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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

Medical therapy of anthrax infection includes antibiotic and antitoxin drugs. Patients should be treated with a multiple antibiotic regimen (≥3 drugs) for 60 days to avoid the creation of drug resistant species and ensure the elimination of remaining spores of the bacteria. These patients should be monitored at all times to evaluate the need for supportive care measures, such as hemodynamic support, mechanical ventilation, corticosteroids, procedures, and surgical interventions in certain occasions.

Medical Therapy

The treatment of anthrax infection includes antibiotic and antitoxin agents. This treatment and postexposure prophylaxis differs from other bacterial infections because anthrax is associated with:[1]

Antibiotic Treatment

Cutaneous Anthrax without Systemic Involvement

Choice of Antibiotics

Duration of the Treatment

  • Duration of treatment for localized or uncomplicated cutaneous disease depends on the B. anthracis exposure source:
    • Naturally acquired (e.g., animals with anthrax, products such as hides from animals with anthrax): 7–10-day course
    • Bioterrorism-related exposure or an aerosol exposure is suspected: 60 days (because the patient is likely to have also inhaled spores.)

Systemic Anthrax When Meningitis Has Been Excluded

Choice of Antibiotics

  • The initial treatment should include ≥2 antimicrobial drugs with activity against B. anthracis:
    • ≥1 should have bactericidal activity, and
    • ≥1 should be a protein synthesis inhibitor
  • Intravenous ciprofloxacin is preferred as the primary bactericidal component in the treatment of systemic disease. Linezolid or clindamycin are the preferred as the first-line protein synthesis inhibitor.
  • Treatment with antimicrobial drugs that have good CNS penetration is not a crucial factor. Thus, meropenem is recommended as an acceptable alternative option than as a first-line antimicrobial drug, and vancomycin is also an acceptable alternative. Clindamycin and linezolid are considered equivalent first-line choices for protein synthesis inhibitors. Doxycycline is added as an alternative protein synthesis inhibitor option if linezolid or clindamycin are contraindicated or unavailable.

Duration of the Treatment

  • Initial intravenous combination treatment should be given for ≥2 weeks or until the patient is clinically stable, whichever is longer.

Follow–up Oral Treatment for Systemic Disease

Once patients with systemic illness who were exposed to aerosolized spores have completed initial combination treatment, they should be transitioned to single-agent oral treatment to prevent relapse from surviving B. anthracis spores.

Systemic Anthrax with Possible/Confirmed Meningitis

Hospitalized patients for systemic anthrax should be immediately treated with a combination of broad-spectrum intravenous antibiotic drug treatment pending confirmatory test results because any delay may prove fatal.

Because meningitis and hemorrhagic brain parenchymal infection was observed in ≤50% of cases, meningitis must be considered in all cases of systemic anthrax. Therefore antibiotics to treat possible meningitis must have good penetration of the central nervous system (CNS).[1] Empiric therapy for anthrax in which anthrax meningitis is suspected or cannot be ruled out should include ≥3 antibiotics with activity against Bacillus anthracis, in which:[1]

  • All should have good CNS penetration

Given the high mortality rate associated with meningitis, 3 weeks of treatment for patients in whom meningitis could not be ruled out is preferred. Because of the presence of a spore form of Bacillus anthracis, antibiotic therapy should be continued for 60 days to clear germinating organisms.[1]

Hospitalization is warranted for all patients with systemic cutaneous anthrax; gastrointestinal, injection, or inhalation anthrax; or anthrax meningitis or bacteremia.

Patients with systemic anthrax commonly have debilitating symptoms, followed first by transitory improvement and then by precipitous hemodynamic deterioration. Because of this potential for sudden decompensation, hospitalized patients should have careful hemodynamic monitoring.[2]


▸ Click on the following categories to expand treatment regimens.[3][4][5]

