This document reflects emerging clinical and scientific advances as of the date issued and is subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed.
ABSTRACT: Anthrax infections are diagnosed by isolating Bacillus anthracis from body fluids or by measuring specific antibodies in the blood of persons suspected to have the disease. It is recommended that asymptomatic pregnant and lactating women who have been exposed to a confirmed environmental contamination or a high-risk source as determined by the local Department of Health (not the women's health care provider) receive prophylactic treatment. A variety of antimicrobial regimens are available. Although some of these drugs may present risks to the developing fetus, these risks are clearly outweighed by the potential morbidity and mortality from anthrax. Guidelines for prophylactic treatment of anthrax and treatment of suspected active cases of anthrax are changing continually, and the Centers for Disease Control and Prevention web site should be consulted for the latest recommendations.
Anthrax is an infection caused by Bacillus anthracis, an aerobic, gram-positive, spore-forming, nonmotile bacillus species. There are three primary clinical manifestations of the disease: 1) cutaneous, 2) inhalational, and 3) gastrointestinal.
Cutaneous: This is the most common presentation, accounting for 95% of naturally occurring infections. The organism's portal of entry is a cut or abrasion on the skin. The areas of greatest exposure are the hands, arms, face or neck. Potential sources of the organism include wool, hides, and leather and hair products of infected animals, particularly goats. Exposure also may result from a bioterrorist act (eg, a contaminated letter). Incubation periods may be as long as 12 days. Skin infection begins as a raised pruritic papule, resembling an insect bite. Within 1–2 days a vesicle develops, followed by a painless ulcer 1–3 cm in diameter with a characteristic black necrotic eschar in the center. Localized lymphangitis and painful lymphadenopathy may occur. Although antibiotic therapy does not appear to change the course of eschar formation and healing, it does decrease the risk of systemic disease. Mortality rates are 20% if untreated, but less than 1% with antibiotic therapy.
Inhalational: This is the most serious presentation, resulting from deposition of spore-bearing particles of 1–5 µm into the alveolar spaces. Macrophages ingest the spores that are then transported to the pulmonary lymphatics where they germinate. The asymptomatic incubation period usually is 1–7 days after exposure, but spores may germinate in the mediastinal lymphatics for up to 60 days. Once germination occurs, replicating bacteria release toxins leading to hemorrhage, edema, and necrosis. Initial symptoms resemble a flulike illness with fever, cough, and headache, but without rhinitis, followed by progressive dyspnea that rapidly progresses to respiratory failure and death within hours. Case-fatality estimates are extremely high, even with supportive care and appropriate antibiotics.
Gastrointestinal: The relatively rare intestinal form of anthrax follows ingestion, deposition, and subsequent germination of spores in the upper or lower gastrointestinal tract. The former leads to the oral-pharyngeal form of the disease marked by oral-esophageal ulcers and regional lymphadenopathy. The latter results in acute inflammation of the intestinal tract with symptoms that include anorexia, malaise, nausea, vomiting, and fever. Subsequently patients infected with gastrointestinal anthrax develop abdominal pain; hematemesis; severe, bloody diarrhea; and sepsis. Intestinal anthrax may be fatal in 25–60% of cases; the effect of early antibiotic therapy is unknown.
Evaluation and Management of Possible Anthrax Exposure Caused by Bioterrorist Acts
The risk of anthrax exposure is remote for people not in direct contact with the contaminated object or site and is greatest for those present in the immediate vicinity of contamination. The disease is not spread by casual contact or by coughing and sneezing.
Anthrax infections are diagnosed by isolating B anthracis from the blood, cerebrospinal fluid, skin lesions, or respiratory secretions or by measuring specific antibodies in the blood of persons suspected to have the disease. Rapid diagnostic immunoassays and polymerase chain reaction are available at national reference laboratories. Strategies of antimicrobial treatment of active anthrax infection are evolving. For the latest recommendations consult the Centers for Disease Control and Prevention (CDC) web site at www.cdc.gov/mmwr and www.bt.cdc.gov.
For asymptomatic individuals with low-risk exposure, antimicrobials are not warranted until there is an evident risk of actual exposure based on microbiologically documented anthrax as determined by law enforcement and public health authorities. The woman's health care provider is not the party to validate a threat.
