Prospective audit and feedback of piperacillin-tazobactam use in a 1115 bed acute care hospital

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Prospective audit and feedback of piperacillin-tazobactam use in a 1115 bed acute care hospital Final Results Nathan Beahm, BSP, PharmD(student) September 10, 2016

Objectives Review background information on piperacillintazobactam use. Summarize the methodology of the study. Evaluate the results of the study.

Disclosures I have no current or past relationships with commercial entities Speaking Fees for current program: I have received no speaker s fee for this learning activity This program has received no financial or in-kind support from any commercial or other organization

Piperacillin-tazobactam (PTZ) Beta-lactam/beta-lactamase inhibitor Broad-spectrum of activity including Gram positive, Gram negative (including Pseudomonas aeruginosa), and anaerobic bacteria Exhibits time-dependent killing

Piperacillin-tazobactam (PTZ) Some studies show appropriate empiric use to only be about 70% 1,2 Another study found appropriate empiric use for SSTI only 58% and for LRTI 62% 3 Piperacillin-tazobactam represents the highest annual antimicrobial expenditure at RAH ($281,698 for April 2014 March 2015) and 7 th highest by volume of use (DDD=9222.5; behind cefazolin, ceftriaxone, ciprofloxacin, metronidazole, vancomycin, and azithromycin) 4 1. J Antimicrob Chemother 2000;46:501-8. 2. P&T 2013;38(8):462-83. 3. Am J Infect Control 2015;43:946-50. 4. Royal Alexandra Hospital Antimicrobial Stewardship Report 2013-14 vs. 2014-15.

Methodology Prospective audit and feedback of new orders for PTZ for all RAH inpatients ordered between January 18 to February 10, 2016 A report was printed daily (weekdays) from pharmacy informatics system (VAX) to identify new orders from the previous 24 hours (Mondays starting after the first Monday included orders for the past 72 hours) Exclusions: - initiation prior to January 18 - received < 2 doses before discontinuation - pediatrics/nicu

Methodology The antimicrobial regimen was reviewed by the primary investigator utilizing Netcare, VAX, the patient/patient s chart, and various members of the health care team, including the pharmacist assigned to the team and/or physicians/nurses The primary investigator then used this information to decide if the regimen was appropriate and, if not appropriate, decide on a recommendation to optimize therapy

Methodology The primary investigator would then discuss the assessment and recommendations with the secondary investigator. Disagreements were resolved by consensus. If consensus could not be reached, or if the diagnosis was uncertain, the inpatient Infectious Diseases (ID) physician on call was consulted by the primary investigator for their input.

Methodology AHS guidelines (modified slightly for purposes of this study): - P/T 1 Empiric therapy of severe infections including sepsis of unknown source or suspected to be polymicrobial (e.g. intra-abdominal, limb threatening diabetic foot). - P/T 2 Empiric therapy of late-onset hospital-acquired pneumonia or ventilator-associated pneumonia, alone or in combination - P/T 3 Empiric therapy in high risk FN patients (oral temp 38.3 C once or 38 C for 1 hour, ANC < 0.5) ± AG - Appropriate (other) circumstances support use outside of guidelines - Not appropriate circumstances do not appear to support use outside of guidelines

Methodology If the regimen was deemed appropriate, no recommendations were left. If the regimen was deemed appropriate, but the dosing was potentially suboptimal, then a recommendation was left to optimize the dosing using the AHS Antimicrobial Stewardship (AS) Feedback Form. If the regimen was deemed inappropriate, a recommendation was left using the same form, unless the regimen was changed before a recommendation could be left.

Methodology The recommendations would also be discussed with the pharmacist assigned to the patient s team. For ICU patients, the recommendations were made to the ICU pharmacist, but the AS Feedback Form was not left for these patients. For patients being followed by ID, recommendations would be made to the ID team, but the AS Feedback Form was not left to avoid potential for conflicting recommendations.

AS Feedback Form

Methodology After initial assessment and recommendations (if applicable), the patient was followed until discharge. If other interventions to the patient s regimen were required at a future follow-up date, then recommendations would be made for the same.

Methodology Data collection included: - Indication - Start/stop date (and doses received) - Ordering physician - Concurrent and/or recent antibiotics - Relevant microbiology - If appropriate or not - Recommendations made/accepted and when Dosage/frequency was only assessed for appropriateness if the use of PTZ was considered appropriate.

