Pharmacists Can Make a Difference in Antibiotic Stewardship at Discharge

In 2019, the CDC updated its core elements of hospital antibiotic stewardship programs (ASPs) and identified an opportunity to optimize antibiotic use in the transitions of care (TOC) setting.^1,2 Up to 1 in 5 hospitalized adults are discharged with antibiotics, but antibiotic use in these instances has been shown to not always be indicated.³

Credit: Jairo - stock.adobe.com

Data have also shown that 49% of prescriptions for antibiotics can be classified as overuse, with excessive duration of therapy as the driving factor.⁴ Specifically, data have shown that 67.8% of patients received excess antibiotic duration for treat-ment of pneumonia, with 93.2% of those patients prescribed these excess antibiotics at discharge.⁵

An additional example can be found in quinolone prescribing at discharge. Data have shown that 75% of quinolone orders involved at least 1 suboptimal quality,⁶ with the largest driver being prolonged therapy in 54% of all quinolone prescriptions. These cases resulted in 272 days of unnecessary exposure to quinolone, with 4% of patients experiencing documented serious adverse events.⁶

Discordant or excessive antibiotic use can increase the risk for patient harm. Each day a patient is adherent with excess antibiotic therapy, the odds of an antibiotic-associated adverse drug event (ADE) increases by 5%.⁵ Further, 20% of hospitalized patients experienced an antibiotic-associated ADE, with more than one-quarter of those events occurring following discharge.⁷

Prolonged duration of therapy is a major contributor to discordant antibiotic prescribing during TOC and raises the risk for ADEs, and up to 70% of antibiotic courses prescribed at discharge could be improved through narrowing antibiotic spectrum, proper dosing, reducing duration, or stopping antibiotics altogether.⁸ Traditional inpatient ASP initiatives, such as audit and feedback, may not impact prescribing practices at discharge; however, there remains a need for institutions to establish a process targeting antibiotic optimizationduring TOC.^3,9,10

Pharmacist-Led Stewardship

Pharmacist-led discharge stewardship initiatives have shown promising results. The results of one study published in JAMA Network Open showed that implementing an institutional model with pharmacists on the front lines optimized oral antibiotic therapy at TOC.³ The study was a nonrandomized stepped-wedge design focused on common infections (eg, respiratory tract, urinary tract, skin and skin structure, and intra-abdominal), which is a setting where the infectious diseases (ID) team is less likely to be consulted.

The primary end point was frequency of optimized antimicrobial prescription at discharge, and findings showed that the postintervention group was more likely to have an optimal prescription (odds ratio [OR], 5.63; 95% CI, 3.69-8.60).³ Additionally, no difference was detected in clinical resolution or mortality. However, fewer severe ADEs were identified in the postintervention group (13 [3.2%]) compared with the preintervention (36 [9.0%]) group (OR, 0.40; 95% CI, 0.18-0.88).³

In another study published in Annals of Pharmacotherapy, data showed that an ID pharmacist reviewing oral antimicrobials at discharge resulted in the identification of drug-related problems in more than 40% of prescriptions. Seventy-five percent of pharmacist interventions were accepted, with the most common changes being duration, dose, or discontinuation of antimicrobials. Duration interventions significantly decreased the length of antimicrobials from a median of 8 to 4 days, demonstrating the positive impact of pharmacist involvement in antimicrobial stewardship during TOC.¹¹

Outpatient Parenteral Antimicrobial Therapy TOC

When transitioning to oral antimicrobials is not feasible, outpatient parenteral antimicrobial therapy (OPAT) programs can assist with administration of intravenous (IV) antimicrobials to patients in various outpatient settings. The Infectious Diseases Society of America (IDSA) defines OPAT as the administration of parenteral antimicrobial therapy in at least 2 doses on different days without intervening hospitalization.¹²

OPAT is commonly employed for disease states that may require prolonged courses of antimicrobial therapy (eg, infective endocarditis or prosthetic joint infections), as it increases patient satisfaction while decreasing hospital length of stay, readmissions, and costs.¹³ Because of the complexities associated with OPAT, IDSA recommends that all patients be reviewed by ID experts, including ID physicians and pharmacists, prior to OPAT initiation.¹²

OPAT is generally coordinated by a multidisciplinary team that may consist of ID physicians, pharmacists, advanced practice providers, nurses, and other health care professionals. One study showed that the addition of an ID pharmacist to an OPAT team led to significantly increased adherence rates to IDSA guideline recommendations for lab monitoring and follow-up visits, as well as increased clinical cure rates.¹⁴ Another study demonstrated that patients discharged on vancomycin who were enrolled in a pharmacist-driven OPAT program experienced reduced readmission rates compared with patients who were discharged without OPAT involvement.¹⁵ Overall, pharmacists are well positioned to assist with antimicrobial optimization in the outpatient setting, and to serve as integral parts of the OPAT team at many institutions.

