What is the recommended treatment for plague?

Treatment of Plague

For the treatment of plague, dual therapy with a fluoroquinolone (such as ciprofloxacin or levofloxacin) plus an aminoglycoside (such as gentamicin or streptomycin) is strongly recommended for 10-14 days. 1, 2

First-Line Treatment Options for Adults

Fluoroquinolones (First-Line)

• Ciprofloxacin: 400 mg IV every 8-12 hours or 500 mg PO every 8-12 hours (maximum 750 mg/dose)
• Levofloxacin: 500-750 mg IV or PO every 24 hours
• Moxifloxacin: 400 mg IV or PO every 24 hours 1, 2, 3

Aminoglycosides (First-Line)

• Gentamicin: 4.5-7.5 mg/kg IV or IM every 24 hours
• Streptomycin: 15 mg/kg IM every 12 hours (maximum 1 g/dose) 1, 2

Treatment Algorithm

1. For naturally occurring plague:

   • Monotherapy is acceptable with any first-line agent
   • Consider dual therapy for patients with large buboes 1

2. For severe pneumonic/septicemic plague or suspected bioterrorism:

   • Always use dual therapy with two distinct antimicrobial classes
   • Combine a fluoroquinolone with an aminoglycoside 1, 2

3. For pediatric patients:

   • Ciprofloxacin: 10 mg/kg IV every 8-12 hours or 15 mg/kg PO every 8-12 hours
   • Levofloxacin: 8 mg/kg every 12 hours if <50 kg (maximum 250 mg/dose)
   • Gentamicin: 4.5-7.5 mg/kg IV or IM every 24 hours 1, 2

Alternative Treatments

If first-line agents are unavailable or contraindicated:

• Doxycycline: 200 mg loading dose, then 100 mg every 12 hours IV or PO 1
• Chloramphenicol: 12.5-25 mg/kg every 6 hours IV (maximum 1 g/dose) 1
• Trimethoprim-sulfamethoxazole: 5 mg/kg (trimethoprim component) every 8 hours IV or PO 1

Evidence Supporting Recommendations

Recent clinical evidence strongly supports the efficacy of both aminoglycosides and fluoroquinolones. A randomized clinical trial in Tanzania demonstrated high cure rates with both gentamicin (94%) and doxycycline (97%) 4. Additionally, a review of 75 plague cases in New Mexico found that gentamicin was as efficacious as streptomycin for treating human plague 5.

Analysis of treatment patterns among U.S. plague patients from 1942-2018 showed significantly lower mortality among patients receiving high-efficacy antimicrobials (aminoglycosides, tetracyclines, fluoroquinolones) compared to those receiving limited-efficacy antimicrobials (9% vs. 51%) 6.

Important Considerations and Monitoring

• Treatment duration: Continue treatment for 10-14 days 1, 2
• Aminoglycoside monitoring: Check drug concentrations as appropriate and adjust dose accordingly 2
• Isolation precautions: Necessary for pneumonic plague to prevent transmission 2
• Pregnancy: Fluoroquinolones remain first-line therapy despite pregnancy, with gentamicin as an acceptable alternative 2, 7

Common Pitfalls to Avoid

1. Delayed treatment: Plague is rapidly progressive and potentially fatal; initiate treatment immediately upon suspicion
2. Using monotherapy in suspected bioterrorism cases: Always use dual therapy with distinct antimicrobial classes
3. Inadequate treatment duration: Complete the full 10-14 day course
4. Failure to consider plague: Consider in endemic areas or with suspicious clinical presentation (buboes, sepsis, pneumonia)
5. Improper isolation: Implement respiratory isolation for pneumonic plague 2

Early recognition and prompt treatment with appropriate antimicrobials are the most critical factors in improving survival of plague patients 6.