Treatment of anthrax

INTRODUCTION — The incidence of anthrax in humans has decreased during the past century, and it is now very rare in developed countries including the United States. However, anthrax remains a concern in the developed world because of its potential as an agent of bioterrorism. Anthrax meningitis and the fulminant phase of inhalation anthrax are associated with extremely high mortality rates.

The treatment of anthrax will be reviewed here. The microbiology, pathogenesis, epidemiology, clinical manifestations, diagnosis, and prevention of anthrax are discussed separately. (See "Microbiology, pathogenesis, and epidemiology of anthrax" and "Clinical manifestations and diagnosis of anthrax" and "Prevention of anthrax".)

TREATMENT — The treatment recommendations presented here are in agreement with the recommendations of the United States Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics (AAP) [1-3].

Overview — Treatment of patients suspected of having systemic anthrax should be started urgently and should include intravenous antimicrobial combination therapy and antitoxin (raxibacumab, obiltoxaximab or anthrax immunoglobulin), drainage of pleural effusions, supportive care, and consideration of adjunctive glucocorticoids [1]. Each of these therapies is discussed in detail below. When selecting an antimicrobial regimen for anthrax, the production of toxin, the potential for antimicrobial drug resistance, the frequent occurrence of meningitis, and the presence of latent spores must be taken into account.

●Contact public health officials – In the United States, anthrax is an immediately notifiable disease, meaning that as soon as clinicians reasonably suspect the diagnosis, they should contact the state health department for assistance in diagnosis and treatment. Since antitoxin treatment is available only through the Strategic National Stockpile, clinicians can obtain them only through a state health department, which coordinates with the CDC. (See 'Public health reporting' below.)

●Initial evaluation – Patients suspected of having systemic anthrax should undergo similar testing as is done in other patients with an acute febrile illness, including pretreatment blood cultures and other appropriate cultures [1]. Unless it is contraindicated, all patients suspected of having systemic anthrax should undergo lumbar puncture to evaluate for meningitis. Other diagnostic testing is discussed separately. (See "Clinical manifestations and diagnosis of anthrax", section on 'Diagnosis'.)

●Hospital admission – All patients with systemic anthrax should be hospitalized [1]. Systemic anthrax is defined as cutaneous anthrax with systemic involvement; gastrointestinal, injection, or inhalation anthrax; anthrax meningitis; or bacteremia. Because inhalation anthrax can have a prodromal phase followed by a fulminant phase characterized by sudden decompensation, hospitalized patients should have careful hemodynamic monitoring, including continuous pulse oximetry and telemetry.

●Principles of antimicrobial regimen selection – Recommended antimicrobial regimens for anthrax include bactericidal agents because of their immediate killing effect and a protein synthesis inhibitor to suppress toxin production [1,4]. Although there is not strong direct evidence supporting this recommendation in anthrax, the benefit of inhibiting toxin production has been demonstrated for streptococcal toxic shock syndrome and clostridial sepsis. (See "Invasive group A streptococcal infection and toxic shock syndrome: Treatment and prevention", section on 'General principles' and "Clostridial myonecrosis", section on 'Treatment'.)

Bacillus anthracis is highly susceptible to a variety of antimicrobial agents including penicillin, chloramphenicol, tetracycline, erythromycin, streptomycin, carbapenems, linezolid, clindamycin, and fluoroquinolones [4-8]. B. anthracis is not susceptible to cephalosporins or trimethoprim-sulfamethoxazole [5-7,9,10]. Because B. anthracis possesses beta-lactamase genes, beta-lactam use can induce resistance during treatment; penicillin or amoxicillin use therefore warrants a high index of suspicion for emergence of resistance [1,11]. Although the few penicillin-resistant isolates tested have been sensitive to amoxicillin-clavulanate, that agent is only expected to inhibit one of the two beta-lactamase gene products of B. anthracis [12]. Thus, pending more experience, amoxicillin-clavulanate and ampicillin-sulbactam are not good choices for penicillin-resistant strains.