Methodology Recommendation types: - Dose optimization - Stop antimicrobials - Narrow spectrum of antimicrobials - Broaden spectrum of antimicrobials - ID consult

Methodology Cost calculations - Calculated using drug-specific average moving price from VAX (which, for pharmacy manufactured items includes cost of drug, minibag, ± diluent) - Actual cost avoidance calculated for accepted suggestions by subtracting cost of new regimen from cost of PTZ if it had continued for the same duration as new regimen - Potential cost avoidance calculated for rejected suggestions by subtracting cost of rejected regimen from cost of PTZ from time of suggestion

Sample Case #1 64y female admitted with fever of unknown origin/hypotension. Likely source of infection left mastectomy wound (also receiving chemotherapy) She had a history of post-op wound infection x 3 in November with reinsertion of JP drain earlier this month. WBCs 17.1 (neuts 13.7), CrCl~95 Started on PTZ 3.375g IV Q6H + vancomycin Cultures pending Appropriate or not?

Sample Case #2 63y male admitted with dyspnea NYD (direct admission to Pulmonary service) Cough and dyspnea x 4 months COPD and smoker (1ppd). Afebrile, BP 125/85, HR105, RR 22, O 2 sat 100% RA, WBC 7.6 Bronchial wash from 5 days prior to admission grew P. aeruginosa sensitive to ceftaz, cipro, gent, pip, tobra CT chest no PE. Cavitary lesion unchanged since September. Possible neoplasms/adenocarcinoma. Opacification in RUL that could be related to postinfections or post-inflammatory changes Started on PTZ 4.5g IV Q6H + tobramycin Appropriate or not?

Results 91 patients Demographics (averages): male 50.5% age 61y WBC @ time of cultures (15.0) 1200 doses of PTZ received Average 13.2 doses/patient

Results Indication Ordered by Skin/soft tissue Intraabdominal Genital Respiratory Undefined Bacteremia 6% 8% 1% 3% 11% 25% Surgery 22% Cardiology 2% Pulmonary 9% ID 5% Medicine 40% Urinary tract Bone & Joint 42% 4% Women's 2% ICU 20%

Results Indication for Use P/T 1 28% Not appropriate 38% P/T 2 12% Appropriate (other) 21% P/T 3 1%

Results Indication Total # Orders # Appropriate % Appropriate Skin/soft tissue 10 7 70.0% Intra-abdominal 23 19 82.6% Genital 4 4 100.0% Respiratory 38 20 52.6% Undefined 5 0 0.0% Bacteremia 7 5 71.4% Urinary tract 1 0 0.0% Bone & Joint 3 1 33.3% Total 91 56 61.5%

Results Ordered by Total # Orders # Appropriate % Appropriate Medicine 36 23 63.9% ICU 18 10 55.6% Women s 2 2 100.0% Surgery 20 12 60.0% Pulmonary 8 4 50.0% Cardiology 2 0 0.0% ID 5 5 100.0% Total 91 56 61.5%

Results Respiratory Total # Orders # Appropriate % Appropriate Community acquired 26 9 34.6% Hospital acquired 12 11 91.7% Total 38 20 52.6%

Results # Recommendations made 20 18 16 14 12 10 8 6 4 2 0 3 0 3 2 18 13 0 0 1 1 19 25 interventions made vs. 19 made by team 16/25 (64%) acceptance rate

Results PTZ doses avoided: 201 Actual cost avoidance of study: $1,592 (Projected $23,653/year) Potential cost avoidance of study: $344 (Projected $5,113/year) Actual + potential cost avoidance of study: $1,936 (Projected $28,766/year)

Results Time spent: ~121.25 hours Roughly 1.3 hr/patient ID consultations: 18/91 (20%) patients (at most ~5 minutes/patient = 90 minutes)

Conclusions The rate of inappropriate PTZ use in this study was high. This study underscores the room for improvement that exists when it comes to PTZ use, as well as the need for and value of antimicrobial stewardship.

Acknowledgements Thank you to the following: - RAH pharmacists/physicians - Dr. Rabia Ahmed, ID - Dr. Isabelle Chiu, ID - Dr. Stuart Rosser, ID - Dr. Mark Joffe, ID - Susan Fryters, AS/ID pharmacist

Questions? Email: nathan.beahm@ualberta.ca or susan.fryters@ahs.ca