Antibiotic Stewardship What is It?

Antibiotic Stewardship What is It? Richard Clarens, PharmD UND School of Medicine & Health Sciences Altru Family Medicine Residency NDSU College of Pharmacy, Nursing, & Allied Sciences

OBJECTIVES Discuss factors that have increased antimicrobial resistance. Define and identify the principles of antibiotic stewardship. Identify strategies to incorporate antimicrobial stewardship to improve antibiotic use.

ANTIBIOTIC PRESCRIBING In 2013 ~269M outpatient antibiotic Rxs CDC. Outpatient antibiotic prescriptions US, 2013. http:// www.cdc.gov/getsmart/community/pdfs/annual-reportsummary_2013.pdf In 2009 ~$10.7B on antibiotics Outpatient $6.5B Inpatient $3.6B LTCF $526.7M MMWR 15;64:871-3. Aug 21, 2015

OUTPATIENT ANTIBIOTIC USE Up to 80% of antibiotics Rx d in primary care Pharm J 10/13/2011. http://www.pharmaceutical-journal.com/news-andanalysis/news/pharmacists-have-a-critical-role-in-the-conservation-of-effectiveantibiotics/11086917.article ~20% peds & 10% adult visits receive abx Rx Pediatrics 11;128:1053-61 J Antimicrob Chemother 14;69:234-40 ~30% of antibiotics unnecessary JAMA. 2016;315:1864-1873

MISUSE OF ANTIBIOTICS Estimated $34.1 B/y in avoidable inpatient costs $1 B/y spent on ~31 M inappropriate Rx Typically for viral infections Bronchitis 11 M Sinusits 9 M Pharyngitis 6 M Otitis media 3 M URI 2 M IMS Institute for Healthcare Informatics. Using Medicines More Responsibly. 6/19/13. http://www.imshealth.com/en/about-us/news/ims-health-study-identifies-$200-billion-annualopportunity-from-using-medicines-more-responsibly

ANTIBIOTIC PRESCRIBING 2011 Antibiotic agent Rx s in millions Azithromycin 54.1 10 th most Rx d drug in 2011 16 th in 2014 Amoxicillin 52.9 11 th most Rx d drug in 2011 and 2014 Amoxicillin-clavulanate 21.2 Ciprofloxacin 20.9 Cephalexin 20.0 Clin Infect Dis 15;60:1308-16 http://www.pharmacytimes.com/publications/issue/2015/july2015/top-drugs-of-2014

ANTIBIOTIC USE perceived low toxicity, antibiotics are seen as ultrasafe miracle drugs by physicians and patients alike. providers dispense antibiotics, often reflexively J Ped ID Soc 15;4:e136-e8

ANTIBIOTIC USE Often overused and used inappropriately Up to 50% Selection, dosing, duration, unnecessary for condition > 25% adult Rxs usually not indicated Inappropriate antibiotic use: Leads to adverse drug effects (ADE) (eg, hypersensitivity, C. difficile) and mortality Increases health care cost (eg, ED visits, Rx) Promotes antibiotic resistance Arch Intern Med 10;170:1314-6 J Antimicrob Chemother. 2014;69(1):234-40 CDC. Grand Rounds: Getting Smart About Antibiotics. MMWR 15;64:871-3 JAMA 16;315:562-70 Editorial. Ann Intern Med 12;157:211-2 Lancet Infect Dis. Online 3/2/16 http://dx.doi.org/10.1016/s1473-3099(16)00065-7

US ED Visits for ADEs by Drug Class, 2013-2014 ED visits for ADE, % ED visits resulting in hospitalization, % Anticoagulants 17.6 48.8 Antibiotics 16.1 7.1 DM agents 13.3 38.5 Opioid Analgesics 6.8 24.6 RAAS inhib 3.5 31.9 Antineoplastics 3 59.7 NSAIDs 2.8 12.6 Antihistamines 1.3 11.9 Cough/Cold 1.3 10.9 JAMA. 2016;316(20):2115-2125

US ED Visits for Adverse Drug Events, 2013-2014 Per-prescription risk is greater than benefits for many outpatient URTIs Rates of antibiotic use is highest for children Higher rate of ED visits for ADEs vs other drugs Reducing inappropriate antibiotic use by using various interventions May reduce the risk of ADEs and resistance CDC. Get smart: know when antibiotics work. http://www.cdc.gov/getsmart/community/improvingprescribing/interventions/index.html. JAMA. 2016;316(20):2115-2125

