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A call to action for outpatient antibiotic stewardship
SCIENCE AND PRACTICE Journal of the American Pharmacists Association xxx (2017) 1e7
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COMMENTARY
A call to action for outpatient antibiotic stewardship Michael E. Klepser, Erica L. Dobson*, Jason M. Pogue, Matthew J. Labreche, Alex J. Adams, Timothy P. Gauthier, R. Brigg Turner, Christy P. Su, David M. Jacobs, Katie J. Suda, on behalf of the SIDP Community Pharmacy Antimicrobial Stewardship Task Force a r t i c l e i n f o
a b s t r a c t
Article history: Received 18 November 2016 Accepted 31 March 2017
Objectives: To address the public health threat of antibiotic resistance, there has been an enhanced call for antibiotic stewardship programs throughout the health care continuum. Summary: While antibiotic stewardship programs have been well described in the inpatient setting, data on effectiveness and guidance on implementing outpatient programs is scarce. Establishing stewardship practices in the outpatient setting is necessary because more than 60% of human antibiotic use occurs in this setting. Conclusion: In this article, we highlight the importance and need for stewardship in the outpatient setting, discuss strategies for the development of stewardship teams, and discuss potential metrics that can be used to assess effectiveness of antibiotic stewardship interventions. © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
Antibiotic resistance among human pathogens has garnered worldwide attention, and it continues to diminish the utility of available antibiotics.1 Moreover, there are few novel compounds in the drug development pipeline.2 To combat this crisis, substantial global interest exists in the implementation of antibiotic stewardship (AS) initiatives geared toward optimizing antibiotic drug use practices.3,4 Historically, the majority of research and national focus on AS has been within the inpatient setting.5,6 Recently, however, attention has begun to shift to outpatient-based AS initiatives. Each year, ambulatory health care providers in the United States prescribe hundreds of millions of courses of antibiotics.7 Unfortunately, antibiotics in this setting continue to be overprescribed for conditions that typically do not warrant antibiotic therapy.8 The use of antibiotics in the outpatient setting contributes to a variety of problems, including the development of adverse events9,10 and the emergence of resistance.11,12 Furthermore, unnecessary antibiotic use results in increased health care expenditures, morbidity, and mortality,
Disclosure: The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the U.S. government. * Correspondence: Erica L. Dobson, PharmD, 601 Elmwood Ave, Box 638, Rochester, NY 14642. E-mail address: [email protected] (E.L. Dobson).
and it jeopardizes patient safety.12 As such, the potential positive effect that AS initiatives could have in the outpatient setting is believed to be significant. Recently, in recognition of the threat that antibiotic resistance presents to the country, the White House issued Executive Order 13676: Combating Antibiotic-Resistant Bacteria in September 2014. One facet of the order was to call for defining and establishing AS across the continuum of care, including, but not limited to, office-based practices and outpatient settings.13 In July 2016, the Joint Commission (TJC) approved a new medication management standard for AS that applies to the acute care setting, and expansion of this standard to ambulatory care is under consideration.14 This article will highlight the problem of outpatient antibiotic overuse and lay the groundwork for justifying outpatient (e.g., ambulatory care clinics, physician offices, convenient care clinics, urgent care clinics, community pharmacies) AS. The importance of antibiotic stewardship Antibiotics are susceptible to a communicable loss of efficacy because of the development of resistance each time they are consumed. Each loss of efficacy in an individual has negative public health consequences and diminishes the effectiveness of these medications for all.15 Outpatient prescribing accounts for greater than 60% of antibiotic use in
http://dx.doi.org/10.1016/j.japh.2017.03.013 1544-3191/© 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
SCIENCE AND PRACTICE M.E. Klepser et al. / Journal of the American Pharmacists Association xxx (2017) 1e7
Key Points Background: There is an urgent need to improve the use of antibiotics in the outpatient setting with the goal of enhancing patient outcomes and safety and to minimize the spread of antibiotic resistant bacteria. Findings: An inclusive and collaborative antibiotic stewardship model in the outpatient setting will be required to implement efforts to measure and improve how antibiotics are prescribed and used. humans.16 In addition, recent data suggest that 30% of prescribing is unnecessary17 and nonefirst-line agents are chosen approximately 50% of the time.18 Factors contributing to suboptimal antibiotic prescribing are numerous and include uncertainty about the presence of infection, delayed laboratory results, clinician time constraints, potential for limited patient follow-up, knowledge of current treatment guidelines, free or discounted antibiotic programs, and fear of litigation if a treatable infection is missed.19,20 Outpatient providers may perceive pressure to prescribe antibiotics by patients, even for clinical syndromes that do not warrant these medications.21 These observations highlight the need for outpatient AS. The World Health Organization has emphasized the rising tide of antimicrobial resistance and the imminent public health crisis it will create with a report documenting resistance to commonly used antibiotics worldwide.22 Estimates suggest that drug-resistant bacteria are responsible for more than 2 million infections and nearly 23,000 deaths annually in the United States.12 Current projections indicate that the infection mortality rate associated with antimicrobialresistant pathogens will exceed that of cancer by the year 2050.23 In addition, antimicrobial resistance generates up to $20 billion in excess direct health care costs and up to $35 billion (2008 U.S. dollars) in lost productivity costs annually.12,24 Although antibiotic resistance is often perceived as a problem for hospitalized patients or long-term care facility residents, increasing rates of resistance have been reported among community-acquired pathogens. Numerous studies have correlated the emergence of resistance with outpatient human antibiotic consumption.25-29 The specter of resistance influences the selection of empiric regimens for common outpatient infections resulting in the use of agents with expanded spectra of activity. For example, the rise in the incidence of community-onset methicillin-resistant Staphylococcus aureus now requires the consideration of this pathogen when selecting an empiric regimen for the treatment of moderate to severe purulent skin infections30,31 and communityacquired pneumonia.31 Expression of drug-resistance in Streptococcus pneumoniae, a key pathogen in respiratory tract infections, was recently reported to be approximately 40% to macrolides and approximately 10% to ceftriaxone.32
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Consumption of antibiotics in the outpatient setting has been identified as a major contributor to the rise in S. pneumoniae resistance.29 Recently, a substantial rise in the rate of resistance of Escherichia coli to agents commonly used to treat urinary tract infections (UTIs) has been described. Local rates of resistance to agents such as trimethoprim-sulfamethoxazole and ciprofloxacin now often exceed 20%, thus limiting their utility as empiric agents.33 In addition, the spread of E. coli producing CTX-M extended-spectrum b-lactamase has been isolated from outpatients without typical risk factors, and it leads to resistance to all penicillins, cephalosporins, and several alternative agents often used in the treatment of outpatient UTIs.34,35 These strains retain activity to nitrofurantoin,36 a first-line treatment for uncomplicated UTI, but are resistant to fluoroquinolones, which are most frequently prescribed for this indication.37 Overuse and misuse of antibiotics, notably for the unnecessary treatment of asymptomatic bacteriuria, is the driving force behind the increasing rates of resistance among E. coli.38 To slow the spread of antibiotic-resistant bacteria and to minimize inadequate treatment for infections caused by antibiotic resistant bacteria, outpatient AS efforts are required. Besides resistance, antibiotic exposure can cause adverse drug reactions (ADRs), life-threatening