Anthrax

Number: 0483

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses anthrax.

1. Medical Necessity

   1. Pre-Exposure Prophylaxis (PrEP) 

      Aetna considers anthrax vaccination for pre-exposure prophylaxis (PrEP) as a medically necessary preventive service according to the recommendations of the Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices (ACIP). The ACIP recommends anthrax vaccination for PrEP for the following groups:

      • Decontamination personnel and persons who work directly with the organism in the laboratory.Footnotes*
      • Military personnel deployed to areas with high-risk for exposure to the organism (as when it is used as a biological warfare weapon).Footnotes*
      • Persons who handle potentially infected animal products in high-incidence areas.  (Incidence is low in the United States, but veterinarians who travel to work in other countries where incidence is higher should consider being vaccinated.)Footnotes*
      • Persons who work with imported animal hides or furs in areas where standards are insufficient to prevent exposure to anthrax spores.Footnotes*
      • Environmental investigators and remediation workers who, as part of their occupation, might repeatedly enter areas contaminated with B. anthracis spores.Footnotes*
      • Responder units engaged in response activities that might lead to exposure to aerosolized B. anthracis spores.Footnotes*  (However, emergency and other responders are not recommended to receive routine pre-event anthrax vaccination because of the lack of a calculable risk assessment.)

      Food and Drug Administration (FDA)-approved anthrax vaccine adsorbed (AVA) injectable suspension (BioThrax) is recommended for PrEP in high-risk adults aged 18 to 65 years. Vaccination schedule consists of 3 initial intramuscular (IM) primary injections administered at 0, 1, and 6 months, followed by booster doses administered IM at 12 and 18 months. After completion of the 5-dose series, an additional booster may be given either annually for persons who remain at high-risk for exposure or every 3 years for those not at high risk but want to maintain protection.

      Footnotes*Note: In general, Aetna does not cover immunizations required solely for the purpose of employment, or because of incarceration. In addition, HMO plans usually exclude coverage of immunizations solely for the purpose of travel. Coverage of medically necessary preventive immunizations is available only to members with preventive service benefits. Check contract language, limitations and exclusions for coverage details.

   2. Post-Exposure Prophylaxis (PEP)

      1. Anthrax vaccination for PEP

         Aetna considers anthrax vaccination for post-exposure prophylaxis (PEP) as medically necessary according to the CDC's ACIP guidelines. The ACIP recommends anthrax vaccination for PEP following aerosolized (inhalation) exposure to Bacillus anthracis spores. For non-aerosol exposures (i.e., cutaneous or gastrointestinal), post-exposure vaccination is considered not medically necessary.

         FDA-approved anthrax vaccines recommended for PEP in persons 18 through 65 years of age include the following:

         Anthrax Vaccine Adsorbed (AVA) (BioThrax®), which consists of 3 subcutaneous (SC) injections administered at 0, 2, and 4 weeks given in conjunction with antibacterial therapy; or

         Anthrax Vaccine Adsorbed adjuvanted (AVA,A) (Cyfendus®), which consists of 2 intramuscular (IM) injections administered 2 weeks apart given in conjunction with antibacterial therapy.

         Parenteral (intravenous) antimicrobial therapy is considered medically necessary for PEP when oral therapy is not feasible or appropriate. For additional information and list of recommended antimicrobials, see CDC Guidelines for the Prevention and Treatment of Anthrax, 2023.

         Note: Medically necessary post-exposure anthrax vaccinations are covered for medically necessary indications regardless of whether the member has preventive services benefits.

         Note: The safety and effectiveness of anthrax vaccines have not been established in individuals younger than 18 or older than 65 years of age. Vaccination for PEP in these individuals are used under an expanded access Investigational New Drug (IND) program or Emergency Use Authorization (EUA) only (Bower et al., 2023; CDC, 2020).

      2. Antitoxins in the setting of PEP

         Per the CDC's ACIP, first-line PEP includes oral antimicrobial drugs plus anthrax vaccine, when indicated. However, a single intravenous anthrax antitoxin (raxibacumab or obiltoxaximab) dose is considered medically necessary for PEP only when antimicrobial drugs are not appropriate or not available. If coadministration of anthrax vaccine and antitoxin are indicated, the preferred antitoxin is raxibacumab (Bower et al., 2019; Bower et al., 2023).

   3. Laboratory Testing 

      Laboratory testing for anthrax is considered medically necessary in individuals with suspected or confirmed exposure to Bacillus anthracis or in persons presenting with clinical features consistent with anthrax infection (e.g., cutaneous, inhalational, or gastrointestinal disease) when results will inform diagnosis, guide antimicrobial management, or support public health response. Appropriate testing modalities may include culture for microbiologic identification of B. anthracis, real-time polymerase chain reaction (PCR) to detect bacterial DNA, anthrax lethal factor (LF) toxin testing performed on plasma or serum to identify circulating toxin, and pathologic evaluation of relevant clinical specimens, with selection based on clinical presentation and exposure history. For additional information, see CDC - Laboratory Information for Anthrax Testing.