Clinical microbiologists should also be aware that the antibiotic breakpoints for B. anthracis are in some cases different from those of Bacillus species in general [13].

●Subsequent oral therapy – If the infection is bioterrorism associated or if aerosol exposure is suspected, patients should switch to single agent oral therapy (table 1) following the initial intravenous regimen to complete a 60-day total course of antibiotics (inclusive of initial therapy) in order to prevent relapse from surviving B. anthracis spores (table 1) [1]. The oral antimicrobial options for postexposure prophylaxis are discussed in detail elsewhere (table 1). Pediatric experts recommend that children potentially exposed to aerosolized anthrax spores also receive anthrax vaccination in addition to prophylactic antibiotics [14]. (See "Prevention of anthrax", section on 'Antimicrobial regimen selection'.)

●Risk of meningitis – Meningitis and hemorrhagic brain infection have been observed in up to one-half of systemic anthrax cases; thus, meningitis must be considered in all cases of systemic anthrax [1]. In a mass casualty situation, especially if resources become limited, it may be necessary to use clinical criteria for the diagnosis of meningitis [15,16]. (See 'Meningitis' below and "Clinical manifestations and diagnosis of anthrax", section on 'Meningitis'.)

Antimicrobial selection and duration

Meningitis — Early and aggressive multidrug therapy of anthrax meningitis is crucial due to the rapid progression and high mortality of the disease [17-19]. Empiric treatment for anthrax cases in which anthrax meningitis cannot be ruled out should include intravenous therapy with at least three antimicrobial agents with activity against B. anthracis, including at least two agents with bactericidal activity, and at least one protein synthesis inhibitor (to reduce exotoxin production) [1,2]. All agents should also have good central nervous system (CNS) penetration. Following initial intravenous antimicrobial therapy, an oral regimen is recommended to prevent relapse. An antitoxin (raxibacumab, obiltoxaximab, or anthrax immunoglobulin) is also recommended for initial therapy. (See 'Antitoxins' below.)

●Initial intravenous regimen – For patients with systemic anthrax with potential meningitis and normal renal function, we suggest [1,2]:

•Ciprofloxacin – In adults: 400 mg intravenously (IV) every 8 hours; in children: 30 mg/kg per day divided every 8 hours, not to exceed 400 mg per dose

PLUS

•Meropenem – In adults: 2 g IV every 8 hours; in children: 120 mg/kg per day divided every 8 hours, not to exceed 2 g per dose

PLUS

•Linezolid – In adults and children ≥12 years of age: 600 mg IV every 12 hours; in children <12 years of age: 30 mg/kg per day divided every 8 hours, not to exceed 600 mg per dose

First-line and alternative agents are reviewed in the following table (table 2).

Ciprofloxacin is the agent of choice for the bactericidal component of therapy based upon efficacy data in nonhuman primate infection models and experience with its use for anthrax cases in humans [1]. Levofloxacin and moxifloxacin are acceptable alternatives. The fluoroquinolones have adequate CNS penetration. There have been no reports of naturally occurring resistance of B. anthracis to fluoroquinolones.

Meropenem is the agent of choice as the second bactericidal agent for treatment of possible meningitis [1]. The carbapenems are highly resistant to beta-lactamases and have good CNS penetration. If meropenem is not available, imipenem is an acceptable alternative. However, imipenem should be used with caution in patients with meningitis since it is associated with an increased seizure risk. For B. anthracis isolates with confirmed susceptibility to penicillin, IV penicillin G, or ampicillin is an acceptable alternative to the carbapenem. If beta-lactam agents are not available, vancomycin is an alternative agent for children [14].

