Kaylee Wentworth, PharmD PGY-1 Pharmacy Resident April 2017 Implementation of FilmArray blood culture identification panel: Assessment of time to appropriate antimicrobial therapy and subsequent impact on patient outcomes Kaylee Wentworth, PharmD PGY-1 Pharmacy Resident April 2017

The speaker has no actual or potential conflict of interest in relation to this presentation

Background

Bloodstream Infections (BSI) Associated with a high risk of mortality Sepsis: 20% Severe sepsis: 40% Septic shock: >60% Delays in appropriate antimicrobial therapy have been shown to: Increase mortality Increase hospital length of stay Increase costs Promote antimicrobial resistance Chang H, et al. JAMA. 2010: 304 (16); 1856. Wisplinghoff H, et al. Clin Infect Dis. 2004: 39; 309-17. Kumar A, et al. Chest. 2009: 136; 1237-48. Fraser A, et al. Am J Med. 2006: 119; 970-6. Lehman LE, et al. Crit Care. 2010: 14; R186. Cameron DR, et al. Clin Infect Dis. 2011: 53; 576-82.

Blood Culture Results Positive Culture Pathogen Gram-positive cocci (staph-like) Staphylococcus aureus 1 or multiple Methicillin-sensitive Beta-lactam Methicillin-resistant Vancomycin Coagulase-negative staphylococcus 1 out of 2 Likely a contaminant No Therapy Positive Culture Pathogen Number of Positive Cultures Identification Appropriate Therapy

FilmArray Blood Culture Identification (BCID) Panel Multiplex polymerase chain reaction (PCR) system Tests simultaneously for: 19 gram positive and gram negative bacteria 5 yeast 3 antibiotic resistance genes Identifies pathogens in ~1 hour http://www.biofiredx.com/products/the-filmarray-panels/

Current Process at MCHS BCID Panel: Organism & Resistance Gene Identification Positive Blood Culture Gram Stain Culture Plate Organism Identification & Susceptibility ~1hr ~24-48hr 18-24hr 6-18hr

Kaylee M. Wentworth, PharmD Implementation of FilmArray blood culture identification panel: Assessment of time to appropriate antimicrobial therapy and subsequent impact on patient outcomes Kaylee M. Wentworth, PharmD Co-Investigators: Theresa Koski, BS, PharmD, Patient Care Pharmacist, Antimicrobial Stewardship; Katrina Reynolds, PharmD, Patient Care Pharmacist; Andrew Caputo, PharmD, BCPS, Patient Care Pharmacist; Dr. Joy Voorhees, BS, DVM

Purpose Analyze the effects of the BCID panel on appropriate antimicrobial use, including duration of vancomycin therapy, and patient outcomes 9

Study Overview Multi-center Retrospective IRB approved Mount Carmel West Mount Carmel East Mount Carmel St. Ann’s Retrospective January 1, 2016 through January 31, 2017 All outcomes were compare 6 months pre- and post-implementation of the BCID panel IRB approved

Inclusion and Exclusion Criteria ≥18 years of age Positive blood culture for Methicillin-sensitive Staphylococcus aureus (MSSA) OR 1 positive culture out of 2 for Coagulase-negative Staphylococcus (CoNS) Positive blood cultures for pathogens other than MSSA or CoNS Vancomycin for indications other than sepsis or bacteremia Patients who expired, left against medical advice, or transferred to palliative care within 24 hours of the positive culture

Outcomes Primary Secondary Length of vancomycin therapy Time to appropriate antimicrobial therapy MSSA: de-escalation to a beta-lactam CoNS: no therapy Hospital length of stay (LOS) Length of vancomycin therapy Measured in hours Length of intensive care unit (ICU) stay Time to negative blood culture Adverse drug events 30-day mortality 30-day readmission

Results

Results 406 Patients included Pre-BCID panel n=182 CoNS n=128 MSSA n=54 Post-BCID panel n=224 CoNS n=173 MSSA n=51 p=0.138

