upon clinical suspicion, without waiting for laboratory confirmation.