Grey Nuns Community Hospital (GNCH) Antimicrobial Stewardship July December 2017

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Grey Nuns Community Hospital (GNCH) Antimicrobial Stewardship July December 217

Table of Contents Table of Contents... 2 I. Executive Summary... 3 II. GNCH Total Antimicrobial Utilization... 4 III. GNCH Inpatient Antibiotic Utilization... 9 A. GNCH Critical Care... 1 B. GNCH Medicine... 12 C. GNCH Surgery... 14 IV. GNCH Outpatient Antimicrobial Utilization... 16 A. GNCH ED... 16 B. GNCH IV Clinic... 19 V. Clostridium difficile (CDI) Prospective Audit and Feedback... 2 VI. Antimicrobial Stewardship Pharmacist Interventions... 21 VII. Appendix I.... 22 A. Antimicrobial Stewardship Overview... 22 B. Covenant Health Antimicrobial Stewardship Committee (CHASC) Initiatives... 23 C. Utilization Reports Methods... 23 D. Glossary of Terms... 25 Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 2

I. Executive Summary (July December 217) Areas of Success: S. aureus bacteremia (SAB) is associated with high rates of morbidity and mortality (3-4%). Management according to evidence based quality of care measures has been shown to improve outcomes and has been incorporated into a bundle used for audit and feedback of all SAB patients since October 215. SAB bundle adherence continues to be at target for Critical Care and Medicine. There were no SAB patients in Surgery. Opportunities for Improvement: Critical Care, Medicine, Surgery and the IV Clinic continue to prescribe the restricted antibiotics appropriately with reliable completion of the restricted antibiotic form. The Emergency Department remains a focus for further education and support. Given the Fluoroquinolone (FQ) Health Canada Safety warning, review of inpatient FQ use started in July with prospective audit and feedback in September. Overall use was reasonable but with continued support, we expect all areas to exceed the 9% target for the next reporting period. C. difficile infection (CDI) continues to be a high priority area with a recent increase in the number of cases in the last quarter. The CDI-attributable mortality rate for the last six months was zero, reflecting the high rates of guideline concordant management across all services. CDI management could be further optimized with increased CDI Preprinted Medication Order Set (PMOS) use. The CDI PMOS ensures appropriate patient isolation, diagnostic testing and promotes the cessation of other CDI offending medications. Revisions are underway and an updated CDI PMOS will be released later in the year that incorporates the updated American and Canadian guidelines on CDI management. Table 1. Quality Indicator Report Card Quality Indicator Critical Care Medicine Surgery ED IV Clinic Restricted Antibiotic 93% 96% 1% 78% 94% Concordant Use Restricted Form Compliance 93% 94% 81% 78% 86% Fluoroquinolone Concordant 88% 9% 86% Use CDI Deaths none CDI Rate (hospital acquired) Jul-Sep 7 cases Rate: 2.1/1, pt days Oct-Dec 15 cases Rate: 4.6/1, pt days CDI Treatment Concordance 1% 94% 1% CDI PMOS Use 5% 69% 2% SAB Bundle Adherence 92% 1% Green: greater than 9%, Yellow: 8-9%, Red less than 8%, Grey: No patients or data collected. Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 3

II. GNCH Total Antimicrobial Utilization Figure 1. GNCH Total Antimicrobial Usage and Expenditures GNCH Total Antibiotic DDD GNCH Total Antibiotic Expenditures 3 $3 25 $25 2 $2 15 $15 1 5 Oral Parenteral $1 $5 $ Oral Parenteral 16 14 12 1 8 6 4 GNCH DDD by Antibiotic Group Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin $14 $12 $1 $8 $6 $4 GNCH Expenditures by Antibiotic Group Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin 2 Fluoroquinolones Vancomycin $2 $ Fluoroquinolones Vancomycin GNCH Restricted Antibiotic DDD GNCH Restricted Antibiotic Expenditures 14 12 1 8 6 4 2 Daptomycin Ertapenem Imipenem Linezolid Meropenem Tigecycline $45 $4 $35 $3 $25 $2 $15 $1 $5 $ Daptomycin Ertapenem Imipenem Linezolid Meropenem Tigecycline DDD = Defined daily dose. Assumed average maintenance dose per day for a drug used for its main indication in adults. Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 4