Cutaneous Anthrax Without Systemic Involvement

  ▸  Adult Patients

  ▸  Pediatric Patients

  ▸  Pregnant Patients

Systemic Anthrax with Possible/Confirmed Meningitis

  ▸  Adult Patients

  ▸  Pediatric Patients

  ▸  Pregnant Patients

Systemic Anthrax Without Meningitis

  ▸  Adult Patients

  ▸  Pediatric Patients

  ▸  Pregnant Patients

Cutaneous Anthrax, Adult Patients
Preferred Regimen
Ciprofloxacin 500 mg PO q12h
OR
Levofloxacin 750 mg PO q24h
OR
Moxifloxacin 400 mg PO q24h
OR
Doxycycline 100 mg PO q12h
Alternative Regimen
Clindamycin 600 mg PO q8h
OR
Penicillin VK 500 mg PO q6h
OR
Amoxicillin 1 g PO q8h
Cutaneous Anthrax, Pediatric Patients
Preferred Regimen
Ciprofloxacin 30 mg/kg/day PO q12h, max: 500 mg/dose
OR
Levofloxacin 16 mg/kg/day PO q12h, max: 250 mg/dose (<50 kg)
OR
Levofloxacin 500 mg PO q24h (≥50 kg)
OR
Doxycycline 4.4 mg/kg/day PO q12h, max: 100 mg/dose (<45 kg)
OR
Doxycycline 100 mg/dose PO q12h (≥45 kg)
Alternative Regimen
Clindamycin 30 mg/kg/day PO q8h, max: 600 mg/dose
OR
Penicillin VK 50–75 mg/kg/day PO q6–8h
OR
Amoxicillin 75 mg/kg/day PO q8h, max: 1 g/dose
Cutaneous Anthrax, Pregnant Patients
Preferred Regimen
Ciprofloxacin 500 mg PO q12h
Systemic Anthrax with Meningitis, Adult Patients
Preferred Regimen
Ciprofloxacin 400 mg IV q8h
OR
Levofloxacin 750 mg IV q24h
OR
Moxifloxacin 400 mg IV q24h
PLUS
Meropenem 2 g IV q8h
OR
Imipenem 1 g IV q6h
OR
Doripenem 500 mg IV q8h
PLUS
Linezolid 600 mg IV q12h
OR
Clindamycin 900 mg IV q8h
OR
Rifampin 600 mg IV q12h
OR
Chloramphenicol 1 g IV q6–8h
Alternative Regimen
Ciprofloxacin 400 mg IV q8h
OR
Levofloxacin 750 mg IV q24h
OR
Moxifloxacin 400 mg IV q24h
PLUS
Penicillin G 4 MU IV q4h
OR
Ampicillin 3 g IV q6h
PLUS
Linezolid 600 mg IV q12h
OR
Clindamycin 900 mg IV q8h
OR
Rifampin 600 mg IV q12h
OR
Chloramphenicol 1 g IV q6–8h
Systemic Anthrax with Meningitis, Pediatric Patients
Preferred Regimen
Ciprofloxacin 30 mg/kg/day IV q8h, max: 400 mg/dose
OR
Levofloxacin 20 mg/kg/day IV q12h, max: 250 mg/dose (<50 kg)
OR
Levofloxacin 500 mg IV q24h (≥50 kg)
OR
Meropenem 60 mg/kg/day IV q12h, max: 2 g/dose
OR
Imipenem/Cilastatin 100 mg/kg/day IV q6h, max: 1 g/dose
OR
Vancomycin 60 mg/kg/day IV q8h
PLUS
Clindamycin 30 mg/kg/day PO q8h, max: 600 mg/dose
OR
Linezolid 30 mg/kg/day IV q8h, max: 1 g/dose (<12 yr)
OR
Linezolid 30 mg/kg/day IV q12h, max: 600 mg/dose (≥12 yr)
OR
Doxycycline 4.4 mg/kg/day IV q12h, max: 100 mg/dose (<45 kg)
OR
Doxycycline 200 mg IV x1 then 100 mg IV q12h, max: 200 mg/dose (≥45 kg)
OR
Rifampin 20 mg/kg/day IV q12h, max: 300 mg/dose
Alternative Regimen
Penicillin G 0.4 MU/kg/day IV q4h, max: 4 MU/dose
OR
Ampicillin 200 mg/kg/day IV q6h, max: 900 mg/dose
PLUS
Clindamycin 30 mg/kg/day PO q8h, max: 600 mg/dose
OR
Linezolid 30 mg/kg/day IV q8h, max: 1 g/dose (<12 yr)
OR
Linezolid 30 mg/kg/day IV q12h, max: 600 mg/dose (≥12 yr)
OR
Doxycycline 4.4 mg/kg/day IV q12h, max: 100 mg/dose (<45 kg)
OR
Doxycycline 200 mg IV x1 then 100 mg IV q12h, max: 200 mg/dose (≥45 kg)
OR
Rifampin 20 mg/kg/day IV q12h, max: 300 mg/dose
Systemic Anthrax with Meningitis, Pregnant Patients
Preferred Regimen
