1. Implementation of a Pharmacist Driven Antimicrobial Stewardship Service for General Medicine Adult Inpatients Receiving Piperacillin/tazobactam or Cefepime – A Pilot Study Yasmine Elbaga, PharmD PGY-1 Pharmacy Resident Newark Beth Israel Medical Center Newark, NJ 1

2. Newark Beth Israel Medical Center & Children’s Hospital of New Jersey 600+ bed teaching institution with approximately 95,000 ED visits annually 3 rd largest heart transplant center by volume in the United States and New Jersey’s only center for lung transplantation Cares for complex patients with life saving modalities such as ECMO, CRRT, and plasmapheresis Only hospital in New Jersey to perform cardiothoracic surgeries on pediatric patients Most recently merged to form RWJBarnabas Health, the 10 th largest health care system in the United States 2

3. Background Piperacillin/tazobactam and cefepime are not restricted by the Infectious Diseases (ID) department at Newark Beth Israel Medical Center (NBIMC) No formal multidisciplinary antibiotic stewardship committee A retrospective medication use evaluation (MUE) was conducted last year evaluating empiric piperacillin/tazobactam use January 1, 2014 to December 31, 2014 3

4. Background Results of previous MUE (n=108): 14/108 (13%) lacked proper documentation of indication 21/94 (22%) treated for an inappropriate indication 19/73 (26%) with appropriate indications treated inappropriate dose Indicated need for prospective intervention 4

5. Study Objective To prospectively evaluate the impact of a pharmacist performing antimicrobial stewardship activities for general medicine adult inpatients receiving piperacillin/tazobactam or cefepime by assessing the number of interventions accepted 5

6. Methods IRB approved, prospective, two-phase interventional study 6 Inclusion Criteria Patients ≥ 18 years old Admitted to an adult in-service November 12, 2015 and April 1, 2016 Receive at least 1 dose of piperacillin/tazobactam or cefepime Indications: community acquired pneumonia (CAP), cellulitis, urinary tract infection (UTI), or Chronic obstructive pulmonary disease (COPD) exacerbation Exclusion Criteria Pregnancy Age < 18 or patients any age admitted to pediatric service ICU or CCU admission ≥ 24 hours Patients who receive an infectious diseases consult Outside of time frame Patients with a least one transplanted organ

7. Data collection Patients identified with a web based surveillance tool Patients screened for at least one hour a day Information collected: Patient demographics Renal function Indication of therapy Documentation of indication Empiric therapy De-escalation IV to PO conversion Duration of therapy 7

8. Institutional Guidelines Developed based on guidelines from the Infectious Diseases Society of America (IDSA) and approved by the Infectious Diseases Department at NBIMC 8

9. Community Acquired Pneumonia 9 Mandell LA, et al. Clin Infec Dis. 2007;44(2):S27-S72. Cultures/ Diagnostic Tests Empiric Therapy Choices Penicillin Allergy Maximum Duration of Therapy Chest X-Ray Blood culture if:  Leukopenia  Cavitary infiltrates  Active alcohol abuse  Severe liver disease  COPD/structural lung disease Sputum culture if:  Failure of outpatient antibiotics  Cavitary infiltrates  Alcohol abuse ceftriaxone AND azithromycin (IV/PO) OR levofloxacin (IV/PO) (doxycycline alternative to azithromycin) levofloxacin IV/PO 5 days

10. Phase 1 10 Initiation of piperacillin/ tazobactam or cefepime 24 hours Evaluation of Therapy Documentation of indication Appropriateness of empiric therapy Cultures and diagnostics ordered Dose based on indication and organ function

11. Phase 2 De-escalation IV to PO conversion Duration of therapy Renal Dose Adjustment 11 Cultures Collected? No Yes Re-evaluated within 24 hours of sensitivity results Re-evaluated after 72 hours

12. Phases 1 & 2: Criteria for Renal Dosing Patient’s creatinine clearance (CrCl) calculated using the Cockcroft-Gault equation Recommended guidance from Lexicomp ® as the institution’s preferred drug reference database 12