   4. Treatment of Active Disease

      1. Intravenous (parenteral) antimicrobial therapy is considered medically necessary for the treatment of cutaneous anthrax when oral therapy is not feasible or appropriate. For antimicrobial drug selection and regimens, see CDC Guidelines for the Prevention and Treatment of Anthrax, 2023;
      2. Intravenous (parenteral) antimicrobial therapy is considered medically necessary for the treatment of systemic anthrax (with or without meningitis). For antimicrobial drug selection and regimens, see CDC Guidelines for the Prevention and Treatment of Anthrax, 2023;
      3. Single dose of an intravenous antitoxin drug (e.g., raxibacumab, obiltoxaximab, or anthrax immune globulin intravenous [AIGIV]) is considered medically necessary as an alternative to antimicrobial therapy for treating cutaneous anthrax only when antimicrobial drugs are not available or not appropriate. For drug selection and regimen, see CDC Guidelines for the Prevention and Treatment of Anthrax, 2023;
      4. Single dose of an intravenous antitoxin drug (e.g., raxibacumab, obiltoxaximab, or AIGIV) is considered medically necessary as an adjunct to antimicrobial therapy for treating persons with systemic anthrax. Antitoxin is not considered medically necessary as monotherapy or as a substitute for antibiotics in systemic anthrax. Additionally, antitoxin is not considered medically necessary for treating uncomplicated localized cutaneous disease. For drug selection and regimen, see CDC Guidelines for the Prevention and Treatment of Anthrax, 2023.

2. Experimental, Investigational, or Unproven

   Aetna considers anthrax vaccine and/or intravenous antitoxin drugs (raxibacumab, obiltoxaximab, or AIGIV) experimental, investigational, or unproven for all other indications because the safety and efficacy have not been established for conditions other than the ones designated as medically necessary.

3. Related Policies

   1. CPB 0002 - Oxygen
   2. CPB 0546 - Extracorporeal Membrane Oxygenation (ECMO)

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Table:

CPT Codes / HCPCS codes / ICD-10 Codes

Code	Code Description
CPT codes covered if selection criteria are met:
87070	Culture, bacterial; any other source except urine, blood or stool, aerobic, with isolation and presumptive identification of isolates
87075	any source, except blood, anaerobic with isolation and presumptive identification of isolates
87077	aerobic isolate, additional methods required for definitive identification, each isolate
87081	Culture, presumptive, pathogenic organisms, screening only
87140	Culture, typing; immunofluorescent method, each antiserum
87150	identification by nucleic acid (DNA or RNA) probe, amplified probe technique, per culture or isolate, each organism probed
87798	Infectious agent detection by nucleic acid (DNA or RNA), not otherwise specified; amplified probe technique, each organism
87801	Infectious agent detection by nucleic acid (DNA or RNA), multiple organisms; amplified probe(s) technique
87899	Infectious agent antigen detection by immunoassay with direct optical (ie, visual) observation; not otherwise specified
88305	Level IV - Surgical pathology, gross and microscopic examination
Intravenous human anthrax immune globulin (Anthrasil) - no specific code:
90581	Anthrax vaccine, for subcutaneous or intramuscular use
Other CPT codes related to the CPB:
90471	Immunization administration (includes percutaneous, intradermal, subcutaneous, or intramuscular injections); 1 vaccine (single or combination vaccine/toxoid)
90472	each additional vaccine (single or combination vaccine/toxoid) (List separately in addition to code for primary procedure)
HCPCS codes covered if selection criteria are met:
Obiltoxaximab (Anthim), Raxibacumab - no specific code:
J0120	Injection, tetracycline, up to 250 mg
J0456	Injection, azithromycin, 500 mg
J0457	Injection, aztreonam, 100 mg
J0458	Injection, aztreonam/avibactam, 7.5 mg/2.5 mg (10 mg)
J0558	Injection, penicillin g benzathine and penicillin g procaine, 100,000 units
J0561	Injection, penicillin g benzathine, 100,000 units
J0742	Injection, imipenem 4 mg, cilastatin 4 mg and relebactam 2 mg
J0743	Injection, cilastatin sodium; imipenem, per 250 mg
J0744	Injection, ciprofloxacin for intravenous infusion, 200 mg
J1271	Injection, doxycycline hyclate, 1 mg
J1956	Injection, levofloxacin, 250 mg
J2183	Injection, meropenem (wg critical care), not therapeutically equivalent to j2185, 100 mg
J2184	Injection, meropenem (b. braun), not therapeutically equivalent to j2185, 100 mg
J2185	Injection, meropenem, 100 mg
J2186	Injection, meropenem and vaborbactam, 10mg/10mg (20mg)
J2510	Injection, penicillin g benzathine, 100,000 units
J2540	Injection, penicillin g potassium, up to 600,000 units
ICD-10 codes covered if selection criteria are met:
A22.0	Cutaneous anthrax [not covered for anthrax vaccine PEP/ non-aerosol exposure]
A22.1	Pulmonary anthrax
A22.2	Gastrointestinal anthrax [not covered for anthrax vaccine PEP/ non-aerosol exposure]
A22.7	Anthrax sepsis
A22.8	Other forms of anthrax
A22.9	Anthrax, unspecified
G01	Meningitis in bacterial diseases classified elsewhere
Z20.810	Contact with and (suspected) exposure to anthrax
Z23	Encounter for immunization
ICD-10 codes not covered for indications listed in the CPB:
L08.9	Local infection of the skin and subcutaneous tissue, unspecified [uncomplicated]

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Background

The following discussion is primarily based on the Centers for Disease Control's Advisory Committee on Immunization Practices (ACIP) guidelines for the prevention and treatment of anthrax.

Anthrax is a serious infectious disease caused by the gram-positive, spore-forming bacterium Bacillus anthracis. This bacterium occurs naturally in soil and primarily affects domestic and wild animals. Human infection is rare in the United States and typically results from exposure to infected animals or contaminated animal products. It can also occur through the ingestion of contaminated food or water, inhalation of spores, or exposure in laboratory or bioterrorism settings.

The disease is not transmitted from person to person. It develops when spores enter the body through the skin, lungs, or gastrointestinal tract, leading to different forms of anthrax (cutaneous, inhalation, or gastrointestinal). Injection anthrax has been identified in heroin-injecting drug users in northern Europe, but it has not been reported in the United States to date. This form is similar to cutaneous anthrax and causes infection deep under the skin or in the muscle at the injection site.