Ciprofloxacin 400 mg IV q8h
PLUS
Clindamycin 900 mg IV q8h
OR
Rifampin 600 mg IV q12h
Alternative Regimen
Levofloxacin 750 mg IV q24h
OR
Meropenem 2 g IV q8h
OR
Penicillin G 4 MU IV q4h
OR
Ampicillin 3 g IV q6h
PLUS
Clindamycin 900 mg IV q8h
OR
Rifampin 600 mg IV q12h
Systemic Anthrax Without Meningitis, Adult Patients
Preferred Regimen
Ciprofloxacin 400 mg q8h
OR
Levofloxacin 750 mg q24h
OR
Moxifloxacin 400 mg PO q24h
OR
Meropenem 2 g q8h
OR
Imipenem 1 g IV q6h
OR
Doripenem 500 mg q8h
OR
Vancomycin 60 mg/kg/day IV q8h, trough: 15–20 μg/mL
PLUS
Clindamycin 900 mg q8h
OR
Linezolid 600 mg q12h
OR
Doxycycline 200 mg x1 then 100 mg IV q12h
OR
Rifampin 600 mg q12h
Alternative Regimen
Penicillin G 4 MU IV q4h
OR
Ampicillin 3 g IV q6h
PLUS
Clindamycin 900 mg q8h
OR
Linezolid 600 mg q12h
OR
Doxycycline 200 mg x1 then 100 mg IV q12h
OR
Rifampin 600 mg q12h
Systemic Anthrax Without Meningitis, Pediatric Patients
Preferred Regimen
Ciprofloxacin 30 mg/kg/day IV q8h, max: 400 mg/dose
OR
Levofloxacin 16 mg/kg/day IV q12h, max: 250 mg/dose (<50 kg)
OR
Levofloxacin 500 mg IV q24h (≥50 kg)
OR
Moxifloxacin 12 mg/kg/day IV q12h, max: 200 mg/dose (3 mo–2 yr)
OR
Moxifloxacin 10 mg/kg/day IV q12h, max: 200 mg/dose (2 yr–5 yr)
OR
Moxifloxacin 8 mg/kg/day IV q12h, max: 200 mg/dose (6 yr–11 yr)
OR
Moxifloxacin 8 mg/kg/day IV q12h, max: 200 mg/dose (12 yr–17 yr, <45 kg)
OR
Moxifloxacin 400 mg IV q24h (12 yr–17 yr, ≥45 kg)
PLUS
Meropenem 120 mg/kg/day IV q8h, max: 2 g/dose
OR
Imipenem/Cilastatin 100 mg/kg/day IV q6h, max: 1 g/dose
OR
Doripenem 120 mg/kg/day IV q8h, max: 1 g/dose
OR
Vancomycin 60 mg/kg/day IV q8h
PLUS
Linezolid 30 mg/kg/day IV q8h, max: 600 mg/dose (<12 yr)
OR
Linezolid 30 mg/kg/day IV q12h, max: 600 mg/dose (≥12 yr)
OR
Clindamycin 40 mg/kg/day IV q8h, max: 900 mg/dose
OR
Rifampin 20 mg/kg/day IV q12h, max: 300 mg/dose
OR
Chloramphenicol 100 mg/kg/day IV q6h
Alternative Regimen
Ciprofloxacin 30 mg/kg/day IV q8h, max: 400 mg/dose
OR
Levofloxacin 16 mg/kg/day IV q12h, max: 250 mg/dose (<50 kg)
OR
Levofloxacin 500 mg IV q24h (≥50 kg)
OR
Moxifloxacin 12 mg/kg/day IV q12h, max: 200 mg/dose (3 mo–2 yr)
OR
Moxifloxacin 10 mg/kg/day IV q12h, max: 200 mg/dose (2 yr–5 yr)
OR
Moxifloxacin 8 mg/kg/day IV q12h, max: 200 mg/dose (6 yr–11 yr)
OR
Moxifloxacin 8 mg/kg/day IV q12h, max: 200 mg/dose (12 yr–17 yr, <45 kg)
OR
Moxifloxacin 400 mg IV q24h (12 yr–17 yr, ≥45 kg)
PLUS
Penicillin G 0.4 MU/kg/day IV q4h, max: 4 MU/dose
OR
Ampicillin 400 mg/kg/day IV q6h, max: 3 g/dose
PLUS
Linezolid 30 mg/kg/day IV q8h, max: 600 mg/dose (<12 yr)
OR
Linezolid 30 mg/kg/day IV q12h, max: 600 mg/dose (≥12 yr)
OR
Clindamycin 40 mg/kg/day IV q8h, max: 900 mg/dose
OR
Rifampin 20 mg/kg/day IV q12h, max: 300 mg/dose
OR
Chloramphenicol 100 mg/kg/day IV q6h
Systemic Anthrax Without Meningitis, Pregnant Patients
Preferred Regimen
Ciprofloxacin 400 mg IV q8h
PLUS
Clindamycin 900 mg IV q8h
OR
Rifampin 600 mg IV q12h
Alternative Regimen
Levofloxacin 750 mg IV q24h
OR
Meropenem 2 g IV q8h
OR
Penicillin G 4 MU IV q4h
OR
Ampicillin 3 g IV q6h
PLUS
Clindamycin 900 mg IV q8h
OR
Rifampin 600 mg IV q12h

