INTRODUCTION

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Background

The term anthrax means coal in Greek, and the disease is named after the appearance of its cutaneous form. Anthrax is described in the Old Testament, by the poet Virgil, and by the Egyptians. At the end of the 19th century, Robert Koch's experiments with anthrax led to the original theory of bacteria and disease. John Bell's work in inhalational anthrax led to wool disinfection processes and the term woolsorter's disease.

Anthrax is caused by inhalation, skin exposure, or gastrointestinal (GI) absorption. Disease caused by inhalation is usually fatal, and symptoms usually begin days after exposure. This delay makes the initial exposure to Bacillus anthracis difficult to track.

An additional concern is use of anthrax as a biologic warfare agent. During the Gulf War, Iraq reportedly produced 8500 L of anthrax. A total of 150,000 US troops were vaccinated with anthrax toxoid. Since October 2001, 22 confirmed or suspected cases of anthrax infection, disseminated via the US postal system, have been identified.

Pathophysiology

Anthrax (B anthracis) is a large, spore-forming, gram-positive rod. Persistence of spores is aided by nitrogen and organic soil content, environmental pH greater than 6, and ambient temperature greater than 15°C. Drought or rainfall can trigger anthrax spore germination, while flies and vultures spread the spores.

B anthracis has a diameter of 1-1.5 µm and a length of 3-10 µm. It grows in culture as gray-white colonies that measure 4-5 mm in diameter and have characteristic comma-shaped protrusions. Anthrax is differentiated from other gram-positive rods on culture by lack of hemolysis and motility and by preferential growth on phenylethyl alcohol blood agar with characteristic gelatin hydrolysis and salicin fermentation.

Virulence depends on the bacterial capsule and the toxin complex. The capsule is a poly-D-glutamic acid that protects against leukocytic phagocytosis and lysis. Experiments by Sterne demonstrated that the capsule is vital for pathogenicity.

Anthrax toxins are composed of 3 entities: a protective antigen, a lethal factor, and an edema factor. The protective antigen is an 83-kd protein that binds to cell receptors within a target tissue. Once bound, a fragment is cleaved free to expose an additional binding site. This site can combine with edema factor to form edema toxin or with lethal factor to form lethal toxin. Edema toxin acts by converting adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). Cellular cAMP levels are increased, leading to cellular edema within the target tissue. Lethal factor is not well understood, but recent work suggests that it may inhibit neutrophil phagocytosis, lyse macrophages, and cause release of tumor necrosis factor and interleukin 1.

Frequency

United States

During the last 20 years, the indigenous US incidence has been less than 1 case per year. From 1955-1994, US cases totaled 235, with 224 cases of cutaneous anthrax, 11 cases of inhalational anthrax, and 20 fatalities. The last fatal case during this period occurred in 1976, when a home craftsman died of inhalational anthrax after working with yarn imported from Pakistan.

Before October 2001, the Centers for Disease Control and Prevention (CDC) investigated several threats in the United States, including Indiana, Kentucky, Tennessee, and California. Since October 2001, 22 confirmed or suspected cases of anthrax infection have been identified. Cases were reported from Florida, New York, New Jersey, the District of Columbia, and Connecticut. There were 11 confirmed cases of inhalational anthrax (5 deaths) and 7 confirmed and 4 suspected cases of cutaneous anthrax (no deaths). Seven cases were associated with occupational exposures in the postal service, and 2 cases had documented exposures to contaminated mail in the business office of a media company. No sources of exposure were identified for 2 women who were presumably exposed to secondarily contaminated mail. No reports in the literature have documented direct human-to-human transmission.

International

In 1958, approximately 100,000 cases of anthrax occurred worldwide. Exact figures do not exist because of reporting difficulties in Africa. Anthrax is endemic in Africa and Asia despite vaccination programs. Sporadic outbreaks have occurred as a result of both agricultural and military disruptions. During the 1978 Rhodesian civil war, failure of veterinary vaccination programs led to a human epidemic, causing 6500 anthrax cases and 100 fatalities. A mishap at a military microbiology facility in the former Soviet Union in 1979 resulted in at least 66 deaths. Human anthrax often is associated with agricultural or industrial workers who come in contact with infected animal tissue.

