Outpatient Antimicrobial Stewardship: The Keys to Developing a Successful Program

Outpatient antimicrobial use accounts for 80% to 90% of total antibiotic use.¹ Findings from studies, however, suggest that 30% to 40% of outpatient antibiotic prescribing is unnecessary.² Additionally, first-line antimicrobials are not used in 50% of cases.

Outpatient antimicrobial stewardship reduces inappropriate antibiotic use to optimize patient care. Increasing the appropriateness of antibiotics can help ensure safe and effective treatment, thereby decreasing risk of treatment failure and subsequent related hospital admissions.³ Reducing unnecessary antibiotic use can help avoid the risk of potential adverse drug reactions and Clostridioides difficile infection (CDI). It can also help to decrease the development of antimicrobial resistance. Over the years, the White House has published several action plans and strategies for combating antibiotic-resistant bacteria. In 2015, the White House called for a decrease in inappropriate outpatient antibiotic use by 50% to help achieve this goal.⁴ The 2020-2025 plan is built upon the previous plan and called for a decrease in the total number of antibiotics prescribed in the outpatient setting.⁵

The reach of outpatient stewardship can be quite expansive, covering primary care clinics, the emergency department (ED), urgent care centers, and home-based primary care clinics. Each area may contribute to inappropriate antibiotic prescribing. Focusing on 1 area at a time can help streamline the stewardship program’s efforts, especially when resources are limited. More than half of all outpatient antibiotics are prescribed in primary care clinics.¹ Results from one study found that primary care clinics had a statistically significant higher rate of inappropriate antibiotic prescribing compared with that of the ED.⁶ Given the large proportion of inappropriate antibiotics prescribed in primary care clinics, focusing on these clinics may be most beneficial for newer or smaller outpatient antimicrobial stewardship programs.

Understanding the various prescribing habits from providers at different outpatient locations can help antimicrobial stewards target specific interventions to build an impactful program. The first step to understanding prescribing habits and identifying stewardship targets is to obtain baseline antibiotic prescribing data. Gathering data may be challenging, considering International Classification of Diseases coding can be unreliable in up to 50% of cases when antibiotics are prescribed.² Once baseline data are established, specific strategies can be employed by outpatient antimicrobial stewards. Such strategies may include patient-level intervention, such as avoiding unnecessary use and optimizing antibiotic choice, dose, and duration. Larger-scale strategies may include antibiotic restriction policies and provider education.

INDICATION

Many factors contribute to the appropriate selection of an antibiotic. Identifying the appropriate indication for treatment is among the most important of these factors. In fact, depending on the indication, antibiotics may not be needed at all. For example, bronchitis, many acute upper respiratory tract infections, and most cases of asymptomatic bacteriuria do not require management with antibiotics. Bronchitis, especially in the absence of chronic obstructive pulmonary disease, is typically of viral etiology, and many cases of pharyngitis (up to 80%) and sinusitis are viral as well.⁷ Despite this, antibiotics are often prescribed for treatment. One study found that 40% of antibiotics prescribed in the outpatient setting were not indicated.² Results from this study also found that azithromycin was the most unnecessarily prescribed antibiotic. Results from another study, which looked at community-acquired pneumonia (CAP), found that 34% of patients received an inappropriate diagnosis of CAP.⁸ In terms of urinary tract infections (UTIs), results from one study found that approximately 32% of antibiotics prescribed were not indicated because these patients were either asymptomatic or had negative urine culture results.⁹ Overmanagement of asymptomatic bacteriuria is a significant issue, because providers often prescribe antibiotics in response to a positive result from urinalysis, turbid urine, or malodorous urine, despite the absence of urinary symptoms.¹⁰ A form of diagnostic stewardship would be to avoid obtaining urine samples from asymptomatic patients and avoid culturing urine samples with negative urinalysis results.¹¹ For example, urine with few to no white blood cells on urinalysis should not be reflexed to culture given the high negative predictive value of pyuria.^12,13

Certain populations are more at risk for receiving unnecessary antibiotics. Older patients, especially those with dementia, are often subject to inappropriate prescribing of antibiotics. Confusion, falls, or behavioral changes often prompt antibiotic usage for suspected UTIs in older individuals. Other potential causes of confusion, however, should be assessed before prescribing antibiotics because these do not always indicate infection.¹⁴ Patients with delirium should have a work-up for both infectious and noninfectious causes of delirium. The confusion assessment method can be used to determine whether the patient has delirium.¹⁵ Guidelines emphasize the importance of assessing for other potential causes and avoiding potentially unnecessary antibiotic use in this vulnerable population because of the risk of CDI, increasing antimicrobial resistance, and adverse drug events.¹⁶

ANTIBIOTIC SELECTION, DOSE, AND DURATION

When antibiotics are indicated for management of an infection, identifying the type and location of infection is the most important step to help guide therapy. Specific antibiotics are preferred for certain infections because of their spectrum of activity and ability to penetrate the affected site. Other factors that should be considered when selecting an antibiotic include patient allergies, drug intolerances, and drug interactions. Renal function should also be taken into consideration because poor renal function may either preclude use of certain antibiotics or require renal dose adjustments.

