Anthrax Post-Exposure Prophylaxis

Description

Provides information for treating patients greater than or equal to 18 years old exposed to anthrax within the past 60 days, who do not have anthrax. It is divided into two parts:
Part #1- For patients that may be symptomatic, it flags the need to conduct a full diagnostic evaluation to rule out anthrax before proceeding with post-exposure prophylaxis (PEP) 
Part #2 - For patients who are asymptomatic (not displaying signs and symptoms of anthrax), it provides recommended PEP regimen

Artifact Type
Creation Date
Version
0.2
Status
Experimental
True

Artifact Creation and Usage

Contributors

The MITRE Corporation

License
IP Attestation The author asserts that this artifact has been developed in compliance with the intellectual property rights attributed to the source material.
Copyrights

© 2019 The MITRE Corporation. All Rights Reserved. Approved for Public Release: 19-2048. Distribution Unlimited.

Repository Information
Approval Date
Publication Date
Last Review Date
Knowledge Level

Structured code that is interpretable by a computer (includes data elements, value sets, logic)

Purpose and Usage
Purpose

Provides clinicians with information for quickly assessing individuals exposed to anthrax unrelated to occupational exposure, for example in bioterrorism events, and provides the recommended post-exposure prophylaxis (PEP) regimen for asymptomatic patients. Includes immediate treatment with antimicrobials and vaccine and follow-up administration of subsequent vaccines to complete the recommended 3-dose vaccination series.

Intended Population

This CDS is intended for symptomatic adults ≥18 years of age exposed to anthrax unrelated to occupational exposure.

Usage

Intended for use by clinicians caring for individuals ≥18 years of age in an outpatient setting.

Cautions
1. BioThrax (anthrax vaccine) is indicated for active immunization for the prevention of disease caused by Bacillus anthracis in persons 18–65 years of age when administered in conjunction with recommended antimicrobial drugs. It should be avoided by individuals with a history of anaphylactic or anaphylactic-like reaction following a previous dose of BioThrax or any component of the vaccine. 
2. f BioThrax is used during pregnancy, or if the patient becomes pregnant during the vaccination series, the patient should be apprised of the potential hazard to the fetus. 
3. This represents the combination of multiple guidelines which are periodically updated with input from CDC anthrax subject matter experts (SMEs). This artifact was created from multiple guidelines and data provided and verified with CDC anthrax SMEs in 2018.
4. An antimicrobial medication is displayed as an option for providers even if the patient has a documented allergy to that medication, with an alert to indicate the allergy. In the event of anthrax exposure due to a bioterrorism event, the allergy might be not an absolute contraindication to a first-line medication regimen. Clinicians should evaluate the allergy prior to determining the appropriate antimicrobial medication.
5. Included is a list of potential signs and symptoms of anthrax derived from the CDC Public Health Information Network Vocabulary Access and Distribution System (PHIN VADS) value set 'PHVS_SignsSymptoms_Anthrax' and from CDC published anthrax guidelines. The list is not exhaustive; key signs and symptoms to alert the provider that the patient may be symptomatic to prompt further diagnostic evaluation are included. The artifact is intended for asymptomatic patients.
6. Individuals who have had a full BioThrax vaccine series for pre-exposure prophylaxis might need a booster dose following anthrax exposure.  This CDS artifact does not include booster doses of BioThrax for persons who have completed a pre-exposure vaccination series.    
Supporting Evidence
Source Description

Centers for Disease Control and Prevention anthrax guidelines and Advisory Committee on Immunization Practices anthrax vaccination guidelines

1. BioThrax Anthrax Vaccine Adsorbed.  Retrieved from: http://www.biothrax.com/whatisbiothrax/

2. Ciprofloxacin for Post-Exposure Prophylaxis of Anthrax.  Emergency Use Instructions for Healthcare Providers (2017)

3. Doxycycline for Post-Exposure Prophylaxis of Anthrax.  Emergency Use Instructions for Healthcare Providers. (2017)

4. Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults. (2014)

5. Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults Technical Report. (2014)

6. Special Considerations for Prophylaxis for and Treatment of Anthrax in Pregnant and Postpartum Women. (2014)

7. Special Considerations for Prophylaxis for and Treatment of Anthrax in Pregnant and Postpartum Women Technical Report. (2014)

8. Use of Anthrax Vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP). (2009)

9.  Public Health Information Network Vocabulary Access and Distribution System (PHIN VADS), PHVS Anthrax Signs and Symptoms (PHVS_SignsSymptoms_Anthrax)

References

1. Emergent BioSolutions. (2016). BioThrax Anthrax Vaccine Adsorbed. Retrieved from http://www.biothrax.com/whatisbiothrax/.