Mortality/Morbidity

Anthrax is primarily zoonotic. Human anthrax cases are due to exposure through agriculture or industry. Those at highest risk are shepherds, farmers, and workers in facilities that use animal products, especially previously contaminated goat hair, wool, or bone. Most anthrax disease is cutaneous (95%). The remaining cases of the disease are inhalational (5%) and GI ( <1%). Without treatment, the mortality rate of inhalational anthrax is approximately 95%.

CLINICAL

Section 3 of 11  

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History

• Exposure may occur by contact with animals or animal products (eg, hides in African export shops).
• Military personnel and civilians may become exposed in biologic warfare situations.
• In October 2001, approximately 10,000 people across the eastern United States were advised to take antibiotics in the aftermath of anthrax exposure.
• No reports of direct human-to-human transmission exist in the literature.

Physical

Physical findings are nonspecific. The incubation period for all clinical manifestations is 1-6 days following exposure. The prodrome includes fever, malaise, and adenopathy. Inhalational anthrax, the most deadly form, can be mistaken for influenzalike illness, especially during the winter season. Unlike those with influenza or other viral respiratory illness, adults with inhalational anthrax are not contagious, they will have shortness of breath and vomiting, and they do not have sore throat or rhinorrhea.

• Cutaneous anthrax
  • In the most common cutaneous form of anthrax, spores inoculate a host through skin lacerations, abrasions, or biting flies. Incubation is 2-5 days.
  • The disease begins as a nondescript papule that becomes a 1-cm vesicle within 2 days. Occasionally, surrounding edema is severe and can lead to airway compromise if present in the neck.
  • The skin in infected areas may become edematous and necrotic but not purulent. Such skin lesions have been described as "malignant pustules" after their characteristic appearance, despite being neither malignant nor pustular. Lesions are painless but on occasion are slightly pruritic.
  • Spore germination occurs within macrophages at the site of inoculation. Anthrax bacilli are isolated easily from the vesicular lesions and can be observed on Gram stain. If prior treatment with antibiotics has occurred, the best way to determine infection is to perform serologic testing and punch biopsy at the edge of the lesion and examine by silver staining and immunohistochemical testing.
  • The initial lesion ruptures after a week and progresses to a characteristic black eschar. The stages of skin infection occur despite treatment with antibiotics.
  • Differential diagnoses of the skin lesion include tularemia, plague, cutaneous diphtheria, Staphylococcus infections, Rickettsia infections, and orf (a viral disease of livestock).
  • Cutaneous anthrax usually remains localized, but without treatment, it disseminates systemically in up to one fifth of cases. Antibiotic therapy prevents dissemination but does not affect the natural history of the lesion. With treatment, the mortality rate is approximately 1%.
• Inhalational anthrax
  • Inhalational anthrax usually occurs in textile and tanning industries among workers handling contaminated animal wool, hair, and hides.
  • Based on previous primate studies, the minimum infective dose ranges from 4000-8000 inhaled spores. Inhaled spores are ingested by pulmonary macrophages and then carried to hilar and mediastinal lymph nodes. Incubation is 1-6 days.
  • The spores undergo germination and multiplication and begin to elaborate toxins. After the lymph nodes become overwhelmed, bacteremia and death quickly ensue.
  • Without treatment, the mortality rate of inhalational anthrax is approximately 95%.
  • The clinical presentation is usually biphasic in nature.
    • The initial stage begins with the onset of myalgia, malaise, fatigue, nonproductive cough, occasional sensation of retrosternal pressure, and fever. A transient improvement in symptomatology may occur after the first few days.