allergic reactions, and infection with Clostridium difficile. C. difficile infection (CDI) was traditionally considered a nosocomial pathogen, but is increasing in the community.39 The U.S. Food and Drug Administration recently enhanced safety warnings regarding serious adverse effects associated with fluoroquinolone antibiotics, advising that the use of these agents for acute respiratory infections and uncomplicated UTI be reserved for those who do not have alternative treatment options.40 Antibiotic-related ADRs are among the leading causes of drug-related visits to emergency departments among all age groups.9,41 In addition, research suggests that antibiotic-induced changes to the human microbiome may contribute to the development of obesity, asthma, allergies, and autoimmune diabetes.42 Thus, antibiotic use can be a risk to patient safety, and all indications should be considered carefully. Addressing inappropriate antibiotic prescribing in all health care settings is critical to combating antibiotic resistance and promoting public health. The patient care continuum interfaces across multiple care settings (e.g., emergency department, hospital, outpatient, long-term care facilities), and coordinated approaches going forward are critical to more completely address the emergence and dissemination of antibiotic resistance and CDI. Furthermore, action is required to minimize the use of antibiotics in agriculture, which represents the overwhelming majority of antibiotic use in the community and an additional transmission risk for antibioticresistant bacteria. A complete review of a One Health approach to antibiotic resistance is beyond the scope of this article, but was recently described in greater detail elsewhere.43,44
Building an outpatient AS team Currently, there is little information on the cost of implementing outpatient AS and financial incentives are largely absent.45 Unlike the hospital setting, outpatient provider practices and community pharmacies are not afforded the opportunity to justify funding based on reductions in antibiotic expenditures or decreased length of stay. Justification
SCIENCE AND PRACTICE Outpatient antibiotic stewardship
for funding of outpatient AS should leverage incentives for participation (e.g., preferred provider status by meeting quality measures for antibiotic prescribing), avoidance of financial penalties (e.g., reductions in hospital readmission rates for community-acquired pneumonia), and compliance with accreditation standards (e.g., TJC mandate for AS in acute care includes ambulatory clinics under the umbrella). Given these financial barriers, the resources available for the development of an outpatient antibiotic stewardship program (ASP) will vary among practice sites and health systems. The first step in the formation of an outpatient ASP is to define the practice community. Once the breadth of the program has been considered, key stakeholders can be identified. This group may include health care entities, patients, state and local health departments, third-party payers, professional societies, local laboratories, and community pharmacies. There are many steps necessary for implementing a successful outpatient ASP, and clear goals and outcomes should be delineated for each step to keep the program focused. Developmental steps and associated goals are outlined in Table 1. Outpatient ASPs will emerge in various forms. One model may be similar to an inpatient model in which the majority of
members are employed by a single entity, such as a health system or clinic. An alternative model consists of individuals with common interests in AS collaborating across organization lines, institutions, or types of settings (e.g., clinics, pharmacies, public health department) within a community. The outpatient model may serve as an umbrella AS team in which some members assemble stewardship resources, perform analytics, build information technology tools, and lead educational sessions and others function in direct patient care roles. Regardless of the model, core members must be identified to lead and maintain the program. Different from an inpatient model, core members of the outpatient AS team may be less involved in direct patient care and more responsible for developing, implementing, and evaluating practice initiatives, education, and monitoring antibiotic use and resistance patterns. At least one core member should possess intimate and contemporary knowledge of infectious diseases and antibiotics. Given their clinical expertise and experience directing ASPs and the interface of efforts between settings, core members may be identified from established inpatient AS teams. Core members should collaborate with outpatient stakeholders to identify translational members with the knowledge and skills
Table 1 Process and goals for developing an outpatient antibiotic stewardship program Step in the development process
Purpose
Goals
Identify program scope
Define the practice community and identify stakeholders
Create an ASP team
Establish an ASP team to collect data and implement initiatives
Assessment of baseline practice and resistance patterns
Define baseline practice and identify stewardship gaps and opportunities for improvement
Develop program priorities for the ASP
Establish focus areas for the program
Develop AS initiatives to address the identified areas of concern and create an implementation strategy
Identify interventions and define the roles and responsibilities of ASP team members as they relate to supporting strategic priorities
Develop and monitor process and outcomes measures
Evaluate the progress toward outcomes and results of interventions
List specific health entities in the community interested in partnering on AS initiatives Identify a point person within each entity willing to coordinate communication within their organization Develop a data dissemination plan among partners List core team members and outline roles List translational team members and outline roles Secure support noting that the individuals on the ASP team have the support of their organization Report data on current usage patterns, at the prescriberepatient level, at each participating practice Compare and interpret prescriber antibiotic usage rates to available metrics Create a regional or local antibiogram of outpatient isolates Summarize and report data regarding outpatient infection control measures and adherence to vaccine recommendations Summarize antibiotic associated complication rates (e.g., readmissions for select infections, secondary infections, and adverse drug reactions) List areas of concern with respect to usage patterns and resistance profiles Identify primary areas of concern Create a process map of the elements that contribute to the problem List primary and secondary desired outcomes (e.g., prescription rate, cost, resistance, hospital admissions) for each area of concern List interventions for each area of concern that would likely result in improvement in outcomes For each intervention, develop a process or workflow describing the intervention Establish a timeline for implementation and assessment of outcomes Seek appropriate approvals if needed Assess the results of each intervention on outcomes Track continued feasibility of each intervention Determine whether identified interventions and outcomes yielded the desired impact on the area of concern Refine initiatives as needed
Abbreviations used: AS, antibiotic stewardship; ASP, antibiotic stewardship program.
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SCIENCE AND PRACTICE M.E. Klepser et al. / Journal of the American Pharmacists Association xxx (2017) 1e7
necessary to translate AS service-driven goals into practice. Translational members provide leadership in day-to-day activities that support the defined AS goals and objectives and are considered accountable for assigned program outcomes. Translational members include provider champions, practice liaisons, community pharmacists and subject matter experts (e.g., information technology vendor or specialist, clinical laboratory staff member, microbiologist or public health representative) that may be brought in as needed during planning, implementation, and maintenance phases of program development. Once team members have been identified, baseline data can be collected and analyzed to identify the focus of the AS program or initiative. The purpose and proposed outcomes of the program must be delineated clearly to avoid creating unmanageable expectations. In addition, approvals may need to be secured (e.g., pharmacy and therapeutics committee approval). A value of the service that is relevant, measurable, and realistic must be established. Table 2 lists a number of possible outcomes.
