The Daniel K. Inouye College of Pharmacy Scripts

Abstract

In recent years the misuse of antimicrobials has contributed to the growing problem of antimicrobial resistance. Antimicrobial Stewardship Programs (ASP) decrease the misuse of antimicrobials by supporting a rational, systematic approach. ASP strategies vary from broad-ranging policies and other decision support tools to prospective audit review of patients on antimicrobials. Many healthcare facilities, however, have been slow to adopt stewardship attributable to the fact that early ASP models required individuals with specialized training, and a significant amount of time and infrastructural investment from facilities. In response to the increasing need for ASPs in Hawai‘i, the Hawai‘i Department of Health (HDOH) partnered with the Daniel K. Inouye College of Pharmacy (DKICP) to develop the Hawai‘i Antimicrobial Stewardship Collaborative (HASC), a voluntary collaboration whose main objective is to assist hospital institutions in the implementation of a simplified model of the Centers for Disease Control and Prevention's Core Elements of Hospital Antimicrobial Stewardship Programs. The work of HASC places Hawai‘i's health care institutions in an advantageous position to be able to comply with impending accreditation standards relating to antibiotics and infections.

Introduction

In recent years the misuse of antimicrobials has contributed to the growing problem of antimicrobial resistance.¹ It is estimated that as much as 50% of all antimicrobial use is inappropriate leading to subsequent antimicrobial resistance.² In particular, pathogens including extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLs), carbapenem resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, vancomycin-resistant Enterococci, and methicillin-resistant Staphylococcus aureus have become a challenge to manage with limited therapeutic options available.³ This problem impacts patient morbidity, mortality, and increases complications such as Clostridium difficile associated diseases as well as increased health care costs.² Antibiotic resistance is recognized as a top priority for the federal government, prompting President Obama to create Executive Order 13676 in September 2014 that launched federal efforts to combat the rise in antibiotic resistant bacteria.⁴

Inappropriate use of antibiotics often includes:

1. Use of antibiotics for non-infectious conditions

2. Unnecessary initiation or continued use of broad spectrum antibiotics

3. Inappropriate or suboptimal dosing

4. Inappropriate duration of therapy

Antimicrobial Stewardship Programs (ASP) support a rational, systematic approach for the use of antimicrobial agents to achieve optimal patient outcomes. Multiple examples in the literature demonstrate that ASP programs can improve patient outcomes and be financially self-supporting.² Studies show that ASP programs will decrease antimicrobial usage, leading to a decline in associated drug acquisition costs by 22%–36% in both large and small healthcare institutions.⁵ Many healthcare facilities, however, have been slow to adopt stewardship attributable because early ASP models required individuals with specialized training and a significant amount of time and infrastructural investment for facilities. For example, the 2007 Infectious Disease Society of America guidelines² stated that an ASP should include an infectious disease physician and a clinical pharmacist with infectious disease training in order to perform the following activities:

• Prospective audit of antimicrobial use with intervention and feedback to prescribers

• Formulary restriction and preauthorization requirements for specific antimicrobial agents

• Staff education pertaining to antimicrobial use

• Development of guidelines and clinical pathways

• Scheduled antimicrobial cycling

• Automatic stop orders or “time outs”

• Streamlining or de-escalation of therapy

• Dose optimization

• Conversion from parenteral intravenous therapy to oral dosage forms

• Development of computer surveillance and decision support

Although individually, some, or all of these activities might be achievable by facilities, such requirements in the context of competing priorities and limited resources pose a barrier to incorporating stewardship.

In November of 2013, the Hawai‘i State Department of Health (HDOH) conducted a survey regarding the establishment of ASP's in acute care institutions across the state. Of the 21 respondents, 12 (57%) reported that the most commonly reported barriers were staffing constraints or that the development of an ASP had not been identified as a priority.