    • The second stage, lasting 24 hours and often culminating in death, develops suddenly with the onset of acute respiratory distress, hypoxemia, and cyanosis. The patient may have mild fever; alternatively, the patient may have hypothermia and develop shock. Diaphoresis often is present; enlarged mediastinal lymph nodes may lead to partial tracheal compression and alarming stridor. Auscultation of the lungs is remarkable for crackles and signs of pleural effusions. Meningeal involvement may be present in up to 50% of cases; it usually is bloody and may be associated with subarachnoid hemorrhage. Decreased level of consciousness, meningismus, and coma may be present.
    • A chest radiograph typically shows widening of the mediastinum and pleural effusions, whereas the parenchyma may appear normal. In a review of the 11 patients infected by anthrax in October 2001, chest radiographs from the initial examination showed mediastinal widening, paratracheal and hilar fullness, and pleural effusions or infiltrates. In some patients, the initial findings were subtle and not detected immediately.
• Gastrointestinal anthrax
  • GI anthrax is a rare form of infection. It occurs from eating infected, undercooked meat. Only 11 cases have been reported, all in underdeveloped countries.
  • Symptoms usually begin a few days after ingestion of the contaminated meat. Abdominal pain and fever occur first, followed by nausea, vomiting, and diarrhea.
  • In this illness, spores invade GI mucosa. As spores are transported to mesenteric lymph nodes, replication and bacteremia begin. Ascites and ileus follow as the lymphatic system becomes occluded with the large number of bacilli. Peritoneal fluid is turbid with the presence of leukocytes and red blood cells from hemorrhagic adenitis. Vascular stasis occurs, and the stomach and intestine become edematous.
  • In some cases, necrosis and ulceration at the site of infection produce GI hemorrhage. Severe abdominal pain, hematemesis, hematochezia, and, less often, watery diarrhea are presenting features. Shock occurs from interstitial and intraperitoneal volume losses.
  • Anthrax toxin further causes intrinsic renal failure independent of prerenal azotemia.
  • Death is rapid without antibiotic therapy and aggressive volume resuscitation. The mortality rate is 50%.
• Oropharyngeal anthrax
  • Oropharyngeal anthrax is a more common form of GI anthrax and has occurred in epidemic settings.
  • As a result of ingesting infected water buffalo meat, an outbreak of 24 cases occurred concurrently with 52 cases of cutaneous anthrax in Thailand in 1982. Of the 24 patients identified in the Thailand outbreak, all had been treated with antibiotics, and 3 died. The mortality rate in reported cases ranged from 12-50%.
  • Typically, 2 days after ingestion of infected meat, fever and neck swelling occur in the presence of an oral cavity lesion. The lesion starts as an edematous area that becomes necrotic and forms a pseudomembrane within 2 weeks. Sore throat, dysphagia, respiratory distress, and oral bleeding also occur. Soft tissue edema and dramatic cervical lymph node enlargement follow.
  • Recovery usually takes 3 weeks with antibiotic therapy.
  • The reason the disease limits itself to the oropharyngeal area is unknown.
• Meningeal anthrax
  • Meningeal anthrax is usually the result of bacteremia from the cutaneous, GI, or inhalational form of the disease. It also has occurred without a primary focus.
  • The meninges are characteristically hemorrhagic and edematous.
  • Of the Soviet cases that underwent autopsy, 21 (50%) of 42 had meningeal involvement.
  • The mortality rate is near 100%.

Causes

Prior exposure to radiation, alcoholism, and underlying pulmonary disease are important risk factors for inhalational anthrax.

Based on several cases of anthrax with no known exposure in the October 2001 postal anthrax release, studies were performed to evaluate increased risks for inhalational anthrax. Risk is determined not only by bacterial virulence factors but also by the balance between infectious aerosol production and removal, pulmonary ventilation rate, duration of exposure, and host susceptibility factors. Dilution ventilation of the indoor environment is an important determinant of the risk for infection. Enhanced room ventilation, UV germicidal irradiation, and other engineering control measures may be used to decrease the risk for infection.

