Misericordia Community Hospital (MCH) Antimicrobial Stewardship Report

Misericordia Community Hospital (MCH) Antimicrobial Stewardship Report July December 216

Table of Contents I. Introduction... 3 II. Executive Summary... 5 III. MCH Antimicrobial Utilization Reports... 7 A. Total MCH Antibiotic DDD and Expenditures... 7 B. Critical Care... 14 C. Emergency Department... 18 D. Medical Dayward and IV Therapy Area... 22 E. Medicine... 26 F. Surgery... 3 IV. Clostridium difficile Infection (CDI) Prospective Audit and Feedback... 35 V. Antimicrobial Stewardship Pharmacist Interventions... 37 VI. Appendix 1 - Villa Caritas (VC)... 38 VII. Appendix 2... 41 A. Utilization Reports - Methods... 41 B. Glossary of Terms... 42 Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 2

I. Introduction Antibiotics are among the most commonly prescribed medications in acute care centres (Figure 1), yet can result in unintended patient toxicities, selection of pathogenic organisms such as C. difficile and promotion of antibiotic resistance. Figure 1. MCH Drug Expenditures July - December 216 Antimicrobial expenditures Total drug expenditures 15% 85% 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. The Covenant Health Antimicrobial Stewardship Committee (CHASC) was developed in May 213 and has since implemented several initiatives including: 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 Clostridium difficile Infection (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 for the combined use of cefazolin and probenecid for simple cellulitis in outpatient areas. 8. Prospective audit and feedback of Staphylococcus aureus bacteremia according to evidencebased guidelines. Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 3

Antibiotic use at Covenant Health acute care sites is collated and examined by CHASC on a quarterly basis in order to: Identify any antibiotic utilization trends or areas in need of intervention on a site and servicespecific basis. 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 MCH Services included: Critical Care Units (CCU and ICU) Emergency (ED) Medical Dayward and IV Therapy Area (similar to an intravenous therapy clinic) Medicine Family and Internal Medicine, Geriatrics, Emergency Inpatients (ERIP) Surgery Orthopedic, Other (General, Obstetrics & Gynecology, Urology) Antibiotic Utilization Graphs: Antibiotic utilization is provided in three graphical formats: 1. Total drug DDD and expenditures for the hospital 2. Total inpatient drug DDD and expenditures per 1 patient days 3. Total outpatient drug DDD and expenditures per 1 patients or visits Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 4

II. Executive Summary Antibiotic utilization data is provided in graphical format from July 213 to December 216. This current semi-annual report describes data for the period of July 1 to December 31, 216 for the following: Guideline concordance rates for the six restricted antibiotics (daptomycin, ertapenem, imipenem, linezolid, meropenem and tigecycline). The restricted antibiotic order form took effect in October 213. prescribing, including indications, guideline concordance rates and rate of streamlining. Audit and feedback on piperacillin-tazobactam use began in March 214. Degree of guideline concordant treatment for C.difficile (CDI) and Preprinted Medication Order Set (PMOS) use which was first introduced in December 213. Overall Antibiotic Use: Overall antibiotic use at MCH has remained stable since July 213. Cephalosporins continue to be the most commonly prescribed antibiotics. Restricted antibiotic use is similar to the previous six month period. use has increased over the last six months and remains elevated since the return of one Internal Medicine unit to the MCH on May 1, 214. Restricted Antibiotics: The carbapenems are the most commonly prescribed restricted antibiotics with the majority of orders deemed guideline concordant. Daptomycin continues to be used in prolonged courses for a few patients in a guideline concordant manner. Linezolid is used in small quantities and there was no use of tigecycline. Compliance with the Restricted Antibiotic Preauthorization Form and Guideline Concordance Rates: For the period of July to December 216, there was an increase in the use of the restricted antibiotics compared to the previous semi-annual report (from 98 to14 orders). The guideline concordance rate remained similar at 88% (previously 87%). Compliance with the restricted antibiotic form decreased slightly from 81% to 79%. Guideline concordant prescribing of ertapenem in Surgery decreased from 8% in the previous semi-annual report to 63%. Audit and Feedback: remains one of the most frequently prescribed antibiotics at MCH and has been targeted for prospective audit and feedback. There was a decrease in guideline concordant prescribing [333/393 (85%)] for the period of July to December 216 compared to the previous six months. Rates of discordant prescribing increased in both the ED (from 13% to 33%) and Medicine units (from 7% to 16%). 184/393 (47%) piperacillin-tazobactam orders were streamlined in 2.2 days on average which is within the de-escalation target of 48 72 hours. Of the remaining 21 patients, 16 received a full course of piperacillin-tazobactam which was deemed appropriate. The remaining 14 patients did not receive a full course due to: death (26), received empiric therapy until definitive diagnosis (42), escalation to a broader antibiotic (18) or transfer to another facility (18). Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 5