Linezolid is the preferred protein synthesis inhibitor [1]. It is favored over clindamycin because it is likely to have better CNS penetration [1,20]. Potential toxicities of linezolid include myelosuppression, peripheral and optic neuropathies, and serotonin syndrome [1]. Linezolid should be used with caution in patients with pre-existing myelosuppression or on selective serotonin reuptake inhibitors (SSRIs). Clindamycin is an acceptable alternative if linezolid is unavailable or is not tolerated. Rifampin is not a protein synthesis inhibitor, but it has been used for its synergistic effect with other agents. Rifampin can be used if linezolid and clindamycin are unavailable. Chloramphenicol is a protein synthesis inhibitor with good CNS penetration. Where available, chloramphenicol can be used if linezolid, clindamycin, and rifampin are unavailable.

Doxycycline is not recommended for adults with suspected meningitis because it does not have adequate CNS penetration [1].

●Considerations during and after pregnancy – The treatment of pregnant, lactating, and postpartum women is similar to the treatment of nonpregnant adults, except that in pregnant individuals, ciprofloxacin is even more strongly preferred as one of the bactericidal agents because it crosses the placental barrier [3]. If ciprofloxacin is not used, another agent that crosses the placenta should be included in the regimen. Such agents are listed in the table (table 2). Because pregnancy can affect drug metabolism, clinicians should consult a clinical pharmacist, if available, for assistance with drug dosing in pregnant patients. Pharmacokinetic data indicate that penicillin, ampicillin, and carbapenems may require higher doses in pregnant and postpartum women than those recommended for nonpregnant adults [3,21]. Serum levels of ciprofloxacin were also lower in pregnant individuals in one study [22].

●Duration of initial therapy – For patients being treated for anthrax meningitis, IV combination therapy should be continued for at least three weeks or until the patient is clinically stable, whichever is longer [1]. All clinical signs and symptoms and laboratory and imaging studies should show resolution of inflammation before antimicrobial therapy is discontinued [2]. In some patients, IV therapy will be necessary for three to six weeks.

●Subsequent oral therapy – Once the course of IV combination therapy has been completed, patients should be switched to single agent oral therapy (table 1) to complete a 60-day postexposure prophylactic course of antibiotics (inclusive of initial therapy) in order to prevent relapse from surviving B. anthracis spores [1]. The oral antimicrobial options for and duration of postexposure prophylaxis are discussed in detail elsewhere. (See "Prevention of anthrax", section on 'Antimicrobial regimen selection'.)

Adjunctive measures (including glucocorticoids and surgery) and supportive care are discussed below. (See 'Adjunctive therapies' below and 'Supportive care' below.)

Systemic anthrax without meningitis — Systemic anthrax without meningitis includes inhalation, injection, and gastrointestinal anthrax and cutaneous anthrax with systemic involvement; meningitis should be ruled out in all patients [1]. Patients with cutaneous anthrax with extensive edema or lesions of the head or neck should also be treated according to the recommendations for systemic anthrax. Antimicrobial therapy should be initiated promptly in any patient with suspected systemic anthrax. Initial therapy should include at least two IV agents with activity against B. anthracis, at least one agent with bactericidal activity, and at least one protein synthesis inhibitor (table 3). Following initial intravenous antimicrobial therapy, an oral regimen is recommended to prevent relapse. An antitoxin (raxibacumab, obiltoxaximab, or anthrax immunoglobulin) is also recommended for initial therapy. (See 'Antitoxins' below.)

●Initial intravenous regimen – For adults with systemic anthrax and normal renal function in whom meningitis has been ruled out, we suggest [1,3]:

•Ciprofloxacin 400 mg intravenously (IV) every 8 hours

PLUS one of the following:

-Clindamycin 900 mg IV every 8 hours or

-Linezolid 600 mg IV every 12 hours

If the B. anthracis strain is susceptible to penicillin, penicillin G is considered equivalent to the fluoroquinolone option for primary bactericidal treatment.

For children with systemic anthrax in whom meningitis has been ruled out, we suggest [2]:

•One of the following:

-Ciprofloxacin 30 mg/kg per day IV divided every 8 hours (not to exceed 400 mg/dose) or

-For penicillin-susceptible strains only, penicillin G 400,000 units/kg per day IV divided every 4 hours (not to exceed 4 million units/dose)

PLUS

•Clindamycin 40 mg/kg per day IV divided every 8 hours (not to exceed 900 mg/dose)

First-line and alternative agents are reviewed in the following table (table 3).