Shortly thereafter, the CDC published a Vital Signs report highlighting the need for improved antibiotic stewardship among hospitalized patients.⁶ Additionally, the President's Council of Advisors of Science and Technology (PCAST) published their report on Combating Antibiotic Resistance that emphasized the need for ASP's in healthcare.⁷

Development of the Hawai‘i Antimicrobial Stewardship Collaborative (HASC)

In response to the increasing need for ASPs in Hawai‘i, the HDOH partnered with the Daniel K. Inouye College of Pharmacy (DKICP) to develop a voluntary collaboration with multiple Hawai‘i healthcare facilities to form the Hawai‘i Antimicrobial Stewardship Collaborative (HASC). HASC's main objective was to assist hospital institutions in implementing a simplified model of the CDC Core Elements of Hospital Antimicrobial Stewardship Programs.⁸ The seven core components include:

1. Leadership Commitment

2. Accountability

3. Drug Expertise

4. Action

5. Tracking

6. Reporting

7. Education

HASC's primary end goal was that each individual institution be able to sustain a self-sufficient ASP program utilizing various decision support tool-kits that encourage antimicrobial best practices. Figure 1 depicts the 12 original HASC facilities that began in October 2014. By October 2015, two additional facilities joined HASC. All of the 14 HASC participating facilities have committed to selecting and implementing antimicrobial stewardship strategies that best fit the staffing constraints and practice environments of their individual institutions. Each facility obtained administrative support and identified a program lead, most frequently a pharmacist or physician. HDOH and faculty from DKICP provide webinars, facility specific technical assistance, and collaborative support forums as each ASP program is implemented.

Figure 1.

Hawai‘i State Facilities participating in HASC as of October 2015

ASP Strategies and Development of Decision Support Tools

ASP strategies vary from broad-ranging policies and other decision support tools to prospective audit review of patients on antimicrobials. The development of decision support tools such as protocols, formulary restrictions or order sets may help to decrease a labor-intensive strategy on a day-to-day basis. These types of strategies have fared well in the smaller sized institutions.

A commonly implemented protocol is the conversion of an intravenous (IV) formulation to the usually lower costing but equally effective oral (PO) dosage form. For instance, IV fluoroquinolones, a class of drugs that have a high oral bioavailability, would be automatically substituted to the PO dosage form based on pre-defined criteria agreed upon by the medical staff and the ASP team. Formulary restriction of selected classes of antibiotics after meeting specific criteria represents another strategy as described in Table 1. Development of order sets supports the appropriate use of empiric antibiotics by offering a finite list of combinations from which providers may choose for treating particular infections.

Table 1.

Example of Criteria for Appropriate Antimicrobial Use

Antimicrobial Agent	Recommend alternative agent(s) if patient does not meet at least one of the following criteria
Carbapenems	Infectious Disease (ID) Consult Documented treatment failure with Pipercillin/Tazobactam Documented suspicion for Extended Spectrum Beta Lactamase (ESBL producing organism

Some institutions have taken a multi-faceted approach targeting several concurrent initiatives. For example, at Castle Medical Center (Kailua, O‘ahu) pharmacists utilize the electronic medical record (EMR) system to print a daily report of all patients on antibiotics and a list of all patients with positive culture results. The pharmacist reviews each patient's chart to ensure the appropriate antibiotic selection and dosing based on the type of infection and patient specific factors. This comprehensive review leads to pharmacist driven changes that may include bug-drug mismatches, IV to PO conversion, renal- and indication-based dosing adjustments, narrowing antibiotic spectrum as well as encouraging an ID consult when broad-spectrum antibiotics are ordered. All pharmacist recommendations are documented in an electronic database that will be used to evaluate the success of each type of ASP activity.

Prospective Review

Although the multi-faceted approach described in the above example is both effective and successful, not all institutions have the ability to perform such a comprehensive review due to limited manpower and workflow challenges. A more streamlined strategy is the prospective review of antibiotic usage in a targeted subset of patients. This strategy utilizes predetermined ASP criteria to identify patients at risk for antibiotic misuse (eg, patients on multiple IV antibiotics, antibiotics with narrow therapeutic ranges, broad-spectrum antibiotics, antibiotics easily converted from IV to PO, or those on antibiotics for an extended period of time; the pharmacist and ASP team then review the medical record for selected patients to identify opportunities to improve antimicrobial utilization. Facilities that have limited manpower may make use of student pharmacists who are readily available through partnerships with the DKICP. This strategy was implemented at a small rural Hawai‘i community hospital. Table 2 lists the criteria that were developed to help identify patients included for prospective review. Student pharmacists were tasked with obtaining data for patients who met the predefined criteria. Issues requiring immediate attention were presented to the overseeing pharmacist and addressed promptly. Less emergent issues and recommendations were presented and discussed during daily patient care rounds and the ASP team as well as the attending physician agreed upon decisions.

Table 2.