13. Patient Screening 13 Patient Encounters Screened (N=534) Included in Phase 1 (n=36) Excluded (n=498) ICU stay ≥ 24 hours (n=31) Transplant patients (n=27) COPD Exacerbation (n=5) UTI (n=19) Cellulitis (n=6) ID Consult (n=239) CAP (n=6) Outside of Time Frame (n=27) Indication (n=171) Pediatric patients (n=3) Excluded (n=10) Included in Phase 2 (n=26) COPD Exacerbation (n=4) UTI (n=13) Cellulitis (n=5) CAP (n=4) Expiration (n=2) ID consult (n=7) ICU (n=1)

14. Baseline Characteristics VariablesN = 36 Age (years), Median + IQR 73 + 22 Weight (kg), Median + IQR 77 + 37 Baseline CrCl (mL/min), Median + IQR 32 + 40 Female, n (%) 25 (69) Dialysis Patients, n (%) 5 (14) 14

15. Results Phase 1 15 27 (75%) 28 (78%) Endpoints Number of Patients 19 (53%)

16. Results Phase 1 Inappropriate cultures (n=8) UTI (n=1) Culture contaminated, never recollected CAP (n=2) Inappropriate blood cultures COPD exacerbation (n=2) Inappropriate blood cultures Cellulitis (n=3) Inappropriate blood cultures 16

17. Phase 1 Interventions 17 Renal Dose Adjustment Empiric De-escalation Number of Patients

18. Phase 2 Interventions 18 De-escalation IV to PO ConversionDuration of Therapy Number of Patients

19. Discussion Many opportunities for pharmacist intervention Further support the current multidisciplinary antimicrobial stewardship committee at NBIMC Results support current literature advocating a pharmacist as the drug expert on an antimicrobial stewardship committee Non-compliance will be able to be escalated Escalations will provide opportunity for active interventions to supplement educational outreach 19 Collins CD. Am J Health-Syst Pharm. 2010;67:575-7. Centers for Disease Control and Prevention (CDC). (2015). Core Elements of Hospital Antibiotic Stewardship Programs

20. Discussion/Limitations Barriers to interventions Inappropriate initial empiric therapy selection Broad empiric coverage Hesitation of IV to PO conversion Interventions were more likely to be accepted with culture results Limitations of data collection Small sample size due to exclusion of ID consults Limited time for data collection Piperacillin/tazobactam national shortage 20

21. Future Direction Developing a clinical competency for pharmacists focused on urinary tract infections ‒ 4 th quarter of 2016 Further discussion by Antibiotic Subcommittee to develop clinical pathways to guide therapy 21

22. Acknowledgements Sheetal Patel, PharmD, BCPS, Residency Program Director and Clinical Coordinator Pamela Giordano, PharmD, BCPS, Clinical Assistant Professor of Pharmacy Practice for Fairleigh Dickinson University School of Pharmacy/Infectious Diseases Clinical Pharmacist Eliahu Bishburg, MD, Chair of the Division of Infectious Diseases 22

23. Questions? Yasmine Elbaga, PharmD PGY-1 Pharmacy Resident Newark Beth Israel Medical Center Newark, NJ Email: yelbaga@barnabashealth.org 23

24. Assessment Question 24 Based on the number of interventions attempted and the number accepted, what can be concluded from the study? A.There are many opportunities for pharmacists to perform stewardship activities B.The perceived need for broad empiric coverage may have been a barrier to intervention acceptance C.There is a small role for pharmacists on an antimicrobial stewardship committee? D.A & B

25. Implementation of a Pharmacist Driven Antimicrobial Stewardship Service for General Medicine Adult Inpatients Receiving Piperacillin/tazobactam or Cefepime – A Pilot Study Yasmine Elbaga, PharmD PGY-1 Pharmacy Resident Newark Beth Israel Medical Center Newark, NJ 25

