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.

For nonpregnant adults aged ≥18 years with systemic anthrax with or without meningitis, bactericidal agents have been found to provide a survival benefit compared with other agents (37) and are preferred over PSIs (Table 8). In vivo and observational clinical data for systemic anthrax have not demonstrated a survival benefit for combination antimicrobial drug therapy over monotherapy. However, translating these analyses to patient treatment is challenging because various animal models and nonvirulent B. anthracis strains were used; the clinical data were retrospective, observational, and drawn from medical literature that is subject to reporting bias; and only a limited number of patients belonged to a particular treatment category.

In contrast, issues surrounding toxin production support at least initial use of combination therapy. Production of one of the B. anthracis virulence toxins (i.e., protective antigen) was found to be reduced in vitro by linezolid (132) and both in vitro and in vivo by clindamycin (133). Ciprofloxacin plus clindamycin demonstrated survival benefit over ciprofloxacin alone in a rabbit model using a virulent B. anthracis strain; the benefit was attributed to inhibition of toxin synthesis by clindamycin (133). In a retrospective analysis of inhalation anthrax among patients receiving heterogeneous treatment, patients treated earlier (before fulminant infection) who received combination antimicrobial drug therapy (ciprofloxacin, clindamycin, and rifampin) experienced a survival advantage over those who received a single antimicrobial drug (28). Finally, combination therapy with a bactericidal antimicrobial drug and a PSI is recommended to rapidly reduce toxin production for other high-mortality toxin-mediated diseases (e.g., necrotizing fasciitis and streptococcal toxic shock syndrome) (134).

The potential for natural and genetically engineered antimicrobial drug–resistant strains also supports at least initial use of combination therapy. Up to 10% of naturally acquired anthrax can be resistant to penicillin-based treatments, and B. anthracis strains genetically engineered to be resistant to multiple antimicrobial drugs are an even greater concern (121–126). Combining two or three antimicrobial drug classes should provide microbiologic activity against most strains that elaborate recognized mechanisms of resistance.

Because of the highly lethal nature of untreated systemic anthrax, particularly when complicated by anthrax meningoencephalitis, combination therapy should be used to address both the toxin-mediated pathogenesis of this infection and potential antibiotic-resistant B. anthracis. Empiric treatment regimens for nonpregnant adults aged ≥18 years with systematic anthrax with or without meningitis (Table 8) are summarized as follows:

• Antimicrobial drugs: Choose two bactericidal drugs from different antimicrobial drug classes plus a PSI or an RNA synthesis inhibitor (RNAI).
  • Antimicrobial drugs are listed in descending order of preference in the table. Listed drugs joined by “or” are considered equivalent.
  • Continue or switch antimicrobial drugs 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 as adjunctive therapy.

If an appropriate combination of bactericidal antimicrobial drug plus a PSI or an RNAI is contraindicated, not well tolerated, or not available or if meningitis is considered unlikely, consider the following regimens in descending order of preference:

• One bactericidal drug plus a PSI (start with this regimen if meningitis is not suspected and susceptibilities are known)
• One bactericidal drug plus a second bactericidal drug from a different antimicrobial drug class
• One bactericidal drug plus an RNAI
• A PSI plus an RNAI
• Two PSIs from different antimicrobial drug classes
• A single bactericidal drug
• A single PSI
• From a PK/PD perspective, minocycline and doxycycline are the preferred PSIs because they provide more robust drug exposures in plasma and CSF compared with clindamycin and linezolid. A single RNAI (i.e., rifampin) should not be used as monotherapy because of the potential for rapid development of resistance (135). In addition, when meningitis is not suspected, certain oral formulations are included as alternatives in case IV formulations are not available.

Duration of antimicrobial drug treatment should be 2 weeks or longer; however, duration can be shortened and IV administration transitioned to oral medication based on patient improvement and clinical judgment. Patients with systemic anthrax resulting from a nonaerosolizing event do not need continued antimicrobial drugs for PEP. If an aerosol exposure might have occurred (e.g., a bioterrorism-related incident or animal skin drum–related event), patients treated for systemic disease who are immunocompetent do not need further antimicrobial drugs for PEP because they will have developed natural immunity. However, patients who are immunocompromised should transition to an oral PEP regimen (Table 6). The total duration of antimicrobial drug therapy (i.e., treatment plus PEP) should be 60 days from onset of illness.