C. difficile (CDI) Audit and Feedback: Prospective audit and feedback is performed on all CDI cases to ensure treatment is guideline concordant. The number of CDI cases increased from 56 in the previous semi-annual report to 63 for the period of July to December 216. Of the 63 patients, 92% received initial guideline concordant therapy. This increased to 1% with ASP pharmacist interventions. Additionally, acid suppressive therapy was stopped in five cases by the ASP pharmacist. Use of the CDI PMOS increased from 41% to 52%. Recommendations: Continue to improve rates of compliance in completing the restricted antibiotic preauthorization form. Continue the judicious use of the six restricted antibiotics by ensuring that these broadspectrum antibiotics are only being used for formulary approved indications and are narrowed upon culture availability if possible. MCH Surgery to optimize their ertapenem prescribing by adhering to the following provincial guidelines: 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 extended-spectrum 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). Continue guideline concordant prescribing of piperacillin-tazobactam with de-escalation within 48 to 72 hours according to culture availability and the clinical status of the patient. MCH ED and Medicine to optimize their piperacillin-tazobactam prescribing. Orders should comply with the following provincial guidelines for use: 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. Work with IPC to improve compliance with the use of the CDI PMOS to ensure optimal CDI management. Please refer to the service specific section of this report for further details regarding service specific prescribing and Antimicrobial Stewardship recommendations. Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 6

III. MCH Antimicrobial Utilization Reports A. Total MCH Antibiotic DDD and Expenditures July 213 December 216 (Figure 2) Parenteral antibiotics account for the majority of the utilization and expenditures hospital-wide. Overall antibiotic use has remained stable for the period July to December 216. Cephalosporins were the most commonly ordered IV antibiotic and carbapenems, cefazolin, and piperacillintazobactam accounted for the majority of costs. Ertapenem is the most frequently prescribed restricted antibiotic. Daptomycin is occasionally being used in orthopedic patients intolerant of vancomycin. Compliance with the restricted antibiotic preauthorization form decreased slightly from 81% to 79% (81/14). Overall, the restricted antibiotics were prescribed in a guideline concordant manner in 88% (92/14) of cases (Table 1). Since the implementation of preauthorization and audit and feedback of the six restricted antibiotics, the number of restricted antibiotic orders has decreased along with the number of discordant orders (Figure 3). use increased for the period of July to December 216 (Figure 2). The most common clinical indications for use were intra-abdominal infections, sepsis NYD and pneumonia (Figure 4). There were 393 orders for the period of July to December 216 with a guideline concordance rate of 85% (333/393) (Table 2). Of these, 47% (184/393) of piperacillin-tazobactam orders were de-escalated, primarily by the attending team, in an average of 2.2 days (Table 3). In the remaining patients (21/393), 16 completed a guideline concordant treatment course with piperacillin-tazobactam. The remaining 14 patients did not complete a full course of piperacillintazobactam for various reasons such as death or transfer to another facility. The most common discordant use of piperacillin-tazobactam was for community acquired pneumonia (CAP) or community acquired aspiration pneumonia with 31 orders (Table 3). Recommendations: Continue to improve rates of completion of the restricted antibiotic preauthorization form. Continue to use the six restricted antibiotics judiciously in a guideline concordant manner. Ensure piperacillin-tazobactam is being prescribed in a guideline concordant manner. Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 7

Figure 2. Total MCH Antimicrobial Usage and Expenditures 25 MCH Total DDD 2 15 1 5 * Oral Parenteral $25 MCH Total Expenditures $2 $15 $1 $5 $ * Oral Parenteral 16 14 12 1 8 6 4 2 * MCH DDD Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin Fluoroquinolones Vancomycin DDD = Defined daily dose. Assumed average maintenance dose per day for a drug used for its main indication in adults. *Return of Internal Medicine Unit to MCH Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 8

$14 $12 $1 $8 $6 $4 $2 $ * MCH Expenditures Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin Fluoroquinolones Vancomycin 12 1 8 6 4 2 * MCH DDD Daptomycin Ertapenem Imipenem Linezolid Meropenem Tigecycline $6 $5 $4 $3 $2 $1 $ * MCH Expenditures 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. *Return of Internal Medicine Unit to MCH Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 9

