Anthrax

Anthrax is a toxin-mediated zoonotic disease caused by the spore-forming, gram-positive rod Bacillus anthracis, classified as a CDC Category A bioterrorism agent. [1] Four clinical forms exist: cutaneous (>95% of natural cases), inhalational, ingestion, and injection (associated with contaminated heroin). [1-2] Anthrax meningitis can complicate any form. [3]

The following figure illustrates the pathophysiology of anthrax from spore entry through systemic toxemia:

• Exposure history is paramount: contact with herbivore animals (sheep, goats, cattle), animal hides/wool/meat, travel to endemic regions (sub-Saharan Africa, central/southwestern Asia, southern/eastern Europe), injection drug use (heroin), or suspicious mail/powder [1-2]
• Incubation periods: cutaneous ~1–7 days; inhalational median 7 days (IQR 4–9), can extend up to 6 weeks (Sverdlovsk) or 9 weeks (primate models); ingestion 1–7 days; injection ~1 day [5-6]
• Cutaneous: painless pruritic papule → vesicle → painless black eschar with surrounding edema disproportionate to lesion size; ~1/3 develop fever [3][7]
• Inhalational: biphasic course — initial nonspecific "flu-like" prodrome (fever, malaise, myalgia, nonproductive cough, absence of rhinorrhea) lasting hours to days, sometimes with brief improvement, followed by fulminant respiratory failure, shock, and hemodynamic collapse [3][6]
• Ingestion: nausea, vomiting, bloody diarrhea, abdominal pain, ascites (>50% of cases) [3][5]
• Injection: severe soft tissue infection at injection site with marked edema [2][8]

• Widened mediastinum on CXR in a febrile patient — essentially pathognomonic of advanced inhalational anthrax [4][9]
• Rapid progression from flu-like illness to shock and respiratory failure within hours [6][10]
• Hemorrhagic meningitis (altered mental status, seizures, nuchal rigidity) — occurs in up to 50% of systemic cases; nearly uniformly fatal [3][6]
• Cutaneous lesion with systemic signs: fever, hypotension, extensive edema, lymphadenopathy, bacteremia, coagulopathy, or neurologic signs [1]
• Clustering of patients with similar respiratory symptoms suggesting intentional release [2][11]
• Pleural/pericardial effusions, especially hemorrhagic [1][6]

Postexposure Prophylaxis (PEP): [1][12]

• anthrax vaccine adsorbed (AVA)[1][13]

Treatment — Cutaneous (uncomplicated): Oral ciprofloxacin or doxycycline for 7–10 days (extend to 60 days if aerosol exposure suspected) [6]

Treatment — Systemic (with or without meningitis): [1]

• Empiric triple therapy: two bactericidal drugs from different classes + a protein synthesis inhibitor (PSI) or RNA synthesis inhibitor
• Preferred: IV ciprofloxacin + meropenem (CNS-penetrating bactericidal) + linezolid (PSI) [6][13]
• If meningitis ruled out by LP: fluoroquinolone + linezolid or clindamycin (two-drug regimen) [6]
• Duration: ≥2 weeks IV, then transition to oral; total 60 days if aerosol exposure [1]
• Adjunctive antitoxin (raxibacumab, obiltoxaximab) recommended for systemic disease [1]

Contraindicated/Cautions

• Extended-spectrum cephalosporins — B. anthracis is naturally resistant [9]
• Penicillins should only be used if susceptibility is confirmed (<10% natural resistance) [1]
• Steroids did not improve survival and may worsen outcomes in shock [1][14]

• No specific dietary triggers or recommendations
• Ingestion anthrax results from consumption of contaminated/undercooked meat from infected herbivores — thorough cooking of meat in endemic areas is critical [1]
• Aggressive IV fluid resuscitation in systemic disease per sepsis protocols [6]

• Constitutional: fever, chills, malaise, diaphoresis, myalgias
• Respiratory: cough (nonproductive), dyspnea, chest tightness — notably rhinorrhea is absent in inhalational anthrax (distinguishing from influenza) [6]
• GI: nausea, vomiting, abdominal pain, bloody diarrhea (ingestion form)
• Neurologic: headache, confusion, altered mental status, seizures, meningismus (meningitis complication) [3]
• Dermatologic: painless skin lesion, vesicles, eschar, disproportionate edema [7]
• Cardiovascular: chest pain, hypotension, tachycardia

• Occupational exposure: agricultural workers, veterinarians, wool/hide processors, laboratory workers [1]
• Travel history: endemic regions (sub-Saharan Africa, central Asia, southern Europe) [1]
• Injection drug use: heroin contaminated with B. anthracis spores (injection anthrax) [2][8]
• Bioterrorism context: suspicious packages, powder exposure, clustering of cases [11]
• No hereditary predisposition; family history is not relevant unless shared exposure
• Comorbidities associated with worse outcomes in cutaneous anthrax: diabetes, obesity, hypertension, COPD [1]