DIFFERENTIALS

Section 4 of 11  

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Other Problems to be Considered

Ecthyma (Pseudomonas aeruginosa and staphylococcal infections)
Glanders (Pseudomonas pseudomallei)
Histoplasmosis
Leprosy
Orf (Rickettsia akari)
Psittacosis
Rat bite fever (Streptococcus moniliformis, Spirillum minus)
Rickettsia
Tularemia
Typhoid

WORKUP

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Lab Studies

• Blood culture and Gram stain are high yield tests in infected persons who have not taken antibiotics. Sputum from patients seldom yields positive smears or cultures. A Gram stain is the easiest means of initially identifying suggested cases. Anthrax appears as a large, gram-positive rod. In October 2001, blood cultures were positive for anthrax in all 8 patients who did not receive antibiotics. Serologic diagnosis of anthrax can be made using a microhemagglutination test specific for the protective antigen (PA) component of the toxin. Any Gram stain results suggestive of anthrax should be reported to the CDC.
• Several biochemical tests aid in differentiating B anthracis from other members of the species (chief among them is Bacillus cereus, which has been associated with outbreaks of human food poisoning). B anthracis is characterized by the absence of hemolysis on sheep blood agar, lack of motility, absence of salicin fermentation, gelatin hydrolysis, and lack of growth on phenylethyl alcohol medium.
• Cerebral spinal fluid contains blood and leukocytosis in meningeal anthrax.
• An enzyme-linked immunosorbent assay (ELISA) to detect immunoglobulin G (IgG) response to B anthracis protective antigen (PA) is 98.6% sensitive and 80% specific. PA–competitive inhibition ELISA is used as a second confirmatory step to improve specificity. Specific IgG anti-PA antibody can be detected as early as 10 days after onset of symptoms, but peak IgG levels may not be observed until 40 days of symptom onset.
• In persons exposed to antibiotics, immunohistochemical examination of the suspected fluid (eg pleural fluid, cerebrospinal fluid [CSF], cutaneous biopsy) using antibodies to B anthracis cell wall and capsule is performed.

Imaging Studies

• Chest radiography: Inhalational anthrax often does not appear on chest radiographs as a typical pneumonia; therefore, pulmonary densities often are absent. A prominent mediastinum with pleural effusions may be present. The prominent mediastinum is caused by hilar lymphadenopathy. An absence of parenchymal involvement exists. In the 11 cases of inhalational anthrax, initial examination was often subtle but showed mediastinal widening, paratracheal and hilar fullness, and pleural effusions and/or infiltrates.
• Computed tomography (CT) of the chest: CT scan of the chest detects hemorrhagic mediastinal and hilar lymph nodes and edema, peribronchial thickening, and pleural effusions. It also may help differentiate from histoplasmosis, sarcoidosis, tuberculosis, and lymphoma.

TREATMENT

Section 6 of 11  

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Prehospital Care

• As with any potential epidemic biologic exposure, patients should be decontaminated in the field when possible, and paramedical health care workers should wear masks and gloves.
• The FBI Weapons of Mass Destruction Unit (WMDU) in conjunction with the CDC recommend responders use splash protection, gloves, and a full-face respirator with high-efficiency particulate air (HEPA) filters (Level C) or self-contained breathing apparatus (SCBA) (Level B) if protection is needed from exposure.
• Persons who are potentially contaminated should wash with soap and water, not bleach solutions. Clothing and evidence/materials should be placed in plastic bags (triple). If the contamination is confirmed, then a 1:10 dilution of household beach may be used to decontaminate any materials and surfaces not sufficiently cleaned by soap and water.
• Chemoprophylaxis with antibiotics should be instituted only if exposure is confirmed.
• For persons not at risk for repeated exposures to aerosolized B anthracis spores through their occupation, preexposure vaccination with anthrax vaccine is not recommended.