INFECTIONS DUE TO RESISTANT PATHOGENS ~ 2 M/y infected with abx-resistant bacteria ~ 23,000/y die as a direct result and more from complications from other conditions ~ 8 million additional hospital days/y Cost of resistance ~ $20B/y in excess costs ~$35B in lost productivity CDC. www.cdc.gov/media/releases/2011/f0407_antimicrobialresistance.pdf. Pew Health. http://www.pewhealth.org/uploadedfiles/phg/supporting_items/factsheet_threat.pdf CDC. www.cdc.gov/drugresistance/diseasesconnectedar.html MMWR 15;64:871-3. Aug 21, 2015

CDC s ANTIBIOTIC-RESISTANT THREATS IN US 2013 (Partial List) Urgent threat level pathogens C. diff N. gonorrhoeae Serious threat level pathogens Extended Spectrum β- Lactamase (ESBL) bacteria P. aeruginosa MRSA Vancomycin-Resistant Enterococcus (VRE) Drug-Resistant S. pneumoniae Of concern threat level pathogens Vanc-Resistant S. aureas Erythro-Resistant GABHS Clindamycin-Resistant GBS White House. National action plan for combating antibiotic-resistant bacteria. 3/15 https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating _antibotic-resistant_bacteria.pdf

C. diff Infection (CDI) in Hospitals CDI discharge diagnosis 2x increase 2000-09 Increases length of stay by 2.8-5.5 d Cost for inpatient 1-4.9 B/y 5-10% mortality ~14,000-20,000 deaths/y Every antibiotic has been associated with CDI FQ commonly implicated due to number of Rx Strategies to prevent CDI include antimicrobial restriction and stewardship Infection Control & Hospital Epidemiology 14;35:628-45 NEJM 15;372:1539-48 CDC

ACUTE BACTERIAL SINUSITIS THERAPY ß-lactams recommended as empiric therapy rather than a FQ Macrolides are not recommended for empiric therapy due to high S. pneumoniae resistance (~30%) TMP/SMX is not recommended for empiric therapy due to high S. pneumoniae and H. flu resistance (~30-40%) Bacterial Rhinosinusitis Guideline. 2012. http://www.idsociety.org/organ_system

ALTRU ANTIBIOGRAM 2015 History E. Coli susceptibility Ciprofloxacin: 2007 96%; 2010 93%; 2011 90%, 2013 88% TMP/SMX : 2007 90%; 2010 87%; 2011 84%, 2013 84%

EMPIRICAL TREATMENT OF ACUTE UNCOMPLICATED PYELONEPHRITIS Outpatient Cipro for 7 d or Levofloxacin for 5 d 1 st -line empiric therapy (2 nd -line for cystitis) If local resistance is < 10% If >10% resistance give initial dose ceftriaxone or aminoglycoside TMP/SMX for 14 d if pathogen susceptible If empiric give initial dose ceftriaxone or aminoglycoside IDSA Guidelines. Clin Infect Dis 11;51:e103-e120. NEJM 12;366:1028-37. Ann Intern Med 12;ITC3 3/6/12 JAMA 14;311:844-54 Dis-a-Mon 15;61:45-59

CASE 81 y/o male with fever to 38.2 C, chills, dysuria h/o BPH and past UTIs U/A + Ciprofloxacin 400 mg IV 2xd UC E. coli R Ampicillin; Ciprofloxacin; TMP/SMX S Amp/sulbactam; Ceftriaxone; Gentamicin; Nitrofurantoin

7 mon prior E coli R Amp, Cipro I Amp/sulbactam S Cefazolin, Ceftriaxone, Gent, Nitrofurantoin, TMP/SMX, 5 mon prior E coli R Amp, Cipro, Amp/sulbactam, TMP/SMX S Cefazolin, Ceftriaxone, Gent, Nitrofurantoin, Tobra 2 mon prior E coli R Amp, Cipro, Amp/sulbactam, TMP/SMX, Nitrofurantoin S Cefazolin, Ceftriaxone, Gent, Tobra 1 mon prior Citrobacter, Enterococcus, Pseudo Not treated Symptomatic UC grew C. albicans Empiric Ceftriaxone Switched to Fluconazole

