Anthrax

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

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

cutaneous anthrax without signs/symptoms of meningitis

1st line – antimicrobial monotherapy

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1st line –

antimicrobial monotherapy

Initial empiric therapy with a single oral antimicrobial drug is recommended.[1]

First-line antimicrobial drugs include doxycycline, minocycline, ciprofloxacin, and levofloxacin. Amoxicillin and penicillin V are options if the Bacillus anthracis strain is known to be penicillin susceptible.[1]

Alternative antimicrobial drugs provide contingencies for intolerances, contraindications, unavailability, and resistance to first-line agents. Options include amoxicillin/clavulanate, moxifloxacin, clindamycin, ofloxacin, omadacycline, linezolid, tetracycline, clarithromycin, dalbavancin, imipenem/cilastatin, meropenem, and vancomycin.[1]

Treatment may be given orally or intravenously depending on the clinical presentation and the chosen antimicrobial drug. Specific recommendations for adults, pregnant and postpartum women, and children may differ. Consult your local guidelines for more information.

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.[1] See Prevention for information on PEP.

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.

Recommended regimens are based on guidelines published by the Centers for Disease Control and Prevention (CDC).[1] Regimens may vary and you should consult your local guidelines for more information.

Primary options

doxycycline: children ≥1 month of age and <45 kg body weight: 2.2 mg/kg orally twice daily, maximum 100 mg/dose; children ≥1 month of age and ≥45 kg body weight and adults: 100 mg orally twice daily

minocycline: children ≥1 month of age: 4 mg/kg (maximum 200 mg/dose) orally as a single dose initially, followed by 2 mg/kg (maximum 100 mg/dose) twice daily; adults: 200 mg orally as a single dose initially, followed by 100 mg twice daily

ciprofloxacin: children ≥1 month of age: 15 mg/kg orally twice daily, maximum 500 mg/dose; adults: 500 mg orally twice daily

levofloxacin: children ≥1 month of age and <50 kg body weight: 8 mg/kg orally twice daily, maximum 250 mg/dose; children ≥1 month of age and ≥50 kg body weight and adults: 750 mg orally once daily

amoxicillin: children ≥1 month of age: 25 mg/kg orally three times daily, maximum 1000 mg/dose; adults: 1000 mg orally three times daily

penicillin V potassium: children ≥1 month of age: 12.5 to 18.7 mg/kg orally four times daily, maximum 500 mg/dose; adults: 500 mg orally four times daily

Secondary options

amoxicillin/clavulanate: children ≥3 months of age and <40 kg body weight: 22.5 to 45 mg/kg orally twice daily, maximum 875 mg/dose; children ≥3 months of age and ≥40 kg body weight: 2000 mg orally (extended-release) twice daily; adults: 875 mg orally twice daily, or 2000 mg orally (extended-release) twice daily

moxifloxacin: children ≥3 months to ≤23 months of age: 6 mg/kg orally twice daily, maximum 200 mg/dose; children ≥2 years to <6 years of age: 5 mg/kg orally twice daily, maximum 200 mg/dose; children ≥6 years to <12 years of age: 4 mg/kg orally twice daily, maximum 200 mg/dose; children ≥12 years to <18 years of age and <45 kg body weight: 4 mg/kg orally twice daily, maximum 200 mg/dose; children ≥12 years to <18 years of age and ≥45 kg body weight and adults: 400 mg orally once daily

clindamycin: children ≥1 month of age: 10 mg/kg orally three times daily, maximum 600 mg/dose; adults: 600 mg orally three times daily

ofloxacin: children ≥1 month of age: 11.25 mg/kg orally twice daily, maximum 400 mg/dose; adults: 400 mg orally twice daily

omadacycline: children ≥8 years of age and adults: 450 mg orally once daily for 2 days, followed by 300 mg once daily

linezolid: children <12 years of age: 10 mg/kg orally three times daily, maximum 600 mg/dose; children ≥12 years of age and adults: 600 mg orally twice daily

tetracycline: children ≥1 month of age: 12.5 mg/kg orally four times daily, maximum 500 mg/dose; adults: 500 mg orally four times daily

clarithromycin: children ≥1 month of age: 7.5 mg/kg orally twice daily, maximum 500 mg/dose; adults: 500 mg orally twice daily

dalbavancin: children ≥3 months to <6 years of age: 22.5 mg/kg intravenously once weekly, maximum 1500 mg/dose; children ≥6 years to <18 years of age: 18 mg/kg intravenously once weekly, maximum 1500 mg/dose; adults: 1000 mg intravenously as a single dose, followed by 500 mg once weekly

imipenem/cilastatin: children ≥1 month of age: 25 mg/kg intravenously every 6 hours, maximum 1000 mg/dose; adults: 1000 mg intravenously every 6 hours

meropenem: children ≥1 month of age: 20 mg/kg intravenously every 8 hours, maximum 2000 mg/dose; adults: 2000 mg intravenously every 8 hours

vancomycin: children ≥1 month of age: 20 mg/kg intravenously every 8 hours; adults: 15 mg/kg intravenously every 12 hours

Consider – surgery

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Consider –

surgery

Treatment recommended for SOME patients in selected patient group

Surgery may be indicated in some patients (e.g., patients with large lesions causing compartment syndrome). 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.