Emergency Department Care

• Workup includes isolation; barrier protection; resuscitation; sampling of blood, wounds, and cerebral spinal fluid (when applicable); radiography; and rapid initiation of intravenous antibiotic therapy.
• If risk of exposure is considerable, initiate postexposure prophylaxis (PEP). This includes chemoprophylaxis with antibiotics and vaccination (if the vaccine is available). Because of a potential preventive benefit of combined antimicrobial PEP and vaccine, and the availability of a limited supply of anthrax vaccine for civilian use, the CDC made anthrax vaccine available in a 3-dose regimen (0, 2, 4 wk) in combination with antimicrobial PEP under an Investigational New Drug (IND) application with the Food and Drug Administration for unvaccinated persons at risk for inhalational anthrax. However, anthrax vaccine is not licensed for postexposure use in preventing anthrax.
• During the recent bioterrorist attacks in the United States, CDC recommendations for antimicrobial PEP included ciprofloxacin or doxycycline; the CDC recommended amoxicillin for children and pregnant or breastfeeding women exposed to strains susceptible to penicillin. The duration of postexposure antimicrobial prophylaxis should be 60 days if used alone for PEP of unvaccinated exposed persons.
• Patients can be placed in a normal hospital room with barrier nursing procedures (ie, gown, gloves, mask) and secretion precautions (ie, special handing of potentially infectious dressings, drainage, and excretions).

Consultations

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

MEDICATION

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Before October 2001, the first-line treatment of anthrax infection and prophylaxis was penicillin; however, this is no longer the case because of the concern for genetically engineered penicillin-resistant anthrax strains. The CDC recommends ciprofloxacin or doxycycline. Doxycycline should not be used in suspected meningitis because it has poor penetration of the central nervous system. Children and women 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 quinolones, rifampin, tetracycline, vancomycin, imipenem, meropenem, chloramphenicol, clindamycin, and the aminoglycosides. After susceptibility testing and clinical improvement, the regimen may be altered.

Cases of gastrointestinal and cutaneous anthrax can be treated with ciprofloxacin or doxycycline for 60 days. Penicillin such as amoxicillin or amoxicillin/clavulanic acid may be used to complete the course if the strain is susceptible.

Measures to prevent anthrax infection include vaccination, decontamination, and prophylactic treatment. For people who have been exposed to anthrax but do not have symptoms, 60 days of ciprofloxacin, tetracyclines (including doxycycline), or penicillin is given to reduce the risk or progression of disease due to inhaled anthrax. Vaccination is recommended as part of postexposure treatment by the CDC; however, this is not a licensed use for this vaccine.

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

Modify treatment in the presence of penicillin-resistant or other antibiotic-resistant strains.

Drug Category: Antibiotics

Therapy must cover all likely pathogens in the context of this clinical setting.

Drug Name	Ciprofloxacin (Cipro)
Description	DOC when mutant strains are suspected (as in germ warfare). Indicated for inhalational anthrax postexposure. Inhibits bacterial DNA synthesis and, consequently, growth by inhibiting DNA-gyrase in susceptible organisms. Initiate treatment immediately following suspected or confirmed anthrax exposure.
Adult Dose	500 mg PO q12h for 60 d Alternatively, 400 mg IV q12h for 60 d; maximum 800 mg/d
Pediatric Dose	15 mg/kg PO q12h for 60 d; not to exceed 500 mg/dose Alternatively, 10 mg/kg IV q12h for 60 d; not to exceed 400 mg/dose
Contraindications	Documented hypersensitivity
Interactions	Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 6 h before or 2 h after taking fluoroquinolones; ciprofloxacin reduces therapeutic effects of phenytoin; probenecid may increase ciprofloxacin serum concentrations; may increase toxicity of theophylline, caffeine, and cyclosporine; may increase effects of anticoagulants (monitor PT)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Note: Use in pregnancy is recommended for anthrax inhalation postexposure In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

Drug Name	Levofloxacin (Levaquin)
Description	Inhibits growth of susceptible organisms by inhibiting DNA gyrase and promoting breakage of DNA strands.
Adult Dose	500 mg PO q24h for 60 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; levofloxacin reduces therapeutic effects of phenytoin; probenecid may increase levofloxacin serum concentrations May increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

