Practice Guidelines

CDC Updates Interim Guidelines for Anthrax Exposure Management and Antimicrobial Therapy

Am Fam Physician. 2001 Dec 1;64(11):1901-1903.

The Centers for Disease Control and Prevention (CDC) has issued an update on the investigation of recent cases of anthrax exposure. This update includes the susceptibility patterns of Bacillus anthracis isolates, and provides interim recommendations for managing potential threats and exposures and for treating anthrax. The complete report appears in the October 26, 2001 issue of Morbidity and Mortality Weekly Report and is available on the CDC Web site at www.cdc.gov/mmwr. A copy of the report is also available on the Web site of the American Academy of Family Physicians at www.aafp.org/resources.

Managing Exposure

The highest priority is to identify at-risk persons and initiate appropriate interventions to protect them. The exposure circumstances are the most important factors that direct decisions about prophylaxis. Persons with an exposure or contact with an environment known, or suspected, to be contaminated with B. anthracis—regardless of laboratory test results—should be offered antimicrobial prophylaxis. Exposure or contact, not laboratory results, is the basis for initiating treatment.

Antimicrobial Treatment

A high index of suspicion and rapid administration of effective antimicrobial therapy is essential for prompt diagnosis and effective treatment of anthrax. Limited clinical experience is available and no controlled trials in humans have been performed to validate current treatment recommendations for inhalational anthrax. Based on studies in nonhuman primates and other animals and in vitro data, ciprofloxacin or doxycycline should be used for initial intravenous therapy until antimicrobial susceptibility results are known (Table 1).

Two or more antimicrobial agents predicted to be effective are recommended because of the mortality associated with inhalational anthrax. Other agents with in vitro activity suggested for use in conjunction with ciprofloxacin or doxycycline include rifampin, vancomycin, imipenem, chloramphenicol, penicillin and ampicillin, clindamycin and clarithromycin, but other than for penicillin, limited or no data exist about using these agents in the treatment of inhalational B. anthracis infection. Cephalosporins and trimethoprim-sulfamethoxazole should not be used for therapy, and penicillin G and ampicillin alone should not be used to treat systemic infection because the combination may not be clinically effective for inhalational anthrax where large numbers of organisms are likely to be present.

Toxin-mediated morbidity is a major complication of systemic anthrax. Corticosteroids have been suggested as adjunct therapy for inhalational anthrax associated with extensive edema, respiratory compromise, and meningitis.

For cutaneous anthrax, ciprofloxacin and doxycycline are first-line therapy (Table 2). Intravenous therapy with a multidrug regimen is recommended if signs of systemic involvement, extensive edema, or lesions on the head and neck are present. Antimicrobial treatment may render lesions culture negative in 24 hours, but progression to eschar formation still occurs. Typically, cutaneous anthrax is treated for seven to 10 days, but with the latest attacks, the risk for simultaneous aerosol exposure appears to be high. Although infection may produce an effective immune response, a potential for reactivation of latent infection may exist, so patients should be treated for 60 days.

TABLE 1

Inhalational Anthrax Treatment Protocol*†

Category Initial therapy (IV)§ Duration

Adults

Ciprofloxacin, 400 mg every 12 hours* or Doxycycline, 100 mg every 12 hours¶ and One or two additional antimicrobials§

IV treatment initially∥; switch to oral antimicrobial therapy when clinically appropriate: Ciprofloxacin, 500 mg orally twice daily or Doxycycline, 100 mg orally twice daily Continue for 60 days (IV and oral combined).#

Children

Ciprofloxacin, 10 to 15 mg per kg every 12 hours**†† or Doxycycline‡‡¶: >8 years and >45 kg: 100 mg every 12 hours; >8 years and ≤45 kg: 2.2 mg per kg every 12 hours; ≤8 years: 2.2 mg per kg every 12 hours; and One or two additional antimicrobials§

IV treatment initially∥; switch to oral antimicrobial therapy when clinically appropriate: Ciprofloxacin, 10 to 15 mg per kg orally every 12 hours††or Doxycycline‡‡: >8 years and >45 kg: 100 mg orally twice daily; >8 years and ≤45 kg: 2.2 mg per kg orally twice daily; ≤8 years: 2.2 mg per kg orally twice daily Continue for 60 days (IV and oral combined).#

Pregnant women§§

Same for nonpregnant adults (the high death rate from infection outweighs the risk posed by the antimicrobial agent)

IV treatment initially; switch to oral antimicrobial therapy when clinically appropriate†: oral therapy regimens are same for nonpregnant adults.

Immunocompromised persons

Same for nonimmunocompromised persons and children

Same for nonimmunocompromised persons and children


IV = intravenous.