Anthrax antitoxin should be provided as adjunctive therapy to antimicrobial drug regimens for all patients with noncutaneous systemic anthrax. The monoclonal antitoxins are preferred over the polyclonal antitoxin. If antitoxin supplies are likely to be limited, reserving their use for patients developing signs of hemodynamic instability or respiratory compromise is warranted.

A review of historical case reports of anthrax in pregnant and postpartum women found that B. anthracis infection in this population is associated with high rates of maternal and fetal death (136). The data from the systematic reviews were too sparse to make specific recommendations for pregnant and lactating persons. Thus, the PEPAbx and treatment recommendations for nonpregnant adults aged ≥18 years were the basis for guidelines for pregnant and lactating persons.

Although fluoroquinolones traditionally have not been prescribed during pregnancy and lactation, three recent systematic reviews evaluated their safety during pregnancy. Two systematic reviews (137,138) found no association between fluoroquinolone exposure throughout pregnancy and adverse pregnancy outcomes, and another found no association between first-trimester fluoroquinolone exposure and adverse pregnancy outcomes (139). Tetracycline and minocycline are not recommended in the second and third trimesters of pregnancy because of risk for hepatotoxicity, cardiovascular birth defects, spontaneous abortion, and tooth staining and the potential for transient suppression of bone growth. Data are limited regarding use of eravacycline or omadacycline during pregnancy.

Recommendations for pregnant and lactating persons aged ≥18 years are similar to those for nonpregnant adults except that neither tetracycline nor minocycline are included. This principle applies for empiric PEP (Table 9), empiric treatment of cutaneous anthrax without signs and symptoms of meningitis (Table 10), and empiric treatment of systemic anthrax with or without meningitis (Table 11). A review of doxycycline studies has indicated that doxycycline, unlike other tetracycline-class antimicrobial drugs, has not been associated with fetal growth delays, infant tooth staining, or maternal fatty liver (140). Because of the potential severity of anthrax in pregnant and lactating persons, omadacycline and eravacycline can be used if other PSIs are not available.


PEP and Treatment Regimens for Cutaneous Anthrax Without Signs and Symptoms of Meningitis
For pregnant and lactating persons aged ≥18 years, empiric PEP (Table 9) and empiric cutaneous anthrax treatment (Table 10) regimens include either a single antimicrobial drug or a single antitoxin. These regimens 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 all pregnant and lactating persons who have an aerosol exposure (e.g., a bioterrorism-related incident or animal skin drum–related event), PEPAbx should continue for 60 days from the exposure whether or not vaccine is given (33). For nonaerosol (i.e., cutaneous or ingestion) exposures, PEPAbx should continue for 7 days and vaccine is not needed.

For pregnant and lactating persons 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 9); the combined regimen should total 60 days from exposure. If no aerosolizing event occurred, patients with cutaneous anthrax do not need to continue PEPAbx.


Treatment Regimens for Systemic Anthrax With or Without Meningitis
For pregnant or lactating persons aged ≥18 years, empiric treatment regimens for those with systemic anthrax with or without meningitis (Table 11) summarized as follows:

• Antimicrobial drugs: Choose two bactericidal drugs from different antimicrobial drug classes plus a PSI or an RNAI.
  • Antimicrobial drugs are listed in descending order of preference in the table. Listed drugs joined by “or” are considered equivalent.
  • Continue or switch antimicrobial drugs 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 as adjunctive therapy.

If an appropriate combination of bactericidal drugs plus a PSI or an RNAI is contraindicated, not well tolerated, or not available or if meningitis is considered unlikely, consider the following regimens in descending order of preference:

• One bactericidal drug plus a PSI (start with this regimen if meningitis is not suspected and susceptibilities are known)
• One bactericidal drug plus a second bactericidal drug from a different antimicrobial drug class
• One bactericidal drug plus an RNAI
• A PSI plus an RNAI
• Two PSIs from different antimicrobial drug classes
• A single bactericidal drug
• A single PSI

From a PK/PD perspective, minocycline and doxycycline are the preferred PSIs because they provide more robust drug exposures in plasma and CSF compared with macrolides or clindamycin. A single RNAI (i.e., rifampin) should not be used as monotherapy because of the potential for rapid development of resistance (135). In addition, when meningitis is not suspected, certain oral formulations are included as alternatives in case IV formulations are not available.