2nd line – anthrax antitoxin

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2nd line –

anthrax antitoxin

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 (i.e., raxibacumab, obiltoxaximab) can cause hypersensitivity reactions and anaphylaxis so patients should be premedicated with an antihistamine before administration.

Supplies of these drugs are held in the national stockpile for use in the event of an emergency.

Primary options

raxibacumab: children ≤10 kg body weight: 80 mg/kg intravenously as a single dose; children >10 to 40 kg body weight: 60 mg/kg intravenously as a single dose; children >40 kg body weight and adults: 40 mg/kg intravenously as a single dose

obiltoxaximab: children ≤15 kg body weight: 32 mg/kg intravenously as a single dose; children >15 to 40 kg body weight: 24 mg/kg intravenously as a single dose; children >40 kg body weight and adults: 16 mg/kg intravenously as a single dose

anthrax immune globulin (human): children: consult specialist for guidance on dose; adults: 420-840 units intravenously as a single dose

Consider – surgery

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Consider –

surgery

Treatment recommended for SOME patients in selected patient group

systemic anthrax with or without meningitis

1st line – combination antimicrobial therapy

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1st line –

combination antimicrobial therapy

Combination intravenous antimicrobial therapy is recommended due to the highly lethal nature of untreated systemic anthrax, particularly when complicated by meningoencephalitis. 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.[1]

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.

First-line bactericidal antimicrobial drugs include meropenem, ciprofloxacin, levofloxacin, imipenem/cilastatin, and ampicillin/sulbactam. Penicillin G or ampicillin are options if the Bacillus anthracis strain is known to be penicillin susceptible. 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]

First-line protein/RNA synthesis inhibitor antimicrobial drugs include minocycline and doxycycline. A single RNA synthesis inhibitor should not be used as monotherapy due to the potential for the development of resistance.[1]

Alternative antimicrobial drugs provide contingencies for intolerances, contraindications, unavailability, and resistance to first-line agents. Alternative bactericidal antimicrobial drugs include piperacillin/tazobactam, moxifloxacin, and vancomycin. Alternative protein/RNA synthesis inhibitor antimicrobial drugs include omadacycline, eravacycline, clindamycin, linezolid, rifampin, and chloramphenicol.[1]

Specific recommendations for adults, pregnant and postpartum women, and children may differ. Consult your local guidelines for more information.

Always consider the choice of regimen in consultation with an infectious diseases specialist. If the recommended 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.[1] See Prevention for information on PEP.

Recommended regimens are based on guidelines published by the Centers for Disease Control and Prevention (CDC).[1] Regimens may vary and you should consult your local guidelines for more information.

The drug regimens detailed here should be used to build an appropriate three-drug combination regimen 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. These drugs should not be used as monotherapy for this indication. If this 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.[1]

Primary options

Bactericidal drug

meropenem: children ≥1 month of age: 40 mg/kg intravenously every 8 hours, maximum 2000 mg/dose; adults: 2000 mg intravenously every 8 hours

Bactericidal drug

ciprofloxacin: children ≥1 month of age: 10 mg/kg intravenously every 8 hours, maximum 400 mg/dose; adults: 400 mg intravenously every 8 hours

Bactericidal drug

levofloxacin: children ≥1 month of age and <50 kg body weight: 10 mg/kg intravenously every 12 hours, maximum 250 mg/dose; children ≥1 month of age and ≥50 kg body weight: 750 mg intravenously every 24 hours; adults: 500 mg intravenously every 12 hours

Bactericidal drug

imipenem/cilastatin: children ≥1 month of age: 25 mg/kg intravenously every 6 hours, maximum 1000 mg/dose; adults: 1000 mg intravenously every 6 hours

Bactericidal drug

ampicillin/sulbactam: children: 50 mg/kg intravenously every 6 hours, maximum 2000 mg/dose; adults: 3000 mg intravenously every 6 hours

Bactericidal drug

penicillin G potassium: children ≥1 month of age: 67,000 units/kg intravenously every 4 hours, maximum 4 million units/dose; adults: 4 million units intravenously every 4 hours

Bactericidal drug

ampicillin: children ≥1 month of age: 50 mg/kg intravenously every 6 hours, maximum 3000 mg/dose; adults: 2000 mg intravenously every 4 hours

Protein/RNA synthesis inhibitor

minocycline: children: 4 mg/kg (maximum 200 mg/dose) intravenously as a single dose initially, followed by 2 mg/kg (maximum 100 mg/dose) every 12 hours; adults: 200 mg intravenously as a single dose initially, followed by 100 mg every 12 hours