GNCH Total Antibiotic Use Summary: Overall antibiotic use has remained stable during the July to December 217 period with cephalosporins accounting for the majority of antibiotic use. Piperacillin-tazobactam is the most frequently ordered broad spectrum antibiotic and accounts for the greatest antibiotic expenditures. Table 2. Top 1 Antimicrobials by Descending Utilization July to December 217 Antimicrobial Total DDD Total Expenditures Cost per Day Ceftriaxone 968 $36545 $2.33 Cefazolin 6772 $3592 $3.9 Metronidazole 2677 $7713 IV $3.64 PO $.24 Piperacillin-tazobactam 267 $62354 $14.1 Nystatin 266 $1395 $.75 Ciprofloxacin 1979 $1432 IV $4.26 PO $.14 Amoxicillin-clavulanate 1972 $1378 $.72 Azithromycin 1752 $4427 IV $6.81 PO $.29 Vancomycin 1714 $19742 $1.6 Cefixime 1498 $4712 $2.76 Subtotal of Top 1 31568 $175622 Grand Total 45846 $42585 Table 3. Top 1 Antimicrobials by Descending Expenditures July to December 217 Antimicrobial Total Expenditures Total DDD Cost per Day Piperacillin-tazobactam $62354 968 $14.1 Ertapenem $49214 912 $52.22 Daptomycin $36591 355 $13.4 Ceftriaxone $36545 968 $2.33 Cefazolin $3592 6772 $3.9 Amphotericin B liposome^ $35721 54 $661.5 Vancomycin $19742 1714 $1.6 Imipenem $17914 534 $25.8 Ceftazidime $158 418 $35.86 Meropenem $1344 247 $48.8 Subtotal of Top 1 $322129 29146 Grand Total $42585 45846 ^ Attribute to one patient in the IV Clinic on a prolonged course of guideline concordant liposomal amphotericin B therapy. Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 5

Restricted Antimicrobial Use Summary: Prior to restriction of our most broad spectrum antibiotics (daptomycin, ertapenem, imipenem, linezolid, meropenem, tigecycline), guideline concordant rates of prescribing these drugs averaged 5%. Since introducing the restricted antibiotic order form and prospective audit and feedback of these antibiotics in October 213, the number of orders halved and the guideline concordant rate of prescribing increased to approximately 9%. Figure 2. GNCH Restricted Antibiotic Orders April 213 to December 217 25 2 15 1 5 GNCH Restricted Antibiotic Orders April 213 to December 217 * Restricted antibiotic form implemented in October 213 Restricted Antibiotic Orders Guideline Concordant Orders Forms Completed Figure 3. GNCH Restricted Antibiotic Guideline Concordance and Form Completion Rates April 213 to December 217 GNCH Restricted Antibiotic and Form Completion Rates 1 9 8 7 6 5 4 3 2 1 *Restricted antibiotic form implemented in October 213 Guideline Concordance (%) Form Compliance (%) Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 6

Restricted Antimicrobial Use Per Service: Overall guideline concordant use of the 6 restricted antibiotics remains high although there is room for improvement with Emergency Department use of ertapenem. Completion rates for the restricted antibiotic order form needs to be improved upon as the form is essential for accurate ASP data collection and serves as one of the accreditation requirements. Table 4. Total GNCH Compliance with Preauthorization Form and Guideline Concordance Rates July to December 217 Service Antibiotic Number of Orders Critical Care Guideline Concordance Change from Previous Form Compliance Imipenem 24 22 (92%) 22 (92%) Meropenem 6 6 (1%) 6 (1%) Total 3 28 (93%) 28 (93%) Emergency Ertapenem 23 18 (78%) 18 (78%) Total 23 18 (78%) 18 (78%) HPT Daptomycin 1 1 (1%) Ertapenem 2 2 (1%) 1 (5%) Imipenem 1 1 (1%) 1 (1%) Total 4 4 (1%) 2 (5%) IV Clinic Daptomycin 4 4 (1%) 2 (5%) Ertapenem 29 27 (93%) 27 (93%) Imipenem 2 2 (1%) 1 (5%) Meropenem 1 1 (1%) 1 (1%) Total 36 34 (94%) 31 (86%) L&D Meropenem 1 1 (1%) 1 (1%) Total 1 1 (1%) 1 (1%) Medicine Daptomycin 3 3 (1%) 3 (1%) Ertapenem 32 31 (97%) 3 (94%) Imipenem 31 29 (91%) 28 (9%) Linezolid 1 1 (1%) 1 (1%) Meropenem 9 9 (1%) 9 (1%) Tigecycline 1 1 (1%) 1 (1%) Total 77 74 (96%) 72 (94%) Surgery Ertapenem 5 5 (1%) 5 (1%) Imipenem 9 9 (1%) 8 (89%) Meropenem 2 2 (1%) Total 16 16 (1%) 13 (81%) Grand Total 187 175 (94%) 164 (88%) Change from Previous Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 7