*—For gastrointestinal and oropharyngeal anthrax, use regimens recommended for inhalational anthrax.

†—Ciprofloxacin or doxycycline should be considered an essential part of first-line therapy for inhalational anthrax.

‡—Steroids may be considered as an adjunct therapy for patients with severe edema and for meningitis based on experience with bacterial meningitis of other etiologies.

§—Other agents with in vitro activity include rifampin, vancomycin, penicillin, ampicillin, chloramphenicol, imipenem, clindamycin, and clarithromycin. Because of concerns of constitutive and inducible beta lactamases in Bacillus anthracis, penicillin and ampicillin should not be used alone. Consultation with an infectious diseases specialist is advised.

∥—Initial therapy may be altered based on clinical course of the patient; one or two antimicrobial agents (e.g., ciprofloxacin or doxycycline) may be adequate as the patient improves.

¶—If meningitis is suspected, doxycycline may be less optimal because of poor central nervous system penetration.

#—Because of the potential persistence of spores after an aerosol exposure, antimicrobial therapy should be continued for 60 days.

**—If intravenous ciprofloxacin is not available, oral ciprofloxacin may be acceptable because it is rapidly and well absorbed from the gastrointestinal tract with no substantial loss by first-pass metabolism. Maximum serum concentrations are attained one to two hours after oral dosing but may not be achieved if vomiting or ileus is present.

††—In children, ciprofloxacin dosage should not exceed 1 g per day.

‡‡—The American Academy of Pediatrics recommends treatment of young children with tetracyclines for serious infections (e.g., Rocky Mountain spotted fever). .

§§—Although tetracyclines are not recommended during pregnancy, their use may be indicated for life-threatening illness. Adverse effects on developing teeth and bones are dose related; therefore, doxycycline might be used for a short time (seven to 14 days) before six months of gestation.

TABLE 1   Inhalational Anthrax Treatment Protocol*†

View Table

TABLE 1

Inhalational Anthrax Treatment Protocol*†

Category Initial therapy (IV)§ Duration

Adults

Ciprofloxacin, 400 mg every 12 hours* or Doxycycline, 100 mg every 12 hours¶ and One or two additional antimicrobials§

IV treatment initially∥; switch to oral antimicrobial therapy when clinically appropriate: Ciprofloxacin, 500 mg orally twice daily or Doxycycline, 100 mg orally twice daily Continue for 60 days (IV and oral combined).#

Children

Ciprofloxacin, 10 to 15 mg per kg every 12 hours**†† or Doxycycline‡‡¶: >8 years and >45 kg: 100 mg every 12 hours; >8 years and ≤45 kg: 2.2 mg per kg every 12 hours; ≤8 years: 2.2 mg per kg every 12 hours; and One or two additional antimicrobials§

IV treatment initially∥; switch to oral antimicrobial therapy when clinically appropriate: Ciprofloxacin, 10 to 15 mg per kg orally every 12 hours††or Doxycycline‡‡: >8 years and >45 kg: 100 mg orally twice daily; >8 years and ≤45 kg: 2.2 mg per kg orally twice daily; ≤8 years: 2.2 mg per kg orally twice daily Continue for 60 days (IV and oral combined).#

Pregnant women§§

Same for nonpregnant adults (the high death rate from infection outweighs the risk posed by the antimicrobial agent)

IV treatment initially; switch to oral antimicrobial therapy when clinically appropriate†: oral therapy regimens are same for nonpregnant adults.

Immunocompromised persons

Same for nonimmunocompromised persons and children

Same for nonimmunocompromised persons and children


IV = intravenous.

*—For gastrointestinal and oropharyngeal anthrax, use regimens recommended for inhalational anthrax.

†—Ciprofloxacin or doxycycline should be considered an essential part of first-line therapy for inhalational anthrax.

‡—Steroids may be considered as an adjunct therapy for patients with severe edema and for meningitis based on experience with bacterial meningitis of other etiologies.

§—Other agents with in vitro activity include rifampin, vancomycin, penicillin, ampicillin, chloramphenicol, imipenem, clindamycin, and clarithromycin. Because of concerns of constitutive and inducible beta lactamases in Bacillus anthracis, penicillin and ampicillin should not be used alone. Consultation with an infectious diseases specialist is advised.

∥—Initial therapy may be altered based on clinical course of the patient; one or two antimicrobial agents (e.g., ciprofloxacin or doxycycline) may be adequate as the patient improves.

¶—If meningitis is suspected, doxycycline may be less optimal because of poor central nervous system penetration.

#—Because of the potential persistence of spores after an aerosol exposure, antimicrobial therapy should be continued for 60 days.