Appropriate patient selection is critical to ensure antimicrobials are safely and effectively administered in the outpatient setting. Factors that must be considered during TOC when determining whether a patient is a candidate for OPAT include but are not limited to: medical stability, discharge setting (eg, home, skilled nursing facility, infusion center), functional ability, and support.¹³ If antimicrobials are administered at home, patients should have a fixed address, refrigeration capability, electricity, running water, and access to a telephone.¹³

Compared with the inpatient setting, choosing an outpatient antimicrobial regimen has numerous additional considerations. Providers must consider the method (eg, gravity infusion, elastomeric device, pump, IV push) and frequency of drug administration, drug stability, safety, and financial burden.¹² Whereas a focus of an inpatient ASP is to use antimicrobials with the narrowest effective spectrum of activity to minimize collateral damage, an outpatient ASP focuses on choosing safe, efficacious regimens while facilitating ease of administration. This may necessitate use of broader-spectrum agents with more convenient administration modalities or dosing frequencies rather than narrower-spectrum agents with more demanding administration requirements.^16,17 For example, once-daily daptomycin (Cubicin; Pfizer Inc), ceftriaxone (Rocephin; Sandoz), or ertapenem (Invanz; Merck) may be preferred over alternative agents that require multiple daily infusions (eg, ampicillin-sulbactam), as less frequent daily infusions have been associated with increased patient adherence.¹⁸ Use of alternative administration strategies, such as continuous infusions of vancomycin or β-lactams, can also be considered to minimize total daily infusions and maximize pharmacokinetic/pharmacodynamic target attainment.¹⁷

OPAT patients should generally receive at least weekly labs and vascular access care. For antimicrobials with narrow therapeutic indices necessitating therapeutic drug monitoring (eg, vancomycin), providers may consider therapeutic substitution to reduce the burden of outpatient lab coordination and risk of ADE.¹⁹ Certain antimicrobial-associated ADEs may occur more commonly with prolonged antimicrobials in the outpatient setting (eg, β-lactam–induced neutropenia), warranting possible therapy modifications. Patients should also be evaluated for response to treatment, which most commonly occurs with ID providers throughout treatment.

Regardless of whether patients are discharging on oral or IV therapy, pharmacist assessment of antimicrobial appropriateness on discharge, including agent selection, dose, duration, and appropriate lab monitoring, is critical to ensure optimal outpatient prescribing during TOC.

References

1. Centers for Disease Control and Prevention (CDC). Antibiotic prescribing and use. CDC website. October 24, 2021. Accessed May 10, 2023. https://www.cdc.gov/antibiotic-use/core-elements/implementation.html

2. Centers for Disease Control and Prevention (CDC). Core elements of hospital antibiotic stewardship programs. CDC website. April 28, 2021. Accessed May 10, 2023. https://www.cdc.gov/antibiotic-use/core-elements/hospital.html

3. Mercuro NJ, Medler CJ, Kenney RM, et al. Pharmacist-Driven Transitions of Care Practice Model for Prescribing Oral Antimicrobials at Hospital Discharge. JAMA Netw Open. 2022;5(5):e2211331. doi:10.1001/jamanetworkopen.2022.11331

4. Vaughn VM, Gandhi TN, Chopra V, et al. Antibiotic Overuse After Hospital Discharge: A Multi-hospital Cohort Study. Clin Infect Dis. 2021;73(11):e4499-e4506. doi:10.1093/cid/ciaa1372

5. Vaughn VM, Flanders SA, Snyder A, et al. Excess Antibiotic Treatment Duration and Adverse Events in Patients Hospitalized With Pneumonia: A Multihospital Cohort Study. Ann Intern Med. 2019;171(3):153-163. doi:10.7326/M18-3640