GNCH Fluoroquinolone Orders July to December 217 Prospective audit and feedback of fluoroquinolone use was initiated September 217 based on increasing concerns with toxicity/adverse events, as outlined in the Health Canada safety warning, strong association with CDI and increasing resistance rates. The majority of fluoroquinolone use consists of levofloxacin for respiratory tract infections and ciprofloxacin for genitourinary or intraabdominal infections. Since prospective audit and feedback began, there has been a reduction in the fluoroquinolone days of therapy and number of fluoroquinolone orders (Figure 4) and (Figure 5). Rates of guideline concordant prescribing are displayed in Table 5 and information on discordant orders can be found in the service specific section of the report. Figure 4. Fluoroquinolone Days of Therapy 5 4 3 2 1 GNCH Fluroquinolone Days of Therapy by Month July Aug *Sep Oct Nov Dec Ciprofloxacin Levofloxacin Moxifloxacin Figure 5. Number of Fluoroquinolone Orders By Indication *Fluoroquinolone audit and feedback began September 217 Table 5. Fluoroquinolone Guideline Concordant Prescribing by Service 9 8 7 6 5 4 3 2 1 GNCH Fluoroquinolone Orders by Indication Jul Aug *Sep Oct Nov Dec Most common discordant uses: Ciprofloxacin empiric therapy and not meeting UTI criteria Levofloxacin not meeting AECOPD criteria Discordant GU IAI Osteoarticular Prophylaxis Resp SSTI Month Internal Medicine July 18/21 (86%) August 32/34 (94%) September 22/23 (96%) October 23/23 (1%) November 12/12 (1%) December 17/17 (1%) Total 124/13 (95%) Guideline Concordant Prescribing by Service Surgery - Critical Family Palliative Other Care Medicine Care 5/7 5/6 3/34 3/3 (71%) (83%) (88%) (1%) 9/1 4/4 21/25 3/5 (9%) (1%) (84%) (6%) 7/7 4/4 16/18 4/5 (1%) (1%) (89%) (8%) 8/8 4/5 14/16 2/2 (1%) (8%) (88%) (1%) 6/6 2/2 16/19 2/4 (1%) (1%) (84%) (5%) 8/8 3/4 22/24 3/3 (1%) (75%) (92%) (1%) 43/46 22/25 119/136 17/22 (94%) (88%) (88%) (77%) Surgery - Vascular 6/7 (86%) 1/4 (25%) 9/9 (1%) 5/6 (83%) 3/4 (75%) 1/3 (33%) 25/33 (76%) Stroke /2 2/2 (1%) 1/2 (5%) 3/6 (5%) Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 8

III. GNCH Inpatient Antibiotic Utilization The services accounting for the most antibiotic use, controlled for inpatient volumes are Critical Care, Surgery, Medicine and Palliative Care. Figure 6. Antibiotic Utilization - Inpatient 12 GNCH Total DDD/1 Patient Days by Service 1 Critical Care 8 Family & Internal Medicine 6 Geriatrics & Stroke 4 L&D 2 Palliative Care Jan-Mar 216 Apr-Jun 216 Jul-Sep 216 Oct-Dec 216 Jan-Mar 217 Apr-Jun 217 Jul-Sep 217 Oct-Dec 217 Psychiatry Surgery Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 9

A. GNCH Critical Care Antibiotic Utilization Antimicrobial use in the Critical Care unit remains largely stable. There has been a recent reduction in the amount of piperacillin-tazobactam use. Guideline concordant use of the restricted antibiotics is reasonable at 93% but fluoroquinolone rates are only 71% in the CCU. Recommendations: 1. CCU to examine use of fluoroquinolones and ensure they are being used for guideline concordant indications where the benefits outweigh the risks. Figure 7. GNCH Critical Care* Antimicrobial Usage and Expenditures per 1 Patient Days 1 8 GNCH Critical Care Total Antibiotic DDD/1 Patient Days $12 $1 GNCH Critical Care Total Antibiotic Expenditures/1 Patient Days 6 4 2 Oral Parenteral $8 $6 $4 $2 Oral Parenteral $ 6 5 4 3 2 1 GNCH Critical Care DDD/1 Patient Days by Antibiotic Group Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin Fluoroquinolones Vancomycin 14 12 1 8 6 4 2 GNCH Critical Care Restricted Antibiotic DDD/1 Patient Days Daptomycin Ertapenem imipenem Linezolid Meropenem Tigecycline *CCU and ICU combined DDD = Defined daily dose. Assumed average maintenance dose per day for a drug used for its main indication in adults. Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 1