Most data on the treatment of anthrax predate the availability of many of the antimicrobial agents that are recommended and/or are derived from animal studies [1]. In a systematic review of 82 cases of inhalation anthrax between 1900 and 2005, the 11 patients in the 2001 United States bioterrorist attack were significantly less likely to die than historical controls (45 versus 92 percent); they were also more likely to receive antibiotics during the prodromal phase of illness (64 versus 13 percent), multidrug regimens (≥2 antimicrobial agents or antiserum plus antimicrobial therapy; 91 versus 50 percent), and pleural fluid drainage (73 versus 11 percent) [17]. Patients who progressed to the fulminant phase had a mortality rate of 97 percent regardless of the treatment they received. All patients with anthrax meningoencephalitis died.

Three antimicrobial agents have received US Food and Drug Administration (FDA) approval for the treatment of anthrax, including inhalation anthrax: ciprofloxacin, doxycycline, and penicillin G procaine (although the last has been discontinued) [23,24]. The multidrug regimens found to be effective in the treatment of patients with inhalation anthrax during the 2001 bioterrorism attacks included ciprofloxacin plus rifampin plus either clindamycin or vancomycin [25].

●Considerations during and after pregnancy – The treatment of pregnant, lactating, and postpartum women is similar to the treatment of nonpregnant adults, except that ciprofloxacin is strongly preferred as the bactericidal agent because it crosses the placental barrier [3]. If ciprofloxacin is not included in the regimen, a different agent that crosses the placental barrier should be included in the regimen. Appropriate choices are listed in the table (table 3). Because pregnancy can affect drug metabolism, clinicians should consult a clinical pharmacist, if available, for assistance with drug dosing in pregnant patients. Pharmacokinetic data indicate that penicillin, ampicillin, and carbapenems may require higher doses in pregnant and postpartum women than those recommended for nonpregnant adults [3,21]. Serum levels of ciprofloxacin were also lower in pregnant individuals in one study [22].

●Duration of initial therapy and transition to a subsequent oral regimen – Patients should be treated with IV therapy for at least two weeks or until clinically stable, whichever is longer [1]. Once the course of IV combination therapy has been completed, patients should be switched to single agent oral therapy (table 1) to complete a 60-day postexposure prophylactic course of antibiotics (inclusive of initial therapy) in order to prevent relapse from surviving B. anthracis spores [1]. The oral antimicrobial options for and duration of postexposure prophylaxis are discussed in detail elsewhere. (See "Prevention of anthrax", section on 'Antimicrobial regimen selection'.)

Children who appear to be well and have no ongoing signs or symptoms of active infection may be transitioned to oral monotherapy before completing two weeks of IV combination therapy [2,14]. More detailed recommendations can be found in American Academy of Pediatrics guidelines on anthrax management.

Adjunctive measures (including glucocorticoids and surgery) and supportive care are discussed below. (See 'Adjunctive therapies' below and 'Supportive care' below.)

Cutaneous anthrax without systemic involvement — The recommendations in this section are intended for patients with cutaneous anthrax without systemic involvement, extensive edema, or lesions of the head or neck. Patients with cutaneous anthrax with systemic involvement, extensive edema, or lesions of the head or neck should be treated according to the recommendations presented above for systemic anthrax. (See 'Systemic anthrax without meningitis' above and 'Meningitis' above.)