Protein/RNA synthesis inhibitor

doxycycline: children ≥1 month of age and <45 kg body weight: 2.2 mg/kg (maximum 200 mg/dose) intravenously as a single dose initially, followed by 2.2 mg/kg (maximum 100 mg/dose) every 12 hours; children ≥1 month of age and ≥45 kg body weight and adults: 200 mg intravenously as a single dose initially, followed by 100 mg every 12 hours

Secondary options

Bactericidal drug

piperacillin/tazobactam: children: 75 mg/kg intravenously every 6 hours, maximum 4000 mg/dose; adults: 3.375 g intravenously every 4 hours

Bactericidal drug

moxifloxacin: children ≥3 months to ≤23 months of age: 6 mg/kg intravenously twice daily, maximum 200 mg/dose; children ≥2 years to <6 years of age: 5 mg/kg intravenously twice daily, maximum 200 mg/dose; children ≥6 years to <12 years of age: 4 mg/kg intravenously twice daily, maximum 200 mg/dose; children ≥12 years to <18 years of age and <45 kg body weight: 4 mg/kg intravenously twice daily, maximum 200 mg/dose; children ≥12 years to <18 years of age and ≥45 kg body weight and adults: 400 mg intravenously every 24 hours

Bactericidal drug

vancomycin: children ≥1 month of age: 20 mg/kg intravenously every 8 hours; adults: 15 mg/kg intravenously every 12 hours

Protein/RNA synthesis inhibitor

omadacycline: adults: 200 mg intravenously as a single dose initially, followed by 100 mg every 24 hours

Protein/RNA synthesis inhibitor

eravacycline: children ≥8 years of age and adults: 1 mg/kg intravenously every 12 hours

Protein/RNA synthesis inhibitor

clindamycin: children ≥1 month of age: 13.3 mg/kg intravenously every 8 hours, maximum 900 mg/dose; adults: 900 mg intravenously every 8 hours

Protein/RNA synthesis inhibitor

linezolid: children <12 years of age: 10 mg/kg intravenously every 8 hours, maximum 600 mg/dose; children ≥12 years of age: 15 mg/kg intravenously every 12 hours, maximum 600 mg/dose; adults: 600 mg intravenously every 12 hours

Protein/RNA synthesis inhibitor

rifampin: children ≥1 month of age: 10 mg/kg intravenously every 12 hours, maximum 300 mg/dose; adults: 600 mg intravenously every 12 hours

Protein/RNA synthesis inhibitor

chloramphenicol: children ≥1 month of age: 25 mg/kg intravenously every 6 hours, maximum 1000 mg/dose; adults: 1000 mg intravenously every 6-8 hours

Plus – anthrax antitoxin

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Plus –

anthrax antitoxin

Treatment recommended for ALL patients in selected patient group

A single antitoxin (i.e., raxibacumab, obiltoxaximab, anthrax immune globulin) is recommended, in addition to antimicrobial therapy, in all patients with noncutaneous systemic anthrax. Raxibacumab and obiltoxaximab are preferred over intravenous anthrax immune globulin for this indication.[1]

Prioritize use for patients developing hemodynamic instability or respiratory compromise if supply is limited.[1]

Monoclonal antibody antitoxins (i.e., raxibacumab, obiltoxaximab) can cause hypersensitivity reactions and anaphylaxis so patients should be premedicated with an antihistamine before administration.

Supplies of these drugs are held in the national stockpile for use in the event of an emergency.

Primary options

Secondary options

anthrax immune globulin (human): children: consult specialist for guidance on dose; adults: 420-840 units intravenously as a single dose

Consider – surgery

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Consider –

surgery

Treatment recommended for SOME patients in selected patient group

Surgical indications are limited, but may include patients with bowel ischemia, necrosis, and perforation, or patients with airway obstruction.[70]

with cerebral edema

Plus – supportive care

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Plus –

supportive care

Treatment recommended for ALL patients in selected patient group

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.[1]

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.[1]

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.[1]

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

with pleural effusion or ascites

Plus – fluid drainage

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Plus –

fluid drainage

Treatment recommended for ALL patients in selected patient group

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 Bacillus anthracis, early and aggressive drainage of these fluid collections is recommended.[1]

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]

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Anthrax

Treatment algorithm

cutaneous anthrax without signs/symptoms of meningitis

antimicrobial monotherapy

Primary options

Secondary options

surgery

anthrax antitoxin

Primary options

surgery

systemic anthrax with or without meningitis

combination antimicrobial therapy

Primary options

Bactericidal drug

Bactericidal drug

Bactericidal drug

Bactericidal drug

Bactericidal drug

Bactericidal drug

Bactericidal drug

Protein/RNA synthesis inhibitor

Protein/RNA synthesis inhibitor

Secondary options

Bactericidal drug

Bactericidal drug

Bactericidal drug

Protein/RNA synthesis inhibitor

Protein/RNA synthesis inhibitor

Protein/RNA synthesis inhibitor

Protein/RNA synthesis inhibitor

Protein/RNA synthesis inhibitor

Protein/RNA synthesis inhibitor

anthrax antitoxin

Primary options

Secondary options

surgery

supportive care

fluid drainage