Approximately 20% of antibiotics prescribed in the outpatient setting are dosed inappropriately. Appropriate dosing is important because this can help to ensure sufficient drug levels to combat infection, deter resistance development, and mitigate the risk of toxicity if dose reductions are necessary. In terms of duration, 25% of outpatient antibiotics are prescribed for inappropriate lengths of time. Inappropriate durations tend to be longer than necessary. For the management of CAP, approximately 40% of regimens are prescribed for excessive durations of therapy (> 7 days).⁸ Antibiotics are not prescribed without potential risks. In accordance with guidelines, limiting length of therapy may help limit risk of related adverse events.

CULTURE REVIEW SERVICE

When starting an outpatient stewardship program, a culture review service is an efficacious way to make a positive impact on patient care. Additionally, this service allows providers to interact with members of the stewardship program. A culture review service follows up on cultures taken in various settings, such as the ED and primary care clinics, and makes interventions to optimize therapy. Findings from one study estimated that interventions are made in approximately 20% of cases.³ Results from this study also found that pharmacist intervention decreased the rates of 30-day treatment failure and 30-day admission. Review of antibiotic orders was estimated to take as little as 5 minutes and up to 30 minutes for some orders with associated cultures that required intervention. Given the minimal time commitment and the significant improvements in patient outcomes, a culture review service is an excellent return on investment. Culture review services are also an excellent way to close the gap between various levels of care in the outpatient setting. These services allow the stewardship team to establish themselves as the experts in antibiotic therapy while collaborating with other members of the health care professional team before expanding the service to further eliminate inappropriate antimicrobial use.

AUDIT AND FEEDBACK

Dashboards can be used to compare antibiotics for specific disease states and various sites and providers. This information can be used for comparison and positive reinforcement to providers. Similarly, academic detailing can be used to start focused discussions with prescribers to try to reduce the overprescribing of antibiotics. The educator must take the time to understand the reasons for overprescribing antibiotics. These can include lack of understanding, inadequate time to review guideline updates, fear of missing bacterial infections, or patient satisfaction. The conversation can then be molded into specific practice-changing recommendations.¹⁷

FLUOROQUINOLONE RESTRICTION

Over the years, the US Food and Drug Administration (FDA) has published numerous warnings for fluoroquinolones. These warnings include tendonitis, tendon rupture, aortic dissection or rupture, peripheral neuropathy, exacerbation of myasthenia gravis, disturbances in blood glucose levels, and central nervous system effects. Given the potential for harm and the overuse associated with these agents, it’s a reasonable intervention to target when setting up a stewardship program. One study used a multimodal initiative to curb fluoroquinolone use.¹⁸ The infectious diseases pharmacist educated providers about the risks and appropriate use of fluoroquinolones, whereas FDA warnings were added to all fluoroquinolone orders as part of the electronic medical record concomitantly. Furthermore, fluoroquinolone susceptibilities were suppressed if the microorganism was susceptible to a third-generation cephalosporin. Lastly, order sets were made to guide prescribing away from fluoroquinolones. As a result, fluoroquinolone usage dropped by 39%.

CONCLUSIONS

Outpatient antimicrobial stewardship programs improve patient care by optimizing antibiotic use. Results from studies have shown that outpatient stewardship programs, especially those that perform culture reviews, can decrease rates of treatment failure, hospital admissions, and health care costs. Various methods can be employed by outpatient antimicrobial stewardship programs to improve patient care. Targeting specific indications that are frequently associated with overuse and targeting specific patient populations can help minimize unnecessary use. Optimizing dosing can help to improve efficacy and reduce toxicity. Furthermore, limiting durations of therapy, in accordance with guidelines, can help minimize risk of potential antibiotic-related adverse drug reactions. Developing a culture review service, restricting certain antibiotics or antibiotic classes, providing prospective audit and feedback, and implementing dashboards are all methods to help establish a successful stewardship program.