Table 1. Total MCH Compliance with Preauthorization Form and Guideline Concordance Rates Service Antibiotic Number of Orders July to December 216 Guideline Concordant Form Compliance Recommendations (Number and percent accepted) ED Ertapenem 2 1 (5%) 2 (1%) Total 2 1 (5%) 2 (1%) HPT Daptomycin 1 1 (1%) 1 (1%) Total 1 1 (1%) 1 (1%) ICU Ertapenem 3 3 (1%) 3 (1%) Imipenem 5 5 (1%) 5 (1%) Linezolid 2 2 (1%) 2 (1%) 1 (1%) Meropenem 3 3 (1%) 2 (67%) Total 13 13 (1%) 12 (92%) 1 (1%) Medical Dayward and IV Therapy Area Daptomycin 2 2 (1%) 2 (1%) Ertapenem 9 8 (89%) 4 (44%) 1 (1%) Total 11 1 (91%) 6 (55%) 1 (1%) Medicine Daptomycin 4 4 (1%) 3 (75%) Ertapenem 12 1 (83%) 9 (75%) 3 (1%) Imipenem 2 19 (95%) 16 (8%) 4 (75%) Linezolid 1 1 (1%) 1 (1%) Meropenem 4 4 (1%) 4 (1%) 2 (1%) Total 41 38 (93%) 33 (8%) 9 (89%) Surgery Daptomycin 7 7 (1%) 7 (1%) 1 (1%) Ertapenem 16 1 (63%) 1 (63%) 3 (1%) Imipenem 8 8 (1%) 7 (88%) Meropenem 5 4 (8%) 3 (6%) 2 (1%) Total 36 29 (81%) 27 (75%) 6 (1%) Grand Total 14 92 (88%) 81 (79%) 16 (94%) Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 1

Figure 3. MCH Restricted Antibiotic Orders April 213 to December 216 MCH Restricted Antibiotic Orders, Guideline Concordance and Form Compliance 12 1 8 6 4 2 Restricted Antibiotic Orders Guideline Concordant Orders Forms Completed Form implemented Oct 213 Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 11

Figure 4. MCH Orders by Service July to December 216 14 MCH Piperacillin-Tazobactam Orders 12 1 8 6 4 2 Bacteremia Discordant Febrile Neutropenia Genital HEENT IAI Osteomyelitis Pneumonia Prosthetic joint Sepsis NYD SSTI UTI Table 2. MCH Orders by Service July to December 216 Prescribing Prosthetic Sepsis Bacteremia FN Genital HEENT IAI OM PNA SSTI UTI Discordant* Total Service Joint NYD Critical Care 2 12 15 18 1 2 2 52 ED 1 3 1 7 2 4 8 6 16 48 Infectious Diseases Medicine Family Medicine Internal 1 1 2 1 1 1 5 1 9 1 7 12 7 5 5 5 8 14 22 3 16 12 26 133 Psychiatry 1 1 Surgery Orthopedics Surgery Other 1 2 3 12 5 13 1 8 45 2 45 7 4 3 61 Wound Care 1 1 Total 1 11 4 2 85 8 62 6 63 56 26 6 393 *Discordant: Bacteremia (1), Genital (1), HEENT (2), IAI (2), Native Joint (3), Pneumonia (31), Sepsis NYD (5), SSTI (1), UTI (5) Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 12

Table 3. MCH Orders Streamlined by Indication July to December 216 Clinical Number of Discordant Streamlined Indication Piperacillintazobactam Orders* Initiated by: Average # of days Orders ASP Attending team Bacteremia 1 1 7 3 Febrile 11 4 1.8 Neutropenia Genital 4 1 1 2 2.3 HEENT 2 2 3 1.3 Intraabdominal 85 2 1 34 3.1 infection Native Joint 3 2 1.5 Osteomyelitis 8 3 2.3 Pneumonia 62 31 5 4 2 Prosthetic 6 1 4 3 Joint Sepsis NYD 63 5 1 27 1.5 SSTI 56 1 2 27 2.7 UTI 26 5 1 19 1.9 Total 333 6 12 172 2.2 * The majority of patients received an average of 2.2 days of therapy before discontinuation or streamlining. Many patients only received one dose. Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 13

B. Critical Care Antibiotic Utilization (Figure 5) The utilization data per 1 patient days is provided for the Cardiac Care Unit (CCU) and Intensive Care Unit (ICU) combined. The DDD per 1 patient days and expenditures have remained stable over the last year. The most common antibiotics used are the cephalosporins followed by piperacillin-tazobactam. There were 13 orders for restricted antibiotics and all were deemed guideline concordant (Table 4). Compliance with the restricted antibiotic preauthorization form has improved greatly from 7% to 1% (Table 4). use has decreased in the last six months and 5/52 (96%) orders were guideline concordant (Table 5). The two discordant orders were stopped after one dose. The most common guideline concordant indications for use were sepsis NYD, pneumonia, and intra-abdominal infections (Table 2). Recommendations: The six restricted antibiotics and piperacillin-tazobactam are primarily prescribed in a guideline concordant manner in the MCH Critical Care areas with excellent form completion rates. No further recommendations for improvement are required at this point in time. Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 14