2. Centers for Disease Control and Prevention. (2017). Ciprofloxacin for Post-Exposure Prophylaxis of Anthrax.  Emergency Use Instructions for Healthcare Providers. Retrieved from https://www.cdc.gov/anthrax/medical-care/cipro-eui-hcp.html7.

3. Centers for Disease Control and Prevention. (2017). Doxycycline for Post-Exposure Prophylaxis of Anthrax.  Emergency Use Instructions for Healthcare Providers. Retrieved from https://www.cdc.gov/anthrax/medical-care/doxy-eui-hcp.html.

4. Centers for Disease Control and Prevention. Public Health Information Network Vocabulary.  PHVS_SignsSymptoms_Anthrax (2009). 

5. Hendricks, K.A., Wright, M.E., Shadomy, S.V., Bradley, J.S., Morrow, M.G., Pava, A.T., Rubinstein, E. , Holty, J.C., Messonnier, N.E., Smith, T.L. Peski, N., Teadwell, T.A., Bower, W.A. & the Workgroup on Anthrax Clinical Guidelines. (2014). Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults. Emerg Infect Dis. 20(20). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901462/?report=printable.

6. Meanye-Delman D, Zotti ME, Creanga AA, et al. Special Considerations for Prophylaxis for and Treatment of Anthrax in Pregnant and Postpartum Women. Emerg Infect Dis 2014; 20 (2); e1–e6.

7. Meanye-Delman D, Zotti ME, Creanga AA, et al. Special Considerations for Prophylaxis for and Treatment of Anthrax in Pregnant and Postpartum Women. Technical Report. Emerg Infect Dis 2014; 20 (2); e1–e6."

8. Public Health Information Network Vocabulary Access and Distribution System (PHIN VADS). (2009)  PHVS_SignsSymptoms_Anthrax.  (OID 2.16.840.1.114222.4.11.3212). Retrieved from https://phinvads.cdc.gov/vads/SearchAllVocab_selectVocabType.action?vocabTypeParam=VALUE_SET.

9.Wright, J.G., Quinn, C.P., Shadomy, S., Messonnier, N., and the Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Bacterial Zoonosis Branch, National Center for Zoonotic, Vectorborne, and Enteric Diseases (2010). Morbidity and Mortality Weeklly Report Recommendations and Reports.   Use of Anthrax Vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009.   July 23, 2010 / 59(RR06);1-30. Retrieved from https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5906a1.htm.

Artifact Representation
Triggers

Part #1:  Exposed to anthrax 
Part #2:  Exposed to anthrax and asymptomatic

Inclusions

Part #1:  Individuals ≥18 years old with documented exposure to anthrax within the past 60 days, without a diagnosis of anthrax, and may be symptomatic 
Part #2:  Individuals ≥18 years old with documented exposure to anthrax within the past 60 days, without a diagnosis of anthrax, and who are asymptomatic 

Exclusions

Part #1:  Individuals <18 years old, with no documented exposure to anthrax, exposure greater than 60 days prior, a diagnosis of anthrax, or who are asymptomatic
Part #2:  Individuals <18 years old, with no documented exposure to anthrax, exposure greater than 60 days prior, a diagnosis of anthrax, or who are symptomatic  

Interventions and Actions
Interventions   1.  If patient is greater than or equal to 18 years of age and patient has been exposed to anthrax within the past 60 days (# of days between date of exposure and current date)
Intervention: Display Alert: “If patient has signs or symptoms consistent with anthrax, conduct a full diagnostic evaluation for anthrax. Signs and symptoms of anthrax include fever, chills, headache, malaise, nausea, vomiting, diarrhea, abdominal pain, diaphoresis, anorexia, nonproductive cough, difficulty breathing, dyspnea, stridor, hypoxemia, hypotension, shock, cyanosis, chest pain, lymphadenopathy, cutaneous ulcer and black eschar.  If patient has NO signs or symptoms consistent with anthrax, document “The patient is asymptomatic."
 