Table 6. GNCH Critical Care Compliance with Preauthorization Form and Guideline Concordance Rates July to December 217 Service Antibiotic Number of Orders Critical Care Guideline Concordance Change from Previous Form Compliance Imipenem 24 22 (92%) 22 (92%) Meropenem 6 6 (1%) 6 (1%) Total 3 28 (93%) 28 (93%) Change from Previous Antibiotic Table 7. GNCH Critical Care Fluoroquinolone Review July to December 217 Number of Orders Guideline Concordance Alternate Therapy Preferred Ω Discordant Indications Genitourinary* Respiratory # CCU Ciprofloxacin 2 1 (5%) 1 Levofloxacin 5 4 (8%) 1 1 Total 7 5 (71%) 1 1 1 ICU Ciprofloxacin 15 15 (1%) Levofloxacin 3 3 (1%) Total 18 18 (1%) *Did not meet criteria for UTI # Did not meet criteria for use of levofloxacin in AECOPD Ω Refers to prescriber selecting a fluoroquinolone when other options are available with fewer risks Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 11

B. GNCH Medicine Antibiotic Utilization Antimicrobial use remains stable with family/internal medicine accounting for the majority of use. Cephalosporins are the most commonly ordered IV antibiotic. There has been stable use of the restricted antibiotics with good form compliance. The fluoroquinolone audit demonstrates that ciprofloxacin is sometimes being ordered for genitourinary indications that are not deemed appropriate (e.g. asymptomatic bacteriuria and symptoms not meeting criteria for a urinary tract infection) which represents an area for improvement. Recommendations: 1. Palliative care and Stroke service to examine the use of fluoroquinolones and ensure they are being used for guideline concordant indications where the benefits outweigh the risks. Figure 8. GNCH Medicine* Antimicrobial Usage and Expenditures per 1 Patient Days 8 7 6 5 4 3 2 1 GNCH Medicine Total DDD/1 Patient Days by Service Family & Internal Medicine Geriatrics & Stroke Palliative Care $7 $6 $5 $4 $3 $2 $1 $ GNCH Medicine Total Expenditures/1 Patient Days by Service Family & Internal Medicine Geriatrics & Stroke Palliative Care 3 25 2 15 1 5 GNCH Medicine DDD/1 Patient Days by Antibiotic Group Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin Fluoroquinolones Vancomycin 3.5 3 2.5 2 1.5 1.5 GNCH Medicine Restricted Antibiotic DDD/1 Patient Days Daptomycin Ertapenem imipenem Linezolid Meropenem Tigecycline *Geriatrics, Stroke, Family Medicine, Internal Medicine, Palliative Care and ERIP DDD = Defined daily dose. Assumed average maintenance dose per day for a drug used for its main indication in adults. Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 12

Table 8. GNCH Medicine Compliance with Preauthorization Form and Guideline Concordance Rates July to December 217 Service Antibiotic Number of Orders Guideline Concordance Change from Previous Form Compliance Change from Previous Medicine Daptomycin 3 3 (1%) 3 (1%) Ertapenem 32 31 (97%) 3 (94%) Imipenem 31 29 (91%) 28 (9%) Linezolid 1 1 (1%) 1 (1%) Meropenem 9 9 (1%) 9 (1%) Tigecycline 1 1 (1%) 1 (1%) Total 77 74 (96%) 72 (94%) Antibiotic Table 9. GNCH Medicine Fluoroquinolone Review July to December 217 Number of Orders Guideline Concordance Alternate Therapy Preferred Ω Genitourinary* Discordant Indication Other# Respiratory SSTI Family Medicine Ciprofloxacin 79 68 (86%) 9 11 Levofloxacin 57 51 (89%) 1 5 Total 136 119 (88%) 9 11 1 5 *2-ASB, 5-did not meet UTI criteria, 4-ciprofloxacin used as empiric therapy #-asthma exacerbation -4 AECOPD not meeting criteria for fluoroquinolone therapy, 1 pneumonia-no symptoms Internal Medicine Ciprofloxacin 81 75 (93%) 5 5 1 Levofloxacin 49 49 (1%) Total 13 124 (95%) 5 5 1 *3-ciprofloxacin used as empiric therapy, 1-ASB, 2-No UTI symptoms coverage too broad Palliative Care Ciprofloxacin 13 9 (69%) 2 4 Levofloxacin 9 8 (89%) 1 1 Total 22 17 (77%) 3 4 1 *1-ASB, 3-did not meet UTI criteria 1-pneumonia-no symptoms Stroke Ciprofloxacin 6 3 (5%) 1 3 Total 6 3 (5%) 1 3 *no UTI symptoms Ω Refers to prescriber selecting a fluoroquinolone when other options are available with fewer risks Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 13