Drug Name	Streptomycin sulfate
Description	Aminoglycoside antibiotic recommended when less potentially hazardous therapeutic agents are ineffective or contraindicated.
Adult Dose	30 mg/kg/d IM; not to exceed 2 g/d
Pediatric Dose	25-30 mg/kg/d IM; not to exceed 1-1.5 g/d
Contraindications	Documented hypersensitivity; non–dialysis-dependent renal insufficiency; nephrotoxicity may be increased with aminoglycosides, cephalosporins, penicillins, amphotericin B, and loop diuretics
Interactions
Pregnancy	D - Unsafe in pregnancy
Precautions	Narrow therapeutic index; not intended for long-term therapy; caution in patients with renal failure not receiving dialysis; caution with myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission

Drug Name	Tetracycline (Sumycin)
Description	Treats susceptible bacterial infections caused by gram-positive and gram-negative organisms and infections caused by Mycoplasma, Chlamydia, and Rickettsia species. Inhibits bacterial protein synthesis by binding with 30S and, possibly, 50S ribosomal subunits of susceptible bacteria.
Adult Dose	500 mg PO/IV q6h
Pediatric Dose	<8 years: Not recommended >8 years: 10-20 mg/lb (25-50 mg/kg) PO/IV q6h
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants
Pregnancy	D - Unsafe in pregnancy
Precautions	Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Drug Name	Doxycycline (Bio-Tab, Doryx, Vibramycin)
Description	Reduces incidence or progression of anthrax, including inhalational anthrax (postexposure), following exposure to aerosolized B anthracis. Inhibits protein synthesis and, thus, bacterial growth by binding with 30S and, possibly, 50S ribosomal subunits of susceptible bacteria. FDA has balanced the nature of effect of tetracyclines on teeth in children <8 y and because the delay in bone development is apparently reversible against the lethality of inhalational anthrax, a pediatric dosing regimen for inhalational anthrax (postexposure) is now recommended. Administer IV therapy only when PO administration not indicated, and do not give over prolonged period of time (may increase risk of thrombophlebitis and other complications). Switch to PO doxycycline or another antimicrobial drug product as soon as possible to complete a 60-d course of therapy.
Adult Dose	100 mg PO/IV q12h for 60 d
Pediatric Dose	<45 kg: 2.2 mg/kg PO/IV q12h for 60 d >45 kg: Administer as in adults
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Pregnancy	D - Unsafe in pregnancy
Precautions	Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; not for use in children <8 y, except in anthrax infection, including inhalational anthrax (postexposure); Fanconilike syndrome may occur with outdated tetracyclines

Drug Name	Penicillin G procaine (Crysticillin A.S., Wycillin)
Description	Reduce 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 wk or less. Treatment for inhalational anthrax (postexposure) must be continued for a total of 60 d. Physicians must consider risks and benefits of continuing administration of penicillin G procaine for more than 2 wk or switching to an effective alternative treatment. In adults, administer by deep IM injection only into upper, outer quadrant of buttock. In infants and small children, the midlateral aspect of the thigh may be a better site for administration.
Adult Dose	Cutaneous anthrax: 600,000 to 1,000,000 U/d IM for 60 d Inhalational anthrax (postexposure): 1,200,000 U IM q12h for 60 d
Pediatric Dose	Inhalational anthrax: 25,000 U/kg; not to exceed 1,200,000 U IM q12h for 60 d
Contraindications	Documented hypersensitivity
Interactions	Increases risk of bleeding when administered concurrently with warfarin; ethacrynic acid, aspirin, indomethacin, and furosemide may compete with penicillin G for renal tubular secretion increasing penicillin serum concentrations
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	In prolonged therapy (particularly with high-dosage schedules), periodic evaluation of renal and hematopoietic systems recommended; when given > 2 wk may increase risk of neutropenia and incidence of serum sickness-like reactions; never use IV route to administer penicillin G procaine

