Anthrax medical therapy: Difference between revisions
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==Overview== | ==Overview== | ||
Medical therapy of anthrax infection includes [[antibiotic]] and [[antitoxin]] drugs. These patients should be monitored at all times to evaluate the need for supportive care measures, such as hemodynamic support, [[mechanical ventilation]] | Medical therapy of anthrax infection includes [[antibiotic]] and [[antitoxin]] drugs. These patients should be monitored at all times to evaluate the need for supportive care measures, such as hemodynamic support, [[mechanical ventilation]], [[corticosteroids]] and procedures and surgical interventions in certain occasions. | ||
==Medical Therapy== | ==Medical Therapy== | ||
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* Evidence of anthrax [[meningitis]] | * Evidence of anthrax [[meningitis]] | ||
* [[Vasopressor]]-resistant [[shock]] | * [[Vasopressor]]-resistant [[shock]] | ||
===Procedures and Surgical Interventions=== | |||
Drainage of [[pleural fluid]] and [[ascites]] is believed to improve survival by reducing the [[toxin]] level and by decreasing mechanical lung compression. These data support the need for early and aggressive drainage of any clinically or radiographically apparent [[pleural effusions]]; [[chest tube]] drainage is recommended 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 and monitored for reaccumulation. | |||
==References== | ==References== | ||
Revision as of 17:58, 17 July 2014
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]
Overview
Medical therapy of anthrax infection includes antibiotic and antitoxin drugs. These patients should be monitored at all times to evaluate the need for supportive care measures, such as hemodynamic support, mechanical ventilation, corticosteroids and procedures and surgical interventions in certain occasions.
Medical Therapy
The treatment of anthrax infection includes antimicrobial and antitoxin agents. This treatment and postexposure prophylaxis differs from other bacterial infections because:[1]
- Production of toxin
- Potential antibiotic resistance
- Frequent occurrence of meningitis
- Presence of latent spores must be taken into account when selecting postexposure prophylaxis or a combination of antibiotics for treatment of anthrax
Hospitalized patients for systemic anthrax should be immediately treated with a combination of broad-spectrum intravenous antimicrobial drug treatment pending confirmatory test results because any delay may prove fatal.
Because meningitis and hemorrhagic brain parenchymal infection was observed in ≤50% of cases, meningitis must be considered in all cases of systemic anthrax. Therefore antibiotics to treat possible meningitis must have good penetration of the central nervous system (CNS).[1] Empiric therapy for anthrax in which anthrax meningitis is suspected or cannot be ruled out should include ≥3 antibiotics with activity against Bacillus anthracis, in which:[1]
- ≥1 drug should have bactericidal activity
- ≥1 should be a protein synthesis inhibitor
- All should have good CNS penetration
Given the high mortality rate associated with meningitis, 3 weeks of treatment for patients in whom meningitis could not be ruled out, is preferred. Because of the presence of a spore form of Bacillus anthracis, antibiotic therapy should be continued for 60 days to clear germinating organisms.[1]
Hospitalization is warranted for all patients with systemic cutaneous anthrax; gastrointestinal, injection, or inhalation anthrax; or anthrax meningitis or bacteremia.
Patients with systemic anthrax commonly have debilitating symptoms, followed first by transitory improvement and then by precipitous hemodynamic deterioration. Because of this potential for sudden decompensation, hospitalized patients should have careful hemodynamic monitoring.[2]
Antibiotic Treatment
Antimicrobial Treatment for Systemic Disease with Possible Meningitis
Antimicrobial Treatment for Systemic Disease If Meningitis Is Ruled Out
Follow-up Oral Treatment for Systemic Disease
Once patients with systemic illness who were exposed to aerosolized spores have completed initial combination treatment, they should be transitioned to single-agent oral treatment to prevent relapse from surviving Bacillus anthracis spores.
Treatment for Cutaneous Anthrax without Systemic Involvement
Antitoxins
An antitoxin should be added to combination antibiotic treatment for any patient for whom there is a high level of clinical suspicion for systemic anthrax. Given that systemic anthrax has a high case-fatality rate and the risk for antitoxin treatment appears to be low, the potential benefit achieved by adding antitoxin to combination antibiotic treatment outweighs the potential risk.
Currently there are 2 antitoxins in the CDC Strategic National Stockpile: raxibacumab and Anthrax Immune Globulin Intravenous (AIGIV). Both antitoxins inhibit binding of Protective Antigen (PA) to anthrax toxin receptors and translocation of the 2 primary toxins (Lethal Toxin (LT) and Edema Toxin (ET)) into cells.[1]
Raxibacumab
Raxibacumab is a recombinant, fully humanized, IgG1λ monoclonal antibody. It appeared safe and well tolerated in 333 healthy adults who received the recommended dose of 40 mg/kg.
