Introduction

Since the terrorist attacks of September 11, 2001, the US has been on high alert.^1-3 The anthrax exposures that followed shortly thereafter amplified the public cognizance that biological weapons remain a potential threat associated with terrorism.^1,3 Bioterrorism, the use of biological agents as a method of terrorism, may include agents such as anthrax, plague, smallpox, viral hemorrhagic fevers, or non-replicating agents such as toxins produced by living organisms.¹ A likely scenario for a biologic attack is via the dispersal of a pathogen in a densely populated area.¹ For this reason, it is imperative that health systems develop a disaster management team that they can quickly deploy in the event of a mass casualty event.

The role of the pharmacist in disaster management was first described in the 1960s.² Pharmacists were acknowledged as medication experts, capable of assisting in the emergent treatment of patients, educating the public, and developing and coordinating emergency preparedness measures.² In 1966, APhA advocated for the development of a national stockpile of medications and for disaster management plans to include plans for the preparation and mobilization of pharmacy activities throughout all phases of public health emergencies.² It was not until after the 2001 attacks that APhA released formal guidelines to address pharmacist involvement in bioterrorism preparedness planning.

These guidelines called for pharmacies to develop their own disaster management plans and to identify team members who should deploy in the event of a public health emergency. Furthermore, they emphasized the need for pharmacists to stay up to date on these procedures.² The following year, ASHP’s statement describing health system pharmacists’ role in counterterrorism measures emphasized that pharmacists are capable of not only medication dispensation but making therapy recommendations as well.⁴ The guidelines stated that as medication experts, pharmacists can help optimize therapy as well as limit the overuse of antibiotics in a setting when the demand often exceeds the available supply.⁴ During the 2001 anthrax exposures, the prescribing rate for ciprofloxacin and doxycycline far exceeded recommendations of the CDC.⁵ In a bioterrorism event, delayed treatment, selection of incorrect antibiotics, and the overuse of antibiotics can increase resistance.³ This further highlights the importance of incorporating pharmacists as members of disaster response teams.

The role of the pharmacist in disaster preparedness has further evolved since these early recommendations.^2,5 Pharmacists have also been incorporated into teams intended to protect their fellow healthcare workers at the front lines of mass casualty events. For example, at Maimonides Medical Center, pharmacists are members of both the hospital’s incident command center and the pharmacy emergency response team (PERT). The PERT was developed with the goal of protecting the health of hospital staff and preventing the contamination of the healthcare facility.² Similarly, pharmacists at Montefiore Medical Center participated in a point-of-distribution exercise in conjunction with the New York City Department of Health and Mental Hygiene to simulate the mass prophylaxis of healthcare workers in the event of a public health emergency.⁵ This exercise demonstrated that allowing pharmacists to immunize in a simulated public health emergency afforded approximately 12,000 healthcare workers the opportunity to receive prophylaxis within a 48 hour period.⁵ Pharmacists have the potential to reduce the financial impact of bioterrorist attacks on both the healthcare facility and the surrounding community.⁵

Case

CC: “I feel like I can’t breathe.”

HPI: PD is a 32-year-old white male (82 kg) who presents to the ED (along with his wife) in severe respiratory distress. For the past 24 to 48 hours, PD’s wife states he had a fever of 102.5⁰F, non-productive cough, shortness of breath, chest pain, and fatigue. His wife denies other respiratory symptoms. He has no other neurological symptoms. He first started to experience respiratory symptoms about two days after attending a professional hockey game.

PMI: Seasonal allergies (spring)

SH: PD works full time at a mail distribution center, is married with one child (five years old), and lives in an urban city with medical insurance and full access to healthcare services. He reports drinking one to two alcoholic drinks per week (beer/wine with dinner) and two cups of coffee per day, but denies any tobacco and illicit drug use.