C. GNCH Surgery Antibiotic Utilization Overall antibiotic use within the surgery department remains stable. Guideline concordant prescribing of the restricted antibiotics is excellent although form completion could be improved upon. Ciprofloxacin is the most commonly ordered fluoroquinolone and is typically prescribed in a concordant manner for intraabdominal infections. There have been discordant orders in vascular surgery for genitourinary symptoms which did not meet criteria for UTI representing an area for improvement. Recommendations: 1. Vascular surgery to ensure that patients meet criteria for UTI (and not asymptomatic bacteriuria) prior to initiating antimicrobial therapy. If empiric UTI therapy is required, ciprofloxacin is no longer recommended due to increased rates of resistance and high side effect profile. Figure 9. GNCH Surgery Antimicrobial Usage and Expenditures per 1 Patient Days $12 $1 $8 $6 $4 $2 GNCH Surgery Total DDD/1 Patient Days Vascular Other $12 $1 $8 $6 $4 $2 GNCH Surgery Total Expenditures/1 Patient Days Vascular Other $ $ 6 5 4 3 2 1 GNCH Surgery DDD/1 Patient Days by Antibiotic Group Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin Fluoroquinolones Vancomycin 8 7 6 5 4 3 2 1 GNCH Surgery Restricted Antibiotic DDD/1 Patient Days Daptomycin Ertapenem imipenem Linezolid Meropenem Tigecycline DDD = Defined daily dose. Assumed average maintenance dose per day for a drug used for its main indication in adults Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 14

Table 1. GNCH Surgery Compliance with Preauthorization Form and Guideline Concordance Rates July to December 217 Service Antibiotic Number of Orders Guideline Concordance Change from Previous Form Compliance Surgery Ertapenem 5 5 (1%) 5 (1%) Imipenem 9 9 (1%) 8 (89%) Meropenem 2 2 (1%) Total 16 16 (1%) 13 (81%) Change from Previous Table 11. GNCH Surgery Fluoroquinolone Review July to December 217 Antibiotic Number of Orders Guideline Concordance Alternate Therapy Preferred Ω Discordant Indication Genitourinary* Surgery - Other Ciprofloxacin 42 39 (93%) 2 2 Levofloxacin 3 3 (1%) Moxifloxacin 1 1 (1%) Total 46 43 (93%) 2 2 *2-ciprofloxacin used as empiric therapy, 1-no UTI symptoms Surgery Vascular Ciprofloxacin 32 24 (75%) 1 7 Levofloxacin 1 1 (1%) Total 33 25 (76%) 1 7 *2-ciprofloxacin used as empiric therapy, 6-no UTI symptoms Ω Refers to prescriber selecting a fluoroquinolone when other options are available with fewer risks Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 15