References

1.CDC. Measuring Outpatient Antibiotic Prescribing. Accessed 8/10/2023, https://www.cdc.gov/antibiotic-use/data/outpatient-prescribing/index.html#f10

2.White AT, Clark CM, Sellick JA, Mergenhagen KA. Antibiotic stewardship targets in the outpatient setting. Am J Infect Control. Aug 2019;47(8):858-863. doi:10.1016/j.ajic.2019.01.027

3.Wattengel BA, Sellick JA, Mergenhagen KA. Outpatient antimicrobial stewardship: Optimizing patient care via pharmacist led microbiology review. Am J Infect Control. Feb 2020;48(2):189-193. doi:10.1016/j.ajic.2019.07.018

4.The White House. National Action Plan for Combating Antibiotic-Resistant Bacteria Accessed 8/11/2023, 2023. https://www.cdc.gov/drugresistance/pdf/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf

5.Federal Task Force on Combating Antibiotic-Resistant Bacteria. National Action Plan for Combating Antibiotic-Resistant Bacteria. 8/11/2023, 2023. Accessed 8/11/2023, 2023. https://www.hhs.gov/sites/default/files/carb-national-action-plan-2020-2025.pdfUS

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7.Mostov PD. Treating the immunocompetent patient who presents with an upper respiratory infection: pharyngitis, sinusitis, and bronchitis. Prim Care. Mar 2007;34(1):39-58. doi:10.1016/j.pop.2006.09.009

8.Wattengel BA, Sellick JA, Skelly MK, Napierala R, Jr., Schroeck J, Mergenhagen KA. Outpatient Antimicrobial Stewardship: Targets for Community-Acquired Pneumonia. Clinical therapeutics. Feb 7 2019;doi:10.1016/j.clinthera.2019.01.007

9.Wattengel BA, DiTursi S, Schroeck JL, Sellick JA, Mergenhagen KA. Outpatient antimicrobial stewardship: Targets for urinary tract infections. American journal of infection control. Sep 2020;48(9):1009-1012. doi:10.1016/j.ajic.2019.12.018

10.Amenta EM, Jump RLP, Trautner BW. Bacteriuria in older adults triggers confusion in healthcare providers: A mindful pause to treat the worry. Antimicrobial stewardship & healthcare epidemiology : ASHE. 2023;3(1):e4. doi:10.1017/ash.2022.343

11.Krouss M, Alaiev D, Shin DW, et al. Choosing wisely initiative for reducing urine cultures for asymptomatic bacteriuria and catheter-associated asymptomatic bacteriuria in an 11-hospital safety net system. Am J Infect Control. Apr 2023;51(4):461-465. doi:10.1016/j.ajic.2023.01.005

12.Claeys KC, Trautner BW, Leekha S, et al. Optimal Urine Culture Diagnostic Stewardship Practice-Results from an Expert Modified-Delphi Procedure. Clin Infect Dis. Aug 31 2022;75(3):382-389. doi:10.1093/cid/ciab987

13.Cheng B, Zaman M, Cox W. Correlation of Pyuria and Bacteriuria in Acute Care. Am J Med. Sep 2022;135(9):e353-e358. doi:10.1016/j.amjmed.2022.04.022

14.Cortes-Penfield NW, Trautner BW, Jump RLP. Urinary Tract Infection and Asymptomatic Bacteriuria in Older Adults. Infect Dis Clin North Am. Dec 2017;31(4):673-688. doi:10.1016/j.idc.2017.07.002

15.Gerber JS, Prasad PA, Fiks AG, et al. Durability of benefits of an outpatient antimicrobial stewardship intervention after discontinuation of audit and feedback. JAMA. Dec 17 2014;312(23):2569-70. doi:10.1001/jama.2014.14042

16.Nicolle LE, Gupta K, Bradley SF, et al. Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. May 2 2019;68(10):e83-e110. doi:10.1093/cid/ciy1121

17.Dobson EL, Klepser ME, Pogue JM, et al. Outpatient antibiotic stewardship: Interventions and opportunities. Journal of the American Pharmacists Association : JAPhA. Jul-Aug 2017;57(4):464-473. doi:10.1016/j.japh.2017.03.014

18.Lin K, Zahlanie Y, Ortwine JK, et al. Decreased Outpatient Fluoroquinolone Prescribing Using a Multimodal Antimicrobial Stewardship Initiative. Open Forum Infect Dis. Jun 2020;7(6):ofaa182. doi:10.1093/ofid/ofaa182