Allergies: NKDA

Medications:

• Loratadine 10 mg by mouth daily PRN seasonal allergies

Vaccinations:

• Wife believes he received all routine childhood vaccines, Tdap booster 2 years ago, and is up to date on his annual flu vaccine (receives flu vaccine every year)

ROS:

• General: Well-nourished male in apparent respiratory distress
• HEENT: WNL
• Chest: Rhonchi present
• CV: No murmurs, gallops or rubs
• Abdomen: NT/ND
• Skin: WNL

VS:

• BP 112/60 mmHg
• RR 22 per minute
• HR 110 bpm
• Temperature 102.5 ⁰F

Labs and Imaging:

• Chest x-ray: pleural effusion
• Chest CT: mediastinal widening, pleural effusions with pericardial effusion
• Lumbar puncture: negative
• Gram stain (sputum): gram-positive rods, square-ended, in pairs
• Sputum specimen sent to a Laboratory Response Network (LRN)

Additional context: Over the next several days, there are increasing numbers of patients complaining of similar symptoms seen at other hospitals throughout the area. The ED has reported ten other admissions with similar symptoms. PD sputum sample came back as culture confirmed detection of B. anthracis by LRN-validated polymerase chain reaction. The state department of public health has identified several other cases in two other hospitals in the state. The Incident Command Center is activated and the state requests Strategic National Stockpile (SNS) activation for mass prophylaxis.

Case Questions

1. During public health outbreaks, epidemiologists must have a working case definition to identify probable and confirmed cases. What clinical signs and laboratory criteria confirm a diagnosis of inhalation anthrax?

Inhalation anthrax is described as a biphasic illness. Early nonspecific symptoms of inhalation anthrax include fever and fatigue. Localized thoracic symptoms such as cough, chest pain, and shortness of breath follow, as may non-thoracic symptoms such as nausea, vomiting, abdominal pain, headache, diaphoresis, and altered mental status. Lung sounds are often abnormal and imaging often shows pleural effusion or mediastinal widening.

Presumptive laboratory criteria are gram stain with gram-positive rods or a positive result on a test with established performance in a CLIA-accredited laboratory.

Confirmatory laboratory criteria:

• Culture and identification from clinical specimens by Laboratory Response Network (LRN), B. anthracis antigens in tissues,
• Evidence of four-fold rise in antibodies using CDC quantitative anti-PA immunoglobulin G (IgG) ELISA testing in an unvaccinated person, and/or
• Detection of B. anthracis or anthrax toxin genes by the LRN-validated polymerase chain reaction forma sterile site (blood or CSF, detection of lethal factor (LF) in clinical serum specimen by LF spectrometry.

2. Which antibiotics are approved for post-exposure prophylaxis for those exposed to B. anthracis?

In 2009, the US Advisory Committee on Immunization Practices recommended 60 days of antimicrobial drug prophylaxis for immediate protection and a 3-dose series of Anthrax Vaccine Adsorbed (AVA). Ciprofloxacin, levofloxacin, and doxycycline are FDA-approved for the antimicrobial drug portion of PEP for inhalation anthrax in adults ≥18 years of age. No safety data are available for levofloxacin use beyond 30 days; thus, oral ciprofloxacin and doxycycline are recommended as first-line antimicrobial drugs for PEP. Alternative antimicrobial drugs for PEP, if first-line agents are not tolerated or are unavailable, include levofloxacin and moxifloxacin; amoxicillin and penicillin VK if the isolate is penicillin susceptible; and clindamycin.

3. What type of inventory can the SNS supply? How long will take from the initial notification to when points of distribution (PODs) will receive SNS assets?

The SNS supplies, medicines, vaccines and supplies to respond to public health emergencies within 12 hours of the decision to deploy. The SNS includes the 12-hour push pack, regional stockpiles, and vendor managed inventory. It may take up to 72 hours for PODs to be set up, however federal requirements for public health dictate plans for prophylaxis points-of-dispensing (POD) be operational within 48 hours.

4. What methods are used to educate the public? Who can dispense these medications?

Multiple methods of education are utilized to educate the public on the health threat including but not limited to: informational videos, posters displayed throughout the POD, written materials in multiple languages, and staff present throughout the POD to answer the questions.

5. Who can dispense post-exposure prophylaxis antibiotics?

Dispensing will vary by the incident and location. Closed POD may dispense to groups such as healthcare professionals, long-term care residents, school system employees, and prisoners. In the incident command structure, the medical group is responsible for screening and dispensing stations. The dispensing area requires credentialed staff with specialized training such as pharmacists, in a supervisory role. The pharmacist may supervise nurses, pharmacy interns, and pharmacy technicians to facilitate with dispensing of medications. Patients with no chronic conditions may receive prophylaxis from nurses. Patients with chronic conditions and multiple routine medications should be evaluated by a pharmacist. Referral may be needed for some.