For cutaneous anthrax without systemic involvement, we recommend monotherapy:

●Nonpregnant adults — For nonpregnant adults, we suggest oral therapy with [1]:

•Ciprofloxacin 500 mg every 12 hours OR

•Doxycycline 100 mg every 12 hours OR

•Levofloxacin 750 mg every 24 hours OR

•Moxifloxacin 400 mg every 24 hours

Alternatives include:

•Clindamycin 600 mg every 8 hours OR

•For penicillin-susceptible strains, penicillin VK 500 mg every 6 hours OR

•For amoxicillin-susceptible strains, amoxicillin 1 g every 8 hours

●Pregnant, lactating, and postpartum women — For pregnant, lactating, and postpartum women, the agent of choice is ciprofloxacin 500 mg orally every 12 hours [3]. If ciprofloxacin is unavailable, alternative agents that are likely to cross the placenta adequately include levofloxacin, amoxicillin, and penicillin; amoxicillin or penicillin can be used for amoxicillin- or penicillin-susceptible strains, respectively. Clindamycin and doxycycline are also likely to cross the placenta, but data are limited.

●Children — For children, we suggest one of the following oral agents [2]:

•Ciprofloxacin 30 mg/kg per day divided every 12 hours (not to exceed 500 mg/dose) OR

•For amoxicillin-susceptible strains, amoxicillin 75 mg/kg per day divided every 8 hours (not to exceed 1 g/dose)

Alternatives include:

•Doxycycline 4.4 mg/kg per day divided every 12 hours (not to exceed 100 mg/dose) OR

•Clindamycin 30 mg/kg per day divided every 8 hours (not to exceed 600 mg/dose) OR

•Levofloxacin

-<50 kg: 16 mg/kg per day divided every 12 hours (not to exceed 250 mg/dose)

-≥50 kg: 500 mg every 24 hours OR

•For penicillin-susceptible strains, penicillin VK 50 to 75 mg/kg per day divided every 6 to 8 hours

Adequate dosing of penicillin and amoxicillin is particularly important because resistance may emerge during treatment with subtherapeutic doses of these agents [1].

For naturally acquired infection (eg, animals with anthrax, hides from animals with anthrax), the duration of therapy is 7 to 10 days. For bioterrorism-associated cases and cases in which an aerosol exposure is suspected, a longer course for postexposure prophylaxis is given. (See 'Overview' above.)

Antitoxins — Antitoxin therapies are a recommended component of treatment of systemic anthrax, with or without meningitis, and are used in combination with antimicrobial therapy. These include the monoclonal antibodies raxibacumab and obiltoxaximab as well as anthrax immunoglobin derived from human plasma. They inhibit binding of protective antigen and translocation of the two primary toxins, lethal toxin (LT) and edema toxin, into cells [1]. These agents may have their greatest benefit when used early in the course of disease [26]. In the United States. supplies are held in the Strategic National Stockpile for use by the CDC in the event of an anthrax emergency. Thus, they are only used by consultation with the CDC through the state health department, should be consulted as soon as anthrax is reasonably suspected.

Data supporting the use of antitoxin therapy are limited. Animal origin antiserum was used with some success in the treatment of anthrax prior to the advent of antimicrobial therapy [27-29]. In a systematic review of inhalation anthrax cases from 1900 to 2005, mortality was significantly lower among patients who received antiserum than in those who received no treatment [17]. In subsequent systematic reviews of randomized trials in animals, antitoxin therapy using the monoclonal antibodies or human anthrax immunoglobulin improved survival compared with placebo [30,31], consistent with the benefit of anthrax antiserum in the pre-antibiotic era [32]. However, there was no clear benefit of these agents compared with antibiotics or when added to antibiotics [30]. Evidence in humans is limited to case series; among the 25 patients reported to receive antitoxin or antiserum since 1960, the mortality rate was approximately 35 percent, even among those considered to have fulminant disease [30]. Antitoxin may thus have the greatest value in mass casualty situations where antibiotics are in short supply. Nevertheless, given the severity of systemic anthrax and the paucity of human data, antitoxin administration as early as possible and in conjunction with antibiotic therapy remains a reasonable approach.

Raxibacumab — Raxibacumab, a human IgG1-gamma monoclonal antibody directed against protective antigen, was found to be effective for the treatment of anthrax in randomized trials involving rabbits, monkeys, and dogs [33,34]. In 2012, raxibacumab was approved by the US Food and Drug Administration for the treatment of inhalation anthrax [35].