Figure 5. MCH Critical Care* Antimicrobial Usage and Expenditures per 1 Patient Days 12 1 8 6 4 2 MCH Total Critical Care DDD/1 Patient Days Oral Parenteral $16 $14 $12 $1 $8 $6 $4 $2 $ MCH Total Critical Care Expenditures/1 Patient Days Oral Parenteral 5 45 4 35 3 25 2 15 1 5 MCH Critical Care DDD/1 Patient Days Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin Fluoroquinolones Vancomycin *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 216 15

$8 $7 $6 $5 $4 $3 $2 $1 $ MCH Critical Care Expenditures/1 Patient Days Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin Fluoroquinolones Vancomycin 8 7 6 5 4 3 2 1 MCH Critical Care DDD/1 Patient Days Daptomycin Ertapenem Imipenem Linezolid Meropenem Tigecycline $4 $35 $3 $25 $2 $15 $1 $5 $ MCH Critical Care Expenditures/1 Patient Days Daptomycin Ertapenem Imipenem Linezolid Meropenem Piperacillintazobactam 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 216 16

Table 4. MCH Critical Care Compliance with Preauthorization Form and Guideline Concordance Rates Antibiotic Number of Orders July to December 216 Guideline Concordant Form Compliance Recommendations (Number and percent accepted) Ertapenem 3 3 (1%) 3 (1%) Imipenem 5 5 (1%) 5 (1%) Linezolid 2 2 (1%) 2 (1%) 1 (1%) Meropenem 3 3 (1%) 3 (1%) Total 13 13 (1%) 13 (1%) Table 5. MCH Critical Care Order Review July to December 216 Number of Orders Guideline Concordant 52 5 (96%) Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 17

C. Emergency Department (ED) Antibiotic Utilization (Figure 6) Drug utilization data was recorded as ED prescribed if the patient resided in the ED and was not admitted as an inpatient at the time of dispensing. Once accepted by an inpatient team, the drug was thereafter recorded as prescribed by the admitting service. There been a steady increase in overall antibiotic use and expenditures since April 216, primarily mediated by an increase in cephalosporin use. Oral antibiotics were ordered more frequently than parenteral although parenteral antibiotics were responsible for the majority of expenditures. The most commonly ordered antibiotics were the cephalosporins and fluoroquinolones. Use of the six restricted antibiotics has been low from July 213 to December 216. Over the last six months, there were two orders for ertapenem, one of which was guideline discordant (Table 6). use increased from 38 orders in the previous semi-annual report to 48 orders from July to December 216. Guideline concordance decreased from 87% to 67% (Table 7). Approximately half of the discordant orders were prescribed for respiratory conditions not meeting criteria for piperacillin-tazobactam use. The most frequent indications of use for piperacillintazobactam were sepsis NYD and intra-abdominal infections (Table 2). Recommendations: Ertapenem is not necessary in the context of a penicillin allergy and in fact, has a higher crossreactivity rate to penicillin than the third generation cephalosporins. Ensure ertapenem is prescribed in a guideline concordant manner according to the provincial guidelines below: Ertapenem: 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 extended-spectrum 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). The rate of discordant piperacillin-tazobactam orders from the MCH ED has increased from 13% to 33% and needs to be improved upon. Please refer to the accompanying table listing the alternatives to piperacillin-tazobactam in those instances where it was ordered in a discordant manner. Of note, piperacillin-tazobactam is excessively broad for community acquired pneumonia where ceftriaxone/azithromycin or levofloxacin should suffice. Please ensure piperacillin-tazobactam is prescribed in a guideline concordant manner according to the provincial guidelines below: 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. Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 18

Figure 6. MCH ED* Antimicrobial Usage and Expenditures per 1 Patient Visits 18 16 14 12 1 8 6 4 2 MCH Total ED DDD/1 Patient Visits Oral Parenteral $7 $6 $5 $4 $3 $2 $1 $ MCH Total ED Expenditures/1 Patient Visits Oral Parenteral 7 6 5 4 3 2 1 MCH ED DDD/1 Patient Visits Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin Fluoroquinolones Vancomycin *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 216 19