Duration of antimicrobial drug treatment should be for 2 weeks or longer; however, duration can be shortened and IV administration transitioned to oral medication based on patient improvement and clinical judgment. Patients with naturally acquired noninhalation cases do not need continuation of antimicrobial drugs for PEP. If an aerosol exposure might have occurred (i.e., a bioterrorism-related incident or animal skin drum–related event), healthy patients treated for systemic disease need no further antimicrobial drugs for PEP because they will have developed natural immunity. However, patients with compromised immune systems should transition to an oral PEP regimen (Table 9). The total duration of antimicrobial drugs (i.e., treatment plus PEP) should be 60 days from onset of illness.

The PEP and treatment guidelines for children aged ≥1 month to <18 years were based on those for nonpregnant adults aged ≥18 years. Thus, the recommendations for children are similar to those for nonpregnant adults. This principle also applies for empiric PEP (Table 12), empiric treatment of cutaneous anthrax without signs and symptoms of meningitis (Table 13), and empiric treatment of systemic anthrax with or without meningitis (Table 14). The pediatric recommendations differ from the adult recommendations because of the potential for adverse events related to the recommended antimicrobial drugs.


PEP and Treatment Regimens for Cutaneous Anthrax Without Signs and Symptoms of Meningitis
For children aged ≥1 month to <18 years, empiric PEP (Table 12) and empiric cutaneous anthrax treatment (Table 13) regimens include either a single antimicrobial drug or a single antitoxin. These regimens 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.
  • If the strain is found to be penicillin susceptible, a penicillin-class antimicrobial drug is preferred for first-line therapy.
  • For penicillin-resistant strains of anthrax, the benefits of therapy with fluoroquinolones and tetracyclines for pediatric anthrax far exceed the potential toxicities.
• Antitoxin: Choose a single antitoxin if no antimicrobial drugs are available.

For all children aged <18 years who have an aerosol exposure (e.g., a bioterrorism-related incident or animal skin drum–related event), PEPAbx should continue for 60 days from the exposure whether or not vaccine is given (33). For nonaerosol (i.e., cutaneous or ingestion) exposures, PEPAbx should continue for 7 days and vaccine is not needed.

For all children aged <18 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 12); the combined regimen should total 60 days from exposure. If no aerosolizing event occurred, patients with cutaneous anthrax do not need to continue PEPAbx.


Treatment Regimens for Systemic Anthrax With or Without Meningitis
Empiric treatment regimens for children aged >1 month to <18 years with systemic anthrax with or without meningitis (Table 14) are summarized as follows:

• Antimicrobial drugs: Choose two bactericidal drugs from different antimicrobial drug classes plus a PSI or an RNAI.
  • Antimicrobial drugs are listed in descending order of preference in the table. Listed drugs joined by “or” are considered equivalent.
  • Continue or switch antimicrobial drugs 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 as adjunctive therapy.

If an appropriate combination of bactericidal drug plus a PSI or an RNAI is contraindicated, not well tolerated, or not available for treatment of noncutaneous systemic anthrax, consider the following regimens in descending order of preference:

• One bactericidal drug plus a PSI (start with this regimen if meningitis is not suspected)
• One bactericidal drug plus a second bactericidal agent from a different antimicrobial drug class
• One bactericidal drug plus an RNAI
• A PSI plus an RNAI
• Two PSIs from different antimicrobial drug classes
• A single bactericidal drug
• A single PSI

From a PK/PD perspective, minocycline and doxycycline are the preferred PSIs because they provide more robust drug exposures in plasma and CSF compared with macrolides or clindamycin. A single RNAI (i.e., rifampin) should not be used as monotherapy because of the potential for rapid development of resistance (135). When meningitis is not suspected, certain oral formulations are included as alternatives in case IV formulations are not available.