The clinical severity of anthrax varies by route of exposure. Cutaneous anthrax is the most common and least fatal form, while inhalation anthrax represents the most severe. However, all forms may progress to systemic disease and death if untreated. Prompt treatment with appropriate antibiotics is essential. Additionally, post-exposure prophylaxis (PEP) with antimicrobial therapy and vaccination, as well as pre-exposure prophylaxis (PrEP) vaccination for individuals at high risk of exposure, may be indicated for prevention.

Anthrax is primarily found in agricultural regions, particularly in South and Central America, Southern and Eastern Europe, Asia, Africa, the Caribbean, and the Middle East, where it affects livestock. Human cases typically arise from occupational exposure to infected animals or their products, especially among workers handling dead animals or animal products from endemic areas. In the United States, anthrax has also been reported in wild livestock.

Anthrax is not transmitted between individuals but can be contracted in four distinct ways, with symptoms varying based on the route of entry into the body. Three main forms include cutaneous (skin), aerosol (inhalation), and gastrointestinal (ingestion). The fourth form, injection anthrax, is relatively new and was identified in heroin-injecting drug users in northern Europe from heroin contaminated with B. anthracis spores (Bowers et al., 2023). However, as of February 2026, there have not been any cases reported in the United States (CDC, 2026).

Symptoms vary based on the route of exposure and usually appear within seven days. Approximately 95% of infections occur when Bacillus anthracis (B. anthracis) enters through cuts or abrasions, often from handling contaminated wool, hides, or hair products. Cutaneous anthrax begins as a raised, itchy bump resembling an insect bite, progressing to a vesicle and then a painless ulcer with a characteristic black necrotic center. Lymphadenopathy may occur in the surrounding area. Without treatment, about 20% of cutaneous cases can be fatal, though fatalities are rare with appropriate antimicrobial therapy. Inhalation anthrax initially presents with cold-like symptoms but can progress to severe respiratory distress and shock, often resulting in death. Gastrointestinal anthrax follows the consumption of contaminated meat and is characterized by acute intestinal inflammation. Initial symptoms include nausea, loss of appetite, vomiting, and fever, which can escalate to abdominal pain, hematemesis, and severe diarrhea, with a mortality rate of 25% to 60%. Injecting heroin contaminated with anthrax can lead to swelling at the injection site, nausea, and sweating. However, all forms of anthrax may present with fever, chills, fatigue, and headache, and if untreated, the infection can spread throughout the body, potentially leading to severe complications, including brain infections and death. Anthrax meningitis has a mortality rate that approaches 100% and is a common complication of anthrax.

Diagnosis involves isolating B. anthracis from blood, skin lesions, or respiratory secretions, or detecting specific antibodies in suspected cases.

While anthrax is globally distributed, it is more prevalent in developing countries or regions lacking effective veterinary public health programs. Human-to-human transmission is exceedingly rare, and communicability is not a concern when managing patients with inhalation anthrax.

The World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) recommend that individuals in endemic countries, particularly where livestock vaccination rates are low, avoid contact with livestock and animal products and refrain from consuming improperly slaughtered and cooked meat. 

B. anthracis is a Tier 1 select agent and considered one of the most likely bioterrorism agents to be used because it is relatively easy to acquire from the natural environment, mass produce, and disseminate as spores via aerosolization. Although approximately 180 countries have agreed to prohibit the development, production, acquisition, transfer, stockpiling, and use of bioweapons, a wide-area aerosol release of B. anthracis spores remains a concern (Bowers et al., 2023). Because anthrax is considered to be a potential agent for use in biological warfare, the Department of Defense (DOD) has begun mandatory vaccination of all active duty military personnel who might be involved in conflict.

The Centers for Disease Control and Prevention (CDC), in conjunction with the Advisory Committee on Immunization Practices (ACIP), provides comprehensive guidance on the prevention, evaluation, and management of anthrax, including recommendations for exposure assessment, diagnostic testing, vaccination, and treatment. These recommendations address both naturally occurring infections and potential bioterrorism-related exposures and are informed by systematic review of available evidence and clinical experience. Guidance emphasizes that clinical management and preventive strategies are dependent on the route and severity of exposure, with subsequent recommendations addressing pre-exposure prophylaxis, post-exposure prophylaxis, diagnostic evaluation, vaccination, and treatment in specific clinical contexts. Early diagnosis of anthrax and initiation of appropriate treatment are critical to improving survival.

Pre-Exposure Prophylaxix (PrEP)

The Centers for Disease Control and Prevention (CDC) and the Advisory Committee on Immunization Practices (ACIP) recommend pre-exposure prophylaxis (PrEP) with anthrax vaccine adsorbed (AVA) for adults aged 18 to 65 years who are at increased risk for occupational exposure to Bacillus anthracis, including certain laboratory workers, persons who handle animals or animal products, and designated military personnel. PrEP consists of a multidose primary vaccination series followed by booster doses to maintain protection. Routine vaccination is not recommended for the general population because the risk of exposure to anthrax in the United States is low (Bowers et al., 2019).

Occupational and Laboratory Exposures

According to the ACIP, routine vaccination with Anthrax Vaccine Adsorbed (AVA) is indicated for persons engaged in:

• Activities with a high potential for aerosol production
• Work involving production quantities or concentrations of Bacillus anthracis cultures.

The ACIP has concluded that laboratorians using standard Biosafety Level 2 practices in the routine processing of clinical samples are not at increased risk for exposure to Bacillus anthracis spores.

The CDC announced that decontamination personnel and state and private laboratory workers who are involved in analyzing possible anthrax exposures will be eligible for vaccination against anthrax.