$45 $4 $35 $3 $25 $2 $15 $1 $5 $ MCH ED Expenditures/1 Patient Visits Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin Fluoroquinolones Vancomycin 8 7 6 5 4 3 2 1 MCH ED DDD/1 Patient Visits Daptomycin Ertapenem Imipenem Linezolid Meropenem Tigecycline $14 $12 $1 $8 $6 $4 $2 $ MCH ED Expenditures/1 Patient Visits Daptomycin Ertapenem Imipenem Linezolid Meropenem Piperacillintazobactam 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 216 2

Table 6. MCH ED Compliance with Preauthorization Form and Guideline Concordance Rates Antibiotic Number of Orders July to December 216 Guideline Form Concordant Compliance Ertapenem 2 1 (5%) 2 (1%) Total 2 1 (5%) 2 (1%) Recommendations (Number and Percent Accepted) Table 7. ED Order Review July to December 216 Number of Orders Guideline Concordant 48 32 (67%) Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 21

D. Medical Dayward and IV Therapy Area Antibiotic Utilization (Figure 7) Overall antibiotic use has remained stable in the past six months. As patient volumes are low relative to inpatient wards, overall antibiotic use is affected by type of patients attending and their duration of therapy. The most frequently prescribed antibiotics were cefazolin and the third generation cephalosporins. Daptomycin use increased in the last quarter and ertapenem use has remained stable over the past year. There were 11 orders for restricted antibiotics and ten were deemed guideline concordant (Table 8). Completion of the restricted antibiotic preauthorization form had improved in the previous semi-annual report but has decreased again from 9% to 55% (Table 8). use has been minimal with only one order (discordant) in the last six months (Table 9). Recommendations: Improve compliance with completion of the restricted antibiotic form in order to facilitate accurate data collection and feedback to stakeholders. The restricted antibiotics are primarily prescribed in a guideline concordant manner. No further recommendations are required at this time. Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 22

Figure 7. MCH Medical Dayward and IV Therapy Area Antimicrobial Usage and Expenditures per 1 Patients 1 9 8 7 6 5 4 3 2 1 MCH Total IV Therapy Area DDD/1 Patients Oral Parenteral $18 $16 $14 $12 $1 $8 $6 $4 $2 $ MCH Total IV Therapy Area Expenditures/1 Patients Oral Parenteral 9 8 7 6 5 4 3 2 1 MCH IV Therapy Area DDD/1 Patients Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin Fluoroquinolones Vancomycin 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 216 23

MCH IV Therapy Area Expenditures/1 Patients $12 $1 $8 $6 $4 $2 $ Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin Fluoroquinolones MCH IV Therapy Area DDD/1 Patients 14 12 1 8 6 4 2 Daptomycin Ertapenem Imipenem Linezolid Meropenem Tigecycline MCH IV Therapy Area Expenditures/1 Patients $14 $12 $1 $8 $6 $4 $2 $ 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 216 24

Table 8. MCH Medical Dayward and IV Therapy Area Compliance with Preauthorization Form and Guideline Concordance Rates Antibiotic Number of Orders July to December 216 Guideline Concordant Form Compliance Recommendations (Number and percent accepted) Daptomycin 2 2 (1%) 2 (1%) Ertapenem 9 8 (89%) 4 (44%) 1 (1%) Total 11 1 (91%) 6 (55%) 1 (1%) Table 9. MCH Medical Dayward and IV Therapy Area Order Review July to December 216 Program Number of Orders Guideline Concordant Medicine Family 1 (%) Total 1 (%) Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 25

E. Medicine Antibiotic Utilization (Figure 8) Medicine applies to Internal Medicine, Family Medicine (cannot be separated due to shared inpatient units), ED inpatients and Geriatrics. An Internal Medicine unit was temporarily relocated to the Royal Alexandra Hospital on May 3, 213 and returned to the MCH on May 1, 214. Data from May 1, 214 forward includes this unit. Overall, DDD and expenditures per 1 patient days have decreased in the July to December 216 period. Cephalosporins and fluoroquinolones were the most commonly prescribed antibiotics. Use of piperacillin-tazobactam and the restricted antibiotics has remained stable since October 215, with a recent decline in piperacillin-tazobactam use. The restricted antibiotics were used in a guideline concordant manner for 93% of the orders (Table 1). This rate is similar to the previous semi-annual report (91%). Compliance with completion of the restricted antibiotic preauthorization form has declined from 89% to 8% (Table 1). The largest proportion of piperacillin-tazobactam orders in MCH are from Internal Medicine prescribers. The guideline concordance rates decreased from 93% to 84% (Table 11). Sepsis NYD and hospital acquired pneumonia were the most common indications for use (Table 2). Prescribing of piperacillin-tazobactam for CAP and aspiration pneumonia continues to account for the majority of discordant orders. Recommendations: Improve compliance with completion of the restricted antibiotic form in order to facilitate accurate data collection and feedback to stakeholders. There has been an increase in the number of guideline discordant piperacillin-tazobactam orders for CAP and aspiration pneumonia. Ensure piperacillin-tazobactam is prescribed in a guideline concordant manner according to the provincial guidelines below: 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. Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 26

