Treatment of Yersinia pestis Infections
For Yersinia pestis infections, dual therapy with two distinct classes of antimicrobials is recommended for treatment, with at least one being a first-line agent (fluoroquinolone or aminoglycoside), administered for 10-14 days. 1
First-Line Treatment Options
Fluoroquinolones (preferred first-line agents)
- 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
Aminoglycosides (alternative first-line agents)
- Gentamicin: 5 mg/kg IV or IM every 24 hours
- Streptomycin: 1 g IV or IM every 12 hours
Treatment Algorithm Based on Clinical Presentation
Pneumonic Plague
- Highest mortality risk - requires immediate treatment
- Start with parenteral (IV) administration of two antimicrobials from different classes
- At least one agent must be a first-line medication (fluoroquinolone or aminoglycoside)
- Switch to oral therapy when clinically improved
Bubonic Plague
- Start with dual therapy as above
- Can transition to oral therapy earlier if clinically improving
- Drain buboes if fluctuant
Septicemic Plague
- Requires aggressive IV antimicrobial therapy with two agents
- Intensive supportive care for sepsis management
- Monitor closely for progression to pneumonic form
Special Populations
Pregnant Women
- Fluoroquinolones remain first-line therapy despite pregnancy
- Gentamicin is an acceptable alternative but requires monitoring
- Avoid tetracyclines if possible due to fetal tooth development concerns 1
Children
- Adjust dosing based on weight
- Fluoroquinolones are recommended despite historical concerns about cartilage toxicity
- Benefit outweighs risk in life-threatening plague infection
Bioterrorism Considerations
In case of suspected bioterrorism:
- Use dual therapy with distinct antimicrobial classes until susceptibility testing results are available
- Consider the possibility of engineered antimicrobial resistance
- Coordinate with public health authorities for surveillance and prophylaxis of exposed individuals 1
Evidence Quality and Considerations
Recent in vitro studies have shown that ciprofloxacin and ceftriaxone demonstrate the highest activity against Y. pestis, which supports the updated guidelines recommending fluoroquinolones as first-line agents 2. The 2021 CDC guidelines represent a shift from previous recommendations that primarily relied on streptomycin, tetracycline, and chloramphenicol.
The efficacy of moxifloxacin against Y. pestis has been demonstrated in animal models, with 100% survival in treated animals compared to 0% in placebo groups 3. Similarly, levofloxacin showed significant protection in animal models of pneumonic plague 4.
Common Pitfalls to Avoid
Delayed treatment: Plague has a high mortality rate if untreated. Do not wait for confirmatory testing before initiating therapy.
Monotherapy in suspected bioterrorism cases: Always use dual therapy initially when bioterrorism is suspected due to potential engineered resistance 1.
Inadequate duration: Complete the full 10-14 day course even if clinical improvement occurs rapidly.
Failure to consider plague: Consider plague in patients with compatible clinical presentations and relevant epidemiological risk factors (travel to endemic areas, exposure to rodents or fleas).
Improper isolation: Pneumonic plague requires strict respiratory isolation to prevent transmission.
Early recognition and prompt administration of effective antimicrobials are critical for reducing mortality in plague infections. The disease is treatable with appropriate antimicrobial therapy, but delays in treatment significantly increase the risk of death.