Raxibacumab is given as a single dose following premedication with diphenhydramine; dosing recommendations are as follows [36]:

●Adults and children >50 kg: 40 mg/kg IV

●Children 15 kg to 50 kg: 60 mg/kg IV

●Children 15 kg or less: 80 mg/kg

The efficacy of raxibacumab has been systematically evaluated only in animals (see 'Antitoxins' above); it is not possible to perform efficacy trials in humans given that inhalation anthrax is both rare and lethal. However, in phase II safety studies in humans, the therapeutic levels of the antibody achieved in humans were equal to or greater than those that provide protection in animal models [37]. Common adverse effects in 326 healthy humans included rash, extremity pain, pruritus, and drowsiness [35].

Obiltoxaximab — Obiltoxaximab, a monoclonal antibody directed against the protective antigen of B. anthracis, was approved in 2016 by the US Food and Drug Administration for the treatment of inhalation anthrax (in combination with antimicrobial therapy) [38,39]. The evidence supporting its efficacy comes from studies in animal models of inhalational anthrax.

Obiltoxaximab is given as a single dose following premedication with diphenhydramine; dosing recommendations are as follows [39]:

●Weight >40 kg: 16 mg/kg IV

●Weight 15 to 40 kg: 24 mg/kg IV

●Weight ≤15 kg: 32 mg/kg IV

The efficacy of obiltoxaximab has been systematically evaluated only in animals (see 'Antitoxins' above); it is not possible to perform efficacy trials in humans given that inhalation anthrax is both rare and lethal. The most common adverse effects in trials of 320 humans included headache, pruritus, upper respiratory tract infection, cough, vessel puncture site bruise, infusion site swelling, urticaria, nasal congestion, infusion site pain, and pain in an extremity [39]. Obiltoxaximab was discontinued in 8 of 320 individuals (2.5 percent) due to hypersensitivity reactions or anaphylaxis.

Anthrax immunoglobulin — Anthrax immunoglobulin is derived from the plasma of Anthrax Vaccine Adsorbed (AVA)-immunized persons and is used in combination with antimicrobial therapy [40,41]. Anthrax immunoglobulin neutralizes toxins produced by B. anthracis.

Nineteen patients with anthrax were treated with anthrax immunoglobulin and antimicrobial therapy under an expanded access program [41]. Three had inhalation anthrax, one had gastrointestinal anthrax, and 15 had injection anthrax caused by contaminated heroin. Of these patients, 13 survived, including two of the three patients with inhalation anthrax.

The safety of anthrax immunoglobulin was tested in 72 healthy human volunteers [41]. The most common side effects were headache, back pain, nausea, and infusion site pain and swelling.

Adjunctive therapies

Glucocorticoids — Glucocorticoids should be considered as adjunctive therapy for patients with anthrax meningitis, cutaneous anthrax with extensive edema involving the head and neck, anthrax in the setting of recent glucocorticoid therapy, or anthrax with vasopressor-resistant shock [1]. Supporting data are limited and there may be no benefit for reducing the inflammation resulting from toxin-mediated tissue edema. Small observational studies of patients with cutaneous anthrax of the head and neck suggest possible benefit [42,43]. A retrospective review of 70 cases of anthrax meningoencephalitis from 1966 to 2002 reported an overall mortality rate of 94 percent, but, among 10 patients treated with glucocorticoids as an adjunct to antimicrobial therapy, mortality was 80 percent [19]. However, it is not possible to draw conclusions from such a small study.

Pleural fluid drainage — Pleural fluid drainage has been associated with improved survival in a case series of 82 patients with inhalation anthrax [17]. Drainage of both pleural fluid and ascites is thought to improve survival by reducing the toxin level and by decreasing mechanical lung compression [1,15]. Pleural fluid should be drained early and aggressively; chest tubes are preferred over thoracentesis because many effusions require prolonged drainage. Thoracotomy or video-assisted thoracic surgery might be required to remove gelatinous or loculated pleural effusions.