Figure 8. MCH Medicine # Antimicrobial Usage and Expenditures per 1 Patient Days 7 6 5 4 3 2 1 * MCH Total Medicine DDD/1 Patient Days Oral Parenteral $5 $45 $4 $35 $3 $25 $2 $15 $1 $5 $ * MCH Total Medicine Expenditures/1 Patient Days Oral Parenteral 35 3 25 2 15 1 5 * MCH Medicine DDD/1 Patient Days Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin Fluoroquinolones Vancomycin # Medicine and ERIP; * Return of Internal Medicine Unit to MCH. 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 216 27

$3 $25 $2 $15 $1 $5 $ * MCH Medicine Expenditures/1 Patient Days Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin Fluoroquinolones Vancomycin 4 3.5 3 2.5 2 1.5 1.5 * MCH Medicine DDD/1 Patient Days Daptomycin Ertapenem Imipenem Linezolid Meropenem Tigecycline $1 $9 $8 $7 $6 $5 $4 $3 $2 $1 $ * MCH Medicine Expenditures/1 Patient Days Daptomycin Ertapenem Imipenem Linezolid Meropenem Tigecycline # Medicine and ERIP; * Return of Internal Medicine Unit to MCH 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 216 28

Table 1. MCH Medicine Compliance with Preauthorization Form and Guideline Concordance Rates Antibiotic Number of Orders July to December 216 Guideline Concordant Form Compliance Recommendations (Number and percent accepted) Daptomycin 4 4 (1%) 3 (75%) Ertapenem 12 1 (83%) 9 (75%) 3 (1%) Imipenem 2 19 (95%) 16 (8%) 4 (75%) Linezolid 1 1 (1%) 1 (1%) Meropenem 4 4 (1%) 4 (1%) 2 (1%) Total 41 38 (93%) 33 (8%) 9 (89%) Table 11. MCH Medicine Order Review July to December 216 Program Number of Orders Guideline Concordant Medicine Family 49 45 (92%) Medicine Internal 133 17 (8%) Total 182 152 (84%) Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 29

F. Surgery Antibiotic Utilization (Figure 9) Surgical data incorporates general surgery, obstetrics and gynecology, orthopedics and urology. Overall antibiotic use remains stable since July 213. Cefazolin accounts for the majority of parenteral antibiotics. Of the restricted antibiotics, there was a decrease in ertapenem use and an increase in daptomycin use. Since the previous semi-annual report, the guideline concordance rate has remained stable at 81%. Completion of the restricted antibiotic preauthorization form increased from 68% in the previous six months to 75% and needs to be improved upon (Table 12). There was a slight improvement in meropenem guideline concordance (71% to 8%) however, concordance for ertapenem decreased from 8% to 63%. use has fluctuated over the July to December 216 period with a guideline concordance rate of 9% (Table 13). The most common indications for use were intra-abdominal infections (Table 2). Recommendations: Improve compliance with completion of the restricted antibiotic preauthorization form to ensure more accurate data collection and timely feedback for prescribers. Ensure the carbapenems are prescribed in a guideline concordant manner according to the provincial guidelines below: Ertapenem: 5. Empiric therapy of polymicrobial complicated skin and skin structure infections, including bite wound infections. 6. Therapy of infections due to Enterobacteriaceae producing inducible (AmpC) ß-lactamases or extended-spectrum ß-lactamases (ESBLs) where there is resistance to first line agents and documented susceptibility to ertapenem. 7. 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). 8. Therapy of community-acquired intra-abdominal infections in patients intolerant or unresponsive to first line therapy (ceftriaxone and metronidazole). Imipenem + Meropenem: Guidelines listed apply to both drugs unless otherwise indicated. 1. Therapy of severe infections involving Gram negative organisms in patients who are intolerant of, or unresponsive to, or whose isolates are suspected or documented to be resistant (e.g. ESBL, inducible (AmpC) ß-lactamases) to, first line agents and piperacillin-tazobactam (imipenem preferred if documented susceptibility) 2. Therapy of severe suspected or documented polymicrobial infections in patients who are intolerant of, or unresponsive to, or whose isolates are suspected or documented to be resistant to, first line agents and piperacillin-tazobactam (imipenem preferred if documented susceptibility) 3. Therapy of infections involving multi-drug resistant Pseudomonas aeruginosa where there is documented susceptibility to the carbapenem (cannot assume meropenem susceptibility from imipenem susceptibility and vice versa). 4. Empiric therapy in high risk febrile neutropenic patients +/- aminoglycoside (imipenem preferred if documented susceptibility). 5. Empiric therapy of post-traumatic/post-neurosurgical meningitis in combination with vancomycin. (MEROPENEM) 6. Alternative to ceftazidime for therapy of central nervous system (CNS) infections due to Pseudomonas aeruginosa. (MEROPENEM) 7. As part of combination therapy of infections with Nocardia spp or nontuberculous Mycobacteria spp. (IMIPENEM) Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 3

