0. Antimicrobial Stewardship Team Interventions in Patients with Bacteremia Utilizing Rapid Pathogen Identification via Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS)
Yi Guo, PharmD
Clinical Pharmacy Manager of Infectious Diseases
Montefiore Medical Center
Albert Einstein College of Medicine
Bronx, NY
September 2015

1. Disclosures
I have no relevant financial or nonfinancial relationship(s) with the manufacturers of the antimicrobial agents described or reviewed in this presentation

2. Objectives
Describe the Antimicrobial Stewardship Team (AST) activities at Montefiore Medical Center
Describe the Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS)
Describe the process of integrating MALDI-TOF MS into the Antimicrobial Stewardship Program for patients with bacteremia
Outline future directions with MALDI-TOF

3. Timely Initiation of Antimicrobials
Bloodstream infections (BSIs) are associated with high rates of morbidity and mortality among hospitalized patients.
Prompt pathogen identification is crucial for optimizing antimicrobial therapy in patients with BSIs
Timely initiation of appropriate antibiotics is associated with improved patient outcomes and decreased healthcare expenditures
Delays in microbiological identification hinder the ability of clinicians to streaming therapy
Vlek A, etal. PLoS One. 2012; 7: e32589.
Lodis TP, etal. Clin Infect Dis 2003;36:

4. Conventional vs. MALDI-TOF MS
Current standard of identification relies largely on phenotypic testing that is time consuming
MALDI-TOF has proven to be a rapid, cost effective, and accurate alternative to conventional identification
MALDI-TOF MS was validated and NYS DOH laboratory approval was received January 2014 for use at Montefiore
NYS DOH = New York State Department of Health
Bizzini A, etal. Clinical Microbiology and Infection. 2010; 16:

5. How does MALDI-TOF MS Work?
Photos courtesy of Mayo Clinic Medical Laboratories

6. How does MALDI-TOF MS Work?
Photos courtesy of Mayo Clinic Medical Laboratories

7. Conventional vs. MALDI by Plate/Bottle
MALDI by Bottle
0 hrs
Growth detected
0-2hrs
Gram Stain
Subculture to plate
18-24hrs
Sufficient colony growth achieved
Set up for ID/susceptibilities
Prelim ID released if available
24-48hrs
Final ID
Susceptibilities
0 hrs
Growth detected
0-2 hrs
Gram Stain
Subculture to plate
8-16 hrs
Minimal colony growth achieved
Final ID by MALDI (or Preliminary ID pending further testing)
24-48hrs
Susceptibilities
0 hrs
Growth detected
0-2 hrs
Gram Stain
BC bottle processing for MALDI
3-6 hrs
Final identification (or Preliminary ID pending further testing)
24-48hrs
Susceptibilities

8. MALDI TOF + Antimicrobial Stewardship
Huang et al.1
Perez et al.2
Type of Pathogen in Blood
Bacteria, Yeast
Resistant Gram-negative Organisms
Pre-I (n=256)
Post-I (n=245)
P value
Pre-I
(n=157)
Post-I
(n=112)
Time to Organism Identification (hour)
84.0
55.9
<0.001
40.9
14.5
Time to Effective Antibiotic Therapy (hour)
30.1
20.4
0.021
89.7 32
Time to Optimal Antibiotic Therapy (hour)
90.3
47.3
80.9
23.2
Duration of ICU stay (day)
14.9
8.3
0.014
16*
10.7**
0.008
Hospital Length of Stay (day)
14.2
11.4
0.066
23.3*
15.3**
0.0001
30-day All Cause-mortality
20.3%
14.5%
21%
8.9%
0.01
Total Average Hospital Costs per Inpatient
N/A
$78,991 + $90,106*
$52,693 +
$83,526**
0.002
Abbreviations: Pre-I, pre-intervention; Post-I, post-intervention; ICU, intensive care unit *n=128, **n=103
1. Huang AM, et al. Clin Infect Dis 2013;57(9):
2. Perez KK, et al. J infect 2014 Sep;69(3):

9. Antimicrobial Stewardship Program
Formally established in 2009
Covers 4 campuses (Moses, Einstein, Wakefield, CHAM)
1512 beds
Antimicrobial stewardship team (AST) consists of:
4 ID attendings (1 pediatric)
4 ID-trained pharmacists (1 pediatric)
Activities:
ID approval/auditing
Making hospital guidelines/protocols
Education
Research
Publication

10. ASP Strategies by Campus
Resources
Restrictions*
Audit**
Highlights
Moses
✔✔✔ ✔✔
ER (CAP, Sepsis)
Zosyn Time Out
Einstein
ER ID Consults
Abd hyst ppx bundle
Wakefield
No fellows
✔Modified at 72 hrs
ASP-Medicine early interventions
CHAM
✔ Peds List
Antiviral & antifungal appropriateness,
Dosing
* Related lists with categories
** Sentri 7 & home grown queries

11. Daily Workflow Before Implementation of MALDI
Microbiology lab notifies primary team physician via phone regarding positive blood culture
Time to initiate appropriate antibiotic depends on timing of the phone call and availability of primary team physician
AST does not receive notification of all positive blood culture routinely
Before Implementation of MALDI
Microbiology lab s positive blood culture reports to AST 3 times a day, 9am-5pm , Monday-Friday
A designated ID MD/PharmD will perform chart review and contact primary team physician
Recommending: streamlining antibiotics, ID consults, diagnostic work up, etc.
After Implementation of MALDI

