Outpatient Antimicrobial Stewardship: Field of Dreams or Land of Opportunity for Pharmacists?

The critical importance of antimicrobial stewardship (AMS) to contain health care costs, combat antimicrobial resistance, and avoid unnecessary medication-related adverse events has become well accepted within the medical community. This widespread recognition has fostered the development of robust, outcome-driven, multidisciplinary AMS programs across a wide range of health care settings, from small, rural community hospitals to large, tertiary health care systems. Formal AMS programs have evolved and remained largely established within acute care hospitals given the prevalence of broad-spectrum antimicrobial use, higher rates of multidrug antimicrobial resistance, and risks of hospital-acquired infections.

Though the majority of AMS efforts have been directed toward inpatient practices, 60% of all antibiotic expenditures in the United States occur in the outpatient setting.¹ In the United States alone during 2013, 269 million antibiotic prescriptions were dispensed from outpatient pharmacies.² It has been estimated that up to 30% of outpatient antibiotic prescriptions may be inappropriate, based upon professional society endorsed national guidelines for infectious syndromes.³ Further, the burden of community acquired Clostridioides difficile is significant, with up to 35% of adult and 70% of pediatric C difficile cases occurring in patients who had no recent overnight stay in a health care facility.^4,5 In response to the need for systematic outpatient AMS, the US Centers for Disease Control and Prevention (CDC) released the Core Elements of Outpatient Antibiotic Stewardship in 2016. The recommendations center around 4 cornerstone elements: commitment, action for policy and practice, tracking and reporting, and education and expertise.⁶

THE PHARMACIST’S ROLE

Pharmacists have garnered an established role on inpatient AMS teams, as evident in the CDC’s Core Elements of Hospital Antibiotic Stewardship Programs. The drug expertise element states that a pharmacist leader should be appointed to improve antibiotic use.⁷ In contrast, the proposed involvement of pharmacists in outpatient-based AMS as described by the Core Elements of Outpatient Antibiotic Stewardship is more subtle.⁶ The document’s intended audience members represent several areas that pharmacists commonly work in, such as primary care clinics, emergency departments, retail health clinics in pharmacies, and health care systems, though pharmacists themselves are not specifically mentioned in these settings. Community pharmacies and pharmacists are described as a potential partner for outpatient AMS activities, along with health insurance companies, local microbiology laboratories, long-term care facilities, and others.⁶ Certainly, community-based pharmacists are well situated to be key players in outpatient AMS. Most outpatient antibiotic prescriptions in the United States are dispensed at community pharmacies, and virtually all of those for acute infectious syndromes would be processed through a local pharmacy.

COMMUNITY PHARMACY AMS

To date, published literature focusing on pharmacist-led AMS interventions in community pharmacies centers around the use of pharmacist—prescriber collaborative practice agreements (CPAs) and point-of-care testing. CPAs create a formal practice agreement between the pharmacist(s) and prescriber(s) that specifies the functions a pharmacist can perform outside the usual scope of practice.⁸ Although legal throughout most of the United States, rules and regulations governing CPAs vary from state to state. Of interest within the realm of outpatient AMS, CPAs may grant pharmacists prescribing authority within predefined infection-related clinical scenarios or specifically for antimicrobials. Point-of-care testing dovetails nicely with community pharmacist CPAs. In nearly all states, pharmacists can use Clinical Laboratory Improvement Amendments (CLIA)—waived tests, which are defined by the FDA as “so simple and accurate as to render the likelihood of erroneous results negligible; or pose no reasonable risk of harm to the patient if the test is performed incorrectly.’’⁹ Two such examples of CLIA-waived tests used in pharmacist-led outpatient AMS are the rapid influenza diagnostic test (RIDT) and group A Streptococcus (GAS) testing.

From December 2013 to April 2014, a pilot program involving 55 community pharmacies in 3 states (Michigan, Nebraska, and Minnesota) used a pharmacist CPA and RIDT with the aim of shortening the time to receipt of antivirals and reducing inappropriate antimicrobial use in patients with suspected influenza infection.¹⁰ Of the 75 adult patients included in the study, just 8 (11%) were positive for influenza by RIDT and, per CPA, were dispensed oral oseltamivir by the pharmacist. Patients with a negative test were counseled on symptomatic management without provision of an antiviral or antibacterial. All patients were followed up in 24 to 48 hours, and no adverse events were reported. Interestingly, patient satisfaction was >90%, despite the majority of patients not receiving an antibacterial or antiviral medication. The authors suggest this program demonstrated that a physician—pharmacist collaboration for seasonal influenzalike illness can improve appropriate use of antivirals and decrease unnecessary antibiotic prescribing. Given that a large proportion of patients presented after regular physician office hours or had no primary care physician (39% and 35%, respectively), the authors hypothesized that emergency department and urgent care visits were also avoided.^10,11