Managing complications of meningitis — Individuals with anthrax meningitis should be managed in a neuro-critical care unit or in consultation with a neuro-critical care specialist, if possible. Intracranial and subarachnoid hemorrhage are frequent complications [44]. Other potential complications include systemic hypertension or hypotension, elevated intracranial pressure, and cerebrovascular vasospasm.

Other invasive procedures — Ascites should be drained; drainage of ascites is done preferably with continuous drainage, although in resource-limited situations repeated drainage is acceptable [15]. Hemodynamically significant pericardial effusions should also be drained. Surgery should not be performed for cutaneous anthrax since it can lead to dissemination and poor outcomes. Tracheostomy may be required for patients with airway obstruction and surgery may be required for large or circumferential extremity lesions causing compartment syndrome. Surgery may be indicated for patients with gastrointestinal anthrax to address potentially fatal complications, including bowel ischemia, necrosis, and perforation. For injection anthrax, surgery may be performed to obtain diagnostic specimens and to differentiate the infection from necrotizing fasciitis and to remove the necrotic nidus of infection, which may serve as a reservoir for toxin and spores.

Supportive care — Standard sepsis care should be administered to patients with systemic anthrax, including intravenous fluids, vasopressors, blood products, and invasive hemodynamic monitoring as needed.

Microangiopathic hemolytic anemia, coagulopathy, thrombocytopenia, and hemorrhage occur frequently with anthrax infection; these complications should be managed aggressively and may be contraindications to central venous catheter placement [1]. Patients with anthrax may require mechanical ventilation for respiratory distress, airway protection (for those with altered mental status), and/or airway edema. Substantial airway edema can occur with cutaneous lesions involving the head, neck, or thorax, and with oropharyngeal lesions. More detailed recommendations for supportive care can be found in the CDC guidelines.

MONITORING — Close monitoring is essential for care of patients with systemic anthrax (table 4). Because there can be a prodromal phase followed by a fulminant phase characterized by sudden decompensation, hospitalized patients should have careful hemodynamic monitoring, including continuous pulse oximetry and telemetry [1].

Routine laboratory monitoring includes complete blood count, electrolytes, kidney function tests, liver enzymes and bilirubin, and prothrombin time (PT) and activated partial thromboplastin time (aPTT). Chest radiographs are performed daily until abnormalities (eg, pleural effusion) are stable or improving. Computed tomography (CT) of the chest may be warranted for major changes in clinical status. Echocardiography is performed to evaluate for pericardial effusions, which were reported in 3 of 10 patients with bioterrorism-related inhalational anthrax [45].

Patients who develop headache, confusion, or other neurologic symptoms should undergo head imaging and repeat lumbar puncture to evaluate for meningitis or other central nervous system complications.

PREVENTION — Anthrax pre-event vaccination and postexposure vaccination, antimicrobial prophylaxis, and raxibacumab prophylaxis are reviewed separately. (See "Prevention of anthrax".)

PUBLIC HEALTH REPORTING — Anthrax is a reportable disease and immediate notification should be made to the local or state health department even if there is only clinical or laboratory suspicion of anthrax or exposure to B. anthracis.

Healthcare providers should consult their local or state public health departments for specific recommendations for the prevention or treatment of bioterrorism-related anthrax. This is critically important in order to ensure that an antimicrobial regimen is selected to which the isolate is fully susceptible because antibiotic-resistant strains might be intentionally used in such cases.

OUTCOMES — Outcomes of anthrax vary depending on the site(s) of involvement:

●The case-fatality rate of cutaneous anthrax is <2 percent with antibiotic therapy; without therapy, mortality has ranged from 16 to 39 percent [1]. In the preantibiotic era in the early 20^th century, the mortality rate in patients who received serum (antitoxin) ranged from 0 to 28 percent.

●Patients with inhalation anthrax frequently present late in the course of their illness. Prior to 2001, mortality rates for patients with inhalation anthrax were nearly 90 percent [1]. From 2001 to 2012, 8 of 15 patients (53 percent) with inhalation anthrax survived. Patients who survived were diagnosed early, given combination antimicrobial therapy to eradicate B. anthracis and inhibit toxin production, and had aggressive management of pleural effusions.