Pharmacists can help to manage conditions that are likely to have noninfectious etiologies and refer patients to other providers as needed. This will result in these patients avoiding a more costly medical office visit and reducing the likelihood of receiving an unnecessary antibiotic. Various authors have reported establishing pharmacy-based, collaborative disease management models for conditions such as influenza and group A streptococcal (GAS) pharyngitis.53 In these models, pharmacists use an evidence-based collaborative practice agreement (CPA) to screen and manage patients in the pharmacy. Results have indicated substantial reductions in antibiotic use in these models. In addition, community pharmacists are in contact with virtually every patient who receives an antibiotic prescription and are the last interaction with the health system before taking the antibiotic. At this terminal point of antibiotic prescribing and dispensing, the pharmacist should serve as a quality check for the entire patient management process and reinforce compliance. In addition, community pharmacists play an important role in advocating and providing immunizations to patients, delabeling antibiotic allergy, and promoting overall wellness.
Pharmacists All pharmacists should promote the optimal use of antibiotic therapy through prescriber and patient education and evaluation of prescribing and resistance patterns. Although pharmacists with formal training in infectious diseases (ID) are preferred for the core member role, any pharmacist can promote AS.6,48-52 As the health care professional who is the initial point of contact for patients seeking symptomatic relief and the last point of contact prior to receiving a prescription, a community pharmacist has a potential role in stewardship. Table 2 Metrics to consider for outpatient antibiotic stewardship programs46,47 Measures Clinical outcome measures
Microbial or resistance measures
Process measures
Suggested metrics Antibiotic-related adverse effects (e.g., adverse drug reactions, drug-drug interactions) Clinical and microbiologic cure Health care utilization (e.g., emergency department visits, hospitalizations, office visits) Treatment failures Antibiotic susceptibility patterns CA-CDI rates Infection rates with multi-drug-resistant organisms Adherence to national or local guidelines Antibiotic deescalation or escalation Antibiotic use (e.g., prescription data, pharmacy purchase data, doses dispensed) Appropriate therapy (e.g., PTR/RTR method or guideline-recommended therapy) Use of antibiotics or use of broad-spectrum antibiotics for indications that rarely require antibiotic therapy (e.g., upper respiratory infection, acute bronchitis, acute pharyngitis [non-GAS], influenza, non-suppurative otitis media) Vaccination rates
Abbreviations used: CA, community-associated; CDI, Clostridium difficile infection; PTR, prescribed therapeutic regimen; RTR, recommended therapeutic regimen; GAS, group A streptococcus.
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Physicians and other providers It is recognized that not all outpatient settings have an IDtrained physician and that the types of infections encountered in the outpatient setting may not preclude a noneID-trained individual from serving in a core member role. In addition to having a core member, it will be useful to identify provider champions at practice sites to help disseminate and improve adherence to guidelines, protocols, and other AS interventions. These individuals can also help to develop treatment algorithms that reflect site-specific formularies and patient demographics. Physician assistants and nurse practitioners should be translational members of the AS team and may be considered for the role of provider champion.
Microbiology and laboratory The majority of outpatient antibiotic prescribing is empiric, with the clinician working from a diagnosis rather than an etiologic pathogen. Working with microbiology laboratories or contract laboratories can help to track pathogens and susceptibility patterns from various specimens and different locations, such as emergency departments, clinics, and longterm care sites. This information can be used to create regional or local outpatient antibiograms that comply with Clinical and Laboratory Standards Institute standards, generate alerts, and help to direct empiric drug therapy. In a less traditional role, the microbiology laboratory specialist may help to develop recommendations for the appropriate use of rapid diagnostic point-of-care tests. These tests, some of which are waived from the Clinical Laboratory Improvement Acts, can be conducted at a variety of testing centers that possess a certificate of waiver including outpatient clinics and community pharmacies.54 Results provided with these tests can quickly assist clinicians in the pathogen differential and serve to guide the optimal use of antibiotics.55
SCIENCE AND PRACTICE Outpatient antibiotic stewardship
Public health The core function of those who work in public health agencies is to prevent disease and improve health.56 Public health officials have expertise in laboratory testing, community education, implementing interventions, and establishing partnerships between patients and clinicians. State and local public health officials routinely advocate for vaccines, administer vaccines, and track disease activity. In addition, medical officers may be willing to function as core members and help to draft and sign CPAs. The Centers for Disease Control and Prevention (CDC) has created the “Get Smart: Know When Antibiotics Work” campaign (http://www.cdc.gov/ getsmart/), which is focused on making sure that antibiotics are prescribed only when they are warranted. This program can serve as an initial guide to facilitate local engagement in outpatient AS activities. Information technology Information technology (IT) specialists at health systems and vendors can help to access data from electronic health record (EHR) and other proprietary databases. IT specialists can assist with integrating electronic stewardship tools into a format suitable for each setting and can play an important role in determining the effects of the current AS initiative. Tracking outpatient antibiotic use One of the primary challenges presented to outpatient AS is benchmarking and tracking antibiotic use. There is no established standard antibiotic metric for outpatient stewardship. However, at a minimum, AS teams should evaluate overall antibiotic prescribing, antibiotic prescribing for specific infections, and agent selection. Methods applied to monitoring outpatient antibiotic consumption include population-, visit-, and prescriber-based rates and proportion of nonefirst-line antibiotics prescribed on the basis of indication. Rates at the population and prescriber levels can be national or for a specific geographic area (i.e., county) and can provide a baseline of antibiotic use to guide larger outpatient efforts. Visit-based rates are better suited to evaluate prescribing patterns for a specific practice or provider and may provide the most sensitive means to assess the effects of AS interventions. There have been attempts to quantify antibiotic consumption in the United States. Many of these efforts have accessed national or regional databases to measure medication consumption and reported antibiotic use over various populations.7,8,57 Although valuable information, population-level data often lag in time and may not be practical to guide AS efforts at the local level. In a hospital or other closed setting, assessing antibiotic consumption can be accomplished by tracking pharmacy purchase data or doses dispensed by the pharmacy generally reported as the number of defined daily doses (DDD) or days of therapy per unit of patient days or admissions. Although these approaches for tracking antibiotic use have been examined in the outpatient setting,26,58,59 the majority of these studies have been conducted in European countries and might not be feasible to implement in the United States. Whereas DDD is the
preferred metric used for European outpatient health care settings, the CDC uses a combination of proportions and population-, provider-, and visit-based rates to evaluate outpatient antibiotic use. Use of prescription records as a means of monitoring antibiotic use allows data on prescribed antibiotics to be linked to individual prescribers and patients; it also enables data collection to occur without needing to reconcile data with outside systems.60,61 For each antibiotic prescribed, the indication for use, or lack thereof, is identified by examining the posted ICD-9 or ICD-10 codes for the clinic visit at which the agent was prescribed. Antibiotics prescribed for various indications can be compared to the agents recommended for use in published and institutional treatment guidelines. If the prescribed antibiotic is not listed as a recommended agent within the guidelines, its use may be deemed inappropriate. Although analysis of prescribed medications (versus dispensed prescriptions) may overestimate medication consumption,62 prescribing records may more accurately measure the effects of an intervention on prescribing behavior. Another method for benchmarking antibiotic prescribing from EHR data that allows for evaluation of the prescribed regimen and the prescribed agent has been described.63 In brief, for each antibiotic prescription and diagnosis identified, an exposure parameter (the prescribed therapeutic regimen [PTR]) can be calculated for each patient episode: PTR ¼ Antibiotic dose (mg or units) Frequency (times per day) Duration (days). A similar parameter can be calculated using published treatment guidelines for recommended agents: Recommended therapeutic regimen (RTR) ¼ Antibiotic dose (mg or units) Frequency (times per day) Duration (days).63 The PTR and RTR can then be compared for congruence. The advantage of this method is that the dose and duration of the prescribed regimen can also be evaluated for the specific diagnosis. Summary outcome reports of antibiotic use can be generated for the state or region, entire clinic or health system, individual clinics, individual prescribers, and by indication. These reports should be used to identify opportunities for education and intervention, guide development of ASPs and future initiatives, and assess the effects of the AS interventions on targeted outcomes. However, few data have been published regarding the use of such approaches in the outpatient setting; thus, additional validation is required.