The risk for persons who come in contact in the workplace with imported animal hides, furs, bone meal, wool, animal hair, or bristles has been reduced by changes in industry standards and import restrictions.  ACIP recommends routine pre-exposure vaccination only for persons in this group for whom these standards and restrictions are insufficient to prevent exposure to anthrax spores.

The ACIP does not recommend routine vaccination of veterinarians in the United States because of the low incidence of animal cases. However, the ACIP guidelines note that vaccination might be indicated for veterinarians and other high-risk persons handling potentially infected animals in areas with a high incidence of anthrax cases.

Bioterrorism Preparedness

Although groups initially considered for pre-exposure vaccination for bioterrorism preparedness included emergency first responders, federal responders, medical practitioners, and private citizens, the ACIP does not recommend vaccination of these groups. The ACIP guidelines note that recommendations regarding pre-exposure vaccination should be based on a calculable risk assessment. The guidelines explain that, at present, the target population for a bioterrorist release of Bacillus anthracis can not be predetermined, and the risk of exposure can not be calculated. In addition, studies suggest an extremely low-risk for exposure related to secondary aerosolization of previously settled Bacillus anthracis spores. Because of these factors, the ACIP does not recommend pre-exposure vaccination for the above groups. The ACIP does state that pre-exposure vaccination may be indicated for the military, decontamination personnel, and other select populations or for groups for which a calculable risk can be assessed.

Options other than pre-exposure vaccination are available to protect personnel working in an area of a known previous release of Bacillus anthracis. According to the ACIP guidelines, if concern exists that persons entering an area of a previous release might be at risk for exposure from a re-release of a primary aerosol of the organism or exposure from a high concentration of settled spores in a specific area, initiation of prophylaxis should be considered with antibiotics alone or in combination with vaccine as is outlined in the section below on post-exposure prophylaxis.

Post-Exposure Prophylaxis (PEP)

CDC guidance indicates that post-exposure prophylaxis (PEP) is dependent on the route of exposure. For non-aerosol exposures, such as cutaneous or ingestion-related exposure, antimicrobial therapy alone for a limited duration (generally 7 days) is recommended, and post-exposure vaccination is not indicated. In contrast, following aerosolized exposure to Bacillus anthracis spores, prolonged antimicrobial prophylaxis is recommended, typically for up to 60 days, because spores may remain dormant and germinate after extended periods. In these cases, antimicrobial therapy may be administered in combination with anthrax vaccination to reduce the risk of disease progression. Antitoxin therapy is not routinely recommended for PEP and is generally reserved for treatment of systemic disease; however, antitoxin may be considered if antimicrobial agents are not available.(Bowers et al., 2023).

According to CDC guidelines, antimicrobial therapy is the primary method for PEP of anthrax, and the routine use of antitoxin is not recommended. Intravenous anthrax antitoxins, such as raxibacumab or obiltoxaximab, may be considered in specific situations where antimicrobial therapy is unavailable, inappropriate, or cannot be administered. When both the anthrax vaccine and antitoxin are indicated for PEP, raxibacumab is preferred due to its compatibility with the vaccine (Bowers et al., 2023).

Penicillin and doxycycline are approved by Food and Drug Administration (FDA) for the treatment of anthrax and are considered the drugs of choice for the treatment of naturally occurring anthrax. In addition, ciprofloxacin and ofloxacin have also demonstrated in- vitro activity against Bacillus anthracis. On the basis of studies that demonstrated the effectiveness of ciprofloxacin in reducing the incidence and progression of inhalation anthrax in animal models, the FDA approved the use of ciprofloxacin following aerosol exposure to Bacillus anthracis spores to prevent development or progression of inhalation anthrax in humans. Although naturally occurring Bacillus anthracis resistance to penicillin is rare, such resistance has been reported.

Antibiotics are active against the vegetative (germinated) form of Bacillus anthracis but are not effective against dormant spores. Following inhalational exposure, spores can persist in host tissues and may germinate over time, a phenomenon demonstrated in nonhuman primate models in which viable spores have been recovered weeks to months after exposure. This delayed germination contributes to a prolonged incubation period and supports the need for extended antimicrobial therapy. Such prolonged latency is primarily associated with inhalational anthrax and is not a recognized feature of other routes of infection.

Ciprofloxacin was the first antibiotic approved by the FDA for use in reducing the incidence or progression of disease after exposure to aerosolized Bacillus anthracis. Several studies have demonstrated that short courses (5 to 10 days) of post-exposure antibiotic therapy are not effective at preventing disease when large numbers of spores are inhaled. Longer courses of antibiotics may be effective.

Anthrax Vaccination

ACIP provides guidance on the use of anthrax vaccine adsorbed (AVA) and anthrax vaccine adsorbed adjuvanted (AVA,A) for both pre-exposure and post-exposure indications. For post-exposure prophylaxis in previously unvaccinated adults aged 18 to 65 years following aerosolized exposure, vaccination may be administered in combination with antimicrobial therapy. The currently available vaccines include AVA (BioThrax®), administered as a 3-dose series over 4 weeks, and AVA,A (Cyfendus®), administered as a 2-dose series given 2 weeks apart. Vaccination is not recommended following non-aerosol exposure and is not used for treatment of active anthrax infection, including systemic disease with or without meningitis. In addition, vaccination is not recommended following recovery from systemic anthrax because survivors are expected to develop natural immunity. Individuals with a history of severe allergic reaction to the vaccine or vaccine components should not receive anthrax vaccination and should instead complete antimicrobial prophylaxis as indicated (Bowers et al., 2019; CDC, 2020; CDC, 2026).