Antibiotic Judo. Working Gently With Prescriber Psychology to Overcome Inappropriate Use Every individual s use of antibiotics contributes to loss of their efficacy over time for everyone else. person takes an antibiotic for an infection that is probably viral, with a small possibility that it is bacterial, there may be a small potential benefit to that person, balanced against a slight collective harm to society. Spellberg B. Commentary. JAMA IM. online Jan 27. 2014

Antibiotic Judo. Working Gently With Prescriber Psychology to Overcome Inappropriate Use When this happens frequently, the collective potential benefit to the users remains small, but harm to society grows. When it occurs hundreds of millions of times per year the aggregate harm to society is catastrophic Need for antibiotic stewardship programs Spellberg B. Commentary. JAMA IM. online Jan 27. 2014

CDC Grand Rounds: Getting Smart About Antibiotics Acute RTIs most inappropriate abx use No abx recommended for acute bronchitis 71% received abx Pharyngitis in adults usually don t require abx 5-10% due to GABHS ~60% received abx Selection of agent may be inappropriate Broad-spectrum (eg, 2 nd - or 3 rd -line abx) often used 2 nd - 3 rd - generation ceph, FQ usually not 1 st -line 2007-09 74% of Rx for RTIs were broad-spectrum MMWR 15;64:871-3. Aug 21, 2015 Gerber JS. Editorial JAMA 16;315:558-9

Despite published clinical guidelines and decades of efforts to change prescribing patterns, antibiotic overuse persists JAMA 16;315:562-70 The CDC recommends that all acute care hospitals implement an antibiotic stewardship program http://www.cdc.gov/longtermcare/prevention/antibiotic-stewardship.html

ANTIBIOTIC STEWARDSHIP DEFINITION Coordinated interventions to: Measure antibiotic prescribing Improve prescribing by clinicians and use by patients used only when needed Minimize misdiagnoses or delayed diagnoses leading to underuse of antibiotics Promote selection of optimal antibiotic and the right dose, duration, and route CDC. Antibiotic resistance threats in the United States, 2013. http://www.cdc.gov/drugresistance/threat-report-2013/index.html Implementing an Antibiotic Stewardship Program: Guidelines by the IDSA and the SHEA. Clin Infect Dis 16;62:e51-77. http://dx.doi.org/10.1093/cid/ciw217

ANTIBIOTIC STEWARDSHIP Inpatient, outpatient, and long-term care settings Is practiced at the Level of the patient Level of a health-care facility or system, or network Should be a core function of healthcare providers Utilizes expertise and experience of clinical pharmacists, microbiologists, infection control practitioners and information technologists Get Smart About Antibiotics. Introduction to Prudent Antibiotic Use. Antibiotic Stewardship Curriculum. Developed by Luther VP, Ohl CA.

EXAMPLES OF ANTIBIOTIC STEWARDSHIP OBJECTIVES Empirical therapy according to local or national guidelines Blood and site of infection cultures before abx De-escalation of therapy Change to narrow spectrum antibiotic or stop as soon as culture and susceptibility results available Adjustment of therapy to renal function Lancet Infect Dis. Online 3/2/16 http://dx.doi.org/10.1016/s1473-3099(16)00065-7

EXAMPLES OF ANTIBIOTIC STEWARDSHIP OBJECTIVES Switch from IV to oral therapy After 48-72 h if stable, oral intake and GI absorption adequate Adequate serum concentrations with oral Documented antibiotic plan Indication, drug name and dose, and administration route and interval Included in note at start of treatment Therapeutic drug monitoring Lancet Infect Dis. Online 3/2/16 http://dx.doi.org/10.1016/s1473-3099(16)00065-7

EXAMPLES OF ANTIBIOTIC STEWARDSHIP OBJECTIVES Discontinuation of empirical treatment based on lack of clinical or microbiological evidence of infection Local antibiotic guide present in the hospital and assessed for update every 3 years Local antibiotic guide in agreement with national antibiotic guidelines except for local resistance patterns Lancet Infect Dis. Online 3/2/16 http://dx.doi.org/10.1016/s1473-3099(16)00065-7

