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].
Important caveats — Treatment of patients suspected of having systemic anthrax should be started urgently and should include intravenous antimicrobial combination therapy, an antitoxin (raxibacumab 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.
●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.
●Antimicrobial therapy – It is important to include bactericidal agents because of their immediate killing effect and a protein synthesis inhibitor to suppress toxin production [1,4]. 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 [4-7]. B. anthracis is not susceptible to cephalosporins or trimethoprim-sulfamethoxazole [5-9]. 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 [1,10].
●Risk of meningitis – Meningitis and hemorrhagic brain infection has 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 [11,12]. (See 'Meningitis' below and "Clinical manifestations and diagnosis of anthrax", section on 'Meningitis'.)
●Reporting cases – Suspected cases of anthrax should be reported to the local or state health department immediately. (See 'Public health reporting' below.)
●Consulting public health officials — 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.
Antimicrobial therapy
Meningitis — In the treatment of anthrax meningitis, early and aggressive multidrug therapy is crucial due to the rapid progression and high mortality of the disease [13-15]. Empiric treatment for anthrax cases in which anthrax meningitis is suspected or 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), and all agents should have good central nervous system (CNS) penetration [1,2]. An antitoxin (raxibacumab or anthrax immunoglobulin) is also an essential part of the regimen. (See 'Antitoxins' below.)
For patients with systemic anthrax with suspected or proven 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: 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; in children ≥12 years of age: 30 mg/kg per day divided every 12 hours, not to exceed 600 mg/dose
First-line and alternative agents are reviewed in the following Table (table 1). The treatment of pregnant, lactating, and postpartum women is similar to the treatment of nonpregnant adults, except that ciprofloxacin is strongly preferred as one of the bactericidal agents [3]. In addition, at least one agent that crosses the placenta is recommended for pregnant women; such agents include ciprofloxacin, levofloxacin, meropenem, ampicillin, penicillin, clindamycin, and rifampin. Pharmacokinetic data indicate that penicillin, ampicillin, and carbapenems may require higher doses in pregnant and postpartum women than those recommended for nonpregnant adults [3,16].
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 (minimum inhibitory concentration [MIC] ≤0.5 mcg/mL [17]), 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 [2].
Linezolid is the preferred protein synthesis inhibitor [1]. It is favored over clindamycin because it is likely to have better CNS penetration [1,18]. 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]. In contrast, the AAP guidelines state that doxycycline can be used in children with suspected meningitis if the preferred agents are unavailable or are not tolerated [2].
For patients being treated for anthrax meningitis, IV combination therapy should be continued for at least two to 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.
Once the course of IV combination therapy has been completed, patients should be switched to single agent oral therapy to complete a 60-day course of antibiotics in order to prevent relapse from surviving B. anthracis spores [1]. Oral antimicrobial options are the same as those used for postexposure prophylaxis (table 2). (See "Prevention of anthrax", section on 'Antimicrobial regimen selection'.)
Adjunctive measures (including immunotherapy, glucocorticoids, and surgery) and supportive care are discussed below. (See 'Adjunctive therapies' below and 'Supportive care' below.)
Systemic anthrax without meningitis — Systemic anthrax is defined as anthrax meningitis; inhalation, injection, and gastrointestinal anthrax; and cutaneous anthrax with systemic involvement [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. An antitoxin (raxibacumab or anthrax immunoglobulin) is also an essential part of the regimen. (See 'Antitoxins' below.)
As noted above, all patients suspected of having systemic anthrax should undergo lumbar puncture to evaluate for meningitis unless it is contraindicated. Patients in whom meningitis has not been ruled out should receive a regimen intended for patients with anthrax meningitis, as outlined above. (See 'Meningitis' above.)
Treatment for patients with systemic anthrax (eg, inhalation anthrax) in whom meningitis has been ruled out should include at least two agents with activity against B. anthracis, at least one agent with bactericidal activity, and at least one protein synthesis inhibitor (table 3). If the B. anthracis strain is susceptible to penicillin (MIC ≤0.5 mcg/mL [17]), penicillin G is considered equivalent to the fluoroquinolone options for primary bactericidal treatment.
