What is the first‑line antibiotic for pneumonic plague caused by Yersinia pestis?

First-line antibiotic for pneumonic plague (Yersinia pestis)

Start levofloxacin 750 mg IV or PO once daily immediately; for severe pneumonic plague, begin dual therapy with levofloxacin plus gentamicin 5 mg/kg IV/IM daily until clinically improved, then continue monotherapy to complete 10–14 days. 1

• Rationale and hierarchy of evidence (mortality/M&M/QoL prioritized):
  • 2021 CDC/US HHS guideline (MMWR) is the most recent, highest‑quality directive; it lists fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) and aminoglycosides (gentamicin, streptomycin) as first‑line for pneumonic plague; for severe pneumonic plague, initial dual therapy with two classes is explicitly recommended to reduce mortality 1.
  • Among first‑line options, levofloxacin offers once‑daily dosing, IV/PO interchangeability, rapid lung penetration, and guideline backing, optimizing time‑to-therapy and adherence in real‑world care 1.
  • Streptomycin is effective but less available and has toxicity/logistical limits; resistance can emerge and IV formulation issues exist, making it less practical as first choice despite historical use 1, 2.

Algorithm (adult, nonpregnant)

• Suspected/confirmed pneumonic plague:
  • Not severe: levofloxacin 750 mg IV or PO q24h for 10–14 days 1.
  • Severe (respiratory failure, shock, sepsis) or bioterrorism scenario: dual therapy now
    • Levofloxacin 750 mg IV q24h PLUS gentamicin 5 mg/kg IV/IM q24h
    • De‑escalate to single agent once stabilized; total duration 10–14 days 1.
• If levofloxacin unavailable: ciprofloxacin 400 mg IV q8h or 750 mg PO q12h; or moxifloxacin 400 mg IV/PO q24h (watch QT) 1.
• If fluoroquinolone contraindicated: gentamicin 5 mg/kg IV/IM q24h or streptomycin 1 g IV/IM q12h (availability/toxicity caveats) 1.

Key nuances and pitfalls

• Do not use beta‑lactams (e.g., ceftriaxone, ceftazidime) for pneumonic plague—inferior outcomes and possible harm in late disease models 3.
• Initiate antibiotics immediately on clinical suspicion to prevent near‑100% mortality without treatment; switch IV↔PO as soon as feasible to complete course 1.
• For children and pregnancy, follow weight‑based first‑line regimens per guideline; fluoroquinolones and gentamicin are included with caution notes; avoid tetracyclines in young children unless necessary 1.
• Monitor for QT prolongation with moxifloxacin; adjust gentamicin for renal function and check levels to avoid toxicity 1.
• Consider resistance rare but possible (including streptomycin resistance); if clinical failure, obtain susceptibilities and keep dual‑class coverage initially in severe cases 4, 1.

Evidence notes:

• Guideline (2021 MMWR) drives the recommendation and explicitly prioritizes dual therapy initially for severe pneumonic/septicemic plague to reduce mortality 1.
• Comparative and historical studies support efficacy of fluoroquinolones and aminoglycosides; streptomycin practicality/resistance concerns reinforce levofloxacin as first pick in modern care 3, 2, 5.