What is the recommended treatment regimen for a patient with confirmed Yersinia pestis infection, including first‑line therapy, alternatives for contraindications, pediatric dosing, and prophylaxis for close contacts?

Yersinia pestis (plague) treatment and prophylaxis

Start parenteral therapy immediately with a fluoroquinolone (levofloxacin 750 mg IV q24h or ciprofloxacin 400 mg IV q8h) or an aminoglycoside (gentamicin 5 mg/kg IV/IM q24h), for 10–14 days; add chloramphenicol if meningitis is present, and use dual therapy in pregnancy to reduce mortality and preserve quality of life 1.

• Rationale and evidence priority
  • 2021 CDC/US HHS MMWR guideline is the most recent, highest‑quality source and drives regimen, route, and duration; parenteral preferred initially for all forms; 10–14 days treatment 1.
  • Chloramphenicol (or levofloxacin/moxifloxacin if unavailable) penetrates CNS for plague meningitis; continue combined regimen 10 additional days after CNS coverage added 1.
  • Systematic review supports effectiveness of fluoroquinolones, tetracyclines, and aminoglycosides, but guideline takes precedence for clinical decisions impacting mortality/QOL 2.

Stepwise regimen selection (adults, nonpregnant)

• First‑line (choose one; start IV; switch to PO when clinically improved) for 10–14 days:
  • Levofloxacin 750 mg IV/PO q24h, or
  • Ciprofloxacin 400 mg IV q8h (PO step‑down 500–750 mg q12h), or
  • Gentamicin 5 mg/kg IV/IM q24h, or
  • Doxycycline 100 mg IV/PO q12h (acceptable per guideline but fluoroquinolone/aminoglycoside preferred for severe disease) 1.
• Alternatives (if contraindications/intolerance or shortages): moxifloxacin 400 mg IV/PO q24h; streptomycin 1 g IV/IM q12h; amikacin 15–20 mg/kg IV/IM q24h; tobramycin 5–7 mg/kg IV/IM q24h; chloramphenicol 12.5–25 mg/kg IV q6h (max 1 g/dose); TMP‑SMX 5 mg/kg (TMP) IV/PO q8–12h; tetracyclines/minocycline/omadacycline per guideline dosing 1.

Special situations

• Pneumonic or septicemic plague: treat as above; maintain droplet plus standard precautions; discontinue droplet after ≥48 h of effective antibiotics with clinical improvement and markedly decreased sputum 1.
• Plague meningitis: add chloramphenicol 25 mg/kg IV q6h (max 1 g/dose). If unavailable or avoided in young children: add levofloxacin 750 mg q24h or moxifloxacin 400 mg q24h; continue the full regimen for an additional 10 days after CNS agent addition 1.
• Pregnancy: dual therapy preferred to maximize maternal survival and fetal safety.
  • Preferred: gentamicin 5 mg/kg IV/IM q24h PLUS ciprofloxacin 400 mg IV q8h (or levofloxacin 750 mg IV q24h). Parenteral route initially is preferred; treat 10–14 days 1.
  • If secondary meningitis: add chloramphenicol to the regimen 1.
• Pediatrics (≥29 days to 17 yrs), first‑line dosing (10–14 days) 1:
  • Ciprofloxacin 15 mg/kg q12h PO (max 750 mg/dose) or IV per local practice.
  • Levofloxacin: <50 kg: 8 mg/kg q12h (max 250 mg/dose); ≥50 kg: 500–750 mg q24h IV/PO.
  • Doxycycline: <45 kg: 2.2 mg/kg q12h; ≥45 kg: 100 mg q12h IV/PO.
  • Meningitis: chloramphenicol per age (neonates and infants with extended intervals; ≥29 days: 25 mg/kg IV q6h; max 1 g/dose). If avoiding chloramphenicol, add levofloxacin or moxifloxacin per guideline pediatric dosing 1.
• Neonates: follow guideline meningitis table for levofloxacin and chloramphenicol dosing intervals; pediatric ID consult advised given toxicity monitoring needs 1.

Postexposure prophylaxis (PEP) for close contacts

• Indication: close (<6 feet), sustained, unprotected exposure to a patient with pneumonic plague; consider for exposed lab workers or direct contact with infected animals 1.
• Duration: 7 days; may stop pre‑exposure prophylaxis 48 h after last perceived exposure if used 1.
• Adults, first‑line (PO): ciprofloxacin 500–750 mg q12h; levofloxacin 500–750 mg q24h; moxifloxacin 400 mg q24h; or doxycycline 100 mg q12h 1.
• Children, first‑line (PO): ciprofloxacin 15 mg/kg q12h (max 750 mg/dose); levofloxacin per weight as above; doxycycline per weight as above 1.
• Pregnancy, PEP: ciprofloxacin 500 mg q8h or 750 mg q12h PO; or levofloxacin 750 mg q24h PO for 7 days. Doxycycline and moxifloxacin are alternatives rather than first‑line in pregnancy 1.

Practical notes to protect morbidity, mortality, and QOL

• Start treatment immediately; delay increases mortality, especially for pneumonic/septicemic forms 1.

• Route: begin parenteral when possible due to severity and potential GI absorption issues; step down to oral when stable 1.

• Aminoglycosides: check drug levels; adjust for renal function; gentamicin preferred over streptomycin in pregnancy due to fetal ototoxicity risk with streptomycin 1.

• Meningitis coverage: do not omit CNS‑penetrating agent; failing to add chloramphenicol (or FQ alternative) risks relapse and death 1.

• Infection control: droplet plus standard precautions for pneumonic cases; discontinue after criteria met; mask/eye protection for splash risks (e.g., bubo aspiration) 1.

• Resistance is rare but reported; if clinical failure or engineered resistance suspected, switch classes guided by susceptibility and consider dual therapy; consult public health 3, 1.

• Common pitfalls and how to avoid them

  • Using oral therapy upfront in unstable patients: start IV to ensure adequate exposure 1.
  • Inadequate duration (<10 days): treat 10–14 days; extend if complications persist 1.
  • Missing PEP for unprotected close contacts of pneumonic plague: give 7‑day PEP promptly 1.
  • Not adding CNS agent in meningitis: add chloramphenicol (or FQ alternative) and continue combined therapy 10 more days 1.