Medication Summary
Before October 2001, the first-line treatment of anthrax infection and prophylaxis was penicillin; however, this is not the case for bioterrorism-related cases because of the concern for genetically engineered penicillin-resistant anthrax strains. The Centers for Disease Control and Prevention (CDC) recommends ciprofloxacin or doxycycline. Doxycycline should not be used in suspected meningitis because it has poor penetration of the central nervous system.
Quinolones are not routinely indicated for pediatric patients because of the risk for musculoskeletal disorders. However, in 2008, the US Food and Drug
Administration (FDA) approved use of levofloxacin in children as young as 6 months for the treatment of inhalational (and inhalational exposure to) anthrax. [ ] 17] Treatment duration is 60 days, but safety has not been evaluated beyond 14 days.
Individuals who are pregnant or breastfeeding can use amoxicillin. Resistance exists to third-generation cephalosporins, trimethoprim, and sulfisoxazole. For patients with severe anthrax, therapy with corticosteroids and intravenous antibiotics is recommended.
Individuals with inhalational anthrax should receive a multidrug regimen of either ciprofloxacin or doxycycline along with at least one more agent, including a quinolone, rifampin, tetracycline, vancomycin, imipenem, meropenem, chloramphenicol, clindamycin, or an aminoglycoside. After susceptibility testing and clinical improvement, the regimen may be altered.
Raxibacumab, a monoclonal antibody directed at the protective antigen of Bacillus anthracis, is available from the CDC for treatment of inhalational anthrax in adults and children. It is used as part of a combination regimen with appropriate antibiotic drugs. It is also approved for prophylaxis of inhalational anthrax when alternative therapies are not available or not appropriate. [ ] 16]
Human anthrax immune globulin (Anthrasil) is indicated for treatment of inhalational anthrax in adults and children in combination with antibiotic therapy. [ ] 11]
Cases of gastrointestinal and cutaneous anthrax can be treated with ciprofloxacin or doxycycline for 60 days. Penicillin such as amoxicillin or amoxicillin-clavulanate may be used to complete the course if the strain is susceptible.
Measures to prevent anthrax infection after exposure include vaccination, decontamination, and prophylactic treatment. For people who have been exposed to anthrax but do not have symptoms, 60 days of ciprofloxacin, a tetracycline (including doxycycline), or penicillin is given to reduce the risk or progression of disease due to inhaled anthrax.
Two vaccines (anthrax vaccine adsorbed [AVA]; AVA adjuvanted) are also available. AVA is indicated for pre-exposure prophylaxis in persons at high risk for exposure and for postexposure prophylaxis following suspected or confirmed B anthracis exposure. AVA adjuvanted is indicated for postexposure prophylaxis.
Antibiotics, Other
Class Summary
Empirical antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Penicillin G (Pfizerpen)
Penicillin interferes with the synthesis of bacterial cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms. Penicillin is the drug of choice for nonbioterrorism-related anthrax. Treatment should begin with intravenous dosing.
Penicillin VK (Pen Vee K, Penicillin V, Veetids)
Penicillin interferes with the synthesis of bacterial cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms. Penicillin is the drug of choice for nonbioterrorism-related anthrax. Treatment should begin with intravenous dosing.
Penicillin G procaine
Penicillin reduces the incidence or progression of anthrax following exposure to aerosolized B anthracis. Available safety data for penicillin G procaine best support a duration of therapy of 2 weeks or less. Treatment for inhalational anthrax (postexposure) must be continued for a total of 60 days. Physicians must consider risks and benefits of continuing administration of penicillin G procaine for more than 2 weeks or switching to an effective alternative treatment.
In adults, administer by deep IM injection only into the upper outer quadrant of a buttock. In infants and small children, the midlateral aspect of the thigh may be a better site for administration.
Doxycycline (Adoxa, Doryx, Vibramycin)
Doxycycline is a second-generation tetracycline that is more active than tetracycline against many pathogens and is not hepatotoxic. Its adverse-effect profile and pharmacokinetics are different than those of tetracycline. Doxycycline reduces the incidence or progression of anthrax, including inhalational anthrax (postexposure) following exposure to aerosolized B anthracis.