Conclusion Rates of antibiotic resistance continue to rise at an alarming rate and are not limited to only pathogens occurring within a hospital setting. This has direct and significant patient care implications, as infections by resistant pathogens are associated with worse outcomes compared with their susceptible counterparts, and deaths caused by infections with antibioticresistant pathogens will continue to increase. The majority of antibiotic use occurs in the outpatient setting, and two-thirds of this use is suboptimal. Antibiotic exposures in the inpatient and outpatient health care settings have been associated with the selection of resistant pathogens and occurrence of ADRs, including CDI. Thus, there is a dire need for ASPs to extend beyond the institutional setting and develop strategies to optimize therapy in the outpatient arena. 5
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25. Albrich WC, Monnet DL, Harbarth S. Antibiotic selection pressure and resistance in Streptococcus pneumoniae and Streptococcus pyogenes. Emerg Infect Dis. 2004;10(3):514e517. 26. Goossens H, Ferech M, Vander Stichele R, Elseviers M, Group EP. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet. 2005;365(9459):579e587. 27. Seppala H, Klaukka T, Lehtonen R, Nenonen E, Huovinen P. Outpatient use of erythromycin: link to increased erythromycin resistance in group A streptococci. Clin Infect Dis. 1995;21(6):1378e1385. 28. Sun L, Klein EY, Laxminarayan R. Seasonality and temporal correlation between community antibiotic use and resistance in the United States. Clin Infect Dis. 2012;55(5):687e694. 29. Hicks LA, Chien YW, Taylor Jr TH, Haber M, Klugman KP. Active Bacterial Core Surveillance Team. Outpatient antibiotic prescribing and nonsusceptible Streptococcus pneumoniae in the United States, 1996-2003. Clin Infect Dis. 2011;53(7):631e639. 30. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10e52. 31. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillinresistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis. 2011;52(3):285e292. 32. Mendes RE, Hollingsworth RC, Costello A, et al. Noninvasive Streptococcus pneumoniae serotypes recovered from hospitalized adult patients in the United States in 2009 to 2012. Antimicrob Agents Chemother. 2015;59(9): 5595e5601. 33. Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103e120. 34. Woerther PL, Burdet C, Chachaty E, Andremont A. Trends in human fecal carriage of extended-spectrum beta-lactamases in the community: toward the globalization of CTX-M. Clin Microbiol Rev. 2013;26(4): 744e758. 35. Mathers AJ, Peirano G, Pitout JD. The role of epidemic resistance plasmids and international high-risk clones in the spread of multidrug-resistant Enterobacteriaceae. Clin Microbiol Rev. 2015;28(3):565e591. 36. Doi Y, Park YS, Rivera JI, et al. Community-associated extended-spectrum beta-lactamase-producing Escherichia coli infection in the United States. Clin Infect Dis. 2013;56(5):641e648. 37. Kobayashi M, Shapiro DJ, Hersh AL, Sanchez GV, Hicks LA. Outpatient antibiotic prescribing practices for uncomplicated urinary tract infection in women in the United States, 2002-2011. Open Forum Infect Dis. 2016;3(3):ofw159. 38. Cai T, Nesi G, Mazzoli S, Meacci F, Lanzafame P, Caciagli P, et al. Asymptomatic bacteriuria treatment is associated with a higher prevalence of antibiotic resistant strains in women with urinary tract infections. Clin Infect Dis. 2015;61(11):1655e1661. 39. Chitnis AS, Holzbauer SM, Belflower RM, et al. Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011. JAMA Intern Med. 2013;173(14):1359e1367. 40. FDA Drug Safety Communication. FDA updates warnings for oral and injectable fluoroquinolone antibiotics due to disabling side effects. Available at: https://www.fda.gov/Drugs/DrugSafety/ucm511530.htm. Accessed: March 1, 2017. 41. Cohen AL, Budnitz DS, Weidenbach KN, et al. National surveillance of emergency department visits for outpatient adverse drug events in children and adolescents. J Pediatr. 2008;152(3):416e421. 42. Langdon A, Crook N, Dantas G. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Genome Med. 2016;8(1):39. 43. Robinson TP, Bu DP, Carrique-Mas J, et al. Antibiotic resistance is the quintessential One Health issue. Trans R Soc Trop Med Hyg. 2016;110(7): 377e380. 44. Aitken SL, Dilworth TJ, Heil EL, Nailor MD. Agricultural applications for antimicrobials. A danger to human health: an official position statement of the Society of Infectious Diseases Pharmacists. Pharmacotherapy. 2016;36(4):422e432. 45. Drekonja DM, Filice GA, Greer N, et al. Antimicrobial stewardship in outpatient settings: a systematic review. Infect Control Hosp Epidemiol. 2015;36(2):142e152. 46. Dodds Ashley ES, Kaye KS, DePestel DD, Hermsen ED. Antimicrobial stewardship: philosophy versus practice. Clin Infect Dis. 2014;59 (Suppl 3):S112e121. 47. McGregor JC, Furuno JP. Optimizing research methods used for the evaluation of antimicrobial stewardship programs. Clin Infect Dis. 2014;59(Suppl 3):S185e192.
