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

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

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

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

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

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

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

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

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

Exclusion Criteria Age ˂ 18 Pregnant women

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

Results: Baseline Characteristics Standard infusion Extended infusion p value n=60 Mean age (years) ± SD63.4 ± ± 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 ± ± Mean BMI (kg/m 2 ) ± SD26.7 ± ±  <18.5 kg/m 2, n (%)4 (6.67)6 (10)0.743  kg/m 2, n (%)21 (35)20 (33.33)1  kg/m 2, n (%)17 (28.33)23 (38.33)0.333  kg/m 2, n (%)14 (23.33)8 (13.33)  ≥40.0 kg/m 2, n (%)4 (6.67)3 (5)1

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

Infections in culture positive patients Results: Baseline Characteristics

Indications for pip-tazo Results: Baseline Characteristics

Other antibiotics used Results: Baseline Characteristics

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= % CI

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= % CI Odds ratio=3.07 p value= % CI Results: Secondary Outcomes

Length of stay 11.83± ± ±17.09 p value= ± p value=0.9948

Results: Secondary Outcomes Duration of therapy 4.41± ± ± ±4.88 p value=0.123p value=0.0749

Results: Secondary Outcomes Cost comparison Prices used: g pip-tazo: $ g pip-tazo: $5.12

Results: Secondary Outcomes Cost comparison Prices used: g pip-tazo: $ 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 $

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

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

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

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

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

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

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

Questions The floor is now open to any questions

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