Drug Name	Chloramphenicol (Chloromycetin)
Description	Binds to 50S bacterial ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria.
Adult Dose	50-100 mg/kg/d PO/IV divided q6h
Pediatric Dose	50-75 mg/kg/d PO/IV divided q6h
Contraindications	Documented hypersensitivity
Interactions	Concurrently with barbiturates, chloramphenicol serum levels may decrease while barbiturate levels may increase, causing toxicity; manifestations of hypoglycemia may occur with sulfonylureas; rifampin may reduce serum chloramphenicol levels, presumably through hepatic enzyme induction; may increase effects of anticoagulants; may increase serum hydantoin levels, possibly resulting in toxicity; chloramphenicol levels may be increased or decreased
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Use only for indicated infections or as prophylaxis for bacterial infections; serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) can occur; evaluate baseline and perform periodic blood studies approximately every 2 d while in therapy; discontinue upon appearance of reticulocytopenia, leukopenia, thrombocytopenia, anemia, or findings attributable to chloramphenicol; adjust dose in liver or kidney dysfunction; caution in pregnancy at term or during labor because of potential toxic effects on fetus (gray syndrome)

Drug Category: Corticosteroids

These agents are used for severe edema, meningitis, or swelling in the head and neck region.

Drug Name	Prednisone (Deltasone, Orasone, Meticorten)
Description	Useful in inflammatory and allergic reactions. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Adult Dose	1-2 mg/kg or 5-60 mg PO qd
Pediatric Dose	0.5-2 mg/kg/d PO
Contraindications	Documented hypersensitivity; viral, fungal, or tubercular skin infections
Interactions	Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Drug Category: Vaccination

The US Food and Drug Administration (FDA) approved a standard anthrax vaccine designated "anthrax vaccine adsorbed" (AVA). Sterile filtrate of cultures of an avirulent strain that elaborates protective antigen. No controlled trials are available. Efficacy in inhalation (biowarfare) anthrax is questionable. Although not endorsed by this site, the Anthrax Vaccine Home Page is a helpful web site with information on current research and controversy.

FOLLOW-UP

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Further Inpatient Care

• Patients should be admitted into the ICU for hemodynamic monitoring and management of septic and hemorrhagic shock, the final common pathway for endstage anthrax infection. In addition, progressive respiratory insufficiency may necessitate the use of ventilatory support.

Further Outpatient Care

• For PEP in adults, the CDC recommends vaccination and the use of oral fluoroquinolones (ciprofloxacin, 500 mg bid; levofloxacin, 500 mg qd; or ofloxacin, 400 mg bid). Doxycycline is an acceptable alternative. Prophylaxis should continue until exposure to B anthracis is excluded or for a period of 4 weeks if exposure is confirmed. Three doses of vaccine should be administered during the 4-week period (at time 0, 2, and 4 wk postexposure). If a vaccine is not available, the antibiotic treatment should continue for at least 60 days. A second option is treatment for 100 days. A third option is 100 days of antibiotic prophylaxis with vaccine.

Prognosis

• Inhalational anthrax and its subsequent systemic infection have a mortality rate approaching 100%. If treatment is initiated in the incubation period of 1-6 days and before the manifestation of symptoms, mortality can decrease to 1%.

Patient Education

• For excellent patient education resources, visit eMedicine's Bioterrorism and Warfare Center. Also, see eMedicine's patient education articles Biological Warfare, Anthrax, and Personal Protective Equipment.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Vaccine: Better protection, more extensive testing, more rigorous FDA approval, reduction of adverse effects, and a simpler dosing schedule are needed. No human studies are available that document efficacy of available vaccines.
• Early diagnosis is difficult and a high index of suspicion is required.