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48. Ernst EJ, Klepser ME, Bosso JA, et al. Recommendations for training and certification for pharmacists practicing, mentoring, and educating in infectious diseases pharmacotherapy. Pharmacotherapy. 2009;29(4):482e488. 49. Heil EL, Kuti JL, Bearden DT, Gallagher JC. The essential role of pharmacists in antimicrobial stewardship. Infect Control Hosp Epidemiol. 2016;37(7):753e754. 50. Chou AF, Graber CJ, Jones M, et al. Characteristics of antimicrobial stewardship programs at Veterans Affairs hospitals: results of a nationwide survey. Infect Control Hosp Epidemiol. 2016;37(6):647e654. 51. Carreno JJ, Kenney RM, Bloome M, et al. Evaluation of pharmacy generalists performing antimicrobial stewardship services. Am J Health Syst Pharm. 2015;72(15):1298e1303. 52. ASHP statement on the pharmacist’s role in antimicrobial stewardship and infection prevention and control. Am J Health Syst Pharm. 2010;67(7):575e577. 53. Klepser ME, Adams AJ, Klepser DG. Antimicrobial stewardship in outpatient settings: leveraging innovative physician-pharmacist collaborations to reduce antibiotic resistance. Health Secur. 2015;13(3):166e173. 54. Gubbins PO, Klepser ME, Dering-Anderson AM, et al. Point-of-care testing for infectious diseases: opportunities, barriers, and considerations in community pharmacy. J Am Pharm Assoc (2003). 2014;54(2):163e171. 55. Kim J, Craft DW, Katzman M. Building an antimicrobial stewardship program: cooperative roles for pharmacists, infectious diseases specialists, and clinical microbiologists. Lab Med. 2015;46(3):e65e71. 56. Stover GN, Bassett MT. Practice is the purpose of public health. Am J Public Health. 2003;93(11):1799e1801. 57. Hicks LA, Taylor Jr TH, Hunkler RJ. U.S. outpatient antibiotic prescribing, 2010. N Engl J Med. 2013;368(15):1461e1462. 58. Bruyndonckx R, Hens N, Aerts M, Goossens H, Molenberghs G, Coenen S. Measuring trends of outpatient antibiotic use in Europe: jointly modelling longitudinal data in defined daily doses and packages. J Antimicrob Chemother. 2014;69(7):1981e1986. 59. Adriaenssens N, Coenen S, Versporten A, et al. European Surveillance of Antimicrobial Consumption (ESAC): quality appraisal of antibiotic use in Europe. J Antimicrob Chemother. 2011;66(Suppl 6):vi71evi77. 60. Jones BE, Sauer B, Jones MM, et al. Variation in outpatient antibiotic prescribing for acute respiratory infections in the veteran population: a cross-sectional study. Ann Intern Med. 2015;163(2):73e80.
61. Gerber JS, Prasad PA, Fiks AG, et al. Effect of an outpatient antimicrobial stewardship intervention on broad-spectrum antibiotic prescribing by primary care pediatricians: a randomized trial. JAMA. 2013;309(22): 2345e2352. 62. Fischer MA, Stedman MR, Lii J, et al. Primary medication non-adherence: analysis of 195,930 electronic prescriptions. J Gen Intern Med. 2010;25(4):284e290. 63. Klepser ME, Altom A, MacCallum C, Nordquist E, Klepser DG. Description of the methods for describing and assessing the appropriateness of antibiotic prescribing and adherence to published treatment guidelines in an academic medical clinic. Innov Pharm. 2016;7(1):Article 2. Michael E. Klepser, PharmD, Ferris State University College of Pharmacy, Kalamazoo, MI Erica L. Dobson, PharmD, Department of Pharmacy, University of Rochester Medical Center, Rochester, NY Jason M. Pogue, PharmD, Department of Pharmacy Services, Sinai-Grace Hospital; and Detroit Medical Center and Wayne State University School of Medicine, Detroit, MI Matthew J. Labreche, PharmD, MSc, Highland Hospital, Oakland, CA Alex J. Adams, PharmD, MPH, Idaho State Board of Pharmacy, Boise, ID; at time of the study, National Association of Chain Drug Stores, Arlington, VA Timothy P. Gauthier, PharmD, Miami Veterans Affairs Healthcare System, Miami, FL R. Brigg Turner, PharmD, Pacific University, School of Pharmacy, Hillsboro, OR Christy P. Su, PharmD, Memorial Hermann Greater Heights Hospital, Houston, TX David M. Jacobs, PharmD, University at Buffalo School of Pharmacy and Pharmaceutical Sciences, Buffalo, NY Katie J. Suda, PharmD, MS, U.S. Department of Veterans Affairs, Center of Innovation of Complex Chronic Healthcare, Edward Hines Jr. VA Hospital, Hines, IL; and University of Illinois at Chicago College of Pharmacy, Chicago, IL
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Journal of the American Pharmacists Association journal homepage: www.japha.org
COMMENTARY
A call to action for outpatient antibiotic stewardship Michael E. Klepser, Erica L. Dobson*, Jason M. Pogue, Matthew J. Labreche, Alex J. Adams, Timothy P. Gauthier, R. Brigg Turner, Christy P. Su, David M. Jacobs, Katie J. Suda, on behalf of the SIDP Community Pharmacy Antimicrobial Stewardship Task Force a r t i c l e i n f o
a b s t r a c t
Article history: Received 18 November 2016 Accepted 31 March 2017
Objectives: To address the public health threat of antibiotic resistance, there has been an enhanced call for antibiotic stewardship programs throughout the health care continuum. Summary: While antibiotic stewardship programs have been well described in the inpatient setting, data on effectiveness and guidance on implementing outpatient programs is scarce. Establishing stewardship practices in the outpatient setting is necessary because more than 60% of human antibiotic use occurs in this setting. Conclusion: In this article, we highlight the importance and need for stewardship in the outpatient setting, discuss strategies for the development of stewardship teams, and discuss potential metrics that can be used to assess effectiveness of antibiotic stewardship interventions. © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
Antibiotic resistance among human pathogens has garnered worldwide attention, and it continues to diminish the utility of available antibiotics.1 Moreover, there are few novel compounds in the drug development pipeline.2 To combat this crisis, substantial global interest exists in the implementation of antibiotic stewardship (AS) initiatives geared toward optimizing antibiotic drug use practices.3,4 Historically, the majority of research and national focus on AS has been within the inpatient setting.5,6 Recently, however, attention has begun to shift to outpatient-based AS initiatives. Each year, ambulatory health care providers in the United States prescribe hundreds of millions of courses of antibiotics.7 Unfortunately, antibiotics in this setting continue to be overprescribed for conditions that typically do not warrant antibiotic therapy.8 The use of antibiotics in the outpatient setting contributes to a variety of problems, including the development of adverse events9,10 and the emergence of resistance.11,12 Furthermore, unnecessary antibiotic use results in increased health care expenditures, morbidity, and mortality,
Disclosure: The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the U.S. government. * Correspondence: Erica L. Dobson, PharmD, 601 Elmwood Ave, Box 638, Rochester, NY 14642. E-mail address: [email protected] (E.L. Dobson).