Most adverse events were transient and mild to moderate in severity. Pruritis was noted in 2.1% of persons treated with raxibacumab and in none treated with placebo. Although raxibacumab has not been given to patients with systemic anthrax, it is FDA-approved for postexposure prophylaxis PEP.[1]
Anthrax Immune Globulin
AIGIV is a human polyclonal antiserum made from plasma of persons immunized with Anthrax Vaccine Absorbed (AVA), which might have some direct effect on Lethal Factor (LF) and Edema Factor (EF). It was evaluated in 74 healthy adult volunteers and appears safe and well tolerated at all doses tested.
The most frequently reported adverse events were headache pharyngolaryngeal pain, and nausea.
AIGIV is not FDA approved and could be made available under an Investigational New Drug protocol or an Emergency Use Authorization during a declared emergency.[1]
Supportive Treatment
Hemodynamic Support
Standard sepsis and septic shock guidelines should be followed for anthrax patients. Common complications of anthrax infections including microangiopathic hemolytic anemia, coagulopathy, thrombocytopenia, and hemorrhage must be aggressively managed, since they might pose contraindications to invasive central catheter placement.[3]
Fresh frozen plasma and plasmapheresis should be considered, and fibrinogen levels should be kept >100 mg/dL.
An echocardiogram might be needed to identify pericardial effusions.[4]
Mechanical Ventilation
In addition to the need for mechanical ventilation for respiratory distress or airway protection for persons with altered mental status, some patients with anthrax might require respiratory support for airway edema. Substantial edema with fatal outcome can occur with cutaneous lesions involving the head, neck, or thorax, and with oropharyngeal lesions.[5]
In inhalation anthrax, although respiratory failure is more consistent with reaccumulating pleural effusions than with adult respiratory distress syndrome, standard mechanical ventilator principles apply.[6] The need for ventilation in some patients and the duration of ventilation in others may be reduced by pleural space drainage.
Adjunctive Corticosteroids
There are limited data on steroid use for documented anthrax meningitis, however, adjunctive intravenous dexamethasone is the standard of care for patients with suspected bacterial meningitis and should be started at the time of initial antibiotic therapy to prevent neurologic sequelae.[7]
Adjunctive corticosteroids should be considered in patients who had a history of use of:[8][9]
- Endocrine
- Corticosteroid therapy
- Edema, especially of the head or neck
- Evidence of anthrax meningitis
- Vasopressor-resistant shock
Procedures and Surgical Interventions
Drainage of pleural fluid and ascites is believed to improve survival by reducing the toxin level and by decreasing mechanical lung compression. These data support the need for early and aggressive drainage of any clinically or radiographically apparent pleural effusions; chest tube drainage is recommended 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 and monitored for reaccumulation.
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults".
- ↑ ALBRINK WS, BROOKS SM, BIRON RE, KOPEL M (1960). "Human inhalation anthrax. A report of three fatal cases". Am J Pathol. 36: 457–71. PMC 1942218. PMID 13792449.
- ↑ Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM; et al. (2013). "Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012". Intensive Care Med. 39 (2): 165–228. doi:10.1007/s00134-012-2769-8. PMID 23361625.
- ↑ Jernigan JA, Stephens DS, Ashford DA, Omenaca C, Topiel MS, Galbraith M; et al. (2001). "Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States". Emerg Infect Dis. 7 (6): 933–44. doi:10.3201/eid0706.010604. PMC 2631903. PMID 11747719.
- ↑ Peck RN, Fitzgerald DW (2007). "Cutaneous anthrax in the Artibonite Valley of Haiti: 1992-2002". Am J Trop Med Hyg. 77 (5): 806–11. PMID 17984330.
- ↑ Artigas A, Bernard GR, Carlet J, Dreyfuss D, Gattinoni L, Hudson L; et al. (1998). "The American-European Consensus Conference on ARDS, part 2: Ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling. Acute respiratory distress syndrome". Am J Respir Crit Care Med. 157 (4 Pt 1): 1332–47. doi:10.1164/ajrccm.157.4.ats2-98. PMID 9563759.
- ↑ de Gans J, van de Beek D, European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators (2002). "Dexamethasone in adults with bacterial meningitis". N Engl J Med. 347 (20): 1549–56. doi:10.1056/NEJMoa021334. PMID 12432041. Review in: ACP J Club. 2003 May-Jun;138(3):60
- ↑ Sejvar JJ, Tenover FC, Stephens DS (2005). "Management of anthrax meningitis". Lancet Infect Dis. 5 (5): 287–95. doi:10.1016/S1473-3099(05)70113-4. PMID 15854884.
- ↑ Annane D, Bellissant E, Bollaert PE, Briegel J, Confalonieri M, De Gaudio R; et al. (2009). "Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review". JAMA. 301 (22): 2362–75. doi:10.1001/jama.2009.815. PMID 19509383.