GNCH Outpatient Antimicrobial Utilization IV. A. GNCH ED Antibiotic Utilization There has been a small increase in antibiotic use over the last quarter. Cephalosporins continue to make up the most commonly prescribed IV antibiotic. Piperacillin-tazobactam is the most commonly used broad spectrum antibiotic with a recent increase in use. Ertapenem is the only restricted antibiotic ordered in the ED, but guideline concordant prescribing remains low at 78% (with only a 78% form compliance rate). Recommendations: 1. Given drug allocation, prospective audit and feedback of piperacillin-tazobactam will resume. Ensure that piperacillin-tazobactam is being used judiciously and according to the below provincial formulary guidelines: 1. Empiric therapy of severe infections including sepsis of unknown source or suspected to be polymicrobial (e.g. intra-abdominal, limb threatening diabetic foot) 2. Alone or in combination, empiric therapy of ventilator-associated pneumonia 3. Empiric therapy in high risk febrile neutropenic patients (oral temperature 38.3 C once or 38 C for 1 hour, absolute neutrophil count <.5 x 1 9 /L) +/- aminoglycoside NB: For monomicrobial infections due to Pseudomonas aeruginosa, options for therapy include ceftazidime, ciprofloxacin, piperacillin (still available), or aminoglycosides, according to susceptibility. 2. Ensure ertapenem is being ordered for guideline concordant indications which include the following: 1. Empiric therapy of polymicrobial complicated skin and skin structure infections, including bite wound infections. 2. Therapy of infections due to Enterobacteriaceae producing inducible (AmpC) ß-lactamases or extendedspectrum ß-lactamases (ESBLs) where there is resistance to first line agents and documented susceptibility to ertapenem. 3. Empiric therapy for patients at high risk (e.g. previous ESBL infection, international travel history) of infections due to Enterobacteriaceae producing extended-spectrum β-lactamases (ESBLs). 4. Therapy of community-acquired intra-abdominal infections in patients intolerant or unresponsive to first line therapy (ceftriaxone and metronidazole). Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 16

Figure 1. GNCH ED* Antimicrobial Usage and Expenditures 25 GNCH Total ED DDD/1 Patient Visits $12 GNCH Total ED Expenditures/1 Patient Visits 2 $1 15 1 5 Oral Parenteral $8 $6 $4 $2 Oral Parenteral $ 12 1 8 6 4 2 GNCH ED DDD/1 Patient Visits by Antibiotic Group Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin Fluoroquinolones Vancomycin 6 5 4 3 2 1 GNCH ED Restricted Antibiotic DDD/1 Patient Visits Daptomycin Ertapenem Imipenem Linezolid Meropenem Tigecycline *Does not include ERIP DDD = Defined daily dose. Assumed average maintenance dose per day for a drug used for its main indication in adults. Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 17

Table 12. GNCH ED Compliance with Preauthorization Form and Guideline Concordance Rates July to December 217 Restricted Antibiotic Number of Orders Guideline Concordant Change from Previous Form Compliance Ertapenem 23 18 (78%) 18 (78%) Total 23 18 (78%) 18 (78%) Change from Previous Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 18

B. GNCH IV Clinic Antibiotic Utilization Antibiotic utilization remains largely stable with cephalosporins accounting for the majority of use. Ertapenem is the most commonly used restricted antibiotic with a guideline concordance rate of 94%. Figure 11. GNCH IV Clinic Antimicrobial Usage and Expenditures 5 4 3 2 1 GNCH Total IV Clinic DDD/1 Patients Oral Parenteral $14 $12 $1 $8 $6 $4 $2 $ GNCH Total IV Clinic Expenditures/1 Patients Oral Parenteral 45 4 35 3 25 2 15 1 5 GNCH IV Clinic DDD/1 Patients by Antibiotic Group Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin Fluoroquinolones Vancomycin 7 6 5 4 3 2 1 GNCH IV Clinic Restricted Antibiotic DDD/1 Patients Daptomycin Ertapenem Imipenem Linezolid Meropenem Tigecycline DDD = Defined daily dose. Assumed average maintenance dose per day for a drug used for its main indication in adults. Table 13. GNCH IV Clinic Compliance with Preauthorization Form and Guideline Concordance Rates July to December 217 Service Antibiotic Number of Orders Guideline Concordance Change from Previous Form Compliance IV Clinic Daptomycin 4 4 (1%) 2 (5%) Ertapenem 29 27 (93%) 27 (93%) Imipenem 2 2 (1%) 1 (5%) Meropenem 1 1 (1%) 1 (1%) Total 36 34 (94%) 31 (86%) Change from Previous Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 19