and it jeopardizes patient safety.12 As such, the potential positive effect that AS initiatives could have in the outpatient setting is believed to be significant. Recently, in recognition of the threat that antibiotic resistance presents to the country, the White House issued Executive Order 13676: Combating Antibiotic-Resistant Bacteria in September 2014. One facet of the order was to call for defining and establishing AS across the continuum of care, including, but not limited to, office-based practices and outpatient settings.13 In July 2016, the Joint Commission (TJC) approved a new medication management standard for AS that applies to the acute care setting, and expansion of this standard to ambulatory care is under consideration.14 This article will highlight the problem of outpatient antibiotic overuse and lay the groundwork for justifying outpatient (e.g., ambulatory care clinics, physician offices, convenient care clinics, urgent care clinics, community pharmacies) AS. The importance of antibiotic stewardship Antibiotics are susceptible to a communicable loss of efficacy because of the development of resistance each time they are consumed. Each loss of efficacy in an individual has negative public health consequences and diminishes the effectiveness of these medications for all.15 Outpatient prescribing accounts for greater than 60% of antibiotic use in
http://dx.doi.org/10.1016/j.japh.2017.03.013 1544-3191/© 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
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Key Points Background: There is an urgent need to improve the use of antibiotics in the outpatient setting with the goal of enhancing patient outcomes and safety and to minimize the spread of antibiotic resistant bacteria. Findings: An inclusive and collaborative antibiotic stewardship model in the outpatient setting will be required to implement efforts to measure and improve how antibiotics are prescribed and used. humans.16 In addition, recent data suggest that 30% of prescribing is unnecessary17 and nonefirst-line agents are chosen approximately 50% of the time.18 Factors contributing to suboptimal antibiotic prescribing are numerous and include uncertainty about the presence of infection, delayed laboratory results, clinician time constraints, potential for limited patient follow-up, knowledge of current treatment guidelines, free or discounted antibiotic programs, and fear of litigation if a treatable infection is missed.19,20 Outpatient providers may perceive pressure to prescribe antibiotics by patients, even for clinical syndromes that do not warrant these medications.21 These observations highlight the need for outpatient AS. The World Health Organization has emphasized the rising tide of antimicrobial resistance and the imminent public health crisis it will create with a report documenting resistance to commonly used antibiotics worldwide.22 Estimates suggest that drug-resistant bacteria are responsible for more than 2 million infections and nearly 23,000 deaths annually in the United States.12 Current projections indicate that the infection mortality rate associated with antimicrobialresistant pathogens will exceed that of cancer by the year 2050.23 In addition, antimicrobial resistance generates up to $20 billion in excess direct health care costs and up to $35 billion (2008 U.S. dollars) in lost productivity costs annually.12,24 Although antibiotic resistance is often perceived as a problem for hospitalized patients or long-term care facility residents, increasing rates of resistance have been reported among community-acquired pathogens. Numerous studies have correlated the emergence of resistance with outpatient human antibiotic consumption.25-29 The specter of resistance influences the selection of empiric regimens for common outpatient infections resulting in the use of agents with expanded spectra of activity. For example, the rise in the incidence of community-onset methicillin-resistant Staphylococcus aureus now requires the consideration of this pathogen when selecting an empiric regimen for the treatment of moderate to severe purulent skin infections30,31 and communityacquired pneumonia.31 Expression of drug-resistance in Streptococcus pneumoniae, a key pathogen in respiratory tract infections, was recently reported to be approximately 40% to macrolides and approximately 10% to ceftriaxone.32
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Consumption of antibiotics in the outpatient setting has been identified as a major contributor to the rise in S. pneumoniae resistance.29 Recently, a substantial rise in the rate of resistance of Escherichia coli to agents commonly used to treat urinary tract infections (UTIs) has been described. Local rates of resistance to agents such as trimethoprim-sulfamethoxazole and ciprofloxacin now often exceed 20%, thus limiting their utility as empiric agents.33 In addition, the spread of E. coli producing CTX-M extended-spectrum b-lactamase has been isolated from outpatients without typical risk factors, and it leads to resistance to all penicillins, cephalosporins, and several alternative agents often used in the treatment of outpatient UTIs.34,35 These strains retain activity to nitrofurantoin,36 a first-line treatment for uncomplicated UTI, but are resistant to fluoroquinolones, which are most frequently prescribed for this indication.37 Overuse and misuse of antibiotics, notably for the unnecessary treatment of asymptomatic bacteriuria, is the driving force behind the increasing rates of resistance among E. coli.38 To slow the spread of antibiotic-resistant bacteria and to minimize inadequate treatment for infections caused by antibiotic resistant bacteria, outpatient AS efforts are required. Besides resistance, antibiotic exposure can cause adverse drug reactions (ADRs), life-threatening allergic reactions, and infection with Clostridium difficile. C. difficile infection (CDI) was traditionally considered a nosocomial pathogen, but is increasing in the community.39 The U.S. Food and Drug Administration recently enhanced safety warnings regarding serious adverse effects associated with fluoroquinolone antibiotics, advising that the use of these agents for acute respiratory infections and uncomplicated UTI be reserved for those who do not have alternative treatment options.40 Antibiotic-related ADRs are among the leading causes of drug-related visits to emergency departments among all age groups.9,41 In addition, research suggests that antibiotic-induced changes to the human microbiome may contribute to the development of obesity, asthma, allergies, and autoimmune diabetes.42 Thus, antibiotic use can be a risk to patient safety, and all indications should be considered carefully. Addressing inappropriate antibiotic prescribing in all health care settings is critical to combating antibiotic resistance and promoting public health. The patient care continuum interfaces across multiple care settings (e.g., emergency department, hospital, outpatient, long-term care facilities), and coordinated approaches going forward are critical to more completely address the emergence and dissemination of antibiotic resistance and CDI. Furthermore, action is required to minimize the use of antibiotics in agriculture, which represents the overwhelming majority of antibiotic use in the community and an additional transmission risk for antibioticresistant bacteria. A complete review of a One Health approach to antibiotic resistance is beyond the scope of this article, but was recently described in greater detail elsewhere.43,44
Building an outpatient AS team Currently, there is little information on the cost of implementing outpatient AS and financial incentives are largely absent.45 Unlike the hospital setting, outpatient provider practices and community pharmacies are not afforded the opportunity to justify funding based on reductions in antibiotic expenditures or decreased length of stay. Justification
SCIENCE AND PRACTICE Outpatient antibiotic stewardship
for funding of outpatient AS should leverage incentives for participation (e.g., preferred provider status by meeting quality measures for antibiotic prescribing), avoidance of financial penalties (e.g., reductions in hospital readmission rates for community-acquired pneumonia), and compliance with accreditation standards (e.g., TJC mandate for AS in acute care includes ambulatory clinics under the umbrella). Given these financial barriers, the resources available for the development of an outpatient antibiotic stewardship program (ASP) will vary among practice sites and health systems. The first step in the formation of an outpatient ASP is to define the practice community. Once the breadth of the program has been considered, key stakeholders can be identified. This group may include health care entities, patients, state and local health departments, third-party payers, professional societies, local laboratories, and community pharmacies. There are many steps necessary for implementing a successful outpatient ASP, and clear goals and outcomes should be delineated for each step to keep the program focused. Developmental steps and associated goals are outlined in Table 1. Outpatient ASPs will emerge in various forms. One model may be similar to an inpatient model in which the majority of