2.  If patient is greater than or equal to 18 years of age and patient has been exposed to anthrax within the past 60 days (# of days between date of exposure and current date) and is asymptomatic
        (2.A.)  If patient is has an existing prescription for ciprofloxacin, doxycycline, levofloxacin, moxifloxacin , or clindamycin
Intervention
                    IF ciprofloxacin, Display “The patient has an active prescription for ciprofloxacin.  Evaluate the dosage and duration to ensure a 60-day regimen of appropriate antibiotic post-anthrax exposure: Ciprofloxacin 500 mg by mouth every 12 hours for 60 days"
                    IF doxycycline , Display “The patient has an active prescription for doxycycline.  Evaluate the dosage and duration to ensure a 60-day regimen of appropriate antibiotic post-anthrax exposure: Doxycycline 100 mg by mouth every 12 hours for 60 days”
                    IF levofloxacin, Display “The patient has an active prescription for levofloxacin.  Evaluate the dosage and duration to ensure a 60-day regimen of appropriate antibiotic post-anthrax exposure: Levofloxacin, 750 mg by mouth once daily for 60 days.”
                    IF moxifloxacin, Display “The patient has an active prescription for Moxifloxacin.  Evaluate the dosage and duration to ensure a 60-day regimen of appropriate antibiotic post-anthrax exposure: “Moxifloxacin 400 mg by mouth once daily for 60 days.“
                    IF clindamycin, Display “The patient has an active prescription for clindamycin.  Evaluate the dosage and duration to ensure a 60-day regimen of appropriate antibiotic post-anthrax exposure: Clindamycin 600 mg by mouth every 8 hours for 60 days”
       (2.B.)  If patient is pregnant AND if patient is allergic to ciprofloxacin  OR doxycycline
Intervention:

                  Display “ Potential patient allergy to ciprofloxacin. Confirm allergy status.”  AND/OR “ Potential patient allergy to doxycycline. Confirm allergy status.” 
                  IF NO, display “Confirm no known allergies.”
                  AND display “Options for treatment, depending on allergies, include first choice ciprofloxacin 500 mg by mouth every 12 hours for 60 days with full glass of water. Provide patient education on medications. CONTRAINDICATIONS: Diagnosis of myasthenia gravis and taking tizanidine (Zanaflex). CAUTIONS: If patient is taking  blood thinners, oral antidiabetic drugs, seizure drugs, theophylline, drugs that prolong QT interval, duloxetine (Cymbalta), zolpidem (Ambien), clozapine or any other drug that may interact and cause serious side effects, consider another antibiotic regimen. ADDITIONAL INSTRUCTIONS:  Pregnant women at risk for inhalation anthrax should receive antimicrobial drug therapy  regardless of pregnancy trimester.
                  OR “Options for treatment, depending on allergies, include second choice doxycycline 100 mg by mouth every 12 hours for 60 days with full glass of water. Provide patient education on medications. CAUTION: If patient is taking blood thinners, seizure drugs, or any other drug that may interact and cause serious side effects, consider another antibiotic regimen. ADDITIONAL INSTRUCTIONS:  Pregnant women at risk for inhalation anthrax should receive antimicrobial drug therapy  regardless of pregnancy trimester.
 
 
             
