Anthrax

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Early diagnosis and initiation of appropriate empiric treatment is critical to improving survival. The approach to management depends on whether anthrax presents as cutaneous or systemic anthrax. Antimicrobial drugs and supportive care (e.g., mechanical ventilation, hemodynamic support, fluid drainage) are the mainstay of therapy. Anthrax antitoxins may be used in some patients.

This section is primarily based on guidelines published by the Centers for Disease Control and Prevention (CDC) and covers the management of both natural exposure and intentional exposure (e.g., from a wide-area aerosol release of Bacillus anthracis spores).[1]

General principles of antimicrobial therapy

The benefits of antimicrobial therapy outweigh any known risks for the treatment of anthrax due to the considerable morbidity and mortality associated with anthrax. The CDC recommends numerous antimicrobial drugs from multiple drug classes to cover the possible intentional production of a multidrug-resistant strain of Bacillus anthracis by bioterrorists.[1]

First-line agents are expected to address most scenarios, while alternative agents provide contingencies for intolerances, contraindications, unavailability, and resistance to first-line drugs. However, antimicrobial drug susceptibility testing is vital, and regimens may need to be modified based on the results. Less than 10% of naturally occurring strains are reported to be resistant to penicillins, and these drugs should only be used if the B anthracis strain is known to be penicillin susceptible.[1]

The choice of agents is based on numerous factors including in vitro effectiveness against B anthracis, in vivo efficacy against B anthracis exposures, animal models, percentage of patients expected to achieve microbiological cerebrospinal fluid cure at recommended doses based on Monte Carlo simulations, treatment outcomes from published human cases, safety profile of drugs, logistical considerations (e.g., formulations available, cost, supply), and expert opinion.

Benefits of treatment of anthrax usually outweigh the risk of adverse effects with antimicrobial drugs. However, it should be noted that fluoroquinolones (e.g., ciprofloxacin, levofloxacin, moxifloxacin) may cause central nervous system effects (e.g., serious psychotic reactions), tendon rupture and tendonitis, peripheral neuropathy, aortic aneurysm and dissection, hepatotoxicity, and altered cardiac condition. Tetracyclines have been associated with tooth staining in children <8 years, but this is uncommon with doxycycline and up to 21 days of doxycycline use is considered acceptable. Carbapenems (e.g., imipenem/cilastatin, meropenem) are associated with seizures.[1]

Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.

Cutaneous anthrax without signs and symptoms of meningitis

For cases of localized and systemic cutaneous infection without signs and symptoms of meningitis, initial empiric therapy with a single oral antimicrobial drug is recommended.[1]

First-line antimicrobial drugs include:
- Doxycycline
- Minocycline
- Ciprofloxacin
- Levofloxacin
- Amoxicillin (penicillin-sensitive only)
- Penicillin V (penicillin-sensitive only)
Alternative antimicrobial drugs include:
- Amoxicillin/clavulanate
- Moxifloxacin
- Clindamycin
- Ofloxacin
- Omadacycline
- Linezolid
- Tetracycline
- Clarithromycin
- Dalbavancin
- Imipenem/cilastatin
- Meropenem
- Vancomycin

Treatment may be given orally or intravenously depending on the clinical presentation and the chosen antimicrobial drug.

Continue or switch the antimicrobial drug based on susceptibility testing once results are available.[1]

Treatment course is 7-10 days or until clinical criteria for stability are met.
Transition patients with a potential aerosol exposure from a treatment regimen to a postexposure prophylaxis (PEP) regimen for a total of 42-60 days of treatment from exposure, depending on anthrax vaccine status and immunocompetence. The treatment course is 60 days in children and pregnant and postpartum women. See Prevention for information on PEP.

Pregnant and postpartum women

Anthrax is associated with high rates of maternal and fetal death in pregnant and postpartum women. Management is similar to nonpregnant adults as the data in pregnant and postpartum women are too limited to make specific recommendations for this group. However, there are some exceptions to which antimicrobial drugs may be used, and the order of drug preference may be slightly different.[1]
Tetracycline and minocycline are not recommended. They may cause tooth staining, hepatotoxicity, cardiovascular defects, transient suppression of bone growth, and spontaneous abortion when used in the second and third trimesters of pregnancy. Data on omadacycline and eravacycline, two other drugs in the tetracycline class, in pregnant women are limited. However, they may be used if no other protein synthesis inhibitors are available. Doxycycline, unlike other tetracyclines, has not been associated with these fetal effects.

Children ages ≥1 month to <18 years

Management is similar to nonpregnant adults. However, amoxicillin/clavulanate and clindamycin are first-line drugs rather than alternative agents in this patient group, and the order of preference may be slightly different.[1]
The treatment of neonates is beyond the scope of this topic, but recommendations are available from the CDC.[1]

A single antitoxin (i.e., raxibacumab, obiltoxaximab, anthrax immune globulin) may be considered in all patients if the recommended antimicrobial drugs are either not available or not appropriate.[1]

While there is a lack of human data, raxibacumab and obiltoxaximab have been found to be effective in animal studies.[65][66] One systematic review found that adjunctive treatment with anthrax antitoxin may play a role in enhancing survival, particularly in patients for whom antimicrobial drugs alone does not work.[67]
Monoclonal antibody antitoxins can cause hypersensitivity reactions and anaphylaxis so patients should be premedicated with an antihistamine.
Supplies of these drugs are held in the national stockpile for use in the event of an emergency.

Surgical resection or manipulation is not recommended in mild cases as disruption of the eschar can lead to disseminated infection.[50] For this reason, care must be taken to help prevent dissemination when obtaining a skin sample. Surgery may be indicated in some patients (e.g., patients with large lesions causing compartment syndrome).