Blood Stream Infections: MSSA

MSSA: Baseline Characteristics Pre-BCID Panel Post-BCID Panel P-value Age** 54.2 (19.3, 23 – 89) 57.4 (14.1, 26-88) 0.4509 Male* 30 (55.6%) 29 (56.9%) 1.000 Antibiotic allergies* 13 (24.1%) 10 (19.6%) 0.6417 Baseline SCr** 2.23 (2.26, 0.43 – 12.27) 1.78 (2.1, 0.44 – 12.01) 0.1946 History of IV drug abuse* 9 (16.7%) 5 (9.8%) 0.3930 Nephrotoxic Agents* Contrast dye 53 (24.4%) 65 (27.2%) 0.5220 Aminoglycosides 7 (3.2%) 11 (4.6%) NSAIDs 39 (17.7%) 30 (12.4%) Loop diuretics 62 (28.2%) 72 (29.9%) Hospital* MCW  19 (35.2%)  25 (49.0%) 0.2504 MCE  20 (37.0%)  12 (23.5%) MCSA  15 (27.8%)  14 (27.5%) *reported in hours; mean (SD, range) **reported as n (%)

MSSA: Baseline Characteristics Pre-BCID Panel Post-BCID Panel P-value Charlson Comorbidity Index 12 (22.2%) 14 (27.5%) 0.0275 1 16 (29.6%) 20 (39.2%) 2 9 (16.7%) 8 (15.7%) 3 2 (3.7%) 6 (11.8%) 4 1 (2.0%) ≥5 6 (11.1%) 2 (3.9%) Pre-BCID Panel Post-BCID Panel P-value Pitt Bacteremia Score 4 (7.4%) 10 (19.6%) 0.6102 1 10 (18.5%) 7 (13.7%) 2 14 (25.9%) 8 (15.7%) 3 13 (25.5%) 4 7 (13.0%) 4 (7.8%) 5 0 (0%) 2 (3.9%) ≥6 5 (9.3%) reported as n (%) reported as n (%)

MSSA: Primary Outcomes Pre-BCID Panel Post-BCID Panel P-value Time to appropriate therapy 82.6 (59.6, 5 – 367) 71.4 (73.9, 1 – 312) 0.0045 Hospital length of stay (LOS) 241 (115, 56 -626) 281 (192, 38 – 992) 0.5357 reported in hours; mean (SD, range)

MSSA: Secondary Outcomes Pre-BCID Panel Post-BCID Panel P-value Time on vancomycin* 39.8 (24.6, 0 – 113) 29.8 (27.2, 0 – 99) 0.0441 Received ≥1 dose of vancomycin* 50 (90.9%) 44 (81.5%) 0.1751 Time to negative culture* 94.2 (85.4, 5-319) 62.8 (56.7, 2-242) 0.0543 Length of ICU stay* 105 (107, 15 – 400) 158 (120, 14 – 461) 0.1359 30-day mortality** 5 (9.1%) 3 (5.6%) 0.7161 30-day readmission** 8 (14.6%) 6 (11.1%) 0.7758 *reported in hours; mean (SD, range) **reported as n (%)

MSSA: Adverse Events Pre-BCID Panel Post-BCID Panel P-value Change in Serum Creatinine No change 41 (85.4%) 40 (93.0%) 0.5395 Risk 4 (8.3%) 1 (2.3%) Injury 1 (2.1%) 0 (0%) Failure 2 (4.2%) 2 (4.7%) reported as n (%)

Contaminants: CoNS

CoNS: Baseline Characteristics Pre-BCID Panel Post-BCID Panel P-value Age** 65.4 (14.8, 27 – 97) 67.7 (16.1, 18 – 99) 0.0985 Male* 68 (53.1%) 84 (48.6%) 0.4845 Antibiotic allergies* 34 (26.6%) 60 (34.7%) 0.1663 Baseline SCr** 1.74 (1.71, 0.32 – 10.63) 2.04 (1.85, 0.54 – 8.63) 0.3983 History of IV drug abuse* 4 (3.2%) 6 (3.6%) 1.000 Nephrotoxic Agents* Contrast dye 53 (24.4%) 65 (27.2%) 0.5220 Aminoglycosides 7 (3.2%) 11 (4.6%) NSAIDs 39 (17.7%) 30 (12.4%) Loop diuretics 62 (28.2%) 72 (29.9%) Hospital* MCW 65 (50.8%) 67 (38.7%) 0.07 MCE 54 (42.2%) MCSA 9 (7.1%) 22 (12.7%) *reported in hours; mean (SD, range) **reported as n (%)

CoNS: Baseline Characteristics Pre-BCID Panel Post-BCID Panel P-value Charlson Comorbidity Index 24 (18.8%) 22 (12.7%) 0.0291 1 21 (16.4%) 56 (32.4%) 2 29 (22.7%) 31 (17.9%) 3 20 (11.6%) 4 17 (13.3%) 17 (9.8%) ≥5 16 (12.5%) 27 (15.6%) Pre-BCID Panel Post-BCID Panel P-value Pitt Bacteremia Score 38 (29.7%) 69 (39.9%) 0.1013 1 9 (7.0%) 22 (12.7%) 2 35 (27.3%) 35 (20.2%) 3 17 (13.3%) 13 (7.5%) 4 15 (11.7%) 15 (8.7%) 5 7 (5.5%) 8 (4.6%) ≥6 11 (6.4%) reported as n (%) reported as n (%)