During the same time frame, this group of investigators evaluated the use of a pharmacist CPA and GAS testing coupled with a bacterial pharyngitis scoring tool in patients who presented with pharyngitis symptoms.^11,12 Adult patients with a Centor score of 1 or greater, younger than 46 years, and clinically stable with a positive GAS test qualified for treatment with amoxicillin or azithromycin per protocol. Of 316 patients screened, 273 were eligible for testing, of which 48 (17.5%) were positive and received antimicrobial treatment. Similar to the pharmacist—physician collaborative pilot on influenzalike illness, there were no adverse outcomes and patient satisfaction was high (>80%), with a large percentage of patients presenting during off-hours and not having primary care providers (43.9%).^12,13 In comparison, the literature suggests rates of 60% to 80% antimicrobial prescribing for adult pharyngitis in usual care. Taken together, these studies offer evidence that community pharmacists armed with the right tools can be a significant asset in guiding the judicious use of outpatient antimicrobials.^14,15

EMERGENCY DEPARTMENTS AND ACADEMIC DETAILING AMS

Data also demonstrate that emergency department (ED) pharmacists can play a key role in AMS efforts. From October 2011 to September 2012 at The University of Utah, ED pharmacists retrospectively reviewed 180 positive urine culture results (>100,000 CFU/mL), patient symptoms, diagnosis, and discharge antibiotics for patients discharged from the ED. Following an ED protocol, the pharmacists determined that 42 (23%) of empiric discharge antibiotics were considered inappropriate and required pharmacist intervention. All but 7 patients (17%), who were lost to follow-up, had a change made in their therapies.¹⁶ The authors concluded that ED pharmacists can improve patient care and reduce inappropriate antimicrobial use after discharge.

Tailored education delivered to health care professionals by a content expert to encourage best practices, also known as academic detailing,¹⁷ is a typical component of inpatient antimicrobial stewardship programs. Outpatient AMS—focused academic detailing had mixed results, with 1 study showing a decrease in cephalexin prescribing after a face-to-face meeting with a pharmacist and others showing no statistically significant change with pharmacist education efforts.^18-22 AMS education is generally recommended to combine with a corresponding AMS intervention such as audit and feedback, clinical decision support, delayed prescribing, and/ or public display of provider pledges to AMS.²³

FUTURE DIRECTIONS

In fall 2018, the Society of Infectious Diseases Pharmacists released a position statement on the essential role of pharmacists in outpatient AMS and, the summer preceding, a call to action for outpatient antimicrobial stewardship in Journal of American Pharmacists Association.^24-26 The aforementioned studies, among others, are cited as evidence that pharmacists must be leaders in outpatient AMS.²⁴ Road maps and other diverse potential areas for outpatient AMS programs, from vaccination to direct patient education (Table), are discussed, along with barriers to outpatient AMS, including perceived lack of financial incentives.

In conclusion, there is widespread recognition of the need for outcomes-based, systematic outpatient AMS programs. Pharmacists, particularly those enabled with a CPA and point-of-care testing, are poised to be change leaders in the betterment of outpatient infectious diseases care.

Rivera is an outpatient infectious disease clinic—based pharmacist at Mayo Clinic in Rochester, Minnesota, and an instructor of pharmacy at Mayo Clinic College of Medicine and Science. She welcomes professional correspondence on this and related topics at rivera. christina@mayo.edu. *She is a member of the Society of Infectious Diseases Pharmacists.

References:

1. Suda KJ, Hicks LA, Roberts RM, Hunkler RJ, Danziger LH. A national evaluation of antibiotic expenditures by healthcare setting in the United States, 2009. J Antimicrob Chemother. 2013;68(3):715-8. doi: 10.1093/jac/dks445.
2. Outpatient antibiotic prescriptions — United States, 2013. US Centers for Disease Control and Prevention website. cdc.gov/antibiotic-use/community/programs-measurement/state-local-activities/outpatient-antibiotic-prescriptions-US-2013.html. Updated September 12, 2017. Accessed April 28, 2019.
3. Fleming-Dutra KE, Hersh AL, Bartoces M, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011. JAMA. 2016;315(17): 1864-1873. doi: 10.1001/jama.2016.4151.
4. Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015;372(9):825-834. doi: 10.1056/NEJMoa1408913.
5. Wendt JM, Cohen JA, Mu Y, et al. Clostridium difficile infection among children across diverse US geographic locations. Pediatrics. 2014;133(4):651-658. doi: 10.1542/peds.2013-3049
6. Core elements of outpatient antibiotic stewardship. US Centers for Disease Control and Prevention website. cdc.gov/antibiotic-use/community/improving-prescribing/core-elements/core-outpatient-stewardship.html. Updated September 24, 2018. Accessed April 28, 2019.
7. Core elements of hospital antibiotic stewardship programs. US Centers for Disease Control and Prevention website. cdc.gov/getsmart/healthcare/implementation/core-elements.html. Updated May 7, 2015. Accessed April 29, 2019.
8. Advancing team-based care through practice agreements: a resource and implementation guide for adding pharmacists to the care team. US Centers for Disease Control and Prevention website. ttps://www.cdc.gov/dhdsp/pubs/docs/CPA-Team-Based-Care.pdf. Published 2017. Accessed TK.
9. Buss VH, Deeks L, Shield A, Kosari A, Naunton M. Analytical quality and effectiveness of point-of-care testing in community pharmacies: a systematic literature review. Res Social Adm Pharm. 2018 Jul 20. pii: S1551-7411(18)30315-2. doi: 10.1016/j.sapharm.2018.07.013.
10. Klepser ME, Klepser DG, Dering-Anderson AM, Morse JA, Smith JK, Klepser SA. Effectiveness of a pharmacist-physician collaborative program to manage influenza-like illness. J Am Pharmaceut Assoc (2003). 2016;56(1):14-21. doi: 10.1016/j.japh.2015.11.008.
11. Klepser ME, Adams AJ, and Klepser DG. Antimicrobial stewardship in outpatient settings: leveraging innovative physician-pharmacist collaborations to reduce antibiotic resistance. Health Secur. 2015;13(3):166-173. doi: 10.1089/hs.2014.0083.
12. Klepser DG, Klepser DG, Dering-Anderson A, et al. Implementation and evaluation of an innovative pharmacist-physician collaborative group A streptococcus disease state management program. National Community Pharmacists Association Annual Meeting. 2014.
13. Klepser DG, Bisanz SE, Klepser ME. Cost-effectiveness of pharmacist-provided treatment of adult pharyngitis. Am J Manag Care. 2012;18(4):e145-e154.
14. Linder JA, Stafford RS. Antibiotic treatment of adults with sore throat by community primary care physicians: a national survey, 1989-1999. JAMA. 2001;286(10):1181-1186.
15. Barnett ML, Linder JA. Antibiotic prescribing to adults with sore throat in the United States, 1997-2010. JAMA Intern Med. 2014;174(1):138-140. doi: 10.1001/jamainternmed.2013.11673.
16. Lingenfelter E, Drapkin Z, Fritz K, Youngquist S, Madsen T, Fix M. ED pharmacist monitoring of provider antibiotic selection aids appropriate treatment for outpatient UTI. Am J Emerg Med. 2016;34(8):1600-1603. doi: 10.1016/j.ajem.2016.05.076.
17. Bishop C, Yacoob Z, Knobloch MJ, Safdar N. Community pharmacy interventions to improve antibiotic stewardship and implications for pharmacy education: a narrative overview [published online September 17, 2018]. Res Social Adm Pharm. doi: 10.1016/j.sapharm.2018.09.017.
18. Avorn J, Soumerai SB. Improving drug-therapy decisions through educational outreach. a randomized controlled trial of academically based “detailing”. N Engl J Med. 1983;308(24):1457-1463. doi: 10.1056/NEJM198306163082406.
19. Ray WA, Schaffner W, Federspiel CF. Persistence of improvement in antibiotic prescribing in office practice. JAMA. 1985;253(12):1774-1776.
20. Schaffner W, Ray WA, Federspiel CF, Miller WO. Improving antibiotic prescribing in office practice. A controlled trial of three educational methods. JAMA. 1983;250(13):1728-1732.
21. Erramouspe J. Impact of education by clinical pharmacists on physician ambulatory care prescribing of generic versus brand-name drugs. DICP. 1989;23(10):770-773.
22. De Santis G, Harvey KJ, Howard D, Mashford ML, Moulds RF. Improving the quality of antibiotic prescription patterns in general practice. the role of educational intervention. Med J Aust. 1994;160(8):502-505.
23. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016;62(10):e51-e77. doi: 10.1093/cid/ciw118.
24. Blanchette L, Gauthier T, Heil E, et al; Outpatient Stewardship Working Group. The essential role of pharmacists in antibiotic stewardship in outpatient care: an official position statement of the Society of Infectious Diseases Pharmacists. JAPhA. 2018;58(5):481-484. doi: 10.1016/j.japh.2018.05.013.
25. Klepser ME, Dobson EL, Pogue JM, et al; SIDP Community Pharmacy Antimicrobial Stewardship Task Force. A call to action for outpatient antibiotic stewardship. J Am Pharm Assoc (2003). 2017;57(4):457-463. doi: 10.1016/j.japh.2017.03.013.
26. Dobson EL, Klepser ME, Pogue JM, et al; SIDP Community Pharmacy Antimicrobial Stewardship Task Force. Outpatient antibiotic stewardship: interventions and opportunities. J Am Pharm Assoc (2003). 2017;57(4):464-473. doi: 10.1016/j.japh.2017.03.014.