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CBRNE - Anthrax Infection: Treatment & Medication
Updated: Oct 26, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
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
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.
Quinolones are not routinely indicated for pediatric patients because of the risk of musculoskeletal disorders. However, in 2008, the FDA approved use of levofloxacin in children as young as 6 months for the treatment of inhalational (and inhalational exposure) anthrax.2 Treatment duration is 60 days, but safety has not been evaluated beyond 14 days. 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 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, 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.
Preexposure vaccination is recommended only for populations at high risk of exposure to aerosolized B anthracis spores, according to the CDC's Advisory Committee on Immunization Practices (ACIP). These populations at high risk are those who:
- work directly with the organism in the laboratory,
- work with imported animal hides or furs in areas where standards are insufficient to prevent exposure to anthrax spores,
- handle potentially infected animal products in high-incidence areas; while incidence is low in the United States, veterinarians who travel to work in other countries where incidence is higher should consider being vaccinated,
- work in the military and are deployed to areas with high risk for exposure to the organism.
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.
Antibiotics
Therapy must cover all likely pathogens in the context of this clinical setting.
Penicillin G (Pfizerpen), Penicillin V (Veetids)
DOC; interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms. Begin treating all patients with IV dosing.
Adult
PCN G: 8-12 million U IV divided q4-6h
PCN V: 200-500 mg PO q6h
Pediatric
PCN V: 25-50 mg/kg/d PO divided bid/qid
PCN G: 100,000-150,000 U/kg/d IV divided q4-6h
Probenecid can increase effects of penicillin; coadministration of tetracyclines can decrease effects of penicillin
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in impaired renal function
Ciprofloxacin (Cipro)
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
500 mg PO q12h for 60 d
Alternatively, 400 mg IV q12h for 60 d; maximum 800 mg/d
Pediatric
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
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)
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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
Levofloxacin (Levaquin)
Inhibits growth of susceptible organisms by inhibiting DNA gyrase and promoting breakage of DNA strands.
Adult
500 mg PO q24h for 60 d
Pediatric
Approved for inhalational anthrax in children >6 mo of age
>50 kg: 500 mg q24h for 60 d
<50 kg: 8 mg/kg (not to exceed 250 mg/dose) q12h for 60 d
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)
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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
Streptomycin sulfate
Aminoglycoside antibiotic recommended when less potentially hazardous therapeutic agents are ineffective or contraindicated.
Adult
30 mg/kg/d IM; not to exceed 2 g/d
Pediatric
25-30 mg/kg/d IM; not to exceed 1-1.5 g/d
Documented hypersensitivity; non–dialysis-dependent renal insufficiency; nephrotoxicity may be increased with aminoglycosides, cephalosporins, penicillins, amphotericin B, and loop diuretics
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
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
Tetracycline (Sumycin)
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
500 mg PO/IV q6h
Pediatric
<8 years: Not recommended
>8 years: 10-20 mg/lb (25-50 mg/kg) PO/IV q6h
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
Documented hypersensitivity; severe hepatic dysfunction
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
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
Doxycycline (Bio-Tab, Doryx, Vibramycin)
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
100 mg PO/IV q12h for 60 d
Pediatric
<45 kg: 2.2 mg/kg PO/IV q12h for 60 d
>45 kg: Administer as in adults
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
Documented hypersensitivity; severe hepatic dysfunction
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
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
Penicillin G procaine (Crysticillin A.S., Wycillin)
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
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
Inhalational anthrax: 25,000 U/kg; not to exceed 1,200,000 U IM q12h for 60 d
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
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
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
Chloramphenicol (Chloromycetin)
Binds to 50S bacterial ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria.
Adult
50-100 mg/kg/d PO/IV divided q6h
Pediatric
50-75 mg/kg/d PO/IV divided q6h
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
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
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)
Corticosteroids
These agents are used for severe edema, meningitis, or swelling in the head and neck region.
Dexamethasone (Decadron, Dexasone)
Used in various inflammatory diseases. May decrease inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Adult
0.75-0.90 mg/kg/d PO/IV/IM divided q6h
Pediatric
0.25-0.5 mg/kg PO/IV/IM q6h
Effects decrease with coadministration of barbiturates, phenytoin, and rifampin; dexamethasone decreases effect of salicylates and vaccines used for immunization
Documented hypersensitivity; active bacterial or fungal infection
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Increases risk of multiple complications, including severe infections; monitor adrenal insufficiency when tapering drug; 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 are possible complications of glucocorticoid use
Prednisone (Sterapred)
Useful in inflammatory and allergic reactions. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Adult
1-2 mg/kg or 5-60 mg PO qd
Pediatric
0.5-2 mg/kg/d PO
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
Documented hypersensitivity; viral, fungal, or tubercular skin infections
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
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
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. In December 2008, the FDA approved a supplement to the biologics application for anthrax vaccine adsorbed (BioThrax, manufactured by Emergent BioSolutions).3 The vaccine administration schedule is now 0 and 4 weeks and 6, 12, and 18 months. Previously, the schedule was 0, 2, and 4 weeks and 6, 12, and 18 months. The newly approved administration route is intramuscular; previously, it was subcutaneous.
