Anthrax Treatment & Management

With doxycycline, a loading regimen should be used (200 mg PO/IV every 12 hours for 72 hours). In severely ill patients, 200 mg IV/PO every 12 hours may be continued (without toxicity) for the duration of therapy. Oral doxycycline and quinolones have excellent bioavailability; the same blood/tissue levels are obtained with PO and IV therapy. Use any quinolone in patients who are unable to take penicillin or doxycycline.

The preferred agent used to treat nonbioterrorist anthrax is penicillin. Penicillin is the preferred agent to treat inhalational anthrax and anthrax meningitis. Use meningeal doses for inhalational anthrax because meningitis is often also present.

For bioterrorist anthrax, use any quinolone or doxycycline for 1-2 weeks. Clindamycin may be added for its anti-exotoxin effect. Use doxycycline or any quinolone (eg, ciprofloxacin, levofloxacin) for postexposure prophylaxis (PEP) to prevent inhalational anthrax. PEP to prevent inhalational anthrax should be continued for 60 days.

Raxibacumab is a human IgG1 gamma monoclonal antibody directed at the protective antigen of Bacillus anthracis. It is produced by recombinant DNA technology in a murine cell expression system. This agent was approved by the FDA in December 2012 for treatment of inhalational anthrax or for prevention when alternative therapies are not available or appropriate. It is used as part of a combination regimen with appropriate antibiotic drugs. ^[8] The efficacy of raxibacumab as a prophylactic agent and after disease onset was assessed in 4 randomized controlled animal model trials to provide surrogate endpoints applicable to human use. ^[9]

Obiltoxaximab is another monoclonal antibody directed at the protective antigen of B anthracis that was approved by the FDA in March 2016. It is a chimeric IgG1 kappa monoclonal antibody. ^[10]

Human anthrax immune globulin (Anthrasil) is indicated for treatment of inhalational anthrax in adults and children in combination with antibiotic therapy. ^[11]

The indication for anthrax vaccine adsorbed (BioThrax) was expanded in November 2015 to include postexposure use following suspected or confirmed B anthracis exposure in combination with antimicrobial therapy. It was originally approved for pre-exposure prophylaxis in high-risk individuals. ^[12]

Antimicrobial therapy renders lesions culture-negative within hours, but the lethal effects of anthrax are related to the effects of the organism's toxin. Patients with septic and hemorrhagic shock, which is the final common pathway for end-stage anthrax infection, should be admitted to the intensive care unit for hemodynamic monitoring and management. In addition, progressive respiratory insufficiency may necessitate the use of ventilatory support.

Despite early treatment, persons infected with inhalational, gastrointestinal, or meningeal anthrax have a very poor prognosis. Although prophylaxis and vaccinations confer almost complete protection, adequately providing immunity to a potentially exposed community is extremely difficult.

The Infectious Diseases Society of America (IDSA) published guidelines for the treatment of both naturally acquired and bioterrorism-related cases of cutaneous anthrax (see Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America). ^[13]

The CDC has issued updated guidelines on anthrax postexposure prophylaxis (PEP) and treatment in nonpregnant and pregnant adults. Recommendations include the following: ^{[14, 15]}

• All individuals exposed to aerosolized B anthracis spores should receive a full 60 days of PEP antimicrobial drugs, regardless of their vaccination status
• Compared with monotherapy, antimicrobial combination therapy is more likely to result in a cure; combined bactericidal and protein synthesis inhibitor agents may be beneficial
• Ciprofloxacin, levofloxacin, and doxycycline are approved by the FDA for PEP for inhalation anthrax in adults aged 18 years or older; ciprofloxacin and doxycycline are first-line treatments
• Treatment for anthrax meningitis should include at least 3 antimicrobial drugs with activity against B anthracis, at least 1 of which should have bactericidal activity, and at least 1 of which should be a protein synthesis inhibitor
• For patients suspected to have systemic anthrax, antitoxin should be added to combination antimicrobial drug treatment
• Uncomplicated cutaneous anthrax can be treated with a single oral agent; fluoroquinolones (ciprofloxacin, levofloxacin, and moxifloxacin) and doxycycline are equivalent first-line drugs
• Treatments for pregnant, postpartum, and lactating women are generally the same as those for nonpregnant patients