6. Mercuro NJ, Kenney RM, Abreu-Lanfranco O, Davis SL. Ambulatory Quinolone Prescribing: Moving From Opportunity to Implementation. Clin Infect Dis. 2018;67(8):1306-1307. doi:10.1093/cid/ciy315

7. Tamma PD, Avdic E, Li DX, Dzintars K, Cosgrove SE. Association of Adverse Events With Antibiotic Use in Hospitalized Patients. JAMA Intern Med. 2017;177(9):1308-1315. doi:10.1001/jamainternmed.2017.1938

8. Vaughn VM, Hersh AL, Spivak ES. Antibiotic Overuse and Stewardship at Hospital Discharge: The Reducing Overuse of Antibiotics at Discharge Home Framework. Clin Infect Dis. 2022;74(9):1696-1702. doi:10.1093/cid/ciab842

9. Vaughn VM, Gandhi TN, Petty LA, et al. Empiric Antibacterial Therapy and Community-onset Bacterial Coinfection in Patients Hospitalized With Coronavirus Disease 2019 (COVID-19): A Multi-hospital Cohort Study. Clin Infect Dis. 2021;72(10):e533-e541. doi:10.1093/cid/ciaa1239

10. 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

11. Parsels KA, Kufel WD, Burgess J, et al. Hospital Discharge: An Opportune Time for Antimicrobial Stewardship. Ann Pharmacother. 2022;56(8):869-877. doi:10.1177/10600280211052677

12. Norris AH, Shrestha NK, Allison GM, et al. 2018 Infectious Diseases Society of America Clinical Practice Guideline for the Management of Outpatient Parenteral Antimicrobial Therapy. Clin Infect Dis. 2019;68(1):e1-e35. doi:10.1093/cid/ciy745

13. Shah AB, Norris AH. Handbook of outpatient parenteral antimicrobial therapy for infectious diseases. 3rd edition. CRG Publishing and Infectious Diseases Society of America. 2016. https://www.idsociety.org/globalassets/idsa/clinical-affairs/opat_epub_finalv3.pdf.

14. Lin A, Nakasone TS, Nguyen NN, Yang C. Impact of an OPAT Pharmacist on Guideline Adherence and Clinical Outcomes. Open Forum Infect Dis. 2021;8(Supplement_1):S83–S84. doi:10.1093/ofid/ofab466.136

15. Epperson TM, Bennett KK, Kupiec KK, et al. Impact of a Pharmacist-Managed Outpatient Parenteral Antimicrobial Therapy (OPAT) Service on Cost Savings and Clinical Outcomes at an Academic Medical Center. Antimicrob Steward Healthc Epidemiol. 2023;3(1):e15. doi:10.1017/ash.2022.374

16. Gilchrist M, Seaton RA. Outpatient parenteral antimicrobial therapy and antimicrobial stewardship: challenges and checklists. J Antimicrob Chemother. 2015;70(4):965-970. doi:10.1093/jac/dku517

17. Mahoney MV, Childs-Kean LM, Khan P, Rivera CG, Stevens RW, Ryan KL. Recent Updates in Antimicrobial Stewardship in Outpatient Parenteral Antimicrobial Therapy. Curr Infect Dis Rep. 2021;23(12):24. doi:10.1007/s11908-021-00766-x

18. Hamad Y, Dodda S, Frank A, et al. Perspectives of Patients on Outpatient Parenteral Antimicrobial Therapy: Experiences and Adherence. Open Forum Infect Dis. 2020;7(6):ofaa205. doi:10.1093/ofid/ofaa205

19. Shrestha NK, Mason P, Gordon SM, et al. Adverse events, healthcare interventions and healthcare utilization during home infusion therapy with daptomycin and vancomycin: a propensity score-matched cohort study. J Antimicrob Chemother. 2014;69(5):1407-1415. doi:10.1093/jac/dkt512

About the Authors

Corey J. Medler, PharmD, MPh, BCIDP, is a clinical pharmacy specialist in infectious diseases at University of Virginia Health in Charlottesville.

Allison M. Field, PharmD, AAHIVP, is a postgraduate year 2 infectious diseases pharmacy resident at University of Virginia Health in Charlottesville.

Jenni Thomas, PharmD, is a clinical pharmacy specialist in infectious diseases at University of Virginia Health in Charlottesville.

Adam Archer, PharmD, is a clinical pharmacy specialist in infectious diseases at University of Virginia Health in Charlottesville.