13. Objective
Analyze early outcomes of MALDI + ASP activities in bacteremic patients

14. Methods Study design: Pre-post interventional observational study
Time frame: March-April 2013 vs. March-April 2014
Inclusion criteria:
Age >18 (Moses, Einstein, Wakefield)
1st episode of bacteremia with gram-negative organism or S. aureus
Exclusion criteria:
Age <18
Death or discharge within 24 hours of blood culture (BC) collection
Repeat episodes of bacteremia
Yeast
Statistical analysis: Description of whole population and by cohort. Outcomes analyzed by Mann-Whitney U-test where applicable. Statistics performed utilizing STATA 13.0 software. p≤ 0.05 denotes significance

15. Outcome Measures Process measures Time to organism identification
Time to streamlined susceptible regimen
Time to ID consultation
Patient outcomes
Time to microbiologic clearance
Mortality
Length of Stay (LOS)

16. Definitions Time to Organism Identification (Org ID) =
Organism identification date/time – BC collected date/time (in hours)
Time to Streamlined Susceptible Regimen =
Date/time of most narrow, directed, susceptible antibiotics as determined by ASP team – BC collected date/time (in hours)
Time to ID consultation
Date/time of initial ID evaluation – BC collected date/time (in hours)
Time to Microbiological Clearance
Date/time first negative blood culture (separated by at least 4 hours from initial blood culture) – BC collected date/time (in hours)
Mortality = Death during same hospitalization
LOS= Discharge date/time – BC collected (in days)

17. Results: Flow Chart of Participants
Preintervention Group
March-April 2013
(n=445)
Included in Preliminary Analysis
(n= 209)
Excluded:
CoNS (n=80)
Other GP (n=127)
Deceased/ER DC/Outpatient (n=16)
Yeast (n=11)
GN (n=2)
Intervention Group
March-April 2014
(n=365)
Included in Preliminary Analysis (n= 183)
(Plate=130, Bottle=53)
Excluded:
CoNS (n=61)
Other GP (n=62)
Deceased/ER DC/Outpatient (n=59)

18. Results: Basic Demographics
Mar-April 2013
(n=209)
Mar-April 2014
(n=183)
Significance
Female (%)
54%
50% NS
Age (median years) 67 58
Origin (%)
Community 40 35
Healthcare 60 65
Severity of illness (%)
None-Sepsis 11 10
Sepsis 44 52
Severe Sepsis 29 23
Septic Shock 17 15
% isolated identified by MALDI
n/a
>95%

19. Results: Distribution of Organisms
Number of Isolates
Percent

20. Results: Process Measures
March-April 2013
(n=209)
March-April 2014
(n=183)
P value
Gram Negative Organism
(n=153)
(n=135)
Time to Org ID (hours*)
51.9
29.6
<0.001
Time to Streamlined Susceptible Regimen (hours*)
68.5
56.2 NS
Time to ID Consultation (hours*)
34.1
16.2
0.02
S. aureus
(n=56)
(n=48)
44.5
<0.005
69.2
58.6
Time to ID consultation (hours*)
32.9
12.6
*Reported in median hours

21. Results: Patient Outcomes
March-April 2013
(n=209)
March-April 2014
(n=183)
P value
Gram Negative Organism
(n=153)
(n=135)
Unadjusted mortality (%)
16.3
9.6 NS
Time to microbiological clearance (hours*t)
47.3
54.2
Length of Stay (days*)
8.9
8.2
S.aureus
(n=56)
(n=48)
21.4
10.4
75.3
65.0
9.1
10.8
* reported in median hours/days
t data under review, adjusted analysis in progress

22. Results: Preliminary Outcomes for Severe Sepsis/Shock
March-April 2013
(n=96)
March-April 2014
(n=69)
Gram Negative Organism and/or S. aureus
Time to Org ID (hours)
51.8
31.8
Time to Streamlined Susceptible Regimen (hours)
74.2
58.1
Time to ID consultation (hours)
35.1
16.3
Time to microbiological clearance (hours)
69.2
55.9
Unadjusted mortality (%)
23.9
18.8
Length of Stay (days)
10.6
10.1

23. Perception/Acceptability

24. Lessons Learned Implementing new technology takes time and planning
Requires multidisciplinary effort
Cultural barriers to overcome (empiric prescribing, early consultation for S. aureus)
Laboratory and AST cost approximately 3-5 additional hours of effort per day
Structured intervention with susceptibility follow up

25. Future Directions Expanding cohort to include all organisms
Collect data over longer period of time
MALDI-TOF paired with earlier susceptibilities
Intermediate rapid testing for ESBL/KPC/MRSA
Cost savings analysis
Formal statistical analysis including multi-variable regressions and adjustment for severity of illness (chronic and acute)

26. Acknowledgements
Stewardship Team Belinda Ostrowsky, MD, MPH Iona Munjal, MD Priya Nori, MD Connie Park, MD Yi Guo, PharmD Philip Chung, PharmD Julie Williamson, PharmD Statistician Rafael Ruiz, PhD
Microbiology Lab Michael Levi, ScD
Wendy Szymczak, PhD
Philip Gialanella
Hitesh Patel
Myrna Intal
Frank Cardenas

27. Antimicrobial Stewardship Team and Microbiology Leadership