1. Clinical comparison of extended versus standard piperacillin-tazobactam infusion Arsheena Yassin, Pharm.D. PGY-1 Pharmacy Resident June 9 th, 2016

2. Background Englewood Hospital and Medical Center (EHMC) 520 beds Community hospital Select specialties: Bloodless medicine Cardiac and vascular surgery Breast care, oncology and joint-replacement services

3. Piperacillin-Tazobactam Standard infusion over 30 mins Potential benefit to using extended infusion Lodise TP et al. Clin Infect Dis. 2007; 44:357-63. Brunetti L et al. Ann Pharmacother. 2015; 49:754-60 Yost RJ et al. Pharmacotherapy. 2012; 31:767-75 Patel N et al. Antimicrob Agents Chemother. 2010; 54:460-65

4. Background Antimicrobial stewardship at EHMC Cefepime: Antipseudomonal drug of choice Pip-tazo: Restricted to Infectious Disease 4/15 Reports of pip-tazo shortage Began restricting use of pip-tazo 7/15 Reports of cefepime shortage 9/15 Education on extended pip-tazo infusion Transition patients from standard to extended infusion 11/15 All pip-tazo orders switched to extended infusion

5. Study Objective Compare the clinical impact of extended versus standard pip-tazo infusion at a community hospital

6. Study Endpoints Primary endpoint: All cause 14-day in-hospital mortality Secondary endpoints: Mean length of stay (days) Mean duration of antibiotic therapy (days) Number of vials used

7. Study Design Investigational Review Board approved Retrospective chart review utilizing McKesson® Horizon Patient Folder for data collection Statistical tests Fishers Exact Test t-Test Mann-Whitney U Test P-value <0.05 considered statistically significant

8. Study Design Groups compared: N=120 patients Extended infusion n=60 3.375 g pip-tazo IV Q8H Infused over 4 H Standard infusion n=60 4.5 g pip-tazo IV Q6-8H Infused over 30 min

9. Inclusion Criteria Admitted at EHMC: Between October 4, 2014 and March 23, 2016 Received at least one dose of pip-tazo infusion Age ≥18 at the time of admission

10. Exclusion Criteria Age ˂ 18 Pregnant women

11. Data Collection Patient’s demographics Doses of pip-tazo Dates Culture results Laboratory parameters Indications for pip-tazo Other antibiotics used

12. Results: Baseline Characteristics Standard infusion Extended infusion p value n=60 Mean age (years) ± SD63.4 ±17.769.7±17.90.0545 Female, n (%)30 (50)31 (51.67)1 Race, n (%)  White40 (66.67)38 (63.33)1  Other20 (33.33)22 (36.67)1 Mean baseline SCr (mg/dl) ± SD0.96 ±0.420.94 ±0.550.78 Mean BMI (kg/m 2 ) ± SD26.7 ±6.6425.3±5.910.2428  <18.5 kg/m 2, n (%)4 (6.67)6 (10)0.743  18.5-24.9 kg/m 2, n (%)21 (35)20 (33.33)1  25.0-29.9 kg/m 2, n (%)17 (28.33)23 (38.33)0.333  30.0-39.9 kg/m 2, n (%)14 (23.33)8 (13.33)0.2378  ≥40.0 kg/m 2, n (%)4 (6.67)3 (5)1

13. Results: Baseline Characteristics Standard infusion Extended infusion p value n=60 Co-morbidities, n (%)  Chronic heart failure13 (21.67)10 (16.67)0.6435  Chronic obstructive pulmonary disease 7 (11.67)4 (6.67)0.5289  Diabetes20 (33.33)21 (35)1  Hypertension21 (35)26 (43.33)0.4546 Mean baseline WBC (1000 cells/µl) ± SD18.88±7.816.31±9.890.1394 Baseline positive procalcitonin level, n (%)16 (26.67)23 (38.33)0.2421 Level of care ICU, n (%)18 (30) 1 Non-ICU, n (%)42 (70) 1 Mean baseline lactate ± SD2.11±1.732.73±2.10.1341 Healthcare facility prior to admission, n (%) 11 (18.33)13 (21.67)0.8199 On antibiotics prior to admission, n (%)10 (16.67)11 (18.33)1

14. Infections in culture positive patients Results: Baseline Characteristics

15. Indications for pip-tazo Results: Baseline Characteristics

16. Other antibiotics used Results: Baseline Characteristics

17. Results: Primary Outcome All cause 14-day in-hospital mortality Total all cause 14-day in-hospital mortality Standard infusion 4 (7%) Extended infusion 7 (12%) Odds ratio=1.75 p value=0.39 95% CI 0.4868-6.2913

18. All cause 14-day in-hospital mortality Overall 14 day in hospital mortality ICU Extended infusion 4 (6.67%) Standard infusion 3 (5%) Non-ICU Extended infusion 3 (5%) Standard infusion 1 (1.67%) Odds ratio=1.26 p value=0.78 95% CI 0.2450-6.4734 Odds ratio=3.07 p value=0.34 95% CI 0.3071-30.7212 Results: Secondary Outcomes

19. Length of stay 11.83±8.73 14.48±14.04 23.5±17.09 p value=0.2273 15.4±10.577 p value=0.9948

20. Results: Secondary Outcomes Duration of therapy 4.41±3.00 4.25±3.79 6.52±5.29 5.43±4.88 p value=0.123p value=0.0749

21. Results: Secondary Outcomes Cost comparison Prices used: 3.375 g pip-tazo: $3.96 4.5 g pip-tazo: $5.12

22. Results: Secondary Outcomes Cost comparison Prices used: 3.375 g pip-tazo: $3.96 4.5 g pip-tazo: $5.12 Total mean extra standard pip-tazo dose per day 5.14 g Extra cost for standard infusion per day $5.85 Extra total cost for standard infusion in 60 patients $1907.57

23. Discussion No difference in: All cause 14 day in-hospital mortality Length of day Duration of therapy Cost savings of about $1907.57 when using extended versus standard infusion Saving of 5.14g of extended pip-tazo per day

24. Relevance to EHMC After switching from standard to extended infusions of pip-tazo Able to save doses of pip-tazo Useful due to shortage Similar efficacy Allowed for dose optimization

25. Relevance to EHMC Will discuss this at Antimicrobial Sub- Committee Continue with extended infusion pip-tazo Increase nursing time One IV line committed to pip-tazo Education Able to get supply of pip-tazo

26. Limitations Small sample Limited the ability to detect significant findings Retrospective study Confounding and information bias possible Mainly used for empiric treatment Restricted to Infectious Disease Lower cost and dose saving

27. Conclusions At similar hospitals like EHMC, implementing extended infusion pip-tazo: May not yield superior efficacy over standard infusion May be useful in limiting antibiotics use within the hospital Drug shortage Restrict use Could represent cost saving at larger institutions where pip-tazo is the empiric drug of choice and not restricted

28. Assessment Question What are the benefits of switching from standard to extended pip-tazo infusions at a community hospital? A.Allow for dose optimization B.Lower doses of pip-tazo used C.Increase the bacteriocidal effects of pip-tazo D.All of the above

29. Acknowledgements Deirdre Minihan, Pharm.D., BCPS Jacqueline Takere, Pharm.D., CCRP Joseph Cruz, Pharm.D., BCPS James Regan, RPh, MS, MIS Jeffrey Nemeth, Pharm.D., BSPh, MPA

30. Questions The floor is now open to any questions

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