(4/4) Gross Lecture: Antimicrobial Stewardship Programs Principal Goal of Antimicrobial Stewardship Programs: Optimize patient outcomes and decrease resistance Principal Source of Resistance: Antibiotics

- Process: Abx are mutagens, meaning they impose upon bacteria a stress-response involving free radicals that can induce DNA changes. These mutations may confer resistance mechanisms. Implementation and proliferation of these adaptations occurs through Natural Selection

Why we need Antimicrobial Stewardship - Identical Trends of Resistance for each abx

o CDC 2013 estimates 2 million MDR infections annually in US - Ongoing Misuse of Abx

o Inappropriate prescribing for viral infections (ie; bronchitis) - Unnecessary Harm invoked by Abx therapy

o Study at John Hopkins: 1 in 5 pts tx with abx was harmed (AE) Antimicrobial Stewardship

- A systematic process to optimize antimicrobial use to improve patient outcomes while minimizing unintended consequences. This can be achieved by using the 5 Ds (Diagnosis, Drug, Dose, De-escalation, Duration)

o Optimal Use: Use each Abx only as indicated per the diagnosis, at the proper frequency and dose. Providing the drug safely is a critical component of optimal use

o Minimizing Consequences: Resistance, Toxicity/AE, C. diff - Ideal ‘positions’ held by an Antimicrobial Steward

o When do we treat for a positive urine culture/UTI? Only when they have symptoms. No Sx à No Tx o “I have abx sitting at home & I feel sick; can I take them?” NO. It can D your flora. Precipitate C. diff o Proper dosing protocols per bug ~ Time above AUC when using beta-lactams ~ extended-infusion

The current state of Antimicrobial stewardship - Government

o White House under Obama 2015: National Action Plan for Combating Antibiotic-Resistant Bacteria o Centers for Medicare & Medicaid Services (CMS) 2015-16 Update to Conditions of Participation (COP)

§ All hospitals that participate in Medicare and Medicaid programs must comply with the COP to receive funding

- Regulatory/Accrediting Bodies o The Joint Commission (2017) has required adherence to the CDC core elements for having an

antimicrobial stewardship program based on current scientific literature – in order to be accredited - Job Market for Pharmacists

o There are 15,600 Nursing homes in the US, and each is required to have a stewardship program in order to receive medicare funding

- Success Stories o Carbapenem Restriction: Recent survey of 22 teaching hospitals that have implemented restriction

practices have shown lower incidence rates of carbapenem-resistant Pseudomonas o IVàPO Levaquin: A pharmacist lead conversion of IV levoàPO showed statistically significant

improvements. Length of Stay shortened by 3.5 days – that’s $3,300 less for the hospital to pay Challenges to Antimicrobial Stewardship (AS)

- AS is seen as the police of abx use (good and bad) - Challenge to physician autonomy - Difficulty implementing: Not enough staff/resources/time - May cause a delay in a patient’s adequate therapy (pre-authorizations)

Antimicrobial Stewardship Programs: Design and Implementation - Anti-infective/Stewardship Committee Members: Pharmacist (ID Core member), Physician (ID Core member)

o Additional: Clinical microbiology, Infection control/epidemiology, Administration, Information technology (IT), and others as needed

- Core Elements: Commitment of leadership, accountability, drug expertise, action, monitoring abx prescribing/resistance patterns, reporting abx use, educating clinicians about resistance

- Core Strategies: These have been deemed to be the most impactful methods to improve anti-infective use o Formulary Management: Include restrictions and pre-authorizations prior to particular abx use

§ Restrict the formulary: Considerations: 1st: Efficacy, 2nd: Safety, 3rd: Cost • Identify redundant, effective, toxic, cost-effective, new agents

§ Pre-authorization: May include (1) ID consult required, (2) Criteria-based restrictions • Aka, requiring the abx to be approved a stewardship member before dispensing or the pt

needs to have met criteria (dx, vitals) to receive the med • Challenges: requires additional resources and time. It may seem like a challenge to

physician autonomy, it may delay a patient’s treatment • Solutions to challenges: Leverage CPOE and establish after-hour protocols

o Prospective audit with intervention and feedback ~ To measure the outcomes § Just-in-time education, providing feedback, forming discussions – learning opportunities

- Supplemental Strategies for systematic interventions o IV to PO Switch

§ Requires: Patient needs to have a functioning GI tract and hemodynamic stability § Effect: Decrease length of stay, Decrease costs, lower the risk of catheter-related BSI § High bioavailability: linezolid, clindamycin, bactrim, metronidazole, FQ, fluconazole

• Not limited to abx! This includes other meds too, PPIs, Keppra, etc § Methods: Computer reminders, automatic switches (pre-determined criteria), pharmacist review

o Indications and Durations § Mandatory indications refer to requiring a particular indication to be present to order an abx

• In addition, a specific duration of therapy can be associated with an anti-infective order § Effect: Facilitates prospective audit and feedback real-time, and communication among teams

o Education § Antimicrobial “Time-Out”: At 48-96h post-abx initiation, reassess the need for continued

therapy. By this time, the pt’s condition should be more clear. This can be implemented by computer-automated alerts

o Dosing Protocols: Optimize PK/PD by using alternative dosing schemes § Method: Automatic computer substitutions OR pharmacist-led protocol for changing therapy § Ex: Renal dosing protocols, extended-infusion beta-lactams (Time above AUC) § Extended-infusion beta-lactams: Efficacy exerted by Time above AUC, so the pharmacist can

play a key role in ensuring proper PK/PD. Ex: 1g Meropenem q8º à 500mg Meropenem q6º o Guideline development

§ Integrate national guidelines, institutional Antibiogram, formulary, policy, demographics about your typical patient population

§ Distribution of information – charts, CPOE, education of new residents o Use of CPOE/CDS (Clinical decision support – reference to guidelines)