Anthrax medical therapy: Difference between revisions

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Revision as of 15:53, 17 July 2014

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

The treatment of anthrax infection includes antimicrobial and antitoxin agents. This treatment and postexposure prophylaxis differs from other bacterial infections because:

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).

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 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.

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.

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 and treatment for anthrax under the Animal Rule Summary

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.

References

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 __NOTOC__
 {{Anthrax}}
-{{CMG}}
+{{CMG}}; {{AE}} {{JS}}
 ==Overview==
 ==Medical Therapy==
-Direct person-to-person spread of anthrax is extremely unlikely; but a patient’s clothing and body may be contaminated with anthrax spores. Effective decontamination of people can be accomplished by a thorough wash down with anti-microbe effective soap and water. Waste water should be treated with bleach or other anti-microbal agent. Effective decontamination of articles can be accomplished by boiling contaminated articles in water for 30 minutes or longer and using common disinfectants. Chlorine is effective in destroying spores and vegetative cells on surfaces. Burning clothing is also effective.  After decontamination, there is no need to immunize,  treat or isolate contacts of persons ill with anthrax unless they also were also exposed to the same source of infection . Early antibiotic treatment of anthrax is essential–delay seriously lessens chances for survival.  Treatment for anthrax infection and other bacterial infections includes large doses of intravenous and oral [[antibiotic]]s, such as fluoroquinolones, like [[ciprofloxacin]] (cipro), [[doxycycline]], [[erythromycin]], [[vancomycin]]  or [[penicillin]]. In possible cases of  inhalation anthrax exposure to unvaccinated personnel early [[prophylaxis|antibiotic prophylaxis]] treatment is crucial to prevent possible death. If death occurs from anthrax the body should be isolated to prevent possible spread of anthrax germs. Burial does not kill anthrax spores.
+The treatment of [[anthrax]] infection includes [[antimicrobial]] and [[antitoxin]] agents. This treatment and postexposure [[prophylaxis]] differs from other [[bacterial infections]] because:
+* Production of [[toxin]]
-If a person is suspected as having died from anthrax every precaution should be taken to avoid skin contact with the potentially contaminated body and fluids exuded through natural body openings. The body should be put in strict quarantine. A blood sample taken in a sealed container and analyzed in an approved lab should be used to ascertain if anthrax is the cause of death. Microscopic visualisation of the encapsulated bacilli, usually in large numbers, in a blood smear stained with polychrome methylene blue (McFadyean reaction) is fully diagnostic. Full isolation of the body is important to prevent possible contamination of others. Protective, impermeable clothing and equipment such as rubber gloves, rubber apron, and rubber boots with no perforations should be used when handling the body. No skin, especially if it has any wounds or scratches, should be exposed. Disposable personal protective equipment is preferable, but if not available, decontamination can be achieved by washing any exposed equipment in hot water, bleach and detergent.  Disposable personal protective equipment and filters should be burned and buried. Bacillus anthracis bacillii range from 0.5-5.0 μm in size. Anyone working with anthrax in a suspected or confirmed victim should wear respiratory equipment capable of filtering this size of particle or smaller. The US National Institute for Occupational Safety and Health (NIOSH) and Mine Safety and Health Administration (MSHA) approved high efficiency-respirator, such as a half-face disposable respirator with a high-efficiency particulate air (HEPA) filter, is recommended. All possibly contaminated bedding or clothing should be isolated in double plastic bags and treated as possible bio-hazard waste. The victim should be sealed in an airtight body bag. Dead victims that are opened and not burned provide an ideal source of anthrax spores. Cremating victims is the preferred way of handling body disposal. No embalming or autopsy should be attempted without a fully equipped biohazard lab and trained and knowledgable personnel.
+* Potential [[antibiotic resistance]]
+* Frequent occurrence of [[meningitis]]
-Delays of only a few days may make the disease untreatable and treatment should be started even without symptoms if possible contamination or exposure is suspected. Animals with anthrax often just die without any apparent symptoms.  Initial symptoms may resemble a common cold – sore throat, mild fever, muscle aches and malaise. After a few days, the symptoms may progress to severe breathing problems and shock and ultimately death. Death can occur from about two days to a month after exposure with deaths apparently peaking at about 8 days after exposure. <ref> ANTHRAX, the investigation of a Deadly Outbreak, Jeanne Guillemin, University of California Press, 1999, ISBN 0=520-22917-7, chart of Russian deaths at Sverdlovsk, 1979, pg 27 </ref> Antibiotic-resistant strains of anthrax are known.
+* 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.
-Aerial spores can be trapped by a simple HEPA or P100 filter. Inhalation of anthrax spores can be prevented with a full-face mask using appropriate filtration.  Unbroken skin can be decontaminated by washing with simple soap and water. All of these procedures do not kill the spores which are very hard to kill and require extensive treatment to eradicate them. Filters, clothes, etc. exposed to possible anthrax contaminated environments should be treated with chemicals or destroyed by fire to minimize the possibility of spreading the contamination.
-==Antibiotics==
+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).
-Early antibiotic treatment of anthrax is essential; and delay in their administration significantly lessens the chances for survival.  Treatment for anthrax infection and other bacterial infections includes large doses of intravenous and oral antibiotics, such as [[fluoroquinolone]]s ([[ciprofloxacin]]), [[doxycycline]], [[erythromycin]], [[vancomycin]], or [[penicillin]]. FDA-approved agents include ciprofloxacin, doxycycline, and penicillin.<ref name="urlCDC Anthrax Q & A: Treatment">{{cite web |url=http://emergency.cdc.gov/agent/anthrax/faq/treatment.asp |title=CDC Anthrax Q & A: Treatment|accessdate=4 April 2011}}</ref>
-In possible cases of inhalation anthrax, early [[prophylaxis|antibiotic prophylaxis]] treatment is crucial to prevent possible death.
+[[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 drug should have bactericidal activity
- If death occurs from anthrax, the body should be isolated to prevent possible spread of anthrax germs. Burial does not kill anthrax spores.
+* ≥1 should be a protein synthesis inhibitor
-In recent years, many attempts have been made to develop new drugs against anthrax, but existing drugs are effective if treatment is started soon enough.
+* 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.
 ==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.