26. Purulent Cellulitis 26 Stevents DL, et al. Clin Infec Dis. 2014; DOI 10.1093/cid/ciu296 Diagnostic Criteria/Risk Factors for MDR Cultures/ Diagnostic Tests Empiric Therapy Choices Penicillin Allergy Maximum Duration of Therapy  Most likely staphylococcus infection  Empiric therapy should cover MRSA until proven otherwise Pus and blood cultures in patients with:  Systemic toxicity  Extensive skin involvement Oral: clindamycin OR sulfamethoxazole/ trimethoprim OR doxycycline OR minocycline IV: vancomycin OR clindamycin clindamycin OR vancomycin 14 days

27. Non-Purulent Cellulitis 27 Diagnostic Criteria/Risk Factors for MDR Cultures/ Diagnostic Tests Empiric Therapy Choices Penicillin Allergy Maximum Duration of Therapy Mild:  Typical cellulitis without systemic signs of infection  Agents active against streptococci Moderate:  Typical cellulitis with systemic signs of infection Cultures not routine Mild, PO: penicillin VK OR cephalexin OR dicloxacillin OR clindamycin Mild, IV: penicillin OR clindamycin OR cefazolin Moderate: cefazolin OR ceftriaxone OR clindamycin OR penicillin clindamycin IV/PO 5 days, can extend therapy to 10 days if cellulitis is slow to respond Transition from IV to PO by day 3 if clinically appropriate Stevents DL, et al. Clin Infec Dis. 2014; DOI 10.1093/cid/ciu296

28. Urinary Tract Infections 28 Gupta K, et al. Clin Infec Dis. 2011;52:e103-e120. Diagnostic Criteria/Risk Factors for MDR Cultures/ Diagnostic Tests Empiric Therapy Choices Penicillin Allergy Maximum Duration of Therapy Uncomplicated UTI (+ symptoms of infection):  Healthy, non- pregnant female Complicated UTI (+ symptoms of infection):  Diabetes  Male  Symptoms > 7 days before seeking care  Renal failure  Indwelling catheter Urine analysis Urine culture with >100,000 CFU Uncomplicated: nitrofurantoin OR trimethoprim/ sulfamethoxazole OR ciprofloxacin (PO) OR levofloxacin Complicated: levofloxacin OR ciprofloxacin (PO) OR ceftriaxone OR gentamicin OR tobramycin Uncomplicated: ciprofloxacin (PO) OR levofloxacin (IV/PO) Complicated: gentamycin OR tobramycin Uncomplicated: 3 days Complicated: 14 days

29. COPD Exacerbation 29 Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2015. Available from: http://www.goldcopd.org/. Diagnostic Criteria/Risk Factors for MDR Cultures/ Diagnostic Tests Empiric Therapy Choices Penicillin Allergy Maximum Duration of Therapy When to treat with antibiotics: 1.Increased dyspnea 2.Increased sputum volume 3.Increased sputum purulence Pseudomonas RF:  Recent hospitalization (≥2 days in the past 90 days)  Frequent admin of antibiotics (≥4 courses in the past year)  Severe COPD (FEV 1 <50% predicted)  Isolation of Pseudomonas during previous exacerbation  Colonization  Systemic glucocorticoid use Sputum cultures often not useful except when Pseudomo- nas is a concern Pseudomonas concern: levofloxacin or ciprofloxacin (PO) OR cefepime OR piperacillin/ tazobactam No Pseudomonas risk: amoxicillin/clavulanate cefuroxime doxycycline levofloxacin sulfamethoxazole/ trimethoprim azithromycin ceftriaxone Levofloxacin 10 days

30. Phase 1 Excluded Patients 30

31. Phase 1 Excluded Patients (n=498) 31

32. Phases 1 & 2: Criteria for Renal Dosing Patient’s creatinine clearance (CrCl) calculated using the Cockcroft- Gault equation Recommended guidance from Lexicomp ® as the institution’s preferred drug reference database CrCl was calculated using utilizing the ideal body weight (IBW) For obese patients (BMI ≥ 30 kg/m 2 ), adjusted body weight (ABW) was used. ABW=IBW + 0.04(actual weight – IBW) For patients ≥ 65 years with serum creatinine (Scr) < 1 mg/dL, dose assessments were based after rounding Scr to 1 32