Prevention and Treatment of Anthrax

Anthrax can be a devastating disease. In one Russian series, one in six patients with cutaneous or ingestion exposures to B. anthracis developed anthrax (62). Mortality rates for adequately treated anthrax range from <2% (119) for cutaneous anthrax to 45% for inhalation anthrax (13,120) and >90% for anthrax meningitis (29,52). On the basis of efficacy described from in vivo data and human clinical experience and known potential risks, the benefits of antimicrobial drugs for PEP or treatment of anthrax outweigh the known risks.

These guidelines address anthrax PEP and treatment for both natural and intentional exposures (e.g., a wide-area aerosol release of B. anthracis spores). The evidence base linking recommendations to data is available (Supplementary Material, https://stacks.cdc.gov/view/cdc/132182). Previously, all B. anthracis strains from a naturally occurring source or an intentional release were thought to be susceptible to the recommended first-line antimicrobial drugs (except for penicillins). However, over the past few decades, studies have demonstrated that antimicrobial-resistant B. anthracis strains can be created with relative ease through serial passaging on selective media (121,122). Consequently, bioterrorists could mass produce a multidrug-resistant B. anthracis strain capable of evading previously recommended first-line antimicrobial medical countermeasures. These updated CDC guidelines provide PEP and treatment recommendations that include numerous antimicrobial drugs from multiple classes. The antimicrobial drugs recommended as first-line agents are expected to address most scenarios. The alternative antimicrobial drugs provide contingencies for contraindications, intolerances, unavailability, and natural or genetically engineered resistance.

The recommended medical countermeasures are preferentially ordered based on 1) in vitro effectiveness against B. anthracis (34) (Table 1); 2) in vivo efficacy against B. anthracis exposures as demonstrated by ORs and CIs for survival compared with no therapy or therapy with a positive control (35,37) (Table 2); 3) the animal model used to generate efficacy data (nonhuman primate or rabbit models were preferred over mouse, guinea pig, or hamster models); 4) treatment outcomes for published human cases (39) (Table 3); 5) the percentage of patients expected to achieve microbiologic CSF cure at recommended antimicrobial drug dosing based on Monte Carlo simulations (Table 5); 6) the safety profiles of the antimicrobial drugs (42); 7) logistical considerations (e.g., available formulations [including availability and palatability of liquid formulations], dosing intervals, cost, and supply and availability patterns); and 8) expert opinion. In addition, certain antimicrobial drugs are included for PEPAbx or treatment on the basis of class efficacy (e.g., levofloxacin, moxifloxacin, and ofloxacin) or for treatment on the basis of demonstrated PEPAbx efficacy (e.g., minocycline).

Early diagnosis of anthrax and initiation of appropriate treatment are critical to improving survival. Although empiric treatment of anthrax or prophylaxis after exposure is needed to save lives, antimicrobial drug susceptibility testing is vital; antimicrobial drug choices might need to be modified based on the results. Data indicate penicillin-class antimicrobial drugs are as effective as other bactericidal agents for PEPAbx and treatment and might be preferred in certain populations. However, although <10% of naturally occurring B. anthracis isolates are reported to be resistant to penicillin-class antimicrobial drugs (123–126), these drugs should only be used if the strain is known to be penicillin susceptible. In vitro data demonstrate that cephalosporins, trimethoprim/sulfamethoxazole, and aztreonam are ineffective against B. anthracis. If liquid formulations are not available for children or adults who cannot swallow pills, instructions are available for preparing oral suspensions of moxifloxacin (127) and doxycycline (128).

PEP regimens for nonpregnant adults aged ≥18 years exposed to B. anthracis include either a single antimicrobial drug or, if antimicrobial drugs are not available, a single anthrax antitoxin (Table 6). Both antimicrobial drugs and antitoxins are highly effective at preventing disease in animals. However, because antitoxins are administered intravenously and are somewhat (i.e., the monoclonals) to moderately (i.e., the polyclonal) less efficacious than antimicrobial drugs (35,37), all oral antimicrobial drugs are preferred over antitoxins. In addition, in a wide-area aerosol release of B. anthracis spores, antitoxins should be prioritized for treatment rather than PEP because they likely provide greater benefit as adjunctive treatments. If coadministration of anthrax vaccine and antitoxin is indicated, the only antitoxin that should be used is raxibacumab (37).