For adults with systemic anthrax and normal renal function in whom meningitis has been ruled out, we suggest IV therapy with [1,3]:
●Ciprofloxacin 400 mg every 8 hours PLUS
●Clindamycin 900 mg every 8 hours or linezolid 600 mg every 12 hours
For children with systemic anthrax in whom meningitis has been ruled out, we suggest IV therapy with [2]:
●Ciprofloxacin 30 mg/kg per day divided every 8 hours (not to exceed 400 mg/dose) or, for penicillin-susceptible strains (MIC ≤0.5 mcg/mL [17]), penicillin G 400,000 units/kg per day divided every 4 hours (not to exceed 4 million units/dose) PLUS
●Clindamycin 40 mg/kg per day divided every 8 hours (not to exceed 900 mg/dose)
First-line and alternative agents are reviewed in the following Table (table 3). The treatment of pregnant, lactating, and postpartum women is similar to the treatment of nonpregnant adults, except that ciprofloxacin is strongly preferred as one of the bactericidal agents [3]. In addition, at least one agent that crosses the placenta is recommended; such agents include ciprofloxacin, levofloxacin, meropenem, ampicillin, penicillin, clindamycin, and rifampin. Pharmacokinetic data indicate that penicillin, ampicillin, and carbapenems may require higher doses in pregnant and postpartum women than those recommended for nonpregnant adults [3,16].
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 to complete a 60-day course of antibiotics in order to prevent relapse from surviving B. anthracis spores [1]. Oral antimicrobial options are the same as those used for postexposure prophylaxis (table 2). (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]. Children who are slow to recover or in whom there is concern for persistent deep infection can be transitioned to oral therapy that includes both a bactericidal antimicrobial agent and a protein synthesis inhibitor to complete the initial two weeks of therapy. More detailed recommendations can be found in the text and in Appendix 5 of the American Academy of Pediatrics guidelines.
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) [13]. 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 [19,20]. 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 [21].
Adjunctive measures (including immunotherapy, 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 with one of the following agents:
●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 (MIC ≤0.5 mcg/mL [17]), penicillin VK 500 mg every 6 hours OR
•For amoxicillin-susceptible strains (MIC ≤0.12 mcg/mL), 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 (MIC ≤0.12 mcg/mL), amoxicillin 75 mg/kg per day divided every 8 hours (not to exceed 1 g/dose)
Alternatives include:
-<45 kg: 4.4 mg/kg per day divided every 12 hours (not to exceed 100 mg/dose)
-≥45 kg: 100 mg every 12 hours OR
•Clindamycin 30 mg/kg per day divided every 8 hours (not to exceed 600 mg/dose) OR
-<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 (MIC ≤0.5 mcg/mL [17]), 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 bioterrorism-associated cases and cases in which an aerosol exposure is suspected, the duration of therapy is 60 days [1]. For naturally acquired infection (eg, animals with anthrax, hides from animals with anthrax), the duration of therapy is 7 to 10 days.
Antitoxins — In addition to antibacterial agents with activity against B. anthracis, a key component of therapy is an adjunctive agent with antitoxin effects [22]. Because of the lethality of the disease and the potential benefit, an antitoxin should be included as soon as possible in the treatment regimen for any patient suspected to have systemic anthrax [1]. These agents have their greatest benefit when used early in the course of disease [23].
Raxibacumab and obiltoxaximab, monoclonal antibodies, and anthrax immunoglobin derived from human plasma inhibit binding of protective antigen and translocation of the two primary toxins, lethal toxin (LT) and edema toxin, into cells [1]. Supplies of raxibacumab and obiltoxaximab are held in the United States Strategic National Stockpile for use by the CDC in the event of an anthrax emergency. Clinicians should consult the CDC if these agents are indicated.
Animal origin antiserum was used with some success in the treatment of anthrax prior to the advent of antimicrobial therapy [24-26]. 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 [13].
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 [27,28]. In 2012, raxibacumab was approved by the US Food and Drug Administration for the treatment of inhalation anthrax [29].
Raxibacumab is given as a single dose following premedication with diphenhydramine; dosing recommendations are as follows [30]:
●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 evaluated only in animals since 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 [31]. Common adverse effects in 326 healthy humans included rash, extremity pain, pruritus, and drowsiness [29].