Doxycycline inhibits protein synthesis and, thus, bacterial growth by binding with 30S and, possibly, 50S ribosomal subunits of susceptible bacteria. Although tetracyclines have an adverse effect on teeth in children younger than 8 years, the delay in bone development is apparently reversible; balancing these risks against the lethality of inhalational anthrax, the US Food and Drug Administration recommends a pediatric dosing regimen for inhalational anthrax (postexposure).
Administer IV therapy only when oral administration is not indicated, and do not give over a prolonged period (may increase the risk of thrombophlebitis and other complications). Switch to oral doxycycline or another antimicrobial drug product as soon as possible to complete a 60-day course of therapy.
Amoxicillin (Moxatag)
Amoxicillin interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.
Ampicillin
Ampicillin has bactericidal activity against susceptible organisms. It is an alternative to amoxicillin for patients who are unable to take medication orally.
Ciprofloxacin (Cipro, Proquin XR)
Ciprofloxacin is the drug of choice for anthrax when mutant strains are suspected (as in biological warfare). It is indicated for inhalational anthrax post exposure. Ciprofloxacin inhibits bacterial DNA synthesis and, consequently, growth by inhibiting DNA gyrase in susceptible organisms. It has high resistance potential. Initiate treatment immediately following suspected or confirmed anthrax exposure.
Levofloxacin (Levaquin)
Levofloxacin is a second-generation quinolone that acts by interfering with DNA gyrase in bacterial cells and promoting breakage of DNA strands. It is highly active against gram-negative and gram-positive organisms. It has low resistance potential.
Chloramphenicol
Chloramphenicol binds to 50 S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. It is effective against gram-negative and gram-positive bacteria.
Streptomycin
Streptomycin is an aminoglycoside antibiotic recommended when less potentially hazardous therapeutic agents are ineffective or contraindicated.
Tetracycline
Tetracycline treats susceptible infections caused by gram-positive and gram-negative bacteria and infections caused by Mycoplasma, Chlamydia, and Rickettsia species. It inhibits bacterial protein synthesis by binding with 30S and, possibly, 50S ribosomal subunits of susceptible bacteria.
Corticosteroids
Class Summary
These agents are used for severe edema, meningitis, or swelling in the head and neck region.
Dexamethasone (Baycadron)
This agent is used in various inflammatory diseases. Dexamethasone may decrease inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Prednisone
Prednisone is useful in inflammatory and allergic reactions. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear neutrophil (PMN) activity.
Antidotes, Other
Class Summary
A monoclonal antibody (raxibacumab) and human anthrax immune globulin have been approved by the FDA using the animal efficacy rule for inhalational anthrax. [8, 11]
Anthrax immune globulin (Anthrasil)
Human anthrax immune globulin is indicated to provide passive immunization for inhalational anthrax in combination with appropriate antibacterial drugs for adults and children. Its effectiveness is based solely on efficacy studies conducted in animal models of inhalational anthrax. It does not cross the blood-brain barrier and does not prevent or treatment meningitis associated with anthrax. It is prepared using plasma collected from healthy, screened donors who have been immunized with anthrax vaccine adsorbed (BioThrax).
Raxibacumab
Raxibacumab is a recombinant human IgG1-gamma monoclonal antibody directed at the protective antigen of Bacillus anthracis. It is indicated for treatment of inhalational anthrax in adults and children and used in combination with appropriate antibacterial drugs. It is also indicated for prophylaxis of inhalational anthrax when alternative therapies are not available or are not appropriate.
Obiltoxaximab (Anthim, Anthrax antitoxin)
Monoclonal antibody that binds to the protective antigen of B anthracis and prevents the formation of the anthrax toxin that directly damages cell. It is indicated in adult and pediatric patients for the treatment of inhalational anthrax due to B anthracis in combination with appropriate antibacterial drugs. It is also indicated for prophylaxis of inhalational anthrax when alternative therapies are not available or not appropriate.
Vaccines
Class Summary
The FDA approved a standard anthrax vaccine designated "anthrax vaccine adsorbed" (AVA), which is a sterile filtrate of cultures of an avirulent strain that elaborates protective antigen. Human controlled trials are not conducted for anthrax vaccines. FDA approval is based solely on studies in animal models of inhalational anthrax.
