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, PharmDClinical Pharmacy Manager of Infectious Diseases

Montefiore Medical CenterAlbert Einstein College of Medicine

Bronx, NYSeptember 2015

Disclosures

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

ObjectivesDescribe 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

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

1. Vlek A, etal. PLoS One. 2012; 7: e32589.2. Lodis TP, etal. Clin Infect Dis 2003;36:1418-23.

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 HealthBizzini A, etal. Clinical Microbiology and Infection. 2010; 16: 1614-1619.

How does MALDI-TOF MS Work?

Photos courtesy of Mayo Clinic Medical Laboratories

Photos courtesy of Mayo Clinic Medical Laboratories

How does MALDI-TOF MS Work?

Conventional vs. MALDI by Plate/Bottle

0 hrs

• Growth detected

0-2hr

s

• Gram Stain• Subculture to plate

18-24hr

s

• 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

Conventional MALDI by Plate MALDI by Bottle

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) P value

Time to Organism Identification (hour) 84.0 55.9 <0.001 40.9 14.5 <0.001

Time to Effective Antibiotic Therapy (hour) 30.1 20.4 0.021 89.7 32 <0.001

Time to Optimal Antibiotic Therapy (hour) 90.3 47.3 <0.001 80.9 23.2 <0.001

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% 0.021 21% 8.9% 0.01

Total Average Hospital Costs per Inpatient N/A N/A 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):1237-452. Perez KK, et al. J infect 2014 Sep;69(3):216-25.

Antimicrobial Stewardship ProgramFormally 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/auditingMaking hospital guidelines/protocolsEducationResearchPublication

ASP Strategies by Campus

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

Daily Workflow

• 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 emails 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

Objective

• Analyze early outcomes of MALDI + ASP activities in bacteremic patients

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

Outcome Measures

Process measuresTime to organism identificationTime to streamlined susceptible

regimenTime to ID consultation

Patient outcomesTime to microbiologic clearanceMortalityLength of Stay (LOS)

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)

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)

Results: Basic DemographicsMar-April 2013

(n=209)Mar-April 2014

(n=183) Significance

Female (%) 54% 50% NS

Age (median years) 67 58 NS

Origin (%)

Community 40 35 NS

Healthcare 60 65 NS

Severity of illness (%)

None-Sepsis 11 10 NS

Sepsis 44 52 NS

Severe Sepsis 29 23 NS

Septic Shock 17 15 NS

% isolated identified by MALDI n/a >95% n/a

Results: Distribution of Organisms

E.coli

K.pneumoniae

P.aeru

ginosa

Proteus

Enterobac

ter

Provid

encia

Acineto

bacter

Morga

nella

Other G

NM

RSAM

SSA

0

10

20

30

40

50

60

70

80

90

100

2013

2014Per

cen

t

Nu

mb

er

of Is

ola

tes

Results: Process MeasuresMarch-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)

Time to Org ID (hours*) 44.5 29.6 <0.005

Time to Streamlined Susceptible Regimen (hours*) 69.2 58.6 NS

Time to ID consultation (hours*) 32.9 12.6 <0.005

*Reported in median hours

Results: Patient OutcomesMarch-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 NS

Length of Stay (days*) 8.9 8.2 NS

S.aureus (n=56) (n=48)

Unadjusted mortality (%) 21.4 10.4 NS

Time to microbiological clearance (hours*t) 75.3 65.0 NS

Length of Stay (days*) 9.1 10.8 NS

* reported in median hours/dayst data under review, adjusted analysis in progress

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

Perception/Acceptability

Series1 94%

74%

60%

69%Ever contacted by AST regarding positive BC by MALDI? ?

Feel like BC results are coming sooner?

Percentage of time already aware of BC result by the time you were notified?

Has MALDI affected your clinical decision making skills and/or added to patient care?

Lessons LearnedImplementing 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

Future Directions

Expanding cohort to include all organisms

Collect data over longer period of time

MALDI-TOF paired with earlier susceptibilitiesIntermediate 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)

Acknowledgements

Stewardship TeamBelinda Ostrowsky, MD, MPH

Iona Munjal, MDPriya Nori, MDConnie Park, MDYi Guo, PharmDPhilip Chung, PharmDJulie Williamson, PharmD

Statistician Rafael Ruiz, PhD

Microbiology Lab Michael Levi, ScD Wendy Szymczak, PhD Philip Gialanella Hitesh Patel Myrna Intal Frank Cardenas

Antimicrobial Stewardship Team and Microbiology Leadership