Systemic anthrax with or without meningitis

Combination intravenous antimicrobial therapy is recommended due to the highly lethal nature of untreated systemic anthrax, particularly when complicated by meningoencephalitis. The combination of two or three antimicrobial drug classes should provide sufficient activity against most B anthracis strains that develop mechanisms of resistance.[1]

An empiric combination three-drug regimen is recommended first-line, with two bactericidal drugs from different antimicrobial drugs classes plus an antimicrobial drug that is either a protein synthesis inhibitor or an RNA synthesis inhibitor.
First-line bactericidal antimicrobial drugs include:
- Meropenem
- Ciprofloxacin
- Levofloxacin
- Imipenem/cilastatin
- Ampicillin/sulbactam
- Penicillin G (penicillin-sensitive only)
- Ampicillin (penicillin-sensitive only)
Alternative bactericidal antimicrobial drugs include:
- Piperacillin/tazobactam
- Moxifloxacin
- Vancomycin
First-line protein/RNA synthesis inhibitor antimicrobial drugs include:
- Minocycline
- Doxycycline
Alternative protein/RNA synthesis inhibitor antimicrobial drugs include:
- Omadacycline
- Eravacycline
- Clindamycin
- Linezolid
- Rifampin
- Chloramphenicol
A single RNA synthesis inhibitor should not be used as monotherapy due to the potential for the development of resistance.

Always consider the choice of regimen in consultation with an infectious diseases specialist.

If the recommended first-line combination regimen is contraindicated, not well tolerated, or not available, or if meningitis is considered unlikely, consult an infectious disease specialist for further guidance on the most appropriate regimen. The CDC recommends numerous possible regimens in these circumstances and you should consult your local guidelines as they are beyond the scope of this topic.[1]

Continue or switch the antimicrobial drug based on susceptibility testing once results are available.[1]

Treatment course is at least 2 weeks. Duration can be shortened and intravenous administration transitioned to oral administration based on clinical judgment and patient improvement.
Patients with systemic anthrax from a nonaerosolizing event do not need to continue on a PEP regimen. However, patients with a potential aerosol exposure and who are immunocompromised should be transitioned to an oral PEP regimen for a total of 60 days treatment from the onset of illness. See Prevention for information on PEP.

Pregnant and postpartum women

Management is similar to nonpregnant adults. However, minocycline and chloramphenicol are not recommended.[1]

Children ages ≥1 month to <18 years

In children with systemic disease, it is important to rule out meningoencephalitis and empirically treat while studies are pending or if meningoencephalitis cannot be ruled out.
Management is similar to nonpregnant adults. A penicillin-class drug is preferred in children if the strain is found to be penicillin susceptible. However, the benefits of fluoroquinolones and tetracyclines far outweigh the risks in children for the treatment of anthrax if the strain is penicillin-resistant.[1]
Imipenem/cilastatin and ampicillin/sulbactam are recommended as alternative agents rather than first-line drugs in this patient group, omadacycline is not recommended, and the order of preference may be slightly different.[1]
The treatment of neonates is beyond the scope of this topic, but recommendations are available from the CDC.[1]

A single antitoxin (i.e., raxibacumab, obiltoxaximab, anthrax immune globulin) is recommended, in addition to antimicrobial therapy, in all patients with noncutaneous systemic anthrax.[1]

Raxibacumab and obiltoxaximab are preferred over intravenous anthrax immune globulin.
Prioritize use for patients developing hemodynamic instability or respiratory compromise if supply is limited.

Additional considerations for inhalation or ingestion anthrax

Pleural effusion and other fluid collections (e.g., ascites, pericardial effusions) are common complications of inhalation and ingestion anthrax, but may also occur in other forms. If a patient has pleural fluid or ascites secondary to infection from B anthracis, early and aggressive drainage of these fluid collections is recommended.

For pleural effusion, chest tube drainage is preferred over thoracentesis because effusions may require prolonged drainage. Thoracotomy or video-assisted thoracic surgery may be required to remove gelatinous or loculated collections.[1] If reaccumulation of fluid occurs in the pleural or peritoneal space, repeat drainage is recommended.

High lethal toxin concentrations have been detected in pleural fluid and ascites, and reduction of this toxin level is thought to improve survival. Drainage of pleural fluid is also thought to improve survival by decreasing mechanical lung compression. A large case series examining this relationship supports early and aggressive drainage of any clinical or radiographic pleural effusions.[68] Surgical indications are limited, but may include patients with bowel ischemia, necrosis, and perforation, or patients with airway obstruction.[69][70]

Adjunctive therapy for anthrax meningitis

Meningitis is a common complication of anthrax and has a mortality rate that approaches 100%. Patients may have rapidly fatal brain swelling and elevated intracranial pressure that requires urgent treatment.[1]

Consider mannitol or hypertonic saline for patients with anthrax meningitis who have evidence of cerebral edema. Patients with systemic anthrax who received mannitol had higher odds of survival compared to those who did not.
Consider corticosteroids if clinically indicated. In adults with systemic anthrax, the odds of survival for the corticosteroid group did not statistically differ compared with patients who did not receive corticosteroids. While corticosteroids have not demonstrated a survival benefit, they did not appear to cause harm.
Consider therapies that target intracranial bleeding and swelling (e.g., nimodipine) in patients with hemorrhagic anthrax meningitis. Although these treatments are standard treatments for intracerebral hemorrhage, there is no data to support the theoretical benefit of these treatments in anthrax meningitis.

Mechanical ventilation and hemodynamic support may also be required depending on the clinical presentation.

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