EXAMPLES OF ANTIBIOTIC STEWARDSHIP OBJECTIVES List of restricted antibiotics Removal of specific antibiotics from formulary Restriction of use by requiring preauthorization by a specialist Allowing use for only 72 h with mandatory approval for further use Bedside consultation Assessment of patients adherence Lancet Infect Dis. Online 3/2/16 http://dx.doi.org/10.1016/s1473-3099(16)00065-7

Current Evidence on Hospital Antimicrobial Stewardship Objectives Systematic Review/Meta-analysis of 145 studies Guideline-adherent empirical therapy: Mortality RRR 35% (p<0 0001) De-escalation: Mortality RRR 66% (p<0 0001) Therapeutic drug monitoring: RRR 50% for nephrotoxicity (p=0.02) Bedside consultation: RRR 66% with S. aureus bacteremia mortality (p=0.008) Lancet Infect Dis. Online 3/2/16 http://dx.doi.org/10.1016/s1473-3099(16)00065-7

NATIONAL ACTION PLAN GOALS Slow the Emergence of Resistant Bacteria and Prevent the Spread of Resistant Infections. Strengthen National One-Health Surveillance Efforts to Combat Resistance. Advance Development and Use of Rapid and Innovative Diagnostic Tests for Identification and Characterization of Resistant Bacteria. White House. National action plan for combating antibiotic-resistant bacteria. 3/15 https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating _antibotic-resistant_bacteria.pdf

Goal to Slow the Emergence of Resistant Bacteria & Prevent Spread of Resistant Infections by 2020 Judicious use of antibiotics essential to slow the emergence of resistance Outcomes will include: Antibiotic stewardship programs in all acute care hospitals & improved antibiotic stewardship across all healthcare settings Based on recommendations from CDC Core Elements of Hospital Antibiotic Stewardship Programs. http://www.cdc.gov/getsmart/healthcare/pdfs/core-elements.pdf White House. National action plan for combating antibiotic-resistant bacteria. 3/15 https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating_antiboticresistant_bacteria.pdf

Goal to Slow the Emergence of Resistant Bacteria & Prevent Spread of Resistant Infections by 2020 Outcomes (continued) Reduction of inappropriate antibiotic use by 50% in outpatient & by 20% in inpatient Antibiotic Resistance Prevention Programs in all states Elimination of medically-important antibiotics in animals. Veterinary oversight of medically-important abx White House. National action plan for combating antibiotic-resistant bacteria. 3/15 https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating_antiboticresistant_bacteria.pdf

LOCATIONS OF STEWARDSHIP PROGRAMS Expansion to ambulatory surgery centers, dialysis centers, nursing homes and other longterm care facilities, and emergency departments and outpatient settings is also recommended. IDSA/SHEA Guideline. Clin Infect Dis (2016). doi: 10.1093/cid/ciw118. First published online: Apr 13, 2016 http://cid.oxfordjournals.org/content/early/2016/04/11/cid.ciw118.full

Core Elements of Antibiotic Stewardship Programs CDC 2014 Core Elements of Hospital Antibiotic Stewardship Programs 2015 Core Elements of Antibiotic Stewardship for Nursing Homes 2016 Core Elements of Outpatient Antibiotic Stewardship

Vital Signs: Improving Antibiotic Use Among Hospitalized Patients ~60% receive at least 1 day of antibiotic Incorrect in up to 50% Indication, choice, or duration can be incorrect 30%, outside of critical care, unnecessary Used for longer than recommended durations Used to treat colonizing or contaminating organisms CDC. MMWR 14;63:194-200

ANTIBIOTIC STEWARDSHIP IN NHs Up to 70%/y receive antibiotics Up to 75% of antibiotics Rx s incorrectly CDC recommends that all nursing homes take steps to improve antibiotic prescribing practices and reduce inappropriate use. CDC The core elements of antibiotic stewardship for nursing homes, 2015. http://www.cdc.gov/longtermcare/index.html.