Duration of antimicrobial drug treatment should be for 2 weeks or longer; however, duration can be shortened and IV administration transitioned to oral medication based on patient improvement and clinical judgment. Patients with naturally acquired noninhalation anthrax do not need continuation of antimicrobial drug therapy for PEP. If an aerosol exposure might have occurred (i.e., a bioterrorism-related incident or animal skin drum–related event), patients who are immunocompetent do not need further antimicrobial drug therapy because they will have developed natural immunity. Patients who are immunocompromised should transition to an oral PEP regimen (Table 12). The total duration of antimicrobial drug therapy (i.e., treatment plus PEP) should be 60 days from onset of illness.

Virtually no data are available on antimicrobial drug dosing in neonates and premature infants. Dosing guidance for anthrax in newborn infants is based on extrapolation of data from older populations by using pharmacologic data modeling that incorporates antimicrobial drug kinetics, safety, and efficacy in newborns and how the broad range of developmental changes in this immature population affects therapy (32,141–171). Recommendations for both preterm and full-term newborns 32–44 weeks’ postmenstrual age (i.e., gestational age plus chronologic age) are available for empiric PEP (Table 15), empiric treatment of cutaneous anthrax without signs and symptoms of meningitis (Table 16), and empiric treatment of systemic anthrax with or without meningitis (Table 17). For neonates of earlier gestational age or without developmentally appropriate renal and hepatic function, providers should consult with a neonatologist, pharmacologist, or infectious diseases physician for appropriate dosing.


PEP and Treatment Regimens for Cutaneous Anthrax Without Signs and Symptoms of Meningitis
For preterm and full-term newborns 32–44 weeks’ postmenstrual age (i.e., gestational age plus chronologic age), empiric PEP (Table 15), and empiric cutaneous anthrax treatment (Table 16) regimens include either a single antimicrobial drug or a single antitoxin. These regimens 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 preterm and full-term newborns 32–44 weeks’ postmenstrual age (i.e., gestational age plus chronologic age), PEPAbx after aerosol exposure should continue for 60 days (33). Vaccine is not currently indicated for this age group. PEPAbx after nonaerosol exposure should continue for 7 days.

For preterm and full-term newborns 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 15); the combined regimen should total 60 days from exposure. If no aerosolizing event occurred, patients with cutaneous anthrax do not need to continue PEPAbx.


Treatment Regimens for Systemic Anthrax With or Without Meningitis
For preterm and full-term newborns 32–44 weeks’ postmenstrual age (i.e., gestational age plus chronologic age), empiric treatment regimens for those with systemic anthrax with or without meningitis (Table 17) are summarized as follows:

• Antimicrobial drugs: Choose two bactericidal drugs from different antimicrobial drug classes plus a PSI or an RNAI.
  • Antimicrobial drugs are listed in descending order of preference in the table. Listed drugs joined by “or” are considered equivalent.
  • Continue or switch antimicrobial drugs 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 as adjunctive therapy.

If an appropriate combination of bactericidal drugs plus a PSI or an RNAI is contraindicated, not well tolerated, or not available or if meningitis is considered unlikely, consider the following regimens in descending order of preference:

• One bactericidal drug plus a PSI (start with this regimen if meningitis is not suspected)
• One bactericidal drug plus a second bactericidal agent from a different antimicrobial drug class
• One bactericidal drug plus an RNAI
• A PSI plus an RNAI
• Two PSIs from different antimicrobial drug classes
• A single bactericidal drug
• A single PSI

From a PK/PD perspective, minocycline and doxycycline are the preferred PSIs because they provide more robust drug exposures in plasma and CSF compared with macrolides or clindamycin. A single RNAI (i.e., rifampin) should not be used as monotherapy because of the potential for rapid development of resistance (135). In addition, when meningitis is not suspected, certain oral formulations are included as alternatives in case IV formulations are not available.

Duration of antimicrobial drug treatment should be for 2 weeks or longer, although as immune-compromised hosts, neonates might require a longer duration of therapy to achieve cure. Transition from IV administration to oral medication for neonates tolerating regular feeding should be based on patient improvement and clinical judgment. Patients with naturally acquired noninhalation cases do not need continuation of antimicrobial drug therapy for PEP. If an aerosol exposure might have occurred (i.e., a bioterrorism-related incident or animal skin drum–related event), preterm and full-term newborns (who are not considered fully immunocompetent) should transition to an oral PEP regimen (Table 15). The total duration of antimicrobial drug therapy (i.e., treatment plus PEP) should be 60 days from onset of illness.