Follow-up Oral Treatment for Systemic Disease

Once patients with systemic illness who were exposed to aerosolized spores have completed the initial combination treatment, they should be transitioned to a single-agent oral treatment to prevent relapse from surviving Bacillus anthracis spores.

Antitoxins

An antitoxin should be added to combination antibiotic treatment for any patient for whom there is a high level of clinical suspicion for systemic anthrax. Given that systemic anthrax has a high case-fatality rate and the risk for antitoxin treatment appears to be low, the potential benefit achieved by adding antitoxin to combination antibiotic treatment outweighs the potential risk.

Currently there are 2 antitoxins in the CDC Strategic National Stockpile: raxibacumab and Anthrax Immune Globulin Intravenous (AIGIV). Both antitoxins inhibit binding of Protective Antigen (PA) to anthrax toxin receptors and translocation of the 2 primary toxins (Lethal Toxin (LT) and Edema Toxin (ET)) into cells.[1]

Raxibacumab

Raxibacumab is a recombinant, fully humanized, IgG1λ monoclonal antibody. It appeared safe and well tolerated in 333 healthy adults who received the recommended dose of 40 mg/kg.

Most adverse events were transient and mild to moderate in severity. Pruritis was noted in 2.1% of persons treated with raxibacumab and in none treated with placebo. Although raxibacumab has not been given to patients with systemic anthrax, it is FDA-approved for postexposure prophylaxis PEP.[1]

Anthrax Immune Globulin

AIGIV is a human polyclonal antiserum made from plasma of persons immunized with Anthrax Vaccine Absorbed (AVA), which might have some direct effect on Lethal Factor (LF) and Edema Factor (EF). It was evaluated in 74 healthy adult volunteers and appears safe and well tolerated at all doses tested.

The most frequently reported adverse events were headache pharyngolaryngeal pain, and nausea.

AIGIV is not FDA approved and could be made available under an Investigational New Drug protocol or an Emergency Use Authorization during a declared emergency.[1]

Supportive Treatment

Hemodynamic Support

Standard sepsis and septic shock guidelines should be followed for anthrax patients. Common complications of anthrax infections including microangiopathic hemolytic anemia, coagulopathy, thrombocytopenia, and hemorrhage must be aggressively managed, since they might pose contraindications to invasive central catheter placement.[6]

Fresh frozen plasma and plasmapheresis should be considered, and fibrinogen levels should be kept >100 mg/dL.

An echocardiogram might be needed to identify pericardial effusions.[7]

Mechanical Ventilation

In addition to the need for mechanical ventilation for respiratory distress or airway protection for persons with altered mental status, some patients with anthrax might require respiratory support for airway edema. Substantial edema with fatal outcome can occur with cutaneous lesions involving the head, neck, or thorax, and with oropharyngeal lesions.[8]

In inhalation anthrax, although respiratory failure is more consistent with reaccumulating pleural effusions than with adult respiratory distress syndrome, standard mechanical ventilator principles apply.[9] The need for ventilation in some patients and the duration of ventilation in others may be reduced by pleural space drainage.

Adjunctive Corticosteroids

There are limited data on steroid use for documented anthrax meningitis, however, adjunctive intravenous dexamethasone is the standard of care for patients with suspected bacterial meningitis and should be started at the time of initial antibiotic therapy to prevent neurologic sequelae.[10]

Adjunctive corticosteroids should be considered in patients who had a history of use of:[11][12]

Interventions

Procedures

Drainage of pleural fluid and ascites is believed to improve survival by reducing the toxin level and by decreasing mechanical lung compression. These data support the need for early and aggressive drainage of any clinically or radiographically apparent pleural effusions; chest tube drainage is recommended over thoracentesis because many effusions will require prolonged drainage. [1]

Thoracotomy or video-assisted thoracic surgery might be required to remove gelatinous or loculated collections. Ascites should also be drained and monitored for reaccumulation.[1]

Surgery

Surgery for cutaneous anthrax can lead to dissemination and poor outcome. Surgery is contraindicated for acute disease, with the exception of tracheotomy for airway obstruction and surgical intervention for large or circumferential extremity lesions causing compartment syndrome.