Anthrax vaccine adsorbed (BioThrax)
AVA is prepared from a cell-free filtrate of Bacillus anthracis (B anthracis) but contains no dead or live bacteria. The virulent components of B anthracis include an antiphagocytic polypeptide capsule and 3 proteins, including protective antigen (PA), lethal factor (LF), and edema factor (EF). They are not cytotoxic individually, but the combination of PA with LF or EF forms cytotoxic lethal toxin and edema toxin, respectively. The immune mechanism of AVA is unknown but, theoretically, antibodies to PA may provide protection by neutralizing the activities of these toxins. It is indicated for pre-exposure prophylaxis in persons aged 18-65 years at high risk for exposure as a 3-dose primary series at 0, 1, and 6 months, plus boosters at 6 and 12 months after the primary series. It is also for postexposure prophylaxis following suspected or confirmed B anthracis exposure as a 3-dose regimen at 0, 2, and 4 weeks in conjunction with recommended antibacterial drugs.
Anthrax vaccine adsorbed, adjuvanted (Cyfendus)
The vaccine is comprised of anthrax vaccine adsorbed (AVA) and an additional adjuvant. It has been demonstrated that by using an additional adjuvant, 2 doses administered over 14 days elicit protective levels of immune response. Indicated for post-exposure prophylaxis of disease following suspected or confirmed exposure to Bacillus anthracis in persons aged 18-65 years when administered in conjunction with recommended antibacterial drugs. It is administered as a 2-dose regimen administered 2 weeks apart.
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Polychrome methylene blue stain of Bacillus anthracis. Image courtesy of Anthrax Vaccine Immunization Program Agency, Office of the Army Surgeon General, United States.
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Histopathology of mediastinal lymph node showing a microcolony of Bacillus anthracis on Giemsa stain. Image courtesy of Marshall Fox, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
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Cutaneous anthrax. Image courtesy of Anthrax Vaccine Immunization Program Agency, Office of the Army Surgeon General, United States.
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Skin lesion of anthrax on face. Image courtesy of the Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
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Skin lesions of anthrax on neck. Cutaneous anthrax showing the typical black eschar. Image courtesy of the Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
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Histopathology of large intestine showing marked hemorrhage in the mucosa and submucosa. Image courtesy of Marshall Fox, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
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Histopathology of the large intestine showing submucosal thrombosis and edema. Image courtesy of Marshall Fox, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
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Inhalation anthrax. Chest radiograph with widened mediastinum 22 hours before death. Image courtesy of P.S. Brachman, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
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Histopathology of mediastinal lymph node showing mediastinal necrosis. Image courtesy of Marshall Fox, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
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Hemorrhagic meningitis resulting from inhalation anthrax. Image courtesy of the Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
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Anthrax infection. Histopathology of hemorrhagic meningitis in anthrax. Image courtesy of Marshall Fox, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
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Microscopic picture of anthrax showing gram-positive rods. Image courtesy of Ramon E. Moncada, MD.
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Seven-month-old infant with anthrax. In this infant, the infection progressed rapidly with significant edema developing the day after exposure. This large hemorrhagic lesion developed within 3 more days. The infant was febrile and was admitted to the hospital on the second day after the symptoms appeared.On September 28, 2001, the infant had visited the mother's workplace. On September 29, nontender massive edema and a weeping erosion developed. On September 30, a 2-cm sore developed over the edematous area. (Note that edema preceded the primary lesion.) On October 2, an ulcer or eschar formed, and the lesion was diagnosed as a spider bite. Hemolytic anemia and thrombocytopenia developed, and the patient was hospitalized. Serum was drawn on October 2; the polymerase chain reaction results were positive for Bacillus anthracis. On October 13, skin biopsy results were positive with immunohistochemical testing for the cell wall antigen.Note that the initial working diagnosis was a Loxosceles reclusa spider bite with superimposed cellulitis. Courtesy of American Academy of Dermatology with permission of NEJM.
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Fourth patient with cutaneous anthrax in New York City, October 2001. This dry ulcer was present. Photo used with permission of the patient. Courtesy of American Academy of Dermatology. Courtesy of Sharon Balter of the New York City Department of Health.