CoNS: Primary Outcomes Pre-BCID Panel Post-BCID Panel P-value Time to appropriate therapy 94.2 (97.6, 4 – 660) 69.6 (103, 3 – 875) <0.0001 Hospital length of stay (LOS) 209 (177, 3-1098) 163 (128, 21 – 886) 0.0377 reported in hours; mean (SD, range)

CoNS: Secondary Outcomes Pre-BCID Panel Post-BCID Panel P-value Time on vancomycin* 42.9 (71.3, 0 – 659) 26.2 (61.6, 0 – 478) <0.0001 Received ≥1 dose of vancomycin* 112 (67.9%) 92 (49.2%) 0.0005 Hospital MCW 60 (73.2%) 40 (54.1%) 0.0189 MCE 44 (63.8%) 38 (42.2%) 0.0102 MCSA 8 (57.1%) 14 (60.9%) 1.00 Length of ICU stay* 133 (110, 13 – 442) 113 (119, 14 – 540) 0.1460 30-day mortality** 10 (7.8%) 16 (9.3%) 0.8360 30-day readmission** 17 (13.3%) 24 (13.9%) 1.000 *reported in hours; mean (SD, range) **reported as n (%)

CoNS: Adverse Events Pre-BCID Panel Post-BCID Panel P-value Change in Serum Creatinine No change 102 (94.4%) 68 (90.7%) 0.0962 Risk 3 (2.8%) 7 (9.3%) Injury 1 (0.9%) 0 (0%) Failure 2 (1.9%) reported as n (%)

Overall Results

Results: Primary Outcomes

Results: Vancomycin

Conclusions

Conclusions Reduced time to appropriate therapy Reduction in unnecessary antibiotic use Trend toward decrease in hospital length of stay in CoNS subgroup Reduction in time on vancomycin and overall vancomycin use

Study Limitations Time to appropriate therapy calculation Serum creatinine was only collected on patients who received vancomycin Potential for variation in reaction time Bias and consistency of data collection

Future Implications Ongoing education Provided pocket guide in addition to electronic link Room for improvement regarding vancomycin use Implementation of other panels Respiratory Meningitis/Encephalitis Gastrointestinal

References Chang H, et al. Sepsis. JAMA. 2010: 304 (16); 1856. Wisplinghoff H, et al. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004: 39; 309-17. Kumar A, et al. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest. 2009: 136; 1237-48. Fraser A, et al. Benefit of appropriate empirical antibiotic treatment: thirty-day mortality and duration of hospital stay. Am J Med. 2006: 119; 970-6. Lehman LE, et al. Cost and mortality predication using polymerase chain reaction pathogen detection in sepsis: evidence from three observational trials. Crit Care. 2010: 14; R186. Cameron DR, et al. The interface between antibiotic resistance and virulence in Staphylococcus aureus and its impact upon clinical outcomes. Clin Infect Dis. 2011: 53; 576-82. Huang AM, et al. Impact of rapid organism identification via matrix-assisted laser desorption/ionization time-of-flight combined with antimicrobial stewardship team intervention in adult patients with bacteremia and candidemia. Clin Infect Dis. 2013: 57; 1237-45. Biofire. Products: The Filmarray Panels .Accessed 18 Mar 2017. http://www.biofiredx.com/products/the-filmarray-panels/ Southern TR, et al. Implementation and performance of the BioFire FilmArray® Blood Culture Identification panel with antimicrobial treatment recommendations for bloodstream infections at a midwestern academic tertiary hospital. Diagn Microbiol Infect Dis. 2015: 81 (2); 96-101.

Kaylee M. Wentworth, PharmD Implementation of FilmArray blood culture identification panel: Assessment of time to appropriate antimicrobial therapy and subsequent impact on patient outcomes Kaylee M. Wentworth, PharmD Co-Investigators: Theresa Koski, BS, PharmD, Patient Care Pharmacist, Antimicrobial Stewardship; Katrina Reynolds, PharmD, Patient Care Pharmacist; Andrew Caputo, PharmD, BCPS, Patient Care Pharmacist; Dr. Joy Voorhees, BS, DVM