Surgery may be indicated for gastrointestinal anthrax to identify and address potentially fatal complications, such as bowel ischemia, necrosis, and perforation.[13]

For injection anthrax, surgery is used to obtain diagnostic specimens to differentiate the infection from necrotizing fasciitis and to remove the necrotic nidus of infection, which may be a toxin and spore reservoir. Surgery for injection anthrax should be more limited than that for necrotizing fasciitis, and resection should be performed only to healthy tissue. Compression of soft tissues can be released by incision, excision, or fasciotomy and might be required for treatment of compartment syndrome.[14]

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 "Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults".
  2. ALBRINK WS, BROOKS SM, BIRON RE, KOPEL M (1960). "Human inhalation anthrax. A report of three fatal cases". Am J Pathol. 36: 457–71. PMC 1942218. PMID 13792449.
  3. Hendricks, Katherine A. (2014-02). "Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults". Emerging Infectious Diseases. 20 (2). doi:10.3201/eid2002.130687. ISSN 1080-6059. PMC 3901462. PMID 24447897. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  4. Bradley, John S. (2014-04-28). "Pediatric Anthrax Clinical Management". Pediatrics. doi:10.1542/peds.2014-0563. ISSN 1098-4275. PMID 24777226. Unknown parameter |coauthors= ignored (help)
  5. Meaney-Delman, Dana (2014-02). "Special considerations for prophylaxis for and treatment of anthrax in pregnant and postpartum women". Emerging Infectious Diseases. 20 (2). doi:10.3201/eid2002.130611. ISSN 1080-6059. PMC 3901460. PMID 24457117. Unknown parameter |coauthors= ignored (help); Check date values in: |date= (help)
  6. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM; et al. (2013). "Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012". Intensive Care Med. 39 (2): 165–228. doi:10.1007/s00134-012-2769-8. PMID 23361625.
  7. Jernigan JA, Stephens DS, Ashford DA, Omenaca C, Topiel MS, Galbraith M; et al. (2001). "Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States". Emerg Infect Dis. 7 (6): 933–44. doi:10.3201/eid0706.010604. PMC 2631903. PMID 11747719.
  8. Peck RN, Fitzgerald DW (2007). "Cutaneous anthrax in the Artibonite Valley of Haiti: 1992-2002". Am J Trop Med Hyg. 77 (5): 806–11. PMID 17984330.
  9. Artigas A, Bernard GR, Carlet J, Dreyfuss D, Gattinoni L, Hudson L; et al. (1998). "The American-European Consensus Conference on ARDS, part 2: Ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling. Acute respiratory distress syndrome". Am J Respir Crit Care Med. 157 (4 Pt 1): 1332–47. doi:10.1164/ajrccm.157.4.ats2-98. PMID 9563759.
  10. de Gans J, van de Beek D, European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators (2002). "Dexamethasone in adults with bacterial meningitis". N Engl J Med. 347 (20): 1549–56. doi:10.1056/NEJMoa021334. PMID 12432041. Review in: ACP J Club. 2003 May-Jun;138(3):60
  11. Sejvar JJ, Tenover FC, Stephens DS (2005). "Management of anthrax meningitis". Lancet Infect Dis. 5 (5): 287–95. doi:10.1016/S1473-3099(05)70113-4. PMID 15854884.
  12. Annane D, Bellissant E, Bollaert PE, Briegel J, Confalonieri M, De Gaudio R; et al. (2009). "Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review". JAMA. 301 (22): 2362–75. doi:10.1001/jama.2009.815. PMID 19509383.
  13. Binkley CE, Cinti S, Simeone DM, Colletti LM (2002). "Bacillus anthracis as an agent of bioterrorism: a review emphasizing surgical treatment". Ann Surg. 236 (1): 9–16. PMC 1422543. PMID 12131080.
  14. Knox D, Murray G, Millar M, Hamilton D, Connor M, Ferdinand RD; et al. (2011). "Subcutaneous anthrax in three intravenous drug users: a new clinical diagnosis". J Bone Joint Surg Br. 93 (3): 414–7. doi:10.1302/0301-620X.93B3.25976. PMID 21357967.


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