IDENTIFY OPPORTUNITIES TO IMPROVE OUTPATIENT RX Identify high-priority conditions for intervention which commonly lead to deviation from best practices for prescribing Overprescribed not indicated eg, not indicated for acute bronchitis, nonspecific URI, viral pharyngitis Overdiagnosed may be appropriate but without fulfilling diagnostic criteria eg, GAS pharyngitis diagnosed without testing for GAS Core Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12 11/11/16. http://www.cdc.gov/mmwr/volumes/65/rr/rr6506a1.htm?s_cid=rr6506a1_e

IDENTIFY OPPORTUNITIES TO IMPROVE OUTPATIENT RX Misprescribed may be indicated but wrong drug, dose or duration eg, azithromycin rather than amox or amox/clav for acute uncomplicated bacterial sinusitis Watchful waiting or delayed use is appropriate but underused eg, AOM, acute uncomplicated sinusitis Underused or timely use not recognized eg, missed STD or severe bacterial infections such as sepsis Core Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12 11/11/16. http://www.cdc.gov/mmwr/volumes/65/rr/rr6506a1.htm?s_cid=rr6506a1_e

IDENTIFY OPPORTUNITIES TO IMPROVE OUTPATIENT RX Identify barriers that may lead to deviation from best practices, eg Clinician: Knowledge about best practices and guidelines Perception of patient expectations for antibiotics Perceived pressure to see patients quickly Concerns about decreased patient satisfaction with clinical visits when antibiotics are not prescribed Core Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12 11/11/16. http://www.cdc.gov/mmwr/volumes/65/rr/rr6506a1.htm?s_cid=rr6506a1_e

IDENTIFY OPPORTUNITIES TO IMPROVE OUTPATIENT RX Establish standards for antibiotics based on evidence-based diagnostic criteria and treatment, eg: Implementation of clinical practice guidelines If applicable, developing facility- or system-specific practice guidelines Establishing expectations for appropriate prescribing Core Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12 11/11/16. http://www.cdc.gov/mmwr/volumes/65/rr/rr6506a1.htm?s_cid=rr6506a1_e

ACTION. Clinicians implement at least 1 of following Use evidence-based diagnostic criteria & treatment recommendations from guidelines Use delayed prescribing practices or watchful waiting, when appropriate Postdated Rx with instructions for filling Patient call or pick up Rx if worsen or no improvement Provide symptomatic relief suggestions Core Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12 11/11/16. http://www.cdc.gov/mmwr/volumes/65/rr/rr6506a1.htm?s_cid=rr6506a1_e

ACTION. Outpatient & health care system leaders at least 1 of following Provide communication skills training for clinicians Strategies to address patient concerns regarding: Prognosis, benefits, and harms of treatment Management of self-limiting conditions Clinician concerns Managing patient expectations for antibiotics during a clinical visit Core Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12 11/11/16. http://www.cdc.gov/mmwr/volumes/65/rr/rr6506a1.htm?s_cid=rr6506a1_e

ACTION. Outpatient & health care system leaders at least 1 of following Require explicit written justification in the medical record for nonrecommended abx Rx ing Hold clinicians accountable in medical record for decisions Provide support for clinical decisions. Clinical decision support in electronic or print form during the typical workflow Can facilitate diagnoses and effective management of common conditions

ACTION. Outpatient & health care system leaders at least 1 of following Use call centers, nurse hotlines, or pharmacist consultations as triage systems to prevent unnecessary visits. These resources can be used to reduce unnecessary visits for conditions that do not require a clinic visit, such as a common cold. Core Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12 11/11/16. http://www.cdc.gov/mmwr/volumes/65/rr/rr6506a1.htm?s_cid=rr6506a1_e

TRACKING & REPORTING. Clinicians implement at least 1 of following Self-evaluate antibiotic prescribing practices Use self-evaluations to align prescribing practices with updated evidence-based recommendations and clinical practice guidelines Participate in CME and quality improvement activities to track and improve antibiotic prescribing Core Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12 11/11/16. http://www.cdc.gov/mmwr/volumes/65/rr/rr6506a1.htm?s_cid=rr6506a1_e

TRACKING & REPORTING. Outpatient & health care system leaders at least 1 of following Implement at least one antibiotic prescribing tracking and reporting system For high-priority conditions that have been identified % of visits leading to Rx Complications of use and resistance trends Outcomes can be tracked and reported by individual clinicians (which is preferred) and by facilities Core Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12 11/11/16. http://www.cdc.gov/mmwr/volumes/65/rr/rr6506a1.htm?s_cid=rr6506a1_e