In one trial, rabbits and monkeys were exposed to 200 times the median lethal dose of aerosolized B. anthracis spores and were monitored for the onset of signs of illness [27]. Animals with detectable protective antigen in the serum, an increase in temperature, or both, received a single intravenous dose of raxibacumab (20 mg/kg or 40 mg/kg) or placebo. The primary endpoint was survival at 14 days in rabbits and survival at 28 days in monkeys. Rabbits that received 40 mg/kg of raxibacumab were significantly more likely to survive than those that received placebo (44 percent versus 0 percent). Likewise, monkeys that received 40 mg/kg of raxibacumab were more likely to survive than those that received placebo (64 percent versus 0 percent). The 20 mg/kg dose was also associated with improved survival in both rabbits and monkeys. In the same report, raxibacumab was well tolerated in humans who were given a single 40 mg/kg dose. It was also effective for the prevention of anthrax in rabbits and monkeys. (See "Prevention of anthrax", section on 'Monoclonal antibodies'.)
In another trial, 40 mechanically ventilated dogs who were challenged with anthrax LT were given no treatment, hemodynamic support alone (fluids and norepinephrine), raxibacumab alone (administered at the start of the LT infusion or 9 or 12 hours later), or combination therapy with hemodynamic support plus raxibacumab [28]. Among the animals that received no treatment, all eight died, compared with six of eight animals who received hemodynamic support alone. In contrast, all five animals that received raxibacumab at the start of the LT infusion survived; however, only two of three animals that received raxibacumab at nine hours survived, and none of four animals that received raxibacumab at 12 hours survived. The animals that received both raxibacumab and hemodynamic support had the best outcomes, regardless of the delay in raxibacumab administration. Of the animals that received combined treatment, four of five animals that received raxibacumab at the start of the LT infusion survived, three of three animals that received raxibacumab at nine hours survived, and four of five animals that received raxibacumab at 12 hours survived.
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) [32,33]. The evidence supporting its efficacy comes from studies in animal models of inhalational anthrax. It does not cross the blood-brain barrier and does not treat anthrax meningitis.
Obiltoxaximab is given as a single dose following premedication with diphenhydramine; dosing recommendations are as follows [33]:
●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 evaluated only in animals since 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 [33]. Obiltoxaximab was discontinued in 8 of 320 individuals (2.5 percent) due to hypersensitivity reactions or anaphylaxis.
The efficacy of obiltoxaximab has been evaluated in studies of macaque monkeys and rabbits with inhalational anthrax [33]. Animals were challenged with aerosolized B. anthracis spores and were treated with obiltoxaximab or placebo after exhibiting signs or symptoms of anthrax. Among the animals that became bacteremic, those that received obiltoxaximab had significantly higher 28-day survival rates than the animals treated with placebo; survival rates ranged from 31 to 93 percent in the studies of animals that received obiltoxaximab compared with 0 to 6 percent with placebo. When obiltoxaximab was given in combination with antimicrobial therapy (levofloxacin, ciprofloxacin, doxycycline), it resulted in higher survival rates that obiltoxaximab alone.
Anthrax immunoglobulin — Anthrax immunoglobulin derived from the plasma of Anthrax Vaccine Adsorbed (AVA)-immunized persons is available from the CDC or through state and local health departments for the treatment of inhalation anthrax, in combination with antimicrobial therapy [34,35]. 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 [35]. 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 use of anthrax immunoglobulin for the treatment of inhalation anthrax has been best studied in animals. Rabbits exposed to an aerosolized dose of 200 times the LD50 of B. anthracis spores and treated with anthrax immunoglobulin at the time of protective antigenemia had 26 percent survival compared with 2 percent survival in animals given intravenous immunoglobulin. Of monkeys exposed to 200 times the LD50 of B. anthracis spores, survival with anthrax immunoglobulin was 36 to 70 percent, depending on the dose, compared with 0 percent in those who received placebo [35]. In another study in which anthrax immunoglobulin was added to levofloxacin in rabbits with systemic anthrax, there was a trend toward better survival in the rabbits who received anthrax immunoglobulin plus levofloxacin compared with those who received intravenous immunoglobulin plus levofloxacin, but only when treatment was delayed to 60 hours or later following anthrax exposure [35,36]. For animals treated earlier, survival was similar in the two groups. The number of animals evaluated was small, so it is difficult to draw conclusions about efficacy, although a post-hoc analysis suggested that animals with a moderate level of antigenemia benefited.