Anthrax Vaccine Adsorbed (AVA)

Anthrax Vaccine Adsorbed (BioThrax; Emergent BioSolutions Inc.) is an FDA-approved vaccine indicated for active immunization for the prevention of disease caused by Bacillus anthracis in persons 18 through 65 years of age, including for pre‑exposure prophylaxis (PrEP) in persons at high risk of exposure and for post‑exposure prophylaxis (PEP) following suspected or confirmed exposure when administered in conjunction with recommended antibacterial drugs. Its effectiveness for PEP is based solely on studies in animal models of inhalational anthrax, as human efficacy trials are not feasible. BioThrax is supplied as an injectable suspension for intramuscular or subcutaneous use, depending on clinical considerations. 

For PrEP, BioThrax is administered intramuscularly (IM) as a primary series at 0, 1, and 6 months, followed by booster doses at 6 and 12 months after completion of the primary series and annually thereafter. In individuals at risk for hematoma formation following intramuscular injection, a subcutaneous schedule may be used, consisting of a primary series at 0, 2, and 4 weeks, and 6 months, followed by booster doses at 6 and 12 months after completion of the primary series and annually thereafter. For PEP, BioThrax is administered subcutaneously as a primary series at 0, 2, and 4 weeks in conjunction with antimicrobial therapy.

BioThrax is contraindicated in individuals with a history of severe allergic reaction, including anaphylaxis, after a previous dose of BioThrax or any component of the vaccine. Warnings and precautions include the potential for fetal harm when administered during pregnancy; therefore, the potential benefits of vaccination should be weighed against the potential risk to the fetus. In addition, the vial stopper contains natural rubber latex and may cause allergic reactions in latex‑sensitive individuals. The most common local (injection‑site) adverse reactions (greater than 10%) include tenderness, pain, erythema, edema, and arm motion limitation. The most common systemic adverse reactions (5% or more) include muscle aches, fatigue, and headache.

Anthrax Vaccine Adsorbed, Adjuvanted (AVA,A)

Anthrax vaccine adsorbed, adjuvanted (Cyfendus; Emergent BioDefense Operations Lansing LLC) is an FDA-approved vaccine indicated for post‑exposure prophylaxis of disease following suspected or confirmed exposure to Bacillus anthracis in persons 18 through 65 years of age when administered in conjunction with recommended antibacterial drugs; however, its effectiveness is based solely on studies in animal models of inhalational anthrax, as human efficacy trials are not feasible. Cyfendus is administered for intramuscular use only and is used as an adjunct to antimicrobial therapy rather than as a standalone treatment. 

Cyfendus is administered as a 2‑dose primary series given intramuscularly 2 weeks apart. The vaccine is supplied as an injectable suspension.

Cyfendus is contraindicated in individuals with a history of severe allergic reaction, including anaphylaxis, after a previous dose of Cyfendus, BioThrax, or any component of the vaccine. 

Warnings and precautions include the need for appropriate medical treatment to be readily available to manage potential anaphylactic reactions following administration. In addition, Cyfendus may cause fetal harm when administered during pregnancy, based on observational data from a related anthrax vaccine with the same active ingredient. The most common injection‑site adverse reactions (10% or more) include tenderness (88.1%), pain (86.3%), arm motion limitation (63.7%), warmth (51.2%), induration (37.5%), itching (21.9%), swelling (19.7%), and erythema/redness (17.9%). The most common systemic adverse reactions (≥10%) include muscle aches (75.2%), tiredness (67.1%), and headache (58.0%). 

Laboratory Testing

The CDC states that laboratory confirmation of anthrax relies on microbiologic identification of Bacillus anthracis, with culture of clinical specimens serving as the gold standard for diagnosis. Diagnostic evaluation is guided by clinical presentation and route of exposure and may include collection of blood, cerebrospinal fluid, pleural fluid, ascites fluid, biopsy tissue, skin lesion fluid, or rectal swabs in cases of suspected gastrointestinal disease. Specimens should be collected, when feasible, prior to initiation of antimicrobial therapy, provided this does not delay treatment. Appropriate testing modalities may include culture for microbiologic identification of B. anthracis, real-time polymerase chain reaction (PCR) to detect bacterial DNA, anthrax lethal factor (LF) toxin testing performed on plasma or serum to identify circulating toxin, and pathologic evaluation of relevant clinical specimens using histopathology, special stains, and immunohistochemistry, with selection based on clinical presentation and exposure history. PCR testing may be used on blood specimens for confirmation of anthrax infection, and plasma and serum samples may be obtained for LF toxin testing within 0 to 18 days following exposure or symptom onset, with earlier collection preferred. Tissue biopsy specimens and lesion swabs may be used for both culture and PCR testing, with additional pathologic evaluation as indicated. Appropriate specimen handling and transport conditions, including temperature control, are required to maintain specimen integrity, and testing is performed through specialized laboratories within the Laboratory Response Network. (CDC, 2026).

Treatment of Anthrax

CDC guidelines for the prevention and treatment of anthrax recommend prompt initiation of antimicrobial therapy for suspected or confirmed infection, with regimen selection based on disease severity and clinical presentation. Antibiotics are used for both post-exposure prophylaxis and treatment, with commonly recommended agents including ciprofloxacin and doxycycline. For localized cutaneous anthrax without systemic involvement, antimicrobial monotherapy is generally recommended for 7 to 10 days. For systemic anthrax, including cases with suspected or confirmed meningitis, combination antimicrobial therapy is recommended using bactericidal agents from different classes to address both bacterial infection and toxin-mediated disease. Adjunctive antitoxin therapy is recommended for systemic anthrax to neutralize circulating toxin. Monoclonal antitoxins are preferred, and antitoxin should be used in conjunction with antimicrobial therapy rather than as monotherapy when antimicrobial agents are available. Duration of treatment is generally at least 2 weeks and may be extended based on clinical response and exposure risk. These recommendations are informed by available human data, animal models, and in vitro studies evaluating antimicrobial activity and toxin-mediated pathophysiology (Bowers et al., 2023; CPC, 2026).