V. Clostridium difficile (CDI) Prospective Audit and Feedback Guideline concordant management of CDI remains high at 93% but management could be further improved with increased use of the CDI PMOS (Table 14), which will be undergoing revisions in light of the udpdated American and Canadian CDI management guidelines. CDI rates had been stable with a recent increase in the July to December 217 period (Figure 12). CDI attributable mortality rates have decreased since implementation of CDI audit and feedback and the CDI PMOS (Figure 13). Table 14. CDI Audit and Feedback July to December 217 Month Number of Cases CDI Attributable Mortality* Guideline Concordant Treatment CDI PMOS Utilized Alter CDI Treatment Pharmacy Interventions Alter CDI Treatment Duration Stop acid suppressive therapy July 6 6 (1%) 3 (5%) 1 1 1 Aug 5 5 (1%) 5 (1%) Sept 7 6 (86%) 2 (29%) 1 1 Stop antibiotic Oct 7 7 (1%) 5 (71%) 1 Nov 8 8 (1%) 6 (75%) 1 2 2 1 Dec 12 1 (83%) 6 (5%) 1 1 Total 45 42/45 (93%) 27/45 (6%) *Accurate at the time of this report but is subject to change due to on-going IPC surveillance 4 5 3 1 Figure 12. GNCH CDI Treatment Concordance, PMOS Use and CDI Rate GNCH CDI Treatment Concordance, PMOS Use and CDI Rates 1 7.7 7.8 7.3 1 5 5.5 3.8 4.9 4.9 4 3 3 3.7 4.2 4.6 3.2 3.6 3.5 3.7 1.2 1.5 1.8 2.1 5 CDI Rate PMOS Implemention % Guideline Concordant Treatment % PMOS Utilization Figure 13. GNCH CDI Treatment Concordance, PMOS Use and Mortality GNCH CDI Treatment Concordance, PMOS Use and Mortality 6 1 4 2 2 4 2 1 2 1 1 1 5 CDI Attributable Deaths PMOS Implemention % Guideline Concordant Treatment % PMOS Utilization Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 2

VI. Antimicrobial Stewardship Interventions During audit and feedback of the restricted antibiotics, the fluoroquinolones and CDI, the antimicrobial stewardship team makes interventions to optimize patient care. The following graph (Figure 14) captures the number, type and indication of antimicrobial stewardship interventions for the period July to December 217. 92% (89/97) of the antimicrobial stewardship recommendations were accepted by the attending physician. Figure 14. GNCH Number of ASP Interventions Accepted July to December 217 4 GNCH Number of ASP Interventions Accepted July to December 217 35 3 AECOPD Bacteremia 25 CDI 2 Febrile Neutropenia 15 IAI 1 Pneumonia Sepsis NYD 5 SSTI Antimicrobial therapy unnecessary Dose optimization Duration of therapy optimized Equivalent efficacy & decreased cost Excellent oral Medication bioavailability discontinued Potential adverse event or allergy Spectrum of antimicrobial agent UTI Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 21

VII. Appendix I. A. Antimicrobial Stewardship Overview Antibiotics are among the most commonly prescribed medications in acute care centres (Figure 15), yet can result in unintended patient toxicities, selection of pathogenic organisms, such as C. difficile and promotion of antibiotic resistance Figure 15. GNCH Drug Expenditures July to December 217 Total Antibiotic Expenditures Total Drug Expenditures 13% 87% Antimicrobial Stewardship is an interdisciplinary activity that promotes the optimization of antibiotic selection, dose, route and duration in order to improve patient clinical outcomes and safety, minimize antibiotic adverse effects and toxicity, decrease the selection of pathogenic organisms and reduce antibiotic resistance rates. An effective Antimicrobial Stewardship Program (ASP) has been demonstrated to achieve the above outcomes and as of 213, has been mandated as a Required Organizational Practice by Accreditation Canada and as such the Covenant Health Antimicrobial Stewardship Committee (CHASC) was developed in May 213. Antibiotic use at Covenant Health acute care sites is collated and examined by CHASC on a semiannual basis in order to: Identify any antibiotic utilization trends or areas in need of intervention Ensure that the use of broad-spectrum antibiotics is guideline concordant. Generate semi-annual reports summarizing antibiotic trends and CHASC recommendations for prescribers as direct feedback on their antibiotic use. Summary of GNCH Services included: Critical Care Units (CCU and ICU) Emergency (ED) Intravenous Therapy Clinic Medicine which includes Palliative Care, Stroke, Geriatrics, Emergency inpatients (ERIP), Family and Internal Medicine Surgery which includes Vascular Surgery, General Surgery, Plastic Surgery, and Gynecology Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 22