6. What are the considerations for pediatric dispensing?

State and local regulations must be followed by may be waived by officials depending on the event. In addition to health conditions, the child’s age, weight, and ability to swallow must be considered. Compounding instructions for liquid formulations are available in the stockpile and are preferred. However, it may be necessary to provide instructions on crushing tablets in some situations.

Author Commentary

Pharmacists remain the most accessible healthcare member in the community. As medication experts, pharmacists are well-positioned to respond to bioterrorism threats. This role has evolved through the decades from public education and medication dispensing to formal training of pharmacists as volunteers, such as members of the Medical Reserve Corps. Following the September 11, 2001, terrorist attacks, thousands of ciprofloxacin and other antimicrobials were prescribed to postal workers, public health officials, and congressional staff members for potential anthrax exposure.⁶ Furthermore, the public was needlessly ordering ciprofloxacin from the internet and stockpiling it for future use without fully understanding the rare but serious adverse effects from unnecessary antibiotic exposure. This prompted the FDA to issue warnings to online vendors to prevent illicit drug sales.⁷

This scenario applies to bioterrorism threats beyond anthrax. Pharmacists can assist public health organizations and responders by administering vaccines, dispensing emergency medications on a mass scale and in a timely manner, providing emergency refills of chronic medications, counseling patients on appropriate antibiotic use and adverse effects, establishing community pharmacies as a point of dispensing (POD), and ensuring an adequate medication supplies are available for the response.

Patient Approaches and Opportunities:

The International Federation of Red Cross and Red Crescent Societies define disaster as “a sudden, calamitous event that seriously disrupts the functioning of a community or society, causing human, material, and economic or environmental loses that exceed the community’s or society’s ability to cope using its own resources.”⁸ Community resilience is the ability of a community to effectively utilize its own resources to respond to and recover from such a disaster.⁹ Pharmacists are essential in community resilience, and the degree to which pharmacists are prepared for a bioterror or pandemic event may have a significant impact on a community’s ability to respond and recover.

Patients may develop strong, trusting relationships with their pharmacists over a lifetime and may be more willing to share concerns and seek information from, or believe information provided by their pharmacists than from news outlets and public health agencies. In this way, pharmacists may mitigate community panic that can lead to drug hoarding, inappropriate medication use and abuse, and dissemination of inappropriate or inaccurate information. Pharmacists are also essential public health partners in infectious disease surveillance. Because social, economic, and cultural factors influence patients’ health-seeking behaviors, in communities where patients are less likely to seek care from a primary care provider, pharmacists may be the first health care practitioners to recognize the emergence of pandemic disease.

Overarching strategies for managing a bioterrorist attack can be applied to the management of pandemic influenza or other emerging, highly contagious, high mortality infectious disease. During a declared disaster or public health emergency such as a bioterror attack or pandemic event, a temporary, legal change may be made to a state’s pharmacy practice act. A state, county, or community-wide standing-order or collaborative practice agreement may be prepared expanding the pharmacist’s scope of practice. This can include diagnosis, assessment, and prescribing of medications specific to the bioterror or pandemic event. Such methods may allow pharmacists to immunize pediatric patients when the health-care system is strained.

Community pharmacies can develop formal, working-relationships with public health agencies before disaster strikes and may develop a memorandum of understanding (MOU), a formal, written agreement that defines the roles of all parties in advance. The Association of State and Territorial Health Officials (ASTHO) has partnered with the National Association of Chain Drug Stores (NACDS), the National Alliance of State Pharmacy Associations (NASPA), the CDC, and APhA to develop a toolkit. This toolkit will help public health agencies and community pharmacies develop a MOU that could “leverage all potential partners’ strengths and promote synergies that can be useful for additional services, beyond immunizations.”¹⁰ An MOU will allow pharmacies to coordinate and collaborate with public health agencies by becoming the POD for their neighborhood. In turn, community pharmacies benefit by receiving early allocation of federal vaccines and antibiotic supplies as needed.

Community pharmacies need to have a plan in place should disaster strike. To support public health, during a bioterror or pandemic event, community pharmacies should consider extending working hours and employing temporary pharmacies in quarantine or refugee areas.