Antitoxins, such as raxibacumab and obiltoxaximab, are specialized treatments designed to neutralize toxins produced by bacteria before they damage host cells.

Raxibacumab

Raxibacumab is a human monoclonal antibody antitoxin that is FDA‑approved for the treatment of adult and pediatric patients with inhalational anthrax due to Bacillus anthracis in combination with appropriate antibacterial drugs, and for prophylaxis of inhalational anthrax when alternative therapies are not available or are not appropriate; however, its effectiveness is based solely on efficacy studies in animal models of inhalational anthrax, as human trials are not feasible. Raxibacumab does not cross the blood–brain barrier and therefore does not prevent or treat anthrax meningitis, and it should always be administered with antibacterial therapy.

Raxibacumab is administered as a single intravenous infusion and includes weight-based dosing in pediatric patients. Premedication with diphenhydramine is necessary to reduce infusion reactions. For adults, the dose is 40 mg/kg. For pediatrics greater than 40 kg, the dose is 40 mg/kg. For pediatrics greater than 10 kg but less than 40 kg, the dose is 60 mg/kg. For pediatrics weighing 10 kg or less, the dose is 80 mg/kg.

A boxed warning highlights the risk of hypersensitivity reactions, including anaphylaxis, requiring administration in monitored settings with appropriate resuscitative support. Common adverse reactions (1.5% or more) reported in healthy adults include injection‑site reactions (erythema, pain), headache, rash, pain in extremity, pruritus, and somnolence. Although indicated for pediatric use, safety and effectiveness have not been directly studied in children, and pediatric dosing was derived using extrapolation approaches based on pharmacokinetic modeling.

Obiltoxaximab

Obiltoxaximab (Anthim; Elusys Therapeutics, Inc.) is an FDA-approved monoclonal antibody antitoxin directed against the protective antigen of Bacillus anthracis. It is indicated in adult and pediatric patients for the treatment of inhalational anthrax due to B. anthracis in combination with appropriate antibacterial drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or are not appropriate; however, its effectiveness is based solely on efficacy studies in animal models of inhalational anthrax, as human trials are not feasible. Obiltoxaximab does not have direct antibacterial activity and should be used in combination with antibacterial therapy, and it is not expected to cross the blood–brain barrier; therefore, it does not prevent or treat anthrax meningitis. Prophylactic use is limited to situations in which the benefit outweighs the risk of hypersensitivity and anaphylaxis, and pediatric safety and pharmacokinetics have not been directly studied, with dosing derived using population pharmacokinetic modeling. [accessdata.fda.gov], [drugs.com] [accessdata.fda.gov]

Obiltoxaximab is administered as a single intravenous infusion following premedication with diphenhydramine to reduce the risk of infusion-related reactions. For adults, the recommended dose is 16 mg/kg. For pediatric patients weighing greater than 40 kg, the dose is 16 mg/kg. For pediatric patients weighing greater than 15 kg to 40 kg, the dose is 24 mg/kg. For pediatric patients weighing 15 kg or less, the dose is 32 mg/kg, administered as an intravenous infusion over approximately 90 minutes. [accessdata.fda.gov], [drugs.com] [accessdata.fda.gov]

A boxed warning highlights the risk of hypersensitivity reactions, including anaphylaxis, requiring administration in monitored settings with personnel trained and equipped to manage severe reactions. The most frequently reported adverse reactions (1.5% or more) in healthy adult subjects include headache, pruritus, upper respiratory tract infection, cough, infusion‑site reactions, nasal congestion, urticaria, and pain in extremity. Although indicated for pediatric use, safety and pharmacokinetics have not been directly studied in pediatric populations, and pediatric dosing is based on extrapolated pharmacokinetic modeling rather than clinical outcome data.

Biron et al. (2015) stated that the B. anthracis anti-toxin monoclonal antibody (MAb) ETI-204 is a high-affinity chimeric de-immunized antibody that targets the anthrax toxin protective antigen (PA). In this study, a partial protection New Zealand White (NZW) rabbit model was used to evaluate the protective effectiveness of adjunct therapy with the MAb. Following the detection of PA in the blood, NZW rabbits were administered either an antibiotic (doxycycline) alone or the antibiotic in conjunction with ETI-204. Survival was evaluated to compare the effectiveness of the combination adjunct therapy with that of the antibiotic alone in treating inhalational anthrax. Overall, the results from this study indicated that a sub-therapeutic regimen consisting of an antibiotic in combination with an anti-PA MAb results in increased survival compared to the antibiotic alone and would provide an effective therapeutic strategy against symptomatic anthrax in non-vaccinated individuals.

Huang et al. (2015) noted that clinical guidelines for the treatment of anthrax recommend anti-toxin therapy in combination with intravenous antimicrobials; however, a large-scale or mass anthrax incident may exceed anti-toxin availability and create a need for judicious anti-toxin use. These researchers conducted a systematic review of anti-toxin treatment of inhalation anthrax in humans and experimental animals to inform anti-toxin recommendations during a large-scale or mass anthrax incident. A comprehensive search of 11 databases and the FDA website was conducted to identify relevant animal studies and human reports, resulting in the identification of 28 animal studies and 3 human cases. Anti-toxin monotherapy at or shortly after symptom onset demonstrated increased survival compared to no treatment in animals. With early treatment, survival did not differ between anti-microbial monotherapy and anti-microbial-antitoxin therapy in non-human primates and rabbits. With delayed treatment, anti-toxin-antimicrobial treatment increased rabbit survival. Among human cases, the addition of anti-toxin to combination anti-microbial treatment was associated with survival in 2 of the 3 cases treated. Despite the paucity of human data, limited animal data suggested that adjunctive anti-toxin therapy may improve survival. Delayed treatment studies suggested improved survival with combined anti-toxin-antimicrobial therapy, although a survival difference compared with anti-microbial therapy alone was not demonstrated statistically. In a mass anthrax incident with limited anti-toxin supplies, anti-toxin treatment of individuals who have not demonstrated a clinical benefit from anti-microbials, or those who present with more severe illness, may be warranted.

