1. Sepsis and Antibiotic Side Effects
Maureen Spencer, M.Ed, BSN, RN, CIC, FAPIC
Infection Preventionist
Director, Clinical Implementation
Accelerate Diagnostics

2. Saving patients from sepsis is a race against time
CDC calls sepsis a medical emergency; encourages prompt action for prevention, early recognition
Sepsis knows no boundaries; It can happen to anyone
When sepsis occurs, it should be treated as a medical emergency
Doctors, nurses, patients, families - can prevent sepsis and ask - could this be sepsis?
CDC - increase awareness of sepsis among the public, healthcare providers, and healthcare facilities
Prevent infections that lead to sepsis and urgently treat suspected sepsis

3. CDC and Sepsis Infection Prevention Strategies
CDC comprehensive campaign to demonstrate that prevention of infections that cause sepsis, and early recognition of sepsis, are integral to overall patient safety
Strategies:
Vaccination
Reducing transmission of pathogens in health care environments
Hand washing to prevent transmission
HAI bundles for prevention
Appropriate management of chronic diseases

4. Epidemiology of Sepsis
Sepsis affects over 26 million people worldwide each year
Largest killer of children – more than 5 million each year
> 1.6 million people in the U.S. are diagnosed with sepsis each year – one every 20 seconds and the incidence is rising 8% every year
258,000 people die from sepsis every year in the U.S. – one every 2 minutes
> 42,000 children develop severe sepsis each year
4,400 (10%) of these children die, more than from pediatric cancers
Every day, 38 sepsis patients require amputations

5. Sepsis-3 Definitions
Sepsis is the body’s overwhelming and life- threatening response to infection that can lead to tissue damage, organ failure, and death1
Sepsis: Life-threatening organ dysfunction caused by dysregulated host response to infection2
Septic Shock: Subset of sepsis with circulatory and cellular/metabolic dysfunction associated with higher risk of mortality2
Approx 50% of patients with sepsis have positive blood cultures3
Fatality rate for severe sepsis is about 40%, and treatment costs over $16 billion annually3 1.
2. JAMA. 2016;315(8): doi: /jama
3. Proc (Bayl Univ Med Cent) Jan; 28(1): 10–13.

6. Infections Associated with Sepsis

7. Post Sepsis Syndrome (PSS)
Sepsis survivors have a shortened life expectancy, are more likely to suffer from an impaired quality of life
42% more likely to commit suicide
~50% of survivors suffer from post-sepsis syndrome
Insomnia, difficulty getting to sleep or staying asleep
Nightmares, vivid hallucinations and panic attacks
Disabling muscle and joint pains
Extreme fatigue
Poor concentration
Decreased mental (cognitive) functioning
Loss of self-esteem and self-belief

8. + Sepsis Treatment If sepsis is suspected: or +/- Draw lactate
Draw 2 sets of blood cultures (prior to antibiotic administration, if possible)
Culture suspected site of infection (urine, wound, lower respiratory tract, etc.)
Begin empiric antibiotic therapy
Gram positive coverage +
Gram negative coverage or
+/-
aminoglycoside
Yeast (Candida) coverage
Define Empiric Therapy
Emphasize – the criticality to time spent by tech/lab/dr., life of the patient

9. Antibiotic Side Effects:
Result of Empiric Antibiotic Use
2) Delayed Antibiotic Sensitivity Tests

11. Clinical Urgency: Surviving Sepsis
>36hrs is when most blood culture antibiotic sensitivity test results are available from standard lab procedures:
Delayed appropriate treatment
Longer empiric antibiotic use
Delayed isolation for MDROs
Every hour of delay to appropriate antimicrobial therapy for patients with severe sepsis decreases the chances of survival by 7.6%1
n = 2,731
1Kumar et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med Jun; 34 (6 ):

12. Antimicrobial Resistance
1) Overuse of Antibiotics
2) Spread from delays in Isolation Precautions for MDROs
“The CDC estimates that the direct costs of antimicrobial resistance on the U.S. economy is $20 billion annually. When you factor in the economic consequences of lost productivity, it adds an additional $35 billion in costs”

13. Resistance is Spreading Across Countries
A real global crisis – for example:
December 2015
Pan-Resistant Enterobacteriaceae seen in 19 countries
mcr-1 >> Colistin resistant
Plasmid mediated
Easily passed between organisms (E. coli/Klebsiella)
Pan Resistance = No drugs work
In the Strategy presentation you were introduced to the fact that antimicrobial resistance is a global threat. Surprisingly, it’s not a new phenomenon, but global concerns have recently heightened due to global impact and the fact that we’ve begun to see resistance to last-resort antibiotics, such as Colistin. Just to review, touch on slide points.
Transition, but there is additional recent news demonstrating the concern…
CDC - Pathogen Distribution and Antimicrobial Resistance
infection control & hospital epidemiology January 2018, vol. 39, no. 1