members are employed by a single entity, such as a health system or clinic. An alternative model consists of individuals with common interests in AS collaborating across organization lines, institutions, or types of settings (e.g., clinics, pharmacies, public health department) within a community. The outpatient model may serve as an umbrella AS team in which some members assemble stewardship resources, perform analytics, build information technology tools, and lead educational sessions and others function in direct patient care roles. Regardless of the model, core members must be identified to lead and maintain the program. Different from an inpatient model, core members of the outpatient AS team may be less involved in direct patient care and more responsible for developing, implementing, and evaluating practice initiatives, education, and monitoring antibiotic use and resistance patterns. At least one core member should possess intimate and contemporary knowledge of infectious diseases and antibiotics. Given their clinical expertise and experience directing ASPs and the interface of efforts between settings, core members may be identified from established inpatient AS teams. Core members should collaborate with outpatient stakeholders to identify translational members with the knowledge and skills
Table 1 Process and goals for developing an outpatient antibiotic stewardship program Step in the development process
Purpose
Goals
Identify program scope
Define the practice community and identify stakeholders
Create an ASP team
Establish an ASP team to collect data and implement initiatives
Assessment of baseline practice and resistance patterns
Define baseline practice and identify stewardship gaps and opportunities for improvement
Develop program priorities for the ASP
Establish focus areas for the program
Develop AS initiatives to address the identified areas of concern and create an implementation strategy
Identify interventions and define the roles and responsibilities of ASP team members as they relate to supporting strategic priorities
Develop and monitor process and outcomes measures
Evaluate the progress toward outcomes and results of interventions
List specific health entities in the community interested in partnering on AS initiatives Identify a point person within each entity willing to coordinate communication within their organization Develop a data dissemination plan among partners List core team members and outline roles List translational team members and outline roles Secure support noting that the individuals on the ASP team have the support of their organization Report data on current usage patterns, at the prescriberepatient level, at each participating practice Compare and interpret prescriber antibiotic usage rates to available metrics Create a regional or local antibiogram of outpatient isolates Summarize and report data regarding outpatient infection control measures and adherence to vaccine recommendations Summarize antibiotic associated complication rates (e.g., readmissions for select infections, secondary infections, and adverse drug reactions) List areas of concern with respect to usage patterns and resistance profiles Identify primary areas of concern Create a process map of the elements that contribute to the problem List primary and secondary desired outcomes (e.g., prescription rate, cost, resistance, hospital admissions) for each area of concern List interventions for each area of concern that would likely result in improvement in outcomes For each intervention, develop a process or workflow describing the intervention Establish a timeline for implementation and assessment of outcomes Seek appropriate approvals if needed Assess the results of each intervention on outcomes Track continued feasibility of each intervention Determine whether identified interventions and outcomes yielded the desired impact on the area of concern Refine initiatives as needed
Abbreviations used: AS, antibiotic stewardship; ASP, antibiotic stewardship program.
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necessary to translate AS service-driven goals into practice. Translational members provide leadership in day-to-day activities that support the defined AS goals and objectives and are considered accountable for assigned program outcomes. Translational members include provider champions, practice liaisons, community pharmacists and subject matter experts (e.g., information technology vendor or specialist, clinical laboratory staff member, microbiologist or public health representative) that may be brought in as needed during planning, implementation, and maintenance phases of program development. Once team members have been identified, baseline data can be collected and analyzed to identify the focus of the AS program or initiative. The purpose and proposed outcomes of the program must be delineated clearly to avoid creating unmanageable expectations. In addition, approvals may need to be secured (e.g., pharmacy and therapeutics committee approval). A value of the service that is relevant, measurable, and realistic must be established. Table 2 lists a number of possible outcomes.
Pharmacists can help to manage conditions that are likely to have noninfectious etiologies and refer patients to other providers as needed. This will result in these patients avoiding a more costly medical office visit and reducing the likelihood of receiving an unnecessary antibiotic. Various authors have reported establishing pharmacy-based, collaborative disease management models for conditions such as influenza and group A streptococcal (GAS) pharyngitis.53 In these models, pharmacists use an evidence-based collaborative practice agreement (CPA) to screen and manage patients in the pharmacy. Results have indicated substantial reductions in antibiotic use in these models. In addition, community pharmacists are in contact with virtually every patient who receives an antibiotic prescription and are the last interaction with the health system before taking the antibiotic. At this terminal point of antibiotic prescribing and dispensing, the pharmacist should serve as a quality check for the entire patient management process and reinforce compliance. In addition, community pharmacists play an important role in advocating and providing immunizations to patients, delabeling antibiotic allergy, and promoting overall wellness.
Pharmacists All pharmacists should promote the optimal use of antibiotic therapy through prescriber and patient education and evaluation of prescribing and resistance patterns. Although pharmacists with formal training in infectious diseases (ID) are preferred for the core member role, any pharmacist can promote AS.6,48-52 As the health care professional who is the initial point of contact for patients seeking symptomatic relief and the last point of contact prior to receiving a prescription, a community pharmacist has a potential role in stewardship. Table 2 Metrics to consider for outpatient antibiotic stewardship programs46,47 Measures Clinical outcome measures
Microbial or resistance measures
Process measures
Suggested metrics Antibiotic-related adverse effects (e.g., adverse drug reactions, drug-drug interactions) Clinical and microbiologic cure Health care utilization (e.g., emergency department visits, hospitalizations, office visits) Treatment failures Antibiotic susceptibility patterns CA-CDI rates Infection rates with multi-drug-resistant organisms Adherence to national or local guidelines Antibiotic deescalation or escalation Antibiotic use (e.g., prescription data, pharmacy purchase data, doses dispensed) Appropriate therapy (e.g., PTR/RTR method or guideline-recommended therapy) Use of antibiotics or use of broad-spectrum antibiotics for indications that rarely require antibiotic therapy (e.g., upper respiratory infection, acute bronchitis, acute pharyngitis [non-GAS], influenza, non-suppurative otitis media) Vaccination rates
Abbreviations used: CA, community-associated; CDI, Clostridium difficile infection; PTR, prescribed therapeutic regimen; RTR, recommended therapeutic regimen; GAS, group A streptococcus.