**—If intravenous ciprofloxacin is not available, oral ciprofloxacin may be acceptable because it is rapidly and well absorbed from the gastrointestinal tract with no substantial loss by first-pass metabolism. Maximum serum concentrations are attained one to two hours after oral dosing but may not be achieved if vomiting or ileus is present.

††—In children, ciprofloxacin dosage should not exceed 1 g per day.

‡‡—The American Academy of Pediatrics recommends treatment of young children with tetracyclines for serious infections (e.g., Rocky Mountain spotted fever). .

§§—Although tetracyclines are not recommended during pregnancy, their use may be indicated for life-threatening illness. Adverse effects on developing teeth and bones are dose related; therefore, doxycycline might be used for a short time (seven to 14 days) before six months of gestation.

All medications may have side effects and allergic reactions. Physicians should be aware of these side effects and consult an infectious diseases specialist as needed. Patients should be urged to inform their health care provider of any adverse events.

TABLE 2

Cutaneous Anthrax Treatment Protocol*

Category Initial therapy (oral) Duration

Adults*

Ciprofloxacin, 500 mg twice daily

60 days‡

or

Doxycycline, 100 mg twice daily

Children*

Ciprofloxacin, 10 to 15 mg per kg every 12 hours (not to exceed 1 g per day)†

60 days‡

or

Doxycycline§: >8 years and >45 kg: 100 mg every 12 hours; >8 years and <=45 kg: 2.2 mg per kg every 12 hours; <=8 years: 2.2 mg per kg every 12 hours

Pregnant women*∥

Ciprofloxacin, 500 mg twice daily

60 days‡

or

Doxycycline, 100 mg twice daily

Immunocompromised persons*

Same for nonimmunocompromised persons and children

60 days‡


*—Cutaneous anthrax with signs of systemic involvement, extensive edema, or lesions on the head or neck require intravenous therapy, and a multidrug approach is recommended. See Table 1.

†—Ciprofloxacin or doxycycline should be considered first-line therapy. Amoxicillin, 500 mg orally three times daily or 80 mg per kg per day divided every eight hours for children, is an option for completion of therapy after clinical improvement. Oral amoxicillin dosage is based on the need to achieve appropriate minimum inhibitory concentration levels.

‡—Previous guidelines have suggested treating cutaneous anthrax for seven to 10 days, but 60 days is recommended in the setting of this attack, given the likelihood of exposure to aerosolized B. anthracis.

§—The American Academy of Pediatrics recommends treatment of young children with tetracyclines for serious infections (e.g., Rocky Mountain spotted fever).

∥—Although tetracyclines or ciprofloxacin are not recommended during pregnancy, their use may be indicated for life-threatening illness. Adverse effects on developing teeth and bones are dose related; therefore, doxycycline might be used for a short time (seven to 14 days) before six months of gestation.

TABLE 2   Cutaneous Anthrax Treatment Protocol*

View Table

TABLE 2

Cutaneous Anthrax Treatment Protocol*

Category Initial therapy (oral) Duration

Adults*

Ciprofloxacin, 500 mg twice daily

60 days‡

or

Doxycycline, 100 mg twice daily

Children*

Ciprofloxacin, 10 to 15 mg per kg every 12 hours (not to exceed 1 g per day)†

60 days‡

or

Doxycycline§: >8 years and >45 kg: 100 mg every 12 hours; >8 years and <=45 kg: 2.2 mg per kg every 12 hours; <=8 years: 2.2 mg per kg every 12 hours

Pregnant women*∥

Ciprofloxacin, 500 mg twice daily

60 days‡

or

Doxycycline, 100 mg twice daily

Immunocompromised persons*

Same for nonimmunocompromised persons and children

60 days‡


*—Cutaneous anthrax with signs of systemic involvement, extensive edema, or lesions on the head or neck require intravenous therapy, and a multidrug approach is recommended. See Table 1.

†—Ciprofloxacin or doxycycline should be considered first-line therapy. Amoxicillin, 500 mg orally three times daily or 80 mg per kg per day divided every eight hours for children, is an option for completion of therapy after clinical improvement. Oral amoxicillin dosage is based on the need to achieve appropriate minimum inhibitory concentration levels.

‡—Previous guidelines have suggested treating cutaneous anthrax for seven to 10 days, but 60 days is recommended in the setting of this attack, given the likelihood of exposure to aerosolized B. anthracis.

§—The American Academy of Pediatrics recommends treatment of young children with tetracyclines for serious infections (e.g., Rocky Mountain spotted fever).

∥—Although tetracyclines or ciprofloxacin are not recommended during pregnancy, their use may be indicated for life-threatening illness. Adverse effects on developing teeth and bones are dose related; therefore, doxycycline might be used for a short time (seven to 14 days) before six months of gestation.


Copyright © 2001 by the American Academy of Family Physicians.
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