MULTIMEDIA

Section 10 of 11  

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• References

Media file 1:  Anthrax infection. Inhalation anthrax. Chest radiograph with widened mediastinum 22 hours before death. Image courtesy of Dr P.S. Brachman, Public Health Image Library, CDC, Atlanta, Ga.
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Media file 2:  Anthrax infection. Cutaneous anthrax showing the typical black eschar. Photo courtesy of the Public Health Image Library, CDC, Atlanta, Ga.
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Media file 3:  Anthrax infection. Polychrome methylene blue stain of Bacillus anthracis. Image courtesy of AVIP agency, Office of the Army Surgeon General, United States.
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Media file 4:  Anthrax infection. Histopathology of mediastinal lymph node showing a microcolony of Bacillus anthracis on Giemsa stain. Image courtesy of Dr Marshall Fox, Public Health Image Library, CDC, Atlanta, Ga.
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Media file 5:  Anthrax infection. Cutaneous anthrax. Image courtesy of AVIP agency, Office of the Army Surgeon General, United States.
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Media type:  Image

Media file 6:  Anthrax infection. Skin lesion of anthrax on face. Photo courtesy of the Public Health Image Library, CDC, Atlanta, Ga.
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Media file 7:  Anthrax infection. Histopathology of large intestine showing marked hemorrhage in the mucosa and submucosa. Image courtesy of Dr Marshall Fox, Public Health Image Library, CDC, Atlanta, Ga.
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Media file 8:  Anthrax infection. Histopathology of the large intestine showing submucosal thrombosis and edema. Image courtesy of Dr Marshall Fox, Public Health Image Library, CDC, Atlanta, Ga.
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Media file 9:  Anthrax infection. Histopathology of mediastinal lymph node showing mediastinal necrosis. Image courtesy of Dr Marshall Fox, Public Health Image Library, CDC, Atlanta, Ga.
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Media file 10:  Anthrax infection. Hemorrhagic meningitis resulting from inhalation anthrax. Photo courtesy of the Public Health Image Library, CDC, Atlanta, Ga.
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Media file 11:  Anthrax infection. Histopathology of hemorrhagic meningitis in anthrax. Image courtesy of Dr Marshall Fox, Public Health Image Library, CDC, Atlanta, Ga.
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Media file 12:  Anthrax infection. Bioterrorist Agents. Signs and symptoms. Chart courtesy of North Carolina Statewide Program for Infection Control and Epidemiology (SPICE), copyright University of North Carolina at Chapel Hill.
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REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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• CDC. Use of anthrax vaccine in the United States. MMWR Recomm Rep. Dec 15 2000;49(RR-15):1-20. [Medline]. [Full Text].
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• Fennelly KP, Davidow AL, Miller SL, et al. Airborne infection with Bacillus anthracis--from mills to mail. Emerg Infect Dis. Jun 2004;10(6):996-1002. [Medline]. [Full Text].
• Friedlander AM. Anthrax. In: Medical Aspects of Chemical and Biological Warfare. 1997: 467-478.
• LaForce FM. Anthrax. Clin Infect Dis. Dec 1994;19(6):1009-13; quiz 1014. [Medline].
• Med Lett Drugs Ther. Anthrax vaccine. Med Lett Drugs Ther. May 8 1998;40(1026):52-3. [Medline].
• Moran GJ. Update on emerging infections from the Centers for Disease Control and Prevention. Bioterrorism alleging use of anthrax and interim guidelines for management--United States, 1998. Ann Emerg Med. Aug 1999;34(2):229-32. [Medline].
• Pile JC, Malone JD, Eitzen EM, Friedlander AM. Anthrax as a potential biological warfare agent. Arch Intern Med. Mar 9 1998;158(5):429-34. [Medline].
• Shafazand S, Doyle R, Ruoss S, et al. Inhalational anthrax: epidemiology, diagnosis, and management. Chest. Nov 1999;116(5):1369-76. [Medline].
• Shepard CW, Soriano-Gabarro M, Zell ER, et al. Antimicrobial postexposure prophylaxis for anthrax: adverse events and adherence. Emerg Infect Dis. Oct 2002;8(10):1124-32. [Medline].

Article Last Updated: Feb 13, 2007