Patients with isolated cutaneous anthrax without systemic involvement (ie, without edema, fever, cough, headache, etc) or complications may be treated on an outpatient basis with antibiotic monotherapy. The treatment of choice has been outlined as recommended by the CDC, IDSA, and AAP.

Table 3. CDC Expert Panel Recommendations for Treatment of Cutaneous Anthrax (Open Table in a new window)

Systemic Anthrax Without Meningitis

All patients with suspected systemic anthrax should be begun immediately on IV antibiotics with co-administration of an antitoxin (raxibacumab or anthrax IgG) and should receive aggressive supportive care. All patients with suspected systemic illness should be admitted to inpatient for treatment. Early diagnosis and clinical suspicion are critical to improving outcomes. Workup should include standard fever workup pending the clinical situation, often including blood cultures and urine samples.

For adults with systemic anthrax (inhalational, intestinal, meningitis, injection), the CDC expert panel recommends the following:

Table 4. CDC Expert Panel Recommendations for Treatment of Systemic Anthrax Without Meningitis ^[15] (Open Table in a new window)

Anthrax Meningitis, Suspected or Confirmed

In patients with suspected or confirmed anthrax meningitis, if not already done, a lumbar puncture should be performed for CSF analysis. Immediate antibiotics are warranted, and lumbar puncture should never delay therapy. Two bactericidal agents plus a protein synthesis inhibitor are indicated. All must be dosed for CSF penetration.

Table 5. CDC Expert Panel Recommendations for Treatment of Anthrax Meningitis ^[15] (Open Table in a new window)

Anticipate a therapy duration of at least three weeks or until clinical improvement, whichever comes last, as clinical improvement may take several weeks. Thereafter, patients should complete a 60-day course of antibiotics with oral monotherapy to prevent relapse involving dormant endospores. Oral antibiotic should be dosed according to guidelines for postexposure prophylaxis.

All suspected cases of inhalational anthrax should be considered a bioterror event until proven to be otherwise. As with any potential epidemic biologic exposure, patients should be decontaminated in the field when possible, and paramedical health care workers should wear masks and gloves. If protection is needed from exposure, responders are advised to use splash protection, gloves, and a full-face respirator with high-efficiency particulate air (HEPA) filters (level C) or self-contained breathing apparatus (SCBA) (level B).

Persons who are potentially contaminated should wash with soap and water, not bleach solutions. Clothing and evidence/materials should be placed in plastic bags (triple). If the contamination is confirmed, then a 1:10 dilution of household beach may be used to decontaminate any materials and surfaces not sufficiently cleaned by soap and water.

Chemoprophylaxis with antibiotics should be instituted only if exposure is confirmed. For persons not at risk for repeated exposures to aerosolized B. anthracis spores through their occupation, preexposure vaccination with anthrax vaccine is not recommended.

The emergency department workup includes rapid initiation of intravenous antibiotic therapy. If risk of exposure is considerable, initiate PEP.

During the 2001 bioterrorist attacks in the United States, the Centers for Disease Control and Prevention (CDC) recommendations for antimicrobial PEP included ciprofloxacin or doxycycline; the CDC recommended amoxicillin for children and pregnant or breastfeeding women exposed to strains susceptible to penicillin. The duration of postexposure antimicrobial prophylaxis should be 60 days if used alone for PEP of unvaccinated exposed persons.

There is a potential preventive benefit of using anthrax vaccine along with an antimicrobial drug for PEP, and the vaccine was made available for this use during the 2001 bioterrorism attacks; however, anthrax vaccine is not licensed for use in PEP.

