Anthrax Guidelines Address Nonpregnant, Pregnant Adults

Laurie Barclay, MD

January 15, 2014

Updated guidelines from the Centers for Disease Control and Prevention (CDC), published online January 15 in Emerging Infectious Diseases, address anthrax postexposure prophylaxis (PEP) and treatment in nonpregnant and pregnant adults.

"Anthrax has been recognized as an infectious disease of animals and humans for millennia," write Katherine A. Hendricks, MD, MPH, from the CDC, Atlanta, Georgia, and other members of the Workgroup on Anthrax Clinical Guidelines. "Within the United States, animal anthrax is reported in most years, but naturally occurring human anthrax is rare.... Biodefense experts often place Bacillus anthracis at or near the top of the list for potential threat agents."

Reasons that B anthracis is a potential threat include its availability and ease of dissemination and the high mortality of systemic anthrax infections. Therefore, anthrax has been a high-priority threat and a major focus of national emergency preparedness planning since the 2001 anthrax attack.

Guidelines for Anthrax Management in Nonpregnant Adults

In 2011-2012, the CDC convened panels of civilian and military anthrax experts and clinicians who had treated patients with anthrax, representing the fields of internal medicine, pediatrics, obstetrics, infectious disease, emergency medicine, critical care, pulmonology, hematology, and nephrology. Their mandate was to review and update guidelines for PEP and for treatment of anthrax in nonpregnant adults.

They considered use of antibiotics and antitoxins, clinical management, and future research priorities. These include development of tests to identify and treat anthrax earlier in its course, as well as animal models to facilitate assessment of currently recommended treatments.

The evidence underlying the updated guidelines includes recent case reports of patients with systemic anthrax; reviews of published, unpublished, and proprietary data concerning antimicrobial drugs and anthrax antitoxins; and critical care interventions that may help patients with anthrax.

Specific topics covered in the newly published guidelines include:

  • updated recommendations for antimicrobial PEP, which should ideally start as soon as possible after exposure;

  • currently available antimicrobial and antitoxin treatment options, considering toxin production, potential for antimicrobial drug resistance, frequent occurrence of meningitis, and presence of latent spores;

  • potentially beneficial critical care measures for persons with anthrax, including clinical procedures for infected nonpregnant adults;

  • expanded discussion, compared with previous guidelines, of critical care and clinical procedures and of additional antimicrobial choices, including preferred antimicrobial drug treatment for possible anthrax meningitis.

Specific recommendations include the following:

  • Regardless of vaccination status, everyone exposed to aerosolized B anthracis spores should receive a full 60 days of PEP antimicrobial drugs.

  • Antimicrobial combination therapy is more likely to be curative than monotherapy, and there is a theoretical benefit for combined use of bactericidal and protein synthesis inhibitor agents.

  • The US Food and Drug Administration has approved ciprofloxacin, levofloxacin, and doxycycline for PEP for inhalation anthrax in adults aged 18 years or older. Because no safety data are available for levofloxacin use beyond 30 days, oral ciprofloxacin and doxycycline are first-line antimicrobial drugs for PEP.

  • When anthrax meningitis is suspected, treatment should include at least 3 antimicrobial drugs with activity against B anthracis. All should have good central nervous system penetration, at least 1 should have bactericidal activity, and at least 1 should be a protein synthesis inhibitor. Intravenous combination treatment should continue for at least 2 to 3 weeks.

  • For any patient with a high level of clinical suspicion for systemic anthrax, the potential benefit achieved by adding antitoxin to combination antimicrobial drug treatment outweighs the potential risk. There are no major considerations clearly favoring use of one antitoxin over another.

  • A single oral fluoroquinolone may successfully treat uncomplicated cutaneous anthrax. Ciprofloxacin, levofloxacin, moxifloxacin, and doxycycline are equivalent first-line agents.

Guidelines for Anthrax Management in Pregnant Women

"As part of a comprehensive plan for anthrax readiness, it is important to plan for the needs of pregnant, postpartum, and lactating (P/PP/L) women because of their unique immunology and physiology and the complexities of balancing maternal and fetal risks," Dana Meaney-Delman, MD, MPH, from the CDC, and colleagues write in a second guideline.

"The purpose of this meeting summary is to provide updated clinical information to health care providers and public health professionals caring for P/PP/L women in the setting of a bioterrorist event involving anthrax."

The CDC and the Association of Maternal and Child Health Programs convened a meeting of national experts in August 2012 to review important interventions regarding anthrax prevention and treatment in P/PP/L women. Participants included infectious disease, obstetrics, maternal-fetal medicine, neonatology, pediatrics, and pharmacy experts, as well as representatives from professional organizations and national, federal, state, and local agencies.

Topics included overall prevention and treatment strategies in P/PP/L women, vaccination, antimicrobial prophylaxis and treatment, clinical considerations and critical care issues, use of antitoxin, delivery issues, infection control measures, and communication.

"Antimicrobial drug use in pregnant women in the setting of anthrax must be viewed in the context of the high mortality risk and the benefits of treatment for the mother and fetus, as well as possible effects on the fetus resulting from the infection or from administration of antimicrobial drugs to the mother," the authors write. "Although safety and pharmacokinetic data for pregnant women are limited, antimicrobial drugs used for anthrax PEP and treatment for P/PP/L women are generally the same as those for nonpregnant adults."

It is unclear whether clinical signs and symptoms of anthrax differ because of the physiologic changes that accompany pregnancy. Clinical indicators of infection may be less reliable in pregnant women

No direct evidence is available to evaluate the safety and efficacy of anthrax immune globulin and raxibacumab in pregnant women and their babies.

"Pharmacokinetic studies designed to determine dosing and to elucidate transplacental passage of antibiotics and antitoxins during pregnancy represent the highest priority research gap," Dr. Meaney-Delman and colleagues conclude.

One expert panel member on the nonpregnant adult guidelines received reagents from Human Genome Sciences, and another expert panel member serves as a consultant for Janssen Pharmaceuticals, makers of Levaquin. The authors on the pregnant women guidelines have disclosed no relevant financial relationships.

Emerging Infect Dis. Published online January 15, 2014.

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