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Physicians and other providers It is recognized that not all outpatient settings have an IDtrained physician and that the types of infections encountered in the outpatient setting may not preclude a noneID-trained individual from serving in a core member role. In addition to having a core member, it will be useful to identify provider champions at practice sites to help disseminate and improve adherence to guidelines, protocols, and other AS interventions. These individuals can also help to develop treatment algorithms that reflect site-specific formularies and patient demographics. Physician assistants and nurse practitioners should be translational members of the AS team and may be considered for the role of provider champion.
Microbiology and laboratory The majority of outpatient antibiotic prescribing is empiric, with the clinician working from a diagnosis rather than an etiologic pathogen. Working with microbiology laboratories or contract laboratories can help to track pathogens and susceptibility patterns from various specimens and different locations, such as emergency departments, clinics, and longterm care sites. This information can be used to create regional or local outpatient antibiograms that comply with Clinical and Laboratory Standards Institute standards, generate alerts, and help to direct empiric drug therapy. In a less traditional role, the microbiology laboratory specialist may help to develop recommendations for the appropriate use of rapid diagnostic point-of-care tests. These tests, some of which are waived from the Clinical Laboratory Improvement Acts, can be conducted at a variety of testing centers that possess a certificate of waiver including outpatient clinics and community pharmacies.54 Results provided with these tests can quickly assist clinicians in the pathogen differential and serve to guide the optimal use of antibiotics.55
SCIENCE AND PRACTICE Outpatient antibiotic stewardship
Public health The core function of those who work in public health agencies is to prevent disease and improve health.56 Public health officials have expertise in laboratory testing, community education, implementing interventions, and establishing partnerships between patients and clinicians. State and local public health officials routinely advocate for vaccines, administer vaccines, and track disease activity. In addition, medical officers may be willing to function as core members and help to draft and sign CPAs. The Centers for Disease Control and Prevention (CDC) has created the “Get Smart: Know When Antibiotics Work” campaign (http://www.cdc.gov/ getsmart/), which is focused on making sure that antibiotics are prescribed only when they are warranted. This program can serve as an initial guide to facilitate local engagement in outpatient AS activities. Information technology Information technology (IT) specialists at health systems and vendors can help to access data from electronic health record (EHR) and other proprietary databases. IT specialists can assist with integrating electronic stewardship tools into a format suitable for each setting and can play an important role in determining the effects of the current AS initiative. Tracking outpatient antibiotic use One of the primary challenges presented to outpatient AS is benchmarking and tracking antibiotic use. There is no established standard antibiotic metric for outpatient stewardship. However, at a minimum, AS teams should evaluate overall antibiotic prescribing, antibiotic prescribing for specific infections, and agent selection. Methods applied to monitoring outpatient antibiotic consumption include population-, visit-, and prescriber-based rates and proportion of nonefirst-line antibiotics prescribed on the basis of indication. Rates at the population and prescriber levels can be national or for a specific geographic area (i.e., county) and can provide a baseline of antibiotic use to guide larger outpatient efforts. Visit-based rates are better suited to evaluate prescribing patterns for a specific practice or provider and may provide the most sensitive means to assess the effects of AS interventions. There have been attempts to quantify antibiotic consumption in the United States. Many of these efforts have accessed national or regional databases to measure medication consumption and reported antibiotic use over various populations.7,8,57 Although valuable information, population-level data often lag in time and may not be practical to guide AS efforts at the local level. In a hospital or other closed setting, assessing antibiotic consumption can be accomplished by tracking pharmacy purchase data or doses dispensed by the pharmacy generally reported as the number of defined daily doses (DDD) or days of therapy per unit of patient days or admissions. Although these approaches for tracking antibiotic use have been examined in the outpatient setting,26,58,59 the majority of these studies have been conducted in European countries and might not be feasible to implement in the United States. Whereas DDD is the
preferred metric used for European outpatient health care settings, the CDC uses a combination of proportions and population-, provider-, and visit-based rates to evaluate outpatient antibiotic use. Use of prescription records as a means of monitoring antibiotic use allows data on prescribed antibiotics to be linked to individual prescribers and patients; it also enables data collection to occur without needing to reconcile data with outside systems.60,61 For each antibiotic prescribed, the indication for use, or lack thereof, is identified by examining the posted ICD-9 or ICD-10 codes for the clinic visit at which the agent was prescribed. Antibiotics prescribed for various indications can be compared to the agents recommended for use in published and institutional treatment guidelines. If the prescribed antibiotic is not listed as a recommended agent within the guidelines, its use may be deemed inappropriate. Although analysis of prescribed medications (versus dispensed prescriptions) may overestimate medication consumption,62 prescribing records may more accurately measure the effects of an intervention on prescribing behavior. Another method for benchmarking antibiotic prescribing from EHR data that allows for evaluation of the prescribed regimen and the prescribed agent has been described.63 In brief, for each antibiotic prescription and diagnosis identified, an exposure parameter (the prescribed therapeutic regimen [PTR]) can be calculated for each patient episode: PTR ¼ Antibiotic dose (mg or units) Frequency (times per day) Duration (days). A similar parameter can be calculated using published treatment guidelines for recommended agents: Recommended therapeutic regimen (RTR) ¼ Antibiotic dose (mg or units) Frequency (times per day) Duration (days).63 The PTR and RTR can then be compared for congruence. The advantage of this method is that the dose and duration of the prescribed regimen can also be evaluated for the specific diagnosis. Summary outcome reports of antibiotic use can be generated for the state or region, entire clinic or health system, individual clinics, individual prescribers, and by indication. These reports should be used to identify opportunities for education and intervention, guide development of ASPs and future initiatives, and assess the effects of the AS interventions on targeted outcomes. However, few data have been published regarding the use of such approaches in the outpatient setting; thus, additional validation is required.
Conclusion Rates of antibiotic resistance continue to rise at an alarming rate and are not limited to only pathogens occurring within a hospital setting. This has direct and significant patient care implications, as infections by resistant pathogens are associated with worse outcomes compared with their susceptible counterparts, and deaths caused by infections with antibioticresistant pathogens will continue to increase. The majority of antibiotic use occurs in the outpatient setting, and two-thirds of this use is suboptimal. Antibiotic exposures in the inpatient and outpatient health care settings have been associated with the selection of resistant pathogens and occurrence of ADRs, including CDI. Thus, there is a dire need for ASPs to extend beyond the institutional setting and develop strategies to optimize therapy in the outpatient arena. 5
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