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Note the hemorrhage that is associated with cutaneous anthrax lesions. The early ulcer has a moist base. Courtesy of American Academy of Dermatology.
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Note the central ulcer and eschar. Courtesy of American Academy of Dermatology.
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An example of a central ulcer and eschar with surrounding edema. Courtesy of American Academy of Dermatology with permission from Boni Elewski, MD.
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Note the black eschar. Courtesy of American Academy of Dermatology. Courtesy of Gorgas Course in Clinical Tropical Medicine.
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Anthrax with facial edema. Courtesy of American Academy of Dermatology.
Tables
- Table 1. Microbiological Differences Between B anthracis and Non– B anthracis Bacilli
- Table 2. Toxins and Protein Toxins of Bacillus anthracis
- Table 3. CDC Expert Panel Recommendations for Treatment of Cutaneous Anthrax
- Table 4. CDC Expert Panel Recommendations for Treatment of Systemic Anthrax Without Meningitis [15]
- Table 5. CDC Expert Panel Recommendations for Treatment of Anthrax Meningitis [15]
B anthracis |
Non–B anthracis bacilli (pseudoanthrax bacilli) |
Nonmotile long chains |
Generally motile short chains |
Capsule formation on bicarbonate agar |
No capsule formation in bicarbonate |
No growth on penicillin agar (10 mcg/mL) |
Usually good growth on penicillin agar |
Growth in gelatin resembles inverted fir tree |
Growth in gelatin absent or resembles atypical fir tree |
Gelatin liquefaction slow |
Gelatin liquefaction usually rapid |
No hemolysis of sheep RBCs |
Hemolysis of sheep RBCs |
Ferments salicin slowly or not at all |
Usually ferments salicin rapidly |
Pathogenic to laboratory animals |
Nonpathogenic to laboratory animals |
Adapted from Cunha CB. Anthrax: Ancient Plague, Persistent Problem. Infect Dis Pract. 1999;23(4):35-9. |
|
Edema factor (EF) + lethal factor (LF) = Host cell penetration by B anthracis |
EF + protective antigen (PA) = Edema toxin |
LF + PA = Lethal toxin (primary virulence factor of B anthracis) |
Edema toxin + lethal toxin = Inhibited PMN function and phagocytosis |
Nonpregnant adults |
Pregnant/lactating women |
Children |
|---|---|---|
Recommended therapy [15] : Treatment duration, 7-10 days |
||
Ciprofloxacin 500 mg every 12 hours |
Ciprofloxacin 500 mg every 12 hours |
Ciprofloxacin 30 mg/kg/day divided every 12 hours (max dose, 500 mg/dose) |
Doxycycline 100 mg every 12 hours |
Amoxicillin 75 mg/kg/day divided every 8 hours (max dose, 1 g/dose) |
|
Levofloxacin 750 mg every 12 hours |
||
Moxifloxacin 400 mg every 24 hours |
||
Alternative therapy |
||
Clindamycin 600 mg every 8 hours |
Levofloxacin 750 mg every 12 hours |
Doxycycline < 45 kg: 4.4 mg/kg/day divided every 12 hours (max dose, 100 mg/dose) >45 kg: 100 mg every 12 hours |
Amoxicillin 1 g every 8 hours (susceptible strain only) |
Amoxicillin 1 g every 8 hours (susceptible strain only) |
Clindamycin 30 mg/kg/day divided every 8 hours (max dose, 600 mg/dose) |
Levofloxacin < 50 kg: 16 mg/kg/day divided every 12 hours (max dose, 250 mg/dose) >50 kg: 500 mg every 24 hours |
||
Adults |
Children |
|---|---|