14. Clostridium difficile from Antibiotics

15. Antibiotic Classes and Risk for Clostridium difficile Infection
Two meta-analyses found risk to be greatest with clindamycin, fluoroquinolones or cephalosporins
465 studies and included 5 published between 1994 and 2011 (total, 26,435 patients) in their meta-analysis1
Risk for CDI to be more than tripled after any antibiotic exposure (odds ratio, 3.55).
Treatment with clindamycin showed the strongest association with subsequent CDI (OR, 16.80)
910 studies and included 8 published between 2005 and 2011 (total, 30,184 patients)2
Risk for CDI to be increased nearly sevenfold after antibiotic treatment (OR, 6.91)
Risk was greatest with clindamycin (OR, 20.43), followed by fluoroquinolones (OR, 5.65), cephalosporins (OR, 4.47)
1. Brown KA et al. Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection. Antimicrob Agents Chemother 2013 May; 57:2326
2. Deshpande A et al. Community-associated Clostridium difficile infection and antibiotics: A meta-analysis. J Antimicrob Chemother 2013 Apr 25

16. Interdisciplinary Sepsis Management Advisor – “Sepsis Alerts”
Sepsis Alert For Faster Diagnosis of Potential Sepsis
Interdisciplinary Sepsis Management Advisor – “Sepsis Alerts”

17. Electronic Sepsis Initiative Increases CDI
Studied over 127,346 total patient days
increased antibiotic use and hospital onset (HO) CDI during sepsis care bundle implementation
period directly following the implementation phase accounting for the highest rate of antibiotic use
Cefepime was the most commonly used antibiotic
Levofloxacin, which was not part of the sepsis care order set, was the main driver of increased antibiotic use
Hiensch R, et al. Impact of an electronic sepsis initiative on antibiotic use and health care facility-onset Clostridium difficile infection rates. American Journal of Infection Control, Volume 45, Issue 10 (October 2017)
Sepsis Bundle Implementation
CDI Rate Per 10,000 Patient Days
Pre-implementation of sepsis care bundle
1.4
During implementation
1.6
After Implementation
10.8
3 yrs. After Implementation
14.4

18. Emerging Technology:
Fast Antibiotic Sensitivity Tests (AST) to Reduce Empiric Use of Antibiotics

21. Accelerate PhenoTM Blood Culture System: Direct from Positive Blood Culture
Fast Results
Identification in under 90 minutes using Fluorescence In-situ Hybridization (FISH)
Antibiotic Susceptibility with MICs reported 5 hours after ID
~7 hours to microbiology report
Easy to Use
<2 min hands-on time
Bring testing closer to the patient
FDA cleared – Feb
First product, blood culture, broad range of ID and susceptibility results

22. Fast ID and AST BC System
Module
Automated pipetting robot
Digital camera
Custom microscope
Kit
48 flow-channel cassette
Reagent cartridge
Sample vial
System
1-4 module(s)
Control & Analysis PCs
Touchscreen monitor
Specimen Prep
Identification
MIC Susceptibility
+BC
RBC Lysis Filtration Immobilization
FISH Probes
Microscopy Imaging

23. Gram-Positive + Yeast Panel
Covers 90% of organisms responsible for BSIs
aCoagulase-negative Staphylococcus spp: Staphylococcus epidermidis,
Staphylococcus haemolyticus,
Staphylococcus hominis,
Staphylococcus capitis,
Staphylococcus lugdunensis,
Staphylococcus warneri, not differentiated
bStreptococcus spp:
Streptococcus mitis,
Streptococcus oralis,
Streptococcus gallolyticus,
Streptococcus agalactiae,
Streptococcus pneumoniae, not differentiated
Gram Positive ID
Ampicillin
Ceftaroline
Erythromycin
Daptomycin
Linezolid
Vancomycin
MRSA (Cefoxitin)
MLSb (Erythromycin-Clindamycin)
Staphylococcus aureus O
Staphylococcus lugdunensis
Coagulase-negative staphylococcia
Enterococcus faecalis
Enterococcus faecium
Streptococcus spp.b
Yeast
Candida albicans
 Candida glabrata