TRACKING & REPORTING. Outpatient & health care system leaders at least 1 of following Assess and share performance on quality measures and established reduction goals addressing appropriate prescribing from health care plans and payers National Strategy for Combating Antibiotic- Resistant Bacteria aims to reduce inappropriate use by 50% for monitored conditions in outpatient settings by 2020 Healthcare Effectiveness Data and Information Set (HEDIS) quality measures

Current National Committee for Quality Assurance HEDIS Measures 2016 Appropriate treatment for children with URI Diagnosed with URI and no antibiotic Rx Appropriate testing for children with pharyngitis Diagnosed with pharyngitis, Rx d antibiotic, and received a GAS test Avoidance of antibiotic treatment in adults with acute bronchitis Diagnosed with acute bronchitis no antibiotic Rx http://www.ncqa.org/hedis-quality-measurement/hedis-measures

EDUCATION & EXPERTISE. Clinicians educate patients by at least 1 Use effective communications strategies to educate patients about when antibiotics are and are not needed, eg: Antibiotics of no benefit for viral infections Some bacterial infections (e.g., AOM and sinus infections) might improve without antibiotics Recommendations for symptom management and when to seek additional care (contingency plan) Improves patient satisfaction Core Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12 11/11/16. http://www.cdc.gov/mmwr/volumes/65/rr/rr6506a1.htm?s_cid=rr6506a1_e

STRATEGIES FOR STEWARDSHIP OF ACUTE RTIs IN COMMUNITY Raise the public s antibiotic threshold Community awareness of stewardship Vaccination as a key strategy Covering more territory to fight resistance Pharmacists, Nurses An antibiotic license to prescribe? Stewardship governance in primary care Leadership commitment, Accountability Clin Pulm Med 16;23:1-10

EDUCATION & EXPERTISE. Clinicians educate patients by at least 1 Educate patients about the potential harms of antibiotic treatment eg, common and sometimes serious side effects: nausea, abdominal pain, diarrhea, C. difficile, allergic reactions, disturbing microbiota Provide patient education materials Many choices at http://www.cdc.gov/getsmart Core Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12 11/11/16. http://www.cdc.gov/mmwr/volumes/65/rr/rr6506a1.htm?s_cid=rr6506a1_e

EDUCATION & EXPERTISE. Outpatient & health care system leaders at least 1 of following Provide face-to-face educational training By peers, colleagues, or opinion leaders, other clinicians and pharmacists Use reinforcement techniques and peer-to-peer comparisons Core Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12 11/11/16. http://www.cdc.gov/mmwr/volumes/65/rr/rr6506a1.htm?s_cid=rr6506a1_e

EDUCATION & EXPERTISE. Outpatient & health care system leaders at least 1 of following Provide CE activities for clinicians. Appropriate prescribing, adverse drug events, and communication strategies about appropriate Rx ing Training to assess patient expectations, discuss risks & benefits, provide recommendations for when to seek medical care if worsening or not improving (contingency plan), and assess patient s understanding of communicated information Decreases inappropriate antibiotic prescribing Core Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12 11/11/16. http://www.cdc.gov/mmwr/volumes/65/rr/rr6506a1.htm?s_cid=rr6506a1_e

EDUCATION & EXPERTISE. Outpatient & health care system leaders at least 1 of following Ensure timely access to persons with expertise eg, pharmacists or medical and surgical consultants who can assist clinicians in improving antibiotic prescribing Pharmacists with ID training effective are important members of stewardship programs Improved patient outcomes and overall cost savings for the hospital Core Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12 11/11/16. http://www.cdc.gov/mmwr/volumes/65/rr/rr6506a1.htm?s_cid=rr6506a1_e

Effect of Behavioral Interventions on Inappropriate Antibiotic Prescribing RCT 248 primary care clinicians in Boston and LA over 18 months Randomized to receive 0, 1, 2, or 3 interventions All groups received education and observation Control group had no study intervention Suggested alternatives intervention in EHR With acute RTI triggered clinician decision supports and electronic order sets suggesting nonantibiotic treatments JAMA 16;315:562-70