In the current crisis, when screening for exposure is deemed necessary, it is conducted by nasal swab. The resultant secretions can be examined by Gram stain and culture. However, given the lack of reliability of nasal swab screening, postexposure prophylaxis is indicated only after confirmed or high-risk suspected exposure. In the latter cases, treatment can be stopped if anthrax is not documented.
For adult postexposure prophylaxis against anthrax infections, the CDC currently recommends 500 mg of ciprofloxacin orally every 12 hours for 60 days or 100 mg of doxycycline orally every 12 hours for 60 days.
Management of Exposed Asymptomatic Pregnant or Lactating Women
At this time, the Committee on Obstetric Practice recommends that prophylaxis of asymptomatic pregnant and lactating women be limited to those women who have had exposure to a confirmed environmental contamination or who are exposed to a high-risk source as determined by the local Department of Health. Prophylaxis for asymptomatic pregnant or lactating women is 500 mg of ciprofloxacin orally every 12 hours for 60 days (6).
Ciprofloxacin and other fluoroquinolones generally are not used during pregnancy and lactation because of suggested irreversible drug-induced arthropathy associated with such treatment in a variety of species of adolescent animals (1–5). However, no clear evidence of teratogenicity has been demonstrated in humans (1–5). Despite these concerns, the potential morbidity and mortality from anthrax clearly outweighs these risks. Thus, if the bacteria are shown to be sensitive to penicillin, the treatment should be switched to 500 mg of amoxicillin orally three times a day for 60 days (6).
If a woman has been prescribed ciprofloxacin and is found to be pregnant, she should continue her course of antibiotics for the full 60 days (6) unless the bacteria are shown to be penicillin-sensitive. She should then be switched to amoxicillin. A 1999 expert review of published data on experiences with ciprofloxacin concluded that therapeutic doses during pregnancy are unlikely to pose substantial teratogenic risk, but the data are insufficient to state that there is no risk (1). In the case of penicillin- and ciprofloxacin-allergic patients, treatment should consist of doxycycline or penicillin desensitization should be considered if the organism is proved sensitive (6). In this situation, the risks of anthrax would far outweigh the risks of doxycycline to the fetus (ie, dental staining of the primary teeth and possible depressed bone growth and defective dental enamel).
The guidelines for prophylactic treatment of anthrax and treatment of suspected active cases of anthrax are continually evolving. Please refer to www.bt.cdc.gov and www.cdc.gov/mmwr for any updates in CDC treatment guidelines.
- Friedman JM, Polifka JE. Ciprofloxacin. In: Teratogenic effects of drugs: a resource for clinicians (TERIS). 2nd ed. Baltimore: The Johns Hopkins University Press, 2000:149–150
- Friedman JM, Polifka JE. Doxycyclicne. In: Teratogenic effects of drugs: a resource for clinicians (TERIS). 2nd ed. Baltimore: The Johns Hopkins University Press, 2000:238–239
- Center for Drug Evaluation and Research. U.S. Food and Drug Administration. CIPRO (Ciprofloxacin) use by pregnant and lactating women. Available at www.fda.gov/cder/drug/infopage/cipro/cipropreg.htm. Retrieved November 2, 2001
- Center for Drug Evaluation and Research. U.S. Food and Drug Administration. Drug preparedness and response to bioterrorism. Available at www.fda.gov/cder/drug prepare/default.htm. Retrieved November 2, 2001
- Center for Drug Evaluation and Research. U.S. Food and Drug Administration. Doxycycline (Vibramycin, Monodox, Doryx, Doxy, Atridox, Periodox, Vibra-Tabs) use by pregnant and lactating women. Available at www.fda.gov/cder/drug/infopage/penG_doxy/doxypreg.htm. Retrieved November 2, 2001
- Updated recommendations for antimicrobial prophylaxis among asymptomatic pregnant women after exposure to bacillus anthracis. MMWR Morb Mortal Wkly Rep 2001;50:960
Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Friedlander AM, et al. Anthrax as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. JAMA 1999;281:1735–1745[erratum JAMA 2000;283:1963]
Update: investigation of anthrax associated with intentional exposure and interim public health guidelines, October 2001. MMWR Morb Mortal Wkly Rep 2001;50:889–893
Use of anthrax vaccine in the United States. MMWR Morb Mortal Wkly Rep 2000;49(RR-15):1–20
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Management of asymptomatic pregnant or lactating women exposed to anthrax.
ACOG Committee Opinion No. 268.
American College of Obstetricians and Gynecologists.
Obstet Gynecol 2002;99:366–368