24. Ampicillin - Sulbactam Piperacillin-Tazobactam
Gram-Negative Panel
Covers 90% of organisms responsible for BSIs
Gram Negative ID
Ampicillin - Sulbactam
Piperacillin-Tazobactam
Cefepime
Ceftazidime
Ceftriaxone
Ertapenem
Meropenem
Amikacin
Gentamicin
Tobramycin
Ciprofloxacin
Aztreonam
Escherichia coli O
Klebsiella spp.c
Enterobacter spp.d
Proteus spp.e
Citrobacter spp.f
Serratia marcescens
Pseudomonas aeruginosa
Acinetobacter baumannii
cKlebsiella spp: Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated
dEnterobacter spp: Enterobacter cloacae, Enterobacter aerogenes, not differentiated
eProteus spp: Proteus mirabilis, Proteus vulgaris, not differentiated
fCitrobacter spp: Citrobacter freundii, Citrobacter koseri, not differentiated

25. Time to ID/AST Results: 48-96 hours
Typical ID & AST Workflow 1 2 3
perform gram stain 4 5
patient blood draw
blood bottle incubation & screening
initial plate streaking
OPTIONAL: ID and resistance markers
Blood culture incubation can be anywhere from 6-18hrs depending on lab and delivery into incubators 6
overnight incubation 7
colony selection 8
OPTIONAL:
MALDI-TOF ID
.5 McFarland 9
ID & susceptibility 10
optimized therapy 11
Time to ID/AST Results: hours
8-24hrs depending on lab

26. Accelerate Pheno™ BC System = FAST Workflow
blood bottle
incubation & screening 1 2 4
ID & susceptibility with MICs
in < 7hrs 5
optimized therapy:
de-escalate or escalate
patient blood draw
Incubation depends on the organism’s growth – typically from 6-18 hours
De-escalate or Escalate empiric antibiotic therapy
Place patients with MDROs on isolation precautions at 7hours

27. Benefits of PhenoTM Blood Culture System
Standardize laboratory procedures for blood cultures
Allows clinicians to evaluate empiric antibiotic therapy faster and de-escalate or escalate therapy
Reduces Pharmacy costs for unnecessary antibiotics Improves care of patients with sepsis
Reduces length and days of antibiotic therapy
Expedites isolation/precautions for multiple drug resistant organisms
Prevents onset of Clostridium difficile and MDROs
Decrease use of antibiotics prevents adverse side effects

28. Is there Clinical Evidence???

29. Standard of Care (Mean ¡¾ SD) Intervention (Mean ¡¾ SD)
ID Week 2018: “Impact of Accelerate Pheno™ Rapid Blood Culture Detection System on Laboratory and Clinical Outcomes in Bacteremic Patients”
Clinical Outcomes
Standard of Care (Mean ¡¾ SD)
 N  = 79
Intervention (Mean ¡¾ SD)
N =75
p-value
 LOS (days)
12.1  (11.9)
9.1 (7.6)
0.03
 TTOT (hours)
73.5 (50.2)
37.5 (32.7)
<0.001
 Total Antibiotic DOT (days)
9.0 (7.5)
7.0 (4.6)
0.05
 Meropenem DOT (days)
6.6 (3.7)
3.7 (2.1)
Cost of Hospitalization*
$39,796
($23,367-$84,902)
$34,495
($18,001-$73,221)
$ savings
0.12
Oral Presentation and Abstract – Clinical Outcomes Study at University of Arkansas for Medical Sciences (UAMS) - ID Week 2018

31. Improving Operations through simplified workflow for ID & AST results
TYPICAL WORKFLOW
ACCELERATE
WORKFLOW
Workflow may differ between laboratories

32. How Fast ID/AST Impacts Hospital Patient Care
Improved sensitivity and MIC results
Standardized Blood culture procedures
Improved bench workflow
Improved turnaround time to ID/AST/MIC
Improved services and staff utilization
Save lives
Sepsis Alerts in EMR
Information Technology
Improved drug/bug orders and standardized order sets
CEO, CFO, COO, CNO, CMO
Administration
Reduction in BC contamination rates
Eliminates broad-spectrum ABX use
Micro Lab
Reduced use of restricted ABX
Reduction in MDROs, CDI, cross infection, less isolation
Reduction isolation beds, PPE. Improved bed utilization
Reduced morbidity/mortality
Infectious Disease Physicians
FAST ID & AST
Infection Prevention
Efficient response to sepsis alerts
Reduction in outbreaks (MDRO,CDI)
Reduction in cases reported to NHSN and CMS Penalties
Reduced Lab draws and drug admin by RNs
Testing complete. Data compiled, reviewed and presented in comparison to previous standard method. Finalize operational pathways.
More efficient use of ICU beds and staff
Rapid transition to targeted therapy
Nursing and Medical Staff
Pharmacy and ASP
More efficient ABX Stewardship Program
Escalation or de-escalation
Expedited transfers of +BC patients back to LTACs
Reduced ABX cost: prep, delivery
Reduced morbidity/mortality, reduced cost of care