1. Bactericidal agent |
|
Ciprofloxacin 400 mg every 8 hours |
Ciprofloxacin 30 mg/kg/day divided every 8 hours (max dose, 400 mg/dose) |
Alternative |
|
Levofloxacin 750 mg every 24 hours -OR- |
Meropenem 60 mg/kg/day divided every 8 hours (max dose, 2 g/dose) -OR- |
Moxifloxacin 400 mg every 24 hours -OR- |
Levofloxacin < 50 kg: 20 mg/kg/day divided every 12 hours (max dose, 250 mg/dose) >50 kg: 500 mg every 24 hours -OR- |
Meropenem 2 g every 8 hours -OR- |
Imipenem 100 mg/kg/day divided every 6 hours (max dose, 1 g/dose) -OR- |
Imipenem 1 g every 6 hours -OR- |
Vancomycin 60 mg/kg/day divided every 8 hours (max dose, 2 g/dose); trough target, 15-20 mcg/mL |
Doripenem 500 mg every 8 hours -OR- |
|
Vancomycin 60 mg/kg/day divided every 8 hours (max dose, 2 g/dose); trough target, 15-20 mcg/mL |
|
PLUS |
|
2. Protein synthesis inhibitor |
|
Clindamycin 900 mg every 8 hours -OR- |
Clindamycin 40 mg/kg/day divided every 8 hours (max dose, 900 mg/dose) |
Linezolid 600 mg every 12 hours |
|
Alternative |
|
Doxycycline 200-mg loading dose followed by 100 mg every 12 hours -OR- |
Linezolid < 12 years: 30 mg/kg/day divided every 8 hours >12 years: 30 mg/kg/day divided every 12 hours (max dose, 600 mg/dose) -OR- |
Rifampin 600 mg every 12 hours |
Doxycycline < 45 kg: 4.4 mg/kg loading dose (max 200 mg) followed by 4.4 mg/kg/day divided every 12 hours (max 100 mg/dose) >45 kg: 200 mg loading dose followed by 100 mg every 12 hours -OR- |
Rifampin 20 mg/kg/day divided every 12 hours (max dose, 300 mg/dose) |
|
Adults |
Children |
|---|---|
1. Bactericidal agent |
|
Ciprofloxacin 400 mg every 8 hours |
Ciprofloxacin 30 mg/kg/day divided every 8 hours (max 400 mg/dose) |
Alternative |
|
Levofloxacin 750 mg every 24 hours -OR- |
Levofloxacin < 50 kg: 16 mg/kg/day divided every 12 hours (max 250 mg/dose) ≥50 kg: 500 mg every 24 hours -OR- |
Moxifloxacin 400 mg every 24 hours |
Moxifloxacin Age 3 months to < 2 years: 12 mg/kg/day divided every 12 hours Age 2-5 years: 10 mg/kg/day divided every 12 hours Age 6-11 years: 8 mg/kg/day divided every 12 hours Age 12-17 years, < 45 kg: 8 mg/kg/day divided every 12 hours (Max 200 mg/dose) Age 12-17 years, ≥45 kg: 400 mg every 24 hours |
PLUS |
|
2. Second bactericidal agent |
|
Meropenem 2 g every 8 hours |
Meropenem 120 mg/kg/dose divided every 8 hours (max 2 g/dose) |
Alternative |
|
Imipenem 1 g every 6 hours -OR- |
Imipenem 100 mg/kg/day divided every 6 hours (max 1 g/dose) -OR- |
Doripenem 500 mg every 8 hours -OR- |
Doripenem 120 mg/kg/day divided every 8 hours (max 1 g/dose) -OR- |
Ampicillin 3 g every 6 hours -OR- |
Vancomycin 60 mg/kg/day divided every 8 hours (max 2 g/dose); target trough, 15-20 mcg/mL -OR- |
Ampicillin 400 mg/kg/day divided every 6 hours (max 3 g/dose) |
|
PLUS |
|
3. Protein synthesis inhibitor |
|
Linezolid 600 mg every 12 hours |
Linezolid < 12 years old: 30 mg/kg/day divided every 8 hours ≥12 years old: 30 mg/kg/day divided every 12 hours (Max 600 mg/dose) |
Alternative |
|
Clindamycin 900 mg every 8 hours -OR- |
Clindamycin 40 mg/kg/day divided every 8 hours (max 900 mg/dose) -OR- |
Rifampin 600 mg every 12 hours -OR- |
Rifampin 20 mg/kg per day divided every 12 hours (max 300 mg/dose) -OR- |
Chloramphenicol 1 g every 6-8 hours |
Chloramphenicol 100 mg/kg per day divided every 6 hours (max 1 g/dose) |