• Contact with infected animals or contaminated animal products (hides, wool, meat, bone meal) [1]
• Occupational exposure (farmers, veterinarians, textile workers, laboratory personnel)
• Travel to or residence in endemic agricultural regions [1]
• Injection drug use (heroin) [2]
• Bioterrorism exposure (aerosolized spores) [1]
• Immunocompromised status (may require extended PEP) [1]

• Prior anthrax vaccination status (AVA series)
• Previous anthrax episodes (rare; natural immunity may develop)
• Chronic conditions worsening prognosis: diabetes, obesity, hypertension, COPD — all significantly associated with severe cutaneous anthrax (p<0.01) [1]
• Immunocompromised states (may require extended antimicrobial prophylaxis post-treatment) [1]

• Vitals: fever (may be absent early), tachycardia, hypotension (late/systemic), tachypnea, hypoxia
• Cutaneous: painless pruritic papule → vesicle → painless black eschar with surrounding non-pitting edema disproportionate to lesion size; regional lymphadenopathy [3][7]
• Respiratory: decreased breath sounds (pleural effusions in 76% of inhalational cases), signs of respiratory distress [1]
• Neurologic: meningismus (nuchal rigidity, Kernig/Brudzinski signs), altered mental status, focal deficits, seizures [3]
• Abdominal: tenderness, distension, ascites (ingestion form) [3]
• Injection site: severe soft tissue edema, induration, compartment syndrome [8]

• Blood cultures (most useful test) — obtain before antibiotics; growth in 6–24 hours; even 1–2 doses of antibiotics can sterilize cultures [6][10]
• Gram stain of blood, vesicular fluid, CSF, or tissue: large, encapsulated, gram-positive, "boxcar-shaped" rods [15-16]
• CBC: hemoconcentration, dramatic neutrophilic leukocytosis with bandemia (especially inhalational) [6][16]
• CMP/LFTs: elevated transaminases [6]
• Coagulation studies: coagulopathy in ~1/3 of systemic cases [1]
• Lumbar puncture: required to rule out meningitis — hemorrhagic CSF with PMN pleocytosis and gram-positive rods [16]
• Confirmatory testing: PCR (pagA, lef, capB targets), immunohistochemistry, gamma phage lysis — performed at LRN reference laboratories [15][17]
• Serology (anti-PA ELISA) — only useful retrospectively [15]

• CXR (first-line): widened mediastinum (pathognomonic in context), bilateral pleural effusions, perihilar infiltrates; notably does NOT show classic lobar pneumonia [9-10]
• CT chest (gold standard): hyperdense (hemorrhagic) mediastinal lymphadenopathy on non-contrast CT, bilateral pleural effusions, mediastinal fat edema, pericardial effusion [6][10]
• Echocardiogram: pericardial effusion [6]
• CT/MRI brain: hemorrhagic meningitis — subarachnoid, subdural, or intraparenchymal hemorrhages [16]
• Abdominal CT: ascites, bowel wall thickening, mesenteric lymphadenopathy (ingestion form)

• CDC Anthrax Triage Checklist: clinical decision tool distinguishing anthrax from non-anthrax illness with 95% sensitivity; correctly classified 95% of anthrax cases and 76% of controls [18]
• Point-of-care Gram stain of peripheral blood — bacilli may be visible on unspun blood smear in advanced bacteremia [9]
• Pleural fluid analysis: drainage recommended for all inhalational cases; spectrographic analysis may detect anthrax lethal factor at levels exceeding serum [1][13]
• CSF analysis: hemorrhagic fluid with PMN pleocytosis; Gram stain and culture [16]
• Nasal swab culture: epidemiologic/investigative tool only — does NOT predict clinical illness risk [15]

• Arrhythmias observed in ~7% of adults with inhalation anthrax [1]
• ECG indicated in all systemic anthrax to evaluate for arrhythmia, pericardial effusion (low voltage, electrical alternans), and hemodynamic compromise
• No pathognomonic ECG pattern; findings are nonspecific and related to sepsis/shock physiology

Severity Stratification: [1]

• Anthrax is fundamentally a toxin-mediated disease — even after bacterial sterilization, toxin effects continue [1][4]
• Predictors of fatal outcome in cutaneous anthrax: constitutional symptoms, thoracic edema, hypotension, neurologic signs, coagulopathy, bacteremia [1]
• Inhalational anthrax has a characteristic biphasic course — brief improvement before fulminant collapse [6]

Initial Stabilization (Systemic Anthrax)

• ICU admission with hemodynamic monitoring, mechanical ventilation as needed, vasopressors, DVT prophylaxis, GI bleeding prophylaxis per sepsis protocols [6]
• Early, aggressive drainage of pleural effusions — recommended for all inhalational cases; pleural fluid contains high concentrations of lethal factor [1][13]

Antimicrobial Therapy

• Systemic/meningitis: IV triple therapy — ciprofloxacin + meropenem + linezolid (or clindamycin); duration ≥2 weeks, then oral step-down [1][6]
• Cutaneous (uncomplicated): oral ciprofloxacin 500 mg q12h or doxycycline 100 mg q12h for 7–10 days [6]
• If bioterrorism-related: extend all courses to 60 days total [1][6]

