What is the most appropriate next step in treating a 45-year-old man with progressive fever, chills, malaise, shortness of breath, and fatigue, with a history of potential exposure to anthrax (inhalational anthrax) via a partially torn envelope containing white powder?

Treatment of Inhalational Anthrax

Intravenous ciprofloxacin should be administered immediately as the most appropriate next step in treating this patient with suspected inhalational anthrax. 1

Clinical Assessment

The patient presents with classic signs of inhalational anthrax:

• Progressive fever, chills, malaise, shortness of breath, and fatigue for 5 days
• History of potential exposure to white powder in mail (workplace exposure)
• Coarse lung sounds and cervical adenopathy on examination
• Chest radiograph showing mediastinal widening, infiltrates, and pleural effusions

These findings strongly suggest inhalational anthrax in the context of potential bioterrorism exposure, requiring immediate treatment.

Treatment Algorithm

First-line Treatment:

1. Begin intravenous ciprofloxacin immediately

   • Adult dosing: 400 mg IV every 12 hours 1
   • Continue for 60 days (IV initially, then transition to oral when clinically appropriate) 2

2. Add one or more additional antimicrobial agents

   • Options include rifampin, vancomycin, clindamycin 1
   • Combination therapy is recommended due to high mortality associated with inhalational anthrax 1

3. Consider corticosteroids as adjunctive therapy

   • Particularly useful for extensive edema, respiratory compromise, or meningitis 1

Medications to Avoid:

• Cephalosporins and trimethoprim-sulfamethoxazole should not be used 1
• Penicillin G or ampicillin alone should not be used due to concerns about beta-lactamases 1

Evidence Strength and Rationale

The CDC guidelines strongly recommend ciprofloxacin or doxycycline as first-line therapy for inhalational anthrax 1. Between these options, ciprofloxacin is preferred for initial treatment in this case because:

1. It has demonstrated efficacy in animal models and human cases 2
2. The CDC specifically recommends it as an essential part of first-line therapy 1
3. It can be administered intravenously for rapid action in this critically ill patient

Important Clinical Considerations

• Timing is critical: Mortality decreases significantly with early antimicrobial administration
• Diagnostic confirmation: While treatment should begin immediately, blood cultures should be obtained before antibiotics if possible
• Monitoring: Close monitoring for pleural effusions is essential as they often reaccumulate and may require repeated drainage 1
• Duration: Full 60-day course is necessary even after clinical improvement due to potential for delayed germination of spores 1

Common Pitfalls to Avoid

1. Delayed treatment: Waiting for confirmatory tests before starting antibiotics increases mortality
2. Monotherapy: Using a single antimicrobial agent is insufficient due to high mortality
3. Inappropriate antibiotics: Using cephalosporins or penicillin alone is ineffective
4. Inadequate duration: Stopping antibiotics prematurely (before 60 days) risks relapse
5. Missing meningitis: Failure to evaluate for and treat CNS involvement

Inhalational anthrax is a medical emergency with high mortality if not treated promptly and appropriately. The combination of clinical presentation, radiographic findings, and exposure history in this case warrants immediate initiation of intravenous ciprofloxacin along with at least one additional effective antimicrobial agent.