Figure 9. MCH Surgery Antimicrobial Usage and Expenditures per 1 Patient Days 12 1 8 6 4 2 MCH Total Surgery DDD/1 Patient Days Ortho Surgery - Other $14 $12 $1 $8 $6 $4 $2 $ MCH Total Surgery Expenditures/1 Patient Days Ortho Surgery - Other 8 7 6 5 4 3 2 1 MCH Surgery DDD/1 Patient Days Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin Fluoroquinolones Vancomycin 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 216 31

$7 $6 $5 $4 $3 $2 $1 $ MCH Surgery Expenditures/1 Patient Days Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin Fluoroquinolones Vancomycin 7 6 5 4 3 2 1 MCH Surgery DDD/1 Patient Days Daptomycin Ertapenem Imipenem Linezolid Meropenem Tigecycline $3 $25 $2 $15 $1 $5 $ MCH Surgery Expenditures/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 216 32

Table 12. MCH Surgery Compliance with Preauthorization Form and Guideline Concordance Rates Antibiotic Number of Orders July to December 216 Guideline Concordant Form Compliance Recommendations (Number and percent accepted) Daptomycin 7 7 (1%) 7 (1%) 1 (1%) Ertapenem 16 1 (63%) 1 (63%) 3 (1%) Imipenem 8 8 (1%) 7 (88%) Meropenem 5 4 (8%) 3 (6%) 2 (1%) Total 36 29 (81%) 27 (75%) 6 (1%) Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 33

Table 13. MCH Surgery Order Review July to December 216 Program Number of Orders Guideline Concordant Surgery General, Obstetrics, 61 58 (95%) Urology Surgery Orthopedics 45 37 (82%) Total 16 95 (9%) Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 34

IV. Clostridium difficile Infection (CDI) Prospective Audit and Feedback The Antimicrobial Stewardship pharmacist performs an audit on all CDI patients to ensure guideline concordant treatment is initiated, to encourage the use of the CDI Preprinted Medication Order Set (PMOS) and to optimize CDI management as necessary. Compared to the previous six months, the number of chart audits performed for the period of July to December increased from 56 to 63 (Table 14). CDI guideline concordant treatment was initiated in 92% of patients (58/63) and this increased to 1% following interventions made by the Antimicrobial Stewardship pharmacist. Additional interventions included optimizing treatment in 13 cases, altering therapy duration in four cases and discontinuing acid suppressive therapy in five. Use of the CDI PMOS upon initial prescribing has continued to increase from 41% during the period of January to June 216 to 52% (33/63) at present. Improvements in this rate will likely achieve better initial guideline concordant treatment and would trigger the assessment of other offending therapies. There were two deaths attributable to CDI for the period July to December 216. Figure 1 and Figure 11 display the rate of CDI PMOS utilization, CDI treatment guideline concordance rate and the association with CDI rate (per 1, patient days) or attributable mortality. Month Number of cases Table 14. MCH C. difficile Infection Audits CDI Attributable Mortality* July to December 216 Guideline Concordant Treatment CDI PMOS Utilized Alter CDI Treatment Pharmacy Interventions Alter CDI Treatment Duration Discontinue acid suppressive therapy July 28 1 25 15 9 4 2 August 1 1 5 1 September 12 1 1 7 3 October 2 2 November 6 6 4 2 December 5 5 2 1 Total 63 2 58 (92%) 33 (52%) 13 4 5 *Accurate at the time of this report but is subject to change due to ongoing IPC surveillance. Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 35