Anthrax vaccine adsorbed (BioThrax)
Vaccine used in high-risk situations. Along with prophylactic antibiotics, AVA can be administered in potential exposure.
The virulent components of B anthracis include an antiphagocytic polypeptide capsule and 3 proteins, including PA, LF, and EF. They are not cytotoxic individually, but the combination of PA with LF or EF forms cytotoxic lethal toxin and edema toxin, respectively. Immune mechanism is unknown, but, theoretically, antibodies to PA may provide protection by neutralizing activities of these toxins.
Adult
0.5 mL IM at 0 and 4 weeks and 6, 12, and 18 mo for 5 total injections. Previously, the schedule was 0, 2, and 4 weeks and 6, 12, and 18 mo. The newly approved administration route is intramuscular; previously, it was subcutaneous. Subsequent booster doses are given at 1-y intervals
Pediatric
<18 years: Not established
>18 years: Administer as in adults
Immunosuppressant agents may decrease effects
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in patients with previous history of anthrax disease (may increase potential for severe local adverse reactions); local edema or swelling at site of injection may occur (rare); discontinue immunization in patients with chills or fever associated with administration; patients on long-term corticosteroid therapy should receive additional dose; Guillain-Barré syndrome; immunosuppressive conditions may result in suboptimal response; postpone vaccination in those with moderate-to-severe illness; latex allergy (vial stopper contains natural rubber); data unavailable for persons >65 y; most frequent adverse reactions include headache, erythema, arthralgia, fatigue, fever, peripheral swelling, pruritus, nausea, injection site edema, pain or tenderness, or dizziness; serious adverse reactions may include nervous system disorders, skin and tissue disorders, musculoskeletal disorders, anaphylaxis, or serious local reactions
More on CBRNE - Anthrax Infection |
| Overview: CBRNE - Anthrax Infection |
| Differential Diagnoses & Workup: CBRNE - Anthrax Infection |
 Treatment & Medication: CBRNE - Anthrax Infection |
| Follow-up: CBRNE - Anthrax Infection |
| Multimedia: CBRNE - Anthrax Infection |
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References
Inglesby TV, O'Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E. Anthrax as a biological weapon, 2002: updated recommendations for management. JAMA. May 1 2002;287(17):2236-52. [Medline].
Food and Drug Administration. 17.5 FDA-Approved Medication Guide. Levaquin (levofloxacin). Accessed August 6, 2009. [Full Text].
CDC. Vaccines and Preventable Diseases:Anthrax Vaccination. Vaccines:VPF-VAD/Anthrax/mainpage. Available at http://www.cdc.gov/vaccines/vpd-vac/anthrax/default.htm#vacc. Accessed July 9, 2009.
Abramova FA, Grinberg LM, Yampolskaya OV, Walker DH. Pathology of inhalational anthrax in 42 cases from the Sverdlovsk outbreak of 1979. Proc Natl Acad Sci U S A. Mar 15 1993;90(6):2291-4. [Medline].
Bell DM, Kozarsky PE, Stephens DS. Clinical issues in the prophylaxis, diagnosis, and treatment of anthrax. Emerg Infect Dis. Feb 2002;8(2):222-5. [Medline].
CDC. Centers for Disease Control and Prevention Anthrax Fact Sheets & Overviews. CDC Anthrax Fact Sheets & Overviews. Available at http://www.bt.cdc.gov/agent/anthrax/basics/factsheets.asp. Accessed July 9, 2009.
Dixon TC, Meselson M, Guillemin J, Hanna PC. Anthrax. N Engl J Med. Sep 9 1999;341(11):815-26. [Medline].
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].
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].
Further Reading
Keywords
anthrax, Bacillus anthracis, , black bane, the fifth plague, wool-sorter's disease, woolsorter's disease, anthrax infection, inhalation anthrax, cutaneous anthrax, GI anthrax, gastrointestinal anthrax, oropharyngeal anthrax, meningeal anthrax, postexposure prophylaxis, PEP, biologic warfare agent, influenzalike illness, malignantpustules, black eschar
acute respiratory distress, hypoxemia, cyanosis, hypothermia, shock, enlarged mediastinal lymph nodes, subarachnoid hemorrhage, pleural effusions, meningismus, ileus, GI hemorrhage, dysphagia, oral bleeding,biological weapon, biological terrorism, biological warfare, biowarfare