B. Covenant Health Antimicrobial Stewardship Committee (CHASC) Initiatives 1. Formulary restriction and preauthorization for daptomycin, ertapenem, imipenem, linezolid, meropenem and tigecycline 2. Prospective audit and feedback of piperacillin-tazobactam and other antimicrobials 3. Development of a C. difficile (CDI) Preprinted Medication Order Set (PMOS) with Prospective Audit and Feedback 4. Collation of antibiotic utilization data 5. Circulation of a Covenant Health Antimicrobial Stewardship e-newsletter (CHASE) quarterly 6. Wide distribution and posting of formulary guidelines for the carbapenems and piperacillintazobactam to promote guideline concordant use 7. Development of a Preprinted Medication Order Set (PMOS) for the combined use of cefazolin and probenecid for simple cellulitis in outpatient areas 8. Prospective audit and feedback of S. aureus bacteremia according to evidence based guidelines 9. Prospective audit and feedback on the fluoroquinolones C. Utilization Reports Methods Data on antibiotic use is extracted directly from BDM (pharmacy computer system). Clinical information acquired from the antibiotic preauthorization form and/or prospective audit and feedback is compared to the provincial formulary recommendations to determine guideline concordance. Drug utilization data is provided in both DDD (Defined Daily Dose) and expenditures. DDD is a World Health Organization measure of drug consumption. The definition is the assumed average maintenance dose per day for a drug used for its main indication in adults. It relates all drug use to a standardized measure which is equivalent to one day s worth. DDD allows us to compare antibiotic use across different classes despite differences in potency and dosing. C. difficile hospital rates and mortality data are obtained from Infection Prevention and Control. Denominator Data: DDDs are now provided over the denominator of actual patient days. This allows us to account for any fluctuations in patient volume over time meaning that changes in antibiotic utilization are due to changes in prescribing rather than changes in patient volume. Denominator Data Inpatient Areas: Patient day denominator data is provided by Analytics (Data Integration, Measurement and Reporting [DIMR]). It is a summary of the number of patient days at the site by unit and includes emergency admitted patients but excludes emergency non-admitted patients and patients less than one year of age. Patient days are calculated as follows: Emergency department inpatient days are counted from the time of decision to admit until the ED departure for patients admitted to an inpatient bed. Inpatient days are a daily census count. Patients admitted and discharged on the same day are counted as one day and the day of admission is counted but the day of discharge/death is not. The data is provided quarterly and is the same data that is used by Infection Prevention and Control (IPC) for monitoring C. difficile rates. Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 23

Patient day data has been integrated into the utilization data to obtain DDDs and expenditures per 1 patient days. Denominator Data Outpatient Areas: Patient visit denominator data for the Emergency Department is provided by Data and Decision Support using the Power Abstract Database. Emergency visits include patients discharged home, transfers to other clinics or facilities and deaths. It excludes patients left without being seen (LWBS), patients left against medical advice (LAMA) and inpatient admissions. IV Clinic unique patient numbers are provided by Alberta Health Services Regional Activity and Costing. Patients are counted only once regardless of how many visits the patient makes to the clinic. Outpatient denominator data has been integrated into the utilization data to obtain DDDs and expenditures per 1 patients (IV Clinic) or visits (ED). Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 24

D. Glossary of Terms AECOPD...Acute Exacerbation of Chronic Obstruction Pulmonary Disease ASB.Asymptomatic Bacteriuria ASP...Antimicrobial Stewardship Program CHASC Covenant Health Antimicrobial Stewardship Committee CCU...Coronary Care Unit CDI..... Clostridium difficile Infection CHASC...Covenant Health Antimicrobial Stewardship Committee CHASE...Covenant Health Antimicrobial Stewardship E-Newsletter DDD...Defined Daily Dose DIMR..Data Integration, Measurement and Reporting ED..Emergency Department ERIP..Emergency Inpatients ESBL.. Extended Spectrum β-lactamase GIM..General Internal Medicine GU Genitourinary HAP.Hospital Acquired Pneumonia IAI. Intra-abdominal Infection ICU. Intensive Care Unit ID...Infectious Diseases IPC..Infection Prevention and Control IMCU...Intermediate Care Unit L&D.. Labour and Delivery LAMA..Left Against Medical Advice LOC Level of Consciousness LWBS... Left Without Being Seen OSA....Obstructive Sleep Apnea MDR..... Multi-drug Resistant PMOS. Preprinted Medication Order Set Resp Respiratory SAB....Staphylococcus aureus bacteremia SSTI Skin and Soft Tissue Infection U/S....Ultrasound UTI...Urinary Tract Infection Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July - December 217 25