Number of CDI Attributable Deaths Guideline Concordnce & PMOS Utilization Rate CDI Rate/1 Patient Days Guideline Concordnce & PMOS Utilization Rate Figure 1. MCH CDI Concordance, PMOS Use and CDI Rate MCH CDI Concordance and Rate 16 14 12 1 8 6 4 2 3.2 8.2 8.4 6.3 3.8 6.5 5.2 4.3 3.3 2.9 3.2 4.1 3.6 5.6 7.7 13.2 3.8 1 9 8 7 6 5 4 3 2 1 CDI Rate PPCO Implemented Dec 213 Guideline Concordant Treatment PPCO Utilization Figure 11. MCH CDI Treatment Concordance, PMOS Use and Mortality MCH CDI Concordance and Mortality 5 4 3 2 1 1 3 1 1 2 1 1 2 1 9 8 7 6 5 4 3 2 1 CDI Attributable Mortality Guideline Concordant Treatment PPCO Utilization PPCO Implemented Dec 213 Recommendations: CHASC to continue to work with IPC to ensure guideline concordant management of CDI and to increase the use of the CDI PMOS as one effective strategy. Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 36

V. Antimicrobial Stewardship Pharmacist Interventions As part of the audit and feedback process of the restricted antibiotics, piperacillin-tazobactam and CDIs, the Antimicrobial Stewardship pharmacist provides recommendations to optimize patient care. Figure 12 highlights the quantity, category and indication of Antimicrobial Stewardship interventions for the period of July to December 216. The attending team accepted 93% (89/96) of the recommendations provided. Figure 12. MCH Antimicrobial Stewardship Pharmacist Interventions Accepted July to December 216 14 12 1 Bacteremia CDI 8 Genital IAI 6 Osteomyelitis Pneumonia 4 prosthetic joint 2 Sepsis NYD SSTI Antimicrobial therapy unnecessary Dose optimization duration of therapy optimized Equivalent efficacy & decreased cost Medication Spectrum of discontinued antimicrobial agent UTI Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 37

VI. Appendix 1 - Villa Caritas (VC) Total VC Antibiotic DDD and Expenditures July 213 December 216 (Figure 1) Antibiotic utilization at Villa Caritas steadily decreased for the period of July to December 216 compared to the previous six month period (Figure 1). There was minimal use of all antibiotic classes including piperacillin-tazobactam. A presentation highlighting Antimicrobial Stewardship initiatives and site specific antibiotic utilization was delivered to VC medical staff in November 216. There was no use of the restricted antibiotics for the period of July to December 216. Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 38

Figure 1. Villa Caritas Antimicrobial Usage and Expenditures per 1 Patient Days 8 7 6 5 4 3 2 1 VC Usage DDD/1 Patient Days Oral Parenteral $4 $35 $3 $25 $2 $15 $1 $5 $ VC Expenditures/1 Patient Days Oral Parenteral VC DDD/1 Patient Days 2.5 2 1.5 1.5 Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin Fluoroquinolones Vancomycin 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 216 39

VC Expenditures/1 Patient Days $25 $2 $15 $1 $5 $ Carbapenems Cefazolin Cephalosporins 3rd generation Clindamycin Fluoroquinolones Vancomycin VC DDD/1 Patient Days.3.25.2.15.1.5 Daptomycin Ertapenem Imipenem Linezolid Meropenem Tigecycline VC Expenditures/1 Patient Days $14 $12 $1 $8 $6 $4 $2 $ 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 216 4

VII. Appendix 2 A. 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 for comparing antibiotic use across different classes despite differences in potency and dosing. Denominator Data DDDs are now provided over the denominator of actual patient days. Incorporating denominator data takes into account changes in utilization that may be due to fluctuations in patient volumes over time. C. difficile hospital rates and mortality data are obtained from Infection Prevention and Control. 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. 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. MCH Medical Dayward and IV Therapy Area 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 (Medical Dayward) or visits (ED). Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 41

B. Glossary of Terms ASP. Antimicrobial Stewardship Program CAP.Community Acquired Pneumonia 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 ED...Emergency Department ERIP...Emergency Inpatients ESBL...Extended Spectrum Beta-Lactamase FN.. Febrile Neutropenia HPT.....Home Parenteral Therapy IAI.. Intra-abdominal infection ICU..Intensive Care Unit ID....Infectious Diseases IPC Infection Prevention and Control L & D.Labour and Delivery Unit MCH......Misericordia Community Hospital MDR.....Multi-drug Resistant MSSA.... Methacillin Sensitive Staphylococcus Aureus NB.. Nota bena or Important, Note well NYD...Not Yet Diagnosed OM.Osteomyelitis PJI.. Prosthetic Joint Infection PMOS..Preprinted Medication Order Set SSTI.Skin and Soft Tissue Infection UTI. Urinary Tract Infection VAP....Ventilator Associated Pneumonia VC Villa Caritas Prepared by the Covenant Health Antimicrobial Stewardship Committee (CHASC) for the period of July December 216 42