Adjunctive Therapies

• Antitoxin (raxibacumab or obiltoxaximab) as adjunct for systemic disease [1]
• Mannitol improved survival in meningitis patients [14]
• Steroids are not recommended — no survival benefit and potential harm [1][14]

Postexposure Prophylaxis

• [1][12]

• Admit to ICU: all systemic anthrax (inhalational, ingestion, injection, cutaneous with systemic signs, meningitis) [6]
• Admit to floor: cutaneous anthrax with extensive edema, head/neck involvement, or concerning features [1]
• Outpatient management: uncomplicated localized cutaneous anthrax without systemic signs, with close follow-up
• Immediate public health notification: contact local/state health department and CDC for any suspected case — anthrax is a nationally notifiable disease [15]
• Specialist consultation: infectious disease (all cases), critical care (systemic), neurosurgery (meningitis with mass effect), surgery (injection anthrax — prompt surgical debridement may be critical) [8]

• PEP follow-up: monitor for medication adherence and adverse effects throughout 60-day course; GI intolerance is common and a major cause of non-compliance [10]
• Post-PEP counseling: after completing prophylaxis, patients must immediately report any flu-like symptoms or febrile illness — spores may remain latent and germinate after antibiotic discontinuation [10]
• Cutaneous anthrax: follow-up in 48–72 hours to assess lesion progression; eschar typically resolves over 1–3 weeks even with treatment [7]
• Post-hospitalization: infectious disease follow-up within 1 week; monitor for late complications including persistent effusions and neurologic sequelae
• Return precautions: fever, dyspnea, chest pain, worsening skin lesion, confusion, headache with neck stiffness, or any new systemic symptoms

1. CDC Guidelines for the Prevention and Treatment of Anthrax, 2023. — William A. Bower MD, Yon Yu PharmD, Marissa K. Person MSPH, et al United States Centers for Disease Control and Prevention. 2025.

2. Anthrax Infection. — Sweeney DA, Hicks CW, Cui X, Li Y, Eichacker PQ. American Journal of Respiratory and Critical Care Medicine. 2011.

3. Clinical Framework and Medical Countermeasure Use During an Anthrax Mass-Casualty Incident. — Bower WA, Hendricks K, Pillai S, Guarnizo J, Meaney-Delman D. MMWR. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports. 2015.

4. Anthrax. — Dixon TC, Meselson M, Guillemin J, Hanna PC. The New England Journal of Medicine. 1999.

5. Clinical Features of Patients Hospitalized for All Routes of Anthrax, 1880-2018: A Systematic Review. — Hendricks K, Person MK, Bradley JS, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2022.

6. Clinical Management of Potential Bioterrorism-Related Conditions. — Adalja AA, Toner E, Inglesby TV. The New England Journal of Medicine. 2015.

7. CDC Issues Guidelines on Illnesses Associated With Intentional Release of Biologic Agents. — Ressel G. American Family Physician. 2001.

8. An Overview of Anthrax Infection Including the Recently Identified Form of Disease in Injection Drug Users. — Hicks CW, Sweeney DA, Cui X, Li Y, Eichacker PQ. Intensive Care Medicine. 2012.

9. Anthrax as a Biological Weapon: Medical and Public Health Management. — Inglesby TV, Henderson DA, Bartlett JG, et al. The Journal of the American Medical Association. 1999.

10. Anthrax as a Biological Weapon, 2002: Updated Recommendations for Management. — Inglesby TV, O'Toole T, Henderson DA, et al. The Journal of the American Medical Association. 2002.

11. Bioterrorism. — Rathjen NA, Shahbodaghi SD. American Family Physician. 2021.

12. Use of Anthrax Vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices, 2019. — Bower WA, Schiffer J, Atmar RL, et al. MMWR. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports. 2019.

13. Conference Report on Public Health and Clinical Guidelines for Anthrax. — Stern EJ, Uhde KB, Shadomy SV, Messonnier N. Emerging Infectious Diseases. 2008.

14. Systematic Review of Hospital Treatment Outcomes for Naturally Acquired and Bioterrorism-Related Anthrax, 1880-2018. — Person MK, Cook R, Bradley JS, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2022.

15. Recognition and Management of Anthrax — An Update. — Swartz MN. The New England Journal of Medicine. 2001.

16. Management of Anthrax Meningitis. — Sejvar JJ, Tenover FC, Stephens DS. The Lancet. Infectious Diseases. 2005.

17. Comparing Microbiological and Molecular Diagnostic Tools for the Surveillance of Anthrax. — Ochai SO, Hassim A, Dekker EH, et al. PLoS Neglected Tropical Diseases. 2024.

18. Development and Performance of a Checklist for Initial Triage After an Anthrax Mass Exposure Event. — Hupert N, Person M, Hanfling D, et al. Annals of Internal Medicine. 2019.