The safety of anthrax immunoglobulin was tested in 72 healthy human volunteers [35]. 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 [37,38]. 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 [15]. 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 [13]. Drainage of both pleural fluid and ascites is thought to improve survival by reducing the toxin level and by decreasing mechanical lung compression [1,11]. 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.
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 [11]. 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 [39].
Patients who develop headache, confusion, or other neurologic symptoms should undergo head imaging and 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 and public health laboratory 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 20th 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
●Sporadic cases and outbreaks of naturally occurring anthrax continue to occur worldwide, although they are rare in developed nations. 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. Anthrax is a reportable disease and immediate notification should be made to the local or state health department and public health laboratory even if there is only clinical or laboratory suspicion of anthrax or exposure to Bacillus anthracis. (See 'Introduction' above and 'Public health reporting' above.)
●Meningitis and hemorrhagic brain infection has been observed in up to one-half of systemic anthrax cases. Unless it is contraindicated, all patients suspected of having inhalation anthrax should undergo lumbar puncture to evaluate for meningitis. Other important caveats are discussed above. (See 'Important caveats' above.)
●Treatment of patients suspected of having systemic anthrax should be started urgently and should include intravenous (IV) antimicrobial combination therapy, an antitoxin (raxibacumab, obiltoxaximab, or anthrax immunoglobulin), drainage of pleural effusions, supportive care, and consideration of adjunctive glucocorticoids. When selecting an antimicrobial regimen, 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. (See 'Important caveats' above.)
●For patients with systemic anthrax in whom meningitis is suspected or cannot be ruled out, we suggest ciprofloxacin plus meropenem plus linezolid (table 1) (Grade 2C). We also recommend that an antitoxin be administered to such patients (Grade 1C). Antitoxins include the monoclonal antibodies, raxibacumab, obiltoxaximab, and anthrax immunoglobulin derived from human plasma; these agents are available from the United States Centers for Disease Control and Prevention (CDC). (See 'Meningitis' above.)
●For patients with systemic anthrax (eg, inhalation anthrax) without meningitis, we suggest one of the antimicrobial regimens reviewed above and in the following Table (table 3) (Grade 2C). We also recommend that an antitoxin be administered to such patients (Grade 1C). Raxibacumab, obiltoxaximab, and anthrax immunoglobulin are available from the CDC. (See 'Systemic anthrax without meningitis' above.)
●Patients with systemic anthrax in whom meningitis is suspected or cannot be ruled out should be treated with IV antimicrobial therapy for at least two to three weeks and until clinically stable, whichever is longer. Patients with systemic anthrax without meningitis should be treated with IV therapy for at least two weeks and until clinically stable, whichever is longer. Once the course of IV combination therapy has been completed, patients should be switched to single agent oral therapy to complete a 60-day course of antibiotics in order to prevent relapse from surviving B. anthracis spores. Oral antimicrobial options are the same as those used for postexposure prophylaxis (table 2). (See 'Systemic anthrax without meningitis' above.)
●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 should receive oral antimicrobial therapy with a single agent. For nonpregnant adults, we suggest ciprofloxacin or doxycycline or 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 (minimum inhibitory concentration ≤0.12 mcg/mL), 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.)
●Glucocorticoids should be considered as adjunctive therapy for patients with systemic anthrax, meningitis, or cutaneous anthrax with extensive edema involving the head and neck. (See 'Glucocorticoids' above.)
●Pleural fluid should be drained early and aggressively; chest tubes are preferred over thoracentesis because many effusions require prolonged drainage. (See 'Pleural fluid drainage' above.)
●Standard sepsis care should be administered to patients with systemic anthrax, including intravenous fluids, vasopressors, blood products, and invasive hemodynamic monitoring as needed. (See 'Supportive care' above.)
●Anthrax postexposure prophylaxis is discussed separately. (See "Prevention of anthrax".)