Studies in animal models (129,130) and a report after an accidental wide-area aerosol release of B. anthracis spores (15) suggest the incubation period for inhalation anthrax in those administered PEPAbx might be up to 60 days. To prevent anthrax after discontinuation of PEPAbx, ACIP recommends AVA for adults aged 18–65 years in conjunction with a course of PEPAbx (33). AVA is administered subcutaneously at 0, 2, and 4 weeks postexposure; it can be administered intramuscularly if the subcutaneous route poses significant materiel, personnel, or clinical challenges. AVA can be used under an appropriate regulatory mechanism (e.g., investigational new drug or emergency use authorization) in persons aged <18 years and >65 years exposed to anthrax. In July 2023, a second-generation anthrax vaccine, anthrax vaccine adsorbed, adjuvanted, was FDA approved for PEPVx against inhalation anthrax. Anthrax vaccine adsorbed, adjuvanted is administered by the IM route as a 2-dose series 2 weeks apart, in conjunction with PEPAbx for adults aged 18–65 years. In persons aged >65 years, anthrax vaccine adsorbed, adjuvanted elicited a higher immune response compared with AVA (131). Anthrax vaccine use in older adults (aged >65 years), pregnant or lactating persons, and children (aged <18 years) would be guided by data available at the time of an anthrax event.

For nonpregnant adults aged ≥18 years, antimicrobial drug monotherapy can be used for treatment of both localized and systemic cutaneous anthrax if the patient does not have signs and symptoms of meningitis (37) (Table 7). A penicillin-class antimicrobial drug can be used as monotherapy if the organism is known to be penicillin susceptible, which will allow combination regimens to be reserved for patients with high-mortality forms of anthrax (e.g., inhalation anthrax). Anthrax antitoxin can be used to treat cutaneous anthrax without signs and symptoms of meningitis if all recommended antimicrobial drugs are not available or not appropriate.

For nonpregnant adults aged ≥18 years, empiric PEP (Table 6) and empiric cutaneous anthrax treatment (Table 7) regimens include either a single antimicrobial drug or a single antitoxin and are summarized as follows:

• Antimicrobial drug: Choose a single antimicrobial drug.
  • Antimicrobial drugs are listed in descending order of preference in the table. Listed drugs joined by “or” are considered equivalent.
  • Continue or switch antimicrobial drug based on susceptibility testing once available.
  • Only choose a “PCN-S only” antimicrobial drug after the strain has been determined to be penicillin susceptible.
• Antitoxin: Choose a single antitoxin if no antimicrobial drugs are available.

For adults aged 18–65 years, when PEPAbx is used without PEPVx after aerosol exposure (e.g., a bioterrorism-related incident or animal skin drum–related event), PEPAbx should be continued for 60 days. When PEPAbx is used with PEPVx for healthy, nonpregnant adults aged 18–65 years, antimicrobial drugs can be discontinued 42 days after the first dose or 2 weeks after the last dose of vaccine, whichever occurs later. For older adults (aged ≥66 years) and persons with immunocompromising conditions, PEPAbx should continue for 60 days (33). For adults aged 18–65 years with nonaerosol (i.e., cutaneous or ingestion) exposures, PEPAbx should continue for 7 days and vaccine is not needed.

For adults aged 18–65 years with cutaneous anthrax without signs and symptoms of meningitis, the treatment regimen should continue for 7–10 days, or until clinical criteria for stability are met. If an aerosol exposure might have occurred, patients should transition from a treatment to a PEP regimen (Table 6); the combined regimen should total 42–60 days from exposure, depending on anthrax vaccine status and immunocompetence. If no aerosolizing event occurred, patients with cutaneous anthrax do not need to continue PEPAbx.