Anthrax Immune Globulin Intravenous

Anthrax Immune Globulin Intravenous [Human] (Anthrasil; ElusysTherapeutics, Inc.) is an FDA-approved plasma‑derived immune globulin indicated for the treatment of inhalational anthrax in adult and pediatric patients in combination with appropriate antibacterial drugs. Its effectiveness is based solely on efficacy studies conducted in animal models of inhalational anthrax, as human trials are not feasible. Anthrasil does not have direct antibacterial activity and should be used in conjunction with antimicrobial therapy. Anthrasil does not have direct antibacterial activity and should be used in conjunction with antimicrobial therapy. It does not cross the blood–brain barrier; therefore, it does not prevent or treat anthrax meningitis. There have been no studies evaluating safety or pharmacokinetics in pediatric, geriatric, or obese populations.

Anthrasil is administered as an intravenous infusion, with dosing based on clinical severity and patient weight. For adults (17 years and older), the recommended initial dose is 420 units (seven vials). For pediatric patients (less than 1 year to 16 years), dosing ranges from 60 to 420 units (1 to 7 vials) based on body weight, using weight‑based infusion rates that do not exceed adult maximum rates. Infusion is initiated at a low rate and titrated upward as tolerated. In patients with severe disease, higher initial dosing (840 units [14 vials] in adults or weight‑based escalation in pediatric patients weighing greater than 5 kg).

A boxed warning highlights the risk of interference with blood glucose monitoring systems due to maltose, which may result in falsely elevated glucose readings and inappropriate insulin administration, as well as the risk of thrombosis associated with immune globulin products. Patients should be monitored using glucose‑specific testing methods, and thrombosis risk factors should be assessed with appropriate precautions, including adequate hydration and use of the lowest feasible infusion rate. Common adverse reactions reported in more than 5% of healthy volunteers include headache, infusion‑site pain or swelling, nausea, and back pain.

Cui and colleagues (2017) studied anthrax immune globulin intravenous (AIG-IV) use during a 2009 to 2010 outbreak of Bacillus anthracis soft tissue infection in injection drug users in Scotland, UK, and compared findings from 15 AIG-IV recipients with findings from 28 non-recipients. Death rates did not differ significantly between recipients and non-recipients (33% versus 21%). However, whereas only 8 (27%) of 30 patients at low risk for death (admission sequential organ failure assessment score of 0 to 5) received AIG-IV, 7 (54%) of the 13 patients at high risk for death (sequential organ failure assessment score of 6 to 11) received treatment. AIG-IV recipients had surgery more often and, among survivors, had longer hospital stays than did non-recipients; AIG-IV recipients were sicker than non-recipients. The authors concluded that whether AIG-IV treatment is effective for systemic anthrax soft tissue infection related to drug injection cannot be answered with currently available data.

Combined Raxibacumab and Anthrax Vaccine for Post-Exposure Prophylaxis Against Inhalational Anthrax

Skoura and colleagues (2020) noted that raxibacumab is a monoclonal antibody against protective antigen, which is the cell-binding part of Bacillus anthracis toxin, and it was FDA-approved for the treatment and post-exposure prophylaxis of inhalational anthrax. Anthrax Vaccine Adsorbed (AVA), used for anthrax prophylaxis, consists primarily of adsorbed protective antigen. In a post-approval study, these researchers examined the effect of raxibacumab on the immunogenicity of AVA. In a randomized, open-label, parallel-group, non-inferiority study at three centers in the U.S., the investigators enrolled healthy volunteers (aged 18 to 65 years) with no evidence of exposure to protective antigen. Subjects were randomly allocated (1:1) according to a pre-generated balanced independent randomization schedule to either subcutaneous 0.5 ml AVA on days 1, 15, and 29 or raxibacumab intravenous infusion (40 mg/kg) immediately before AVA on day 1, followed by AVA only on days 15 and 29. It was an open-label study for both researchers and subjects; however, the sponsor remained blinded during the study. The primary outcome was the ratio of geometric mean concentrations (GMCs) of anti-protective antigen antibodies (attributable to the immune response to AVA) between AVA and AVA plus raxibacumab four weeks after the first AVA dose in the per-protocol population. The per-protocol population comprised all individuals who received the allocated treatment within the protocol-specified visit window and completed the primary study outcome assessment, without a protocol deviation requiring exclusion. The non-inferiority margin for the ratio of GMCs was pre-defined (upper limit of 90% CI < 1.5). Between February 24, 2015, and June 6, 2017, a total of 873 subjects were screened for eligibility, of whom 300 were excluded; 573 were randomly allocated either to AVA (n = 287) or AVA plus raxibacumab (n = 286). The per-protocol population comprised 276 individuals assigned to AVA and 269 allocated to AVA plus raxibacumab. At week 4, the GMC of anti-protective antigen antibodies in subjects allocated to AVA was 26.5 μg/ml (95% CI: 23.6 to 29.8) compared with 22.5 μg/ml (20.1 to 25.1) among individuals allocated to AVA plus raxibacumab. The ratio between groups was 1.18 (90% CI: 1.03 to 1.35; p = 0.0019), which met the pre-defined non-inferiority margin. Adverse events (AEs) in the safety population were similar across groups (87 [30%] of 286 in the AVA group versus 80 [29%] of 280 in the AVA plus raxibacumab group), and no treatment-related serious AEs were reported. The authors concluded that co-administration of raxibacumab with AVA did not negatively affect AVA immunogenicity. These researchers stated that this finding suggested that combining raxibacumab with AVA might provide added benefit in post-exposure prophylaxis against inhalational anthrax.