     (2.C.)  If patient is not pregnant AND if patient is allergic to ciprofloxacin OR doxycycline
Intervention:  
                 Display “ Potential patient allergy to ciprofloxacin. Confirm allergy status.”  AND/OR “ Potential patient allergy to doxycycline. Confirm allergy status.” 
                  IF NO, display “Confirm no known allergies.”
                  AND display “Options for treatment, depending on allergies, include ciprofloxacin 500 mg by mouth every 12 hours for 60 days with full glass of water. Provide patient education on medications. CONTRAINDICATIONS: Diagnosis of myasthenia gravis and taking tizanidine (Zanaflex). CAUTIONS: If patient is taking  blood thinners, oral antidiabetic drugs, seizure drugs, theophylline, drugs that prolong QT interval, duloxetine (Cymbalta), zolpidem (Ambien), clozapine or any other drug that may interact and cause serious side effects, consider another antibiotic regimen.
           OR “Options for treatment, depending on allergies, include doxycycline 100 mg by mouth every 12 hours for 60 days with full glass of water. Provide patient education on medications. CAUTION: If patient is taking blood thinners, seizure drugs, or any other drug that may interact and cause serious side effects, consider another antibiotic regimen.
       (2.D.)  For all patients, If patient is allergic to levofloxacin OR moxifloxacin OR clindamycin
Intervention: 
                 Display “Potential patient allergy to levofloxacin. Confirm allergy status.” AND/OR “Potential patient allergy to moxifloxacin. Confirm allergy status.” AND/OR   "Potential patient allergy to clindamycin. Confirm allergy status.”
                  IF NO: “Confirm no known allergies.”
                  AND Display “If patient allergic to ciprofloxacin or doxycycline, second-tier antibiotics include the following options, depending on allergies:"
                  AND Display “Levofloxacin 750 mg by mouth once daily for 60 days. ADDITIONAL INSTRUCTIONS:  Pregnant women at risk for inhalation anthrax should receive antimicrobial drug therapy regardless of pregnancy trimester.” 
                  OR Display “Moxifloxacin 400 mg by mouth once daily for 60 days. ADDITIONAL INSTRUCTIONS:  Pregnant women at risk for inhalation anthrax should receive antimicrobial drug therapy regardless of pregnancy trimester.“
                  OR Display "Clindamycin 600 mg by mouth every 8 hours for 60 days. ADDITIONAL INSTRUCTIONS:  Pregnant women at risk for inhalation anthrax should receive antimicrobial drug therapy regardless of pregnancy trimester.”
               AND IF YES TO ALL – “Consider allergies and alternative antibiotic regimens.”
       (2.E.)  For all patients, if patient is allergic to BioThrax
Intervention: 
                  Display “Potential patient allergy to BioThrax (anthrax vaccine). Assess for BioThrax vaccine allergy. Epinephrine solution (1:1000) should be available for immediate use in the event that an anaphylactic reaction occurs."
                   IF NO, display "Confirm no known allergies.”

Rationale: BioThrax (anthrax vaccine) is contraindicated for persons who have experienced an anaphylactic reaction after a previous dose of BioThrax or any of the vaccine components.

  (2.F.)  For all patients, if patient is allergic to latex
Intervention: 
                 Display “Patient has a history of latex allergy. The stopper of the BioThrax (anthrax vaccine) vial contains latex .  Confirm allergy status. Epinephrine solution (1:1000) should be available for immediate use in the event that an anaphylactic reaction occurs."
                  IF NO, display "Confirm no known allergies.”

Rationale: The stopper of the BioThrax (anthrax vaccine) vial contains natural rubber latex and may cause allergic reactions in latex-sensitive individuals
      (2.G.)  For all patients
               (2.G.1) IF an anthrax vaccination date is missing OR IF there is a missing or non-sequential anthrax vaccination
Intervention: Display "Potential BioThrax vaccine series problem(s) identified. A vaccine in the recommended series might be missing or a vaccination date might be missing. Review BioThrax vaccine series history."
               (2.G.2) IF Third anthrax vaccination OR fourth anthrax vaccination is documented
Intervention:  Stop
               (2.G.3)  IF Second anthrax vaccination is documented AND Procedure date minus current date is >14 days
Intervention:  Display “Administer BioThrax 0.5 mL subcutaneous and document third anthrax vaccination.”
               (2.G.4)  IF First anthrax vaccination is documented AND Procedure date minus current date is >14 days 
Intervention:  Display “Administer BioThrax 0.5 mL subcutaneous and document second anthrax vaccination.”
               (2.G.5)  IF not 
Intervention:  Display “Administer BioThrax 0.5 mL subcutaneous and document first anthrax vaccination.”
 