Raxibacumab and obiltoxaximab are monoclonal antibodies available from the CDC for treatment of inhalational anthrax or as prophylaxis when other therapies are not available or appropriate. These monoclonal antibodies are used as part of a combination regimen with appropriate antibiotic drugs. ^{[9, 10, 16]}

Human anthrax immune globulin was approved by the FDA in March 2015. It provides passive immunity to adults and children exposed to inhalational anthrax. It is used in conjunction with appropriate antibiotic therapy. ^[11]

The indication for anthrax vaccine adsorbed (BioThrax) was expanded in November 2015 to include postexposure use following suspected or confirmed B anthracis exposure in combination with antimicrobial therapy. It was originally approved for pre-exposure prophylaxis in high-risk individuals. ^[12]

Patients can be admitted to a normal hospital room with barrier nursing procedures (ie, gown, gloves, mask) and secretion precautions (ie, special handing of potentially infectious dressings, drainage, and excretions).

Anthrax is a reportable disease; notify local health care authorities and the Centers for Disease Control and Prevention of suspected cases. In addition, consultation with an infectious disease specialist may be warranted, although treatment of patients in whom anthrax is suspected is straightforward. If biologic terrorism is a threat, consider contacting the Federal Bureau of Investigation (FBI) through the local police department.

For PEP in adults, the CDC recommends vaccination and the use of oral fluoroquinolones (ciprofloxacin, 500 mg bid; levofloxacin, 500 mg qd; or ofloxacin, 400 mg bid). Doxycycline is an acceptable alternative. Prophylaxis should continue until exposure to B anthracis is excluded or for a period of 4 weeks if exposure is confirmed.

The monoclonal antibodies raxibacumab and obiltoxaximab are indicated for prophylaxis of inhalational anthrax when alternative therapies are not available or not appropriate. They should be used as part of a combination regimen with appropriate antibiotic drugs. ^{[9, 10, 16]}

Three doses of vaccine should be administered during the 4-week period (at 0, 2, and 4 weeks post exposure). If a vaccine is not available, the antibiotic treatment should continue for at least 60 days. A second option is treatment for 100 days. A third option is 100 days of antibiotic prophylaxis with vaccine.

Anthrax vaccine

A vaccine exists but is not readily available. Preexposure vaccination is recommended only for populations at high risk of exposure to aerosolized B anthracis spores, according to the CDC's Advisory Committee on Immunization Practices (ACIP). The populations at high risk are the following:

• Those who work directly with the organism in the laboratory
• Those who work with imported animal hides or furs in areas where standards are insufficient to prevent exposure to anthrax spores
• Those who handle potentially infected animal products in high-incidence areas; while incidence is low in the United States, veterinarians who travel to work in other countries where incidence is higher should consider being vaccinated
• Those who work in the military and are deployed to areas with high risk for exposure to the organism

The anthrax vaccine adsorbed pre-exposure prophylaxis regimen is as follows:

• Three-dose primary series: 0.5 mL IM at 0, 1, and 6 months
• Booster series: 0.5 mL IM at 6 and 12 months after primary series initiation and then at 1-year intervals thereafter for persons who remain at risk
• In persons who are at risk for hematoma formation following IM injection, the vaccine may be administer SC as a 4-dose primary series at 0, 2, 4 weeks and at 6 months
• Note: Individuals are not considered protected until completion of the primary series
• Administer in deltoid region

Anthrax vaccine adsorbed is also approved for postexposure prophylaxis following suspected or confirmed B anthracis exposure.

The anthrax vaccine adsorbed postexposure prophylaxis regimen is as follows:

• 0.5 mL SC at 0, 2, and 4 weeks postexposure combined with antimicrobial therapy
• Administer over deltoid region

Better protection, more extensive testing, more rigorous FDA approval, reduction of adverse effects, and a simpler dosing schedule are needed for anthrax vaccine. No human studies are available that document efficacy of available vaccines.