Combined Antitoxin and Anti-Microbial Therapy in the Prevention and Treatment of Anthrax Disease

Hesse et al. (2022) noted that Bacillus anthracis is a high-priority threat agent because of its widespread availability, easy dissemination, and ability to cause substantial morbidity and mortality. Although timely and appropriate antimicrobial therapy can reduce morbidity and mortality, the role of adjunctive therapies continues to be examined. These investigators searched 11 databases for studies that reported the use of anthrax antitoxins in the treatment or prevention of systemic anthrax disease published through July 2019. They identified other data sources via reference searches and communication with experts. These researchers included English-language studies on antitoxin products with approval by the FDA for anthrax in humans, non-human primates, and rabbits. Two researchers independently reviewed studies for inclusion and abstracted relevant data. They abstracted data from 12 publications and 2 case reports. All 3 FDA-approved anthrax antitoxins demonstrated significant improvement in survival as monotherapy over placebo in rabbits and non-human primates. No study found significant improvement in survival with combination antitoxin and antimicrobial therapy compared to antimicrobial monotherapy. Case reports and case series described 25 patients with systemic anthrax disease treated with antitoxins, of whom 17 survived. Animal studies that used antitoxin monotherapy as post-exposure prophylaxis (PEP) showed significant improvement in survival over placebo, with the greatest improvements coming with early administration. The authors concluded that limited human and animal evidence demonstrated that adjunctive antitoxin treatment may improve survival from systemic anthrax infection. Antitoxins may also provide an alternative therapy to antimicrobials for treatment or PEP during an intentional anthrax incident that could involve a multidrug-resistant B. anthracis strain or when antimicrobials are not tolerated.

The authors stated that this review had several drawbacks. First, there was a dearth of relevant human clinical data on the use of antitoxins in the treatment of systemic anthrax; obiltoxaximab has never been used to treat anthrax in humans. Of the human case studies that do exist, there was no standardization of antimicrobial or adjunctive therapies, an inherent challenge when examining the treatment of rare and often fatal diseases. Second, the FDA approved all 3 antitoxin products based on animal studies that conformed to the “Animal Rule.” When antitoxin was compared to or added to an antimicrobial regimen in animal studies, the antimicrobials were administered for sub-therapeutic durations compared to what would be administered to human patients. Many of these animal studies also failed to capture clinical indices, even when those were available, and the pathophysiology of rabbits and non-human primates was difficult to correlate with that of humans. Third, these researchers limited their search to studies available in English, which may have excluded animal or human case studies published elsewhere. Fourth, this review was subject to publication and reporting biases, which are intrinsic to all systematic reviews.

Kennedy et al. (2022) stated that without effective antimicrobial PEP (PEPAbx) and treatment, the mortality of systemic anthrax is high. To inform clinical guidelines for PEPAbx and treatment of B. anthracis infections in humans, these researchers systematically examined animal anthrax treatment model studies. They searched for survival outcome data in 9 scientific search engines for studies describing antimicrobial PEPAbx or treatment of anthrax in animals in any language through February 2019. These investigators carried out meta-analyses on the effectiveness of antimicrobial PEPAbx and treatment for each drug or drug combination using random-effects models. Pharmacokinetic/pharmacodynamic relationships were developed for 5 antimicrobials with available pharmacokinetic data. Monte Carlo simulations were employed to predict unbound drug exposures in humans. These researchers synthesized data from 34 peer-reviewed studies with 3,262 animals. For PEPAbx and treatment of infection by susceptible B. anthracis, effective monotherapy could be accomplished with fluoroquinolones, tetracyclines, β-lactams (including penicillin, amoxicillin-clavulanate, and imipenem-cilastatin), and lipopeptides or glycopeptides. For naturally occurring strains, unbound drug exposures in humans were predicted to adequately cover the minimal inhibitory concentrations (MICs; those required to inhibit the growth of 50% or 90% of organisms [MIC50 or MIC90]) for ciprofloxacin, levofloxacin, and doxycycline for both the PEPAbx and treatment targets. Dalbavancin covered its MIC50 for PEPAbx. The authors concluded that these animal studies demonstrated that many reviewed antimicrobials are good choices for PEPAbx or treatment of susceptible B. anthracis strains, and some are also promising options for combating resistant strains. Monte Carlo simulations suggested that oral ciprofloxacin, levofloxacin, and doxycycline are especially robust choices for PEPAbx or treatment. Combination antitoxin and antimicrobial therapy is not mentioned as a management option.

Special Populations

Bower et al. (2023) describe that CDC recommendations for treatment of anthrax are generally consistent across adults, children, and pregnant or lactating individuals, with antimicrobial therapy as the primary intervention and antitoxin used in selected clinical scenarios; however, differences across populations relate to antimicrobial selection, dosing, and safety considerations. Pediatric patients are treated using the same overall regimen as adults, with age- and weight-based dosing adjustments and consideration of drug-specific safety profiles. Pregnant and lactating individuals are similarly treated with standard antimicrobial regimens because of the high risk of morbidity and mortality associated with untreated anthrax, with selection of agents guided by risk–benefit considerations to avoid withholding effective therapy. For postexposure prophylaxis, Bower et al. (2019) indicate that antimicrobial therapy remains the primary intervention across all populations, with anthrax vaccine used as an adjunct when indicated. Recommendations emphasize that treatment duration and regimen selection may be modified based on age and pregnancy status, but the overall preventive strategy remains consistent.

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References