Criteria for Prospective Review in Pilot Antibiotic Stewardship Program

Patients Medical Records are assessed if they meet any of the following criteria:

Two or more intravenous antimicrobials

Broad spectrum/expensive antimicrobials Daptomycin (Cubicin®) Doripenem (Doribax®) Ertapenem (Invanz®) Imipenem/Cilastatin (Primaxin®) Linezolid (Zyvox®) Meropenem (Merrem®) Tigecycline (Tygacil®)

Antimicrobials that require laboratory monitoring or dose adjustments for renal function

Antimicrobials eligible for intravenous to oral conversion Fluconazole (Diflucan®) Levofloxacin (Levaquin®) Linezolid (Zyvox®) Metronidazole (Flagyl®)

Intravenous antimicrobials for 14 days or more

Through this type of prospective review, the ASP model can improve antimicrobial prescribing practices, provide opportunities to educate providers, and strengthen the relationships between prescribers and the ASP team. Institutions that opt for this strategy can also collect data regarding the type of recommendations provided and assess trends to identify areas for process improvement or development of new policies and procedures. Recommendations can generally be grouped into 15 categories (Table 3). ASP teams may opt to focus on a select number of recommendation types, depending on resources available and the comfort level of pharmacy staff with making antibiotic-related recommendations.

Table 3.

General Categories of ASP Recommendations

	Type of Recommendation	Description
1	Intravenous to Oral Conversion	Recommend converting an IV antimicrobial agent to an equivalent oral agent
2	Narrow Empiric Therapy	Recommend discontinuing antimicrobial coverage of a certain (but not all) pathogen, based on lack of risk BEFORE culture results
3	Broaden Empiric Therapy	Recommend adding additional coverage of antimicrobial for pathogens not being covered by current regimen based on patient specific risk factors BEFORE culture results
4	Streamline Based on Culture Results	Recommend discontinuing coverage of antimicrobial for certain (but not all) pathogens, based on culture results
5	Change Therapy based on culture- treatment mismatch	Recommend changing antimicrobial therapy based on the presence of a pathogen in culture results that was not previously being covered by antimicrobial regimen
6	Change to less expensive agent with similar spectrum	Recommend changing to a cheaper antimicrobial agent
7	Change due to risk of adverse event	Recommend changing antimicrobial agent due to risk of adverse effects
8	Discontinue based on lack of indication	Recommend discontinuing antimicrobials due to lack of infectious condition
9	Discontinue duplicate therapy	Recommend discontinuing an antimicrobial agent due to duplication in spectrum of activity with another agent
10	Clarify Indication	Request documentation of infectious indication
11	Change in duration of therapy	Request change in duration of therapy based on recommendations for specific infection
12	Reorder antibiotics stopped by automatic stop order	Request new order for an antibiotics stopped by an automatic stop order
13	Order laboratory monitoring	Order a laboratory test to better monitor and assess efficacy or safety of antimicrobial agent
14	Recommend infectious disease consult	Recommend further evaluation by infectious disease specialist
15	Dose of frequency change	Recommend change in dose to optimize efficacy and safety

Challenges and the Future of HASC

Since the inception of HASC, discussions during site-visits or open forums have brought up various site-specific challenges. The biggest challenge has been the ability to maintain ASP initiatives due to rapid staff and leadership turnover at the various facilities. The collaborative HASC team continues to work with each individual site to overcome these constant personnel changes.

Another challenge has been the ability to collect uniform data metrics from each of the 14 facilities. Due to differences in EMR software and institution specific data-mining techniques, not all institutions were able to provide the original metric of total patient antibiotic days. Subsequently, the uniform metric collected changed to the total daily dose (TDD) with respect to the antibiotic(s) of interest for each institution and this data is submitted to HASC.

Data collection continues from each of the participating institutions in order to determine standards of care with respect to antimicrobial stewardship. Preliminary results collected will be used to seek continued funding to fulfill HASC's primary end goal of sustaining that each individual institution be able to sustain a self-sufficient ASP program utilizing various decision support tool-kits that encourage antimicrobial best practices.

Conclusion

HDOH, DKICP, and the 14 HASC facilities have demonstrated their commitment to combating the development of antibiotic resistant organisms through the creation and implementation of ASPs. The accrediting body for health care institutions, The Joint Commission, recently released their preliminary standards for ASP's.⁹ The work of HASC places Hawai‘i's health care institutions in an advantageous position to comply with impending accreditation standards relating to antibiotics and infections.