Effect of Behavioral Interventions on Inappropriate Antibiotic Prescribing Interventions continued Accountable justification intervention (EHR) Prompted clinicians to enter free-text justifications for prescribing antibiotics Triggered for both inappropriate and appropriate antibiotic RTI diagnoses Peer comparison intervention Sent monthly emails to clinicians that compared their antibiotic prescribing rates with those of top performers (lowest inappropriate prescribing rates) JAMA 16;315:562-70

Effect of Behavioral Interventions on Inappropriate Antibiotic Prescribing Antibiotic Rx rates baseline vs. month 18 Control group 24.1% to 13.1% Suggested alternatives 22.1% to 6.1% P=0.66 Accountable justification 23.2% to 5.2% P<0.001 Peer comparison 19.9% to 3.7% P<0.001 Significant reductions in inappropriate antibiotic prescribing Accountable justification and peer comparison JAMA 16;315:562-70

STRATEGIES FOR STEWARDSHIP OF ACUTE RTIs IN COMMUNITY Treat bacterial infection only Judicious antibiotic prescribing principles Use pharmacokinetic/pharmacodynamics to choose most effective agents and appropriate dosage Optimize the duration of therapy Know your bugs : local antibiograms Use abx associated with < selection of resistance Prescription strategies Immediate vs delayed vs no Rx Clin Pulm Med 16;23:1-10

STRATEGIES FOR STEWARDSHIP OF ACUTE RTIs IN COMMUNITY Raise the public s antibiotic threshold Community awareness of stewardship Vaccination as a key strategy Covering more territory to fight resistance Pharmacists, Nurses An antibiotic license to prescribe? Stewardship governance in primary care Leadership commitment, Accountability Clin Pulm Med 16;23:1-10

RTI 1 st -LINE ANTIBIOTIC USE 2010-11 Nat Amb Med Care Survey AOM 67% Amoxicillin or amoxicillin/clavulanate ~12% macrolide, ~17% ceph Acute bacterial sinusitis ~37% Amoxicillin or amoxicillin/clavulanate ~27% macrolide, ~10% FQ GAS pharyngitis Peds ~60%, Adult ~40% Penicillin or amoxicillin Peds ~20% macrolide, 5% ceph Adult ~12% amox/clav, ~35% macrolide JAMA IM 16;176:1870-1. Letter

Duration of Antibiotics in CAP: Multicenter RCT Duration minimum of 5 d if responding and stable vs. standard therapy (at least 10 d) 5 d duration in 70% of patients in intervention group Clinical success ~94% intervention vs. ~93% control (P = 0.33) Stopping antibiotics if clinically stabile after a minimum of 5 d is not inferior to traditional treatment duration JAMA Intern Med 16;176:1257-65

Short course, d Long course, d CAP 3-5 7-10 Nosocomial pneumonia < 8 10-15 ABECB < 5 > 7 AOM (varies with age & severity) SHORT-COURSE THERAPY Not severe: 5 (>6y); 7 (2-5y); < 3 (>2y) 10 (2y, severe) Acute bact sinusitis 5-7 10 Uncomp cystitis 3 (FQ, TMP/SMX) 7-10 Pyelonephritis 5-7 (FQ) 10-14 Cellulitis 5-6 10 Spellberg. JAMA IM 15;176:1254-5 Pharmacist s Letter/Prescriber s Letter. 11/16 & 12/16

DURATION OF THERAPY Finish all the pills even if you feel better Age old instruction to patients Increase in curing the infection? Reduce resistance by eradicating all the organisms? Prevent a relapse of the infection? Historically in multiples of 7 d (eg, 7-14 d) for many common infections Often not based on clinical outcome studies JAMA Intern Med 16;176:1257-65 Pharmacist s Letter/Prescriber s Letter. November 2016

DURATION OF THERAPY Shorter courses now have demonstrated efficacy for some common infections Potential benefits of shorter courses of antibiotic Lower resistance with less normal flora exposure May reduce cost May reduce risk of adverse effects Fewer antibiotic side effects Less superinfections from altering normal flora (C. diff) May increase adherence JAMA Intern Med 16;176:1257-65 Pharmacist s Letter/Prescriber s Letter. November 2016

The New Antibiotic Mantra No evidence for illogical statement that to prevent antibiotic resistance, it is necessary to complete the entire prescribed course of therapy, even after resolution of symptoms Longer courses increase selection for resistance Overtreating is likely a major source of selective pressure that drives antibiotic resistance in society Spellberg B. edit. JAMA IM 15;176:1254=5