●Even with antimicrobial therapy and modern intensive care, the mortality rates of injection, gastrointestinal, and inhalation anthrax have been estimated to be 28 percent, ≥40 percent, and 45 percent, respectively [1].

●With treatment, the mortality rate for anthrax meningitis approaches 100 percent [1,2].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Anthrax".)

SUMMARY AND RECOMMENDATIONS

●Contact public health officials – In the United States, anthrax is an immediately notifiable disease, and clinicians should contact the state health department for assistance in diagnosis and treatment as soon as there is reasonable suspicion for anthrax. (See 'Public health reporting' above.)

●Overview of systemic anthrax treatment – Systemic anthrax includes gastrointestinal, injection, or inhalation anthrax; anthrax meningitis; cutaneous anthrax with systemic involvement; or bacteremia. All patients with systemic anthrax should be hospitalized, be evaluated for meningitis, and urgently receive combination intravenous (IV) antimicrobial therapy and antitoxin therapy. The latter includes the monoclonal antibodies raxibacumab and obiltoxaximab as well as anthrax immunoglobulin; in the United States, these antibody-based therapies are only available through the Centers for Disease Control and Prevention (CDC), usually by way of the state health department. (See 'Overview' above.)

●Treatment regimens for systemic anthrax

•Meningitis – For patients with systemic anthrax in whom meningitis is suspected or cannot be ruled out, we suggest IV therapy with ciprofloxacin plus meropenem plus linezolid (table 2) (Grade 2C). We also recommend antitoxin (Grade 1C). (See 'Meningitis' above.)

•Systemic anthrax without meningitis – For patients with systemic anthrax (eg, inhalation anthrax) without meningitis, we suggest IV therapy with ciprofloxacin plus either clindamycin or linezolid (table 3) (Grade 2C). We also recommend antitoxin (Grade 1C). (See 'Systemic anthrax without meningitis' above.)

•Duration of antimicrobial therapy – The initial antimicrobial regimen is continued until the patient is clinically stable and for at least three weeks (for meningitis) or two weeks (for systemic anthrax without meningitis). If aerosol exposure has occurred, the patient should then switch to single oral agent (table 1) to complete a postexposure prophylactic course to prevent relapse from surviving B. anthracis spores. (See 'Antimicrobial selection and duration' above and "Prevention of anthrax", section on 'Antimicrobials'.)

●Cutaneous anthrax without systemic involvement – Patients with cutaneous anthrax involving the head or neck and patients with cutaneous anthrax associated with extensive edema should be treated as patients with systemic involvement. Otherwise, patients with cutaneous anthrax without systemic involvement can receive a single oral antimicrobial agent. For nonpregnant adults, we suggest ciprofloxacin, doxycycline, levofloxacin, or moxifloxacin (Grade 2C). For pregnant, lactating, and postpartum women, we suggest ciprofloxacin (Grade 2C). For children, we suggest ciprofloxacin or, for amoxicillin-susceptible strains, amoxicillin (Grade 2C). For bioterrorism-associated cases and other cases in which an aerosol exposure is suspected, the duration of therapy is 60 days. For naturally acquired infection (eg, animals with anthrax, hides from animals with anthrax), the duration of therapy is 7 to 10 days. (See 'Cutaneous anthrax without systemic involvement' above.)

●Adjunctive therapies – Adjunctive therapies include glucocorticoids (for systemic anthrax, meningitis, or cutaneous anthrax with extensive edema involving the head and neck), early and aggressive pleural fluid drainage with chest tubes, and management of complications of meningitis (such as intracerebral hemorrhage or elevated intracranial pressure). (See 'Glucocorticoids' above.)

●Supportive care and monitoring – Standard sepsis care should be administered to patients with systemic anthrax, including IV fluids, vasopressors, blood products, and invasive hemodynamic monitoring as needed. (See 'Supportive care' above.)