Pleural effusion and other fluid collections are common complications of anthrax (28,36). Hypothetically, draining pleural fluid or ascites might reduce the amount of lethal factor, thereby reducing illness severity and decreasing mortality. In addition, drainage of pleural fluid is believed to improve survival by decreasing mechanical lung compression. Early and aggressive drainage of any clinically or radiographically apparent pleural effusion is recommended; chest tube drainage is preferred over thoracentesis because many effusions will require prolonged drainage. Thoracotomy or video-assisted thoracic surgery might be required to remove gelatinous or loculated collections. Ascites should also be drained, if feasible, and monitored for reaccumulation; continuous drainage might be required. Standard precautions are sufficient when caring for anthrax patients. The exception is when the patient is potentially contaminated with B. anthracis spores. In such cases, the patient should be isolated in an airborne infection isolation room until decontamination is completed (172).

Anthrax meningitis has a mortality rate that approaches 100% (29,38) and is a common complication of anthrax. Meningitis can either be primary (i.e., have no obvious route of transmission) or secondary (i.e., develop as a complication of any other form of anthrax). Depending on the route of transmission, 14%–37% of patients with injection, ingestion, systemic cutaneous, or inhalation anthrax develop meningitis (38). Thus, all patients with symptoms or signs of systemic disease should be evaluated for meningitis. In a wide-area aerosol release of B. anthracis spores mass casualty event, conventional standards of care for diagnosing meningitis (i.e., imaging and lumbar puncture followed by analysis of CSF) might be limited or not available. For such situations, a screening tool has been developed to identify patients likely to have anthrax meningitis. On the basis of this screening tool (Figure), patients are likely to have meningitis if they have either

• ≥2 of the following signs or symptoms: severe headache, altered mental status, meningeal signs, or other neurologic deficits, or
• ≥1 of the following signs or symptoms: severe headache, altered mental status, meningeal signs, or other neurologic deficits and ≥1 of the following signs or symptoms: nausea/vomiting, abdominal pain, or fever (either subjective or measured) or chills.

Patients are unlikely to have meningitis if they do not have severe headache, altered mental status, meningeal signs, and other neurologic deficits. Patients who have bacteremia; those with obesity, diabetes, hypertension, and chronic obstructive pulmonary disease; and current and former smokers appear to be at increased risk for meningitis.

The combined effects of infection and intercranial bleeding predispose patients to malignant, rapidly fatal brain swelling and elevated intracranial pressure. Mannitol or hypertonic saline should be considered for patients with anthrax meningitis and evidence of cerebral edema (98). The data did not demonstrate a survival benefit in those who received steroids compared with those who did not. However, steroids did not appear to cause harm and should be used if clinically indicated. In addition, therapies that target intracranial bleeding and swelling (e.g., nimodipine) have been reported to improve outcomes in aneurysmal subarachnoid hemorrhage and intracerebral hemorrhage and might be applicable to the treatment of hemorrhagic anthrax meningitis. However, at present no data from animal studies or human patients with anthrax are available to support the theoretical benefit of these treatments (51).

Anthrax continues to occur in certain places around the world, with an estimated 20,000–100,000 cases occurring annually (173). B. anthracis also continues to be considered the most likely bioweapon to be used during a bioterrorist event because of its availability, ease of dissemination, and high mortality rate associated with systemic anthrax. Biopreparedness efforts are made more challenging by the ease with which B. anthracis can be made resistant to first-line antimicrobial drugs for PEP and treatment. This report describes updated CDC guidelines and recommendations for the preferred prevention and treatment regimens for naturally occurring anthrax. Also provided are a wide range of alternative regimens to first-line antimicrobial drugs for use if patients have contraindications or intolerances or after a wide-area aerosol release of B. anthracis spores if resources become limited or a multidrug-resistant B. anthracis strain is used. Future revisions to these guidelines will be supported by new research and technological advancements for prevention and clinical management of anthrax.