The New Antibiotic Mantra Shorter courses greatly preferable Customize duration to the patient s response Contact clinic if symptoms resolve before completing antibiotic assess for stopping early Clinicians should be encouraged to allow patients to stop antibiotic treatment as early as possible on resolution of symptoms Spellberg B. edit. JAMA IM 15;176:1254=5

The New Antibiotic Mantra Ultimately, we should replace the old dogma of continuing therapy past resolution of symptoms with a new, evidence-based dogma of shorter is better. Spellberg B. edit. JAMA IM 15;176:1254=5

ANTIBIOTIC STEWARDSHIP Infection & Syndrome Specific Interventions CAP Improving diagnostic accuracy, tailoring of therapy to culture results and optimizing the duration of treatment to ensure compliance with guidelines UTIs Many have asymptomatic bacteriuria and not infections Ensure appropriate therapy based on local susceptibilities and for the recommended duration CDC Core Elements of Hospital Antibiotic Stewardship Programs. 2014. http://www.cdc.gov/getsmart/healthcare/implementation/core-elements.html

UTI in Advanced Dementia 19% of treated UTIs met minimal criteria for antibiotics well recognized that asymptomatic bacteriuria should not be treated UTI diagnosis is often made but should not be made vague changes in MS without objective signs Urinalyses and UCs are often positive in advanced dementia Negative tests rule out but positive test do not necessarily justify the use of antibiotics NEJM 15;372:2533-40

ANTIBIOTIC STEWARDSHIP Infection & Syndrome Specific Interventions Skin and soft tissue infections Do no use overly broad-spectrum antibiotics and ensure correct duration of treatment Empiric coverage of MRSA infections In many cases, therapy can be stopped if the patient does not have an MRSA infection or changed to a ß- lactam if the cause is MSSA CDC Core Elements of Hospital Antibiotic Stewardship Programs. 2014. http://www.cdc.gov/getsmart/healthcare/implementation/core-elements.html

ANTIBIOTIC STEWARDSHIP Infection & Syndrome Specific Interventions C difficile infections Stop unnecessary antibiotics which often does not occur Treatment of culture proven invasive infections. Provides information to tailor antibiotics or discontinue them if contaminants CDC Core Elements of Hospital Antibiotic Stewardship Programs. 2014. http://www.cdc.gov/getsmart/healthcare/implementation/core-elements.html

ANTIBIOTIC STEWARDSHIP Infection & Syndrome Specific Interventions Upper respiratory infections not otherwise specified Antibiotic use does not enhance illness resolution or prevent complications and is not recommended Acute pharyngitis Limit antibiotic use to those with highest liklihood of GABHS. Penicillin is preferred CDC Get Smart. Updated 4/17/15 http://www.cdc.gov/getsmart/community/materialsreferences/print-materials/hcp/adult-approp-summary.html

ANTIBIOTIC STEWARDSHIP Infection & Syndrome Specific Interventions Rhinosinusitis Most cases viral assess criteria for bacterial Reserve antibiotics for those that meet criteria for bacterial etiology with moderate to severe symptoms Use most narrow-spectrum agent against S. pneumoniae and H. influenzae Uncomplicated acute bronchitis Routine antibiotic use not recommended regardless the duration of cough CDC Get Smart. Updated 4/17/15 http://www.cdc.gov/getsmart/community/materialsreferences/print-materials/hcp/adult-approp-summary.html

WHAT SHOULD PATIENTS BE TOLD ABOUT THEIR ANTIBIOTIC? Clear instructions on intended duration Emphasize importance of taking properly What to do when symptoms resolve: Should they contact the office to discuss? Should they complete the prescribed course, even if symptoms resolve? Dispose of remaining doses to avoid temptation to self-treat in the future Pharmacist s Letter/Prescriber s Letter. November 2016

Physicians should be comfortable with making the following statement to most of their patients with acute RTIs: For your infection, there is an 1 in 4000 chance that an antibiotic will prevent a serious complication, a 5% 25% chance that it will cause diarrhea, and an 1 in 1000 chance that you will require a visit to the ED because of a bad reaction to the antibiotic. Clinical Infectious Diseases 08;47:744-6. Editorial