  Rationale:  In 2009, the US Advisory Committee on Immunization Practices recommended in addition to antimicrobial therapy, a   3-dose series of Anthrax Vaccine Adsorbed (AVA) BioThrax (Emergent BioSolutions Inc., Rockville, MD, USA) for long-term protection after exposure to anthrax  in individuals without any previous vaccine.  After exposure to aerosolized B. anthracis spores, antimicrobial therapy should be initiated as soon as possible. Ideally, the first dose of vaccine should be administered within 10 days.   ACIP recommends a post exposure regimen of 60 days of appropriate antimicrobial prophylaxis (covered previously) combined with 3 subcutaneous doses of AVA (administered at 0, 2, and 4 weeks post exposure) as the most effective protection against inhalation anthrax for previously unvaccinated persons aged ≥18 years who have been exposed to aerosolized B. anthracis spores. In general, the peak serologic response to anthrax vaccine occurs 10–14 days after the third dose. ( Use of Anthrax Vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices pg. 14).  Additionally, the Advisory Committee on Immunization Practices subsequently reviewed all safety data available as of March 2008, including the final results of a retrospective study, and concluded that AVA is safe to administer to anthrax-exposed women during pregnancy. In the setting of an anthrax event that poses a high risk for exposure to aerosolized B. anthracis spores, pregnancy is neither a precaution nor a contraindication to vaccination. Pregnant women at risk for inhalation anthrax should receive AVA and antimicrobial drug therapy regardless of pregnancy trimester (Pregnancy guideline 2014)  
Actions DOCUMENT    Asymptomatic if no signs and symptoms of anthrax
DOCUMENT    Reason(s) for prescribing antimicrobials if patient has a current prescription for a recommended antimicrobial but dosage and duration are not consistent with recommendations 
PRESCRIBE      Antimicrobial therapy
DOCUMENT    Antimicrobial therapy prescribed indicating the dosage and duration
ADMINISTER   BioThrax vaccine
DOCUMENT    Administration of BioThrax as the first, second or third dose
PROVIDE          Patient education materials on medications
Testing Experience
Pilot Experience

This artifact was not tested in a live clinical setting, however it was tested via the process outlined below:

The Anthrax PEP CQL was written using a test-driven development (TDD) approach [1]. With TDD, an iterative approach is taken whereby executable tests are written before the corresponding functionality exists in the software. These tests naturally fail at first, and only pass when enough software has been written to implement the functionality under test. Software written using a TDD approach is said to have fewer bugs since only enough software is written to ensure the desired functionality is implemented.


An automated testing framework written in Node.js [2] has been used to support a TDD approach of the Anthrax PEP CQL. This framework accepts test cases specified in YAML (a recursive acronym that expands to YAML Ain’t Markup Language) [3]. Each test is specified in terms of an input synthetic patient record as well as the expected output from the CQL. The framework automatically loads each test, runs the CQL against the input synthetic patient records, and compares the actual and expected outputs from the CQL. If the actual and expected outputs from the CQL match, the test passes. If the actual and expected outputs do not match, the test fails.


Sixty-one automated tests were developed in the process of writing the Anthrax PEP CQL. Each test has been designed against specific aspects of the Anthrax PEP CQL. For example, the first test written input a synthetic patient who was older than 18 years of age, and the expected output required that the CQL correctly determine that the patient was indeed older than 18. The 61 YAML test files are included in a zip file entitled “Anthrax_Post_Exposure_Prophylaxis_FHIRv102_Tests.” Implementers should review their organizational priorities and develop a similar testing framework and test cases prior to implementation in a production environment.


Testing the CQL itself is just one of the many levels of testing required prior to deployment of a CDS artifact. As discussed in Section 10 of the Implementation Guide, integration of CQL into an EHR requires both a capability to execute CQL CDS artifacts, as well as ensuring the required data inputs are mapped from their local formats into what is expected by the CQL. A set of integration tests which parallel the test cases referenced above should be considered a necessary step prior to live deployment of the CQL. For the Anthrax CDS project, this step has been replaced with a synthetic pilot, which is described in the Anthrax CDS Validation Report attached to this artifact. 

[1] Wikipedia, "Test-driven development," [Online]. Available: https://en.wikipedia.org/wiki/Test-driven_development.


[2] Node.js Foundation, "Node.js," [Online]. Available: https://nodejs.org/en/. [Accessed 12 April 2018].


[3] "YAML," [Online]. Available: http://yaml.org/. [Accessed 30 July 2018].