1. Rapid Diagnostic Testing and Antibiotic Stewardship Debra A
Rapid Diagnostic Testing and Antibiotic Stewardship Debra A. Goff, Pharm.D., FCCP Clinical Associate Professor Infectious Diseases Specialist The Ohio State University Medical Center Columbus, Ohio, USA

2. Objectives
Discuss the clinical studies that incorporate rapid diagnostic tests (RDT) in ASPs
Describe the impact of RDT with ASP interventions on patient outcomes
Identify how to incorporate RDT into ASP

3. As William Osler, said in “There are three phases to treatment: diagnosis, diagnosis and diagnosis.”

4. “Action is not optional, and diagnosis is an essential weapon in our fight against antimicrobial resistance”
JIM O’NEILL
UK Economist

5. Diagnosis as the first prescription

6. Question
What organizations recommend RDT? A. Bill and Melinda Gates Foundation B. IDSA C. WHO D. SIDP E. all of the above

7. FIND: Foundation for Innovative New Diagnostics
A Global Perspective
At FIND, we envision a world where diagnostics guide the way to health for all people.
FIND: Foundation for Innovative New Diagnostics
support of the Bill & Melinda Gates Foundation
We recommended that the richest countries, including all the G7 countries, should mandate into law that a validated diagnostic assay demonstrating the need for antibiotic therapy must be used prior to writing a prescription.
Without such a big, bold step, it is unlikely that rapid progress can be made to reduce the scale of inappropriate use and limit the rapid emergence of resistance to our available drugs.

8. 1. Should ASPs Advocate for Use of Rapid Viral Testing for Respiratory Pathogens to Reduce the Use of Inappropriate Antibiotics?
We suggest the use of rapid viral testing for respiratory pathogens to reduce the use of inappropriate antibiotics
2. Should ASPs Advocate for Rapid Diagnostic Testing on Blood Specimens to Optimize Antibiotic Therapy and Improve Clinical Outcomes?
We suggest rapid diagnostic testing in addition to conventional culture and routine reporting on blood specimens if combined with active ASP support and interpretation
Ref: Clin Inf Dis 2016

9. May 2017 Report

11. Informing and educating the public about RDT

13. Question
RDTs with ASP interventions have been shown to A. decrease mortality B. decrease time to effective therapy C. decrease LOS D. all of the above

14. RDT
Bacterial infections

15. A meta-analysis to evaluate the impact of mRDT in improving clinical outcomes in BSIs.
31 studies with 5,920 patients
Conclusion: mRDT should be considered as part of the standard of care in patients with BSIs.

17. Time to effective therapy 5 hours
RDT WITH ASP interventions
decrease
Mortality 36%
Time to effective therapy 5 hours
LOS 2.5 days

18. Time to effective therapy
RDT WITHOUT ASP interventions
No change
Mortality
Time to effective therapy
LOS

19. REF: Bauer, Perez, Forrest, Goff Clinical Infectious Diseases 2014;59(S3):S134–45

21. Knowledge Deficit?
156 MDs surveyed Nebraska only 60% would adjust ATB only 29% viewed the RDT interpretation guide on the intranet
Ref: Donner LM et al J Clin Microbiol 2017;55(5):

22. Knowledge Deficit?
224 Pharmacists surveyed (9 countries) 45% with ID training 68% had NOT assessed patient outcomes only 53% receive alerts in real-time
Ref: Foster R et al. ICHE 2017;38:7

23. Wang F. et al. Implementation of a Patient Scoring System for a Pharmacist-Driven Initiative for the
Management of Staphylococcus aureus Bacteremia Through the Use of an Electronic
Medical Record accepted to AJHP

24. Study Methods
Retrospective, single-center quasi-experimental study of hospitalized patients with SAB.
Intervention period: RDT test result/pharmacists alerted to patients with SAB via a patient scoring tool integrated into the electronic medical record.
ALL Pharmacists utilized scoring tool + OSU evidence-based practice guideline to make standardized recommendations 1. to promote adherence to SAB quality-of-care measures 2. encourage ID consultation

25. Primary objective
Evaluate overall compliance with adherence to quality-of-care components for managing S. aureus bacteremia
ID consult
Repeat blood cultures
Echocardiogram
Initiation of SAB-targeted antimicrobial treatment

26. An Automated, Pharmacist-Driven Initiative Improves Quality of Care for Staphylococcus aureus Bacteremia
Initiation of targeted antibiotics for SAB 40 hours sooner in intervention group p
ID consults
Repeat blood cultures
84% %
75% %
95%
100%
P=0.01
P=0.01
P=0.49
Wenzler E, Wang F, Goff D, Prier B, Mellett J, Mangino J, Bauer K.
Clin Infect Dis 2017

27. 15% 2% 92% 93% 92% 68% Echocardiogram
An Automated, Pharmacist-Driven Initiative Improves Quality of Care for Staphylococcus aureus Bacteremia p
Echocardiogram
Mortality
6-fold decrease in intervention group
Overall compliance
93% %
15% %
92%
68%
P<0.06
P<0.008
Wenzler E, Wang F, Goff D, Prier B, Mellett J, Mangino J, Bauer K
Clin Infect Dis 2017

28. Urinary tract infections
Urine dipstick sensitivity rates: able to detect infection in as few as 30% of cases
The UK Longitude Prize: teams will compete for a total of 5 years, and a £10 million prize, with a final winning team being announced in 2019.
contrasting ideas show the vast possibilities for potential technologies that point-of-care tests may be based on: bacterial identification India team credit-card-sized device to detect UTI from a few drops of urine DNA hybridization to identify resistance genes
Ref:

29. Nat. Rev. Urol. doi:10.1038/nrurol.2017.20
Figure 1 Overview of the clinical workflow of existing and future diagnostic technologies for UTI
Figure 1 | Overview of the clinical workflow of existing and future diagnostic technologies for UTI. In current practice (illustrated in the grey boxes) once a urine sample is collected it is transferred to a clinical microbiology laboratory. In the laboratory, sample processing is initiated with a screening assay to assess for the presence of bacteria followed by pathogen identification, and, if positive, antimicrobial-susceptibility testing (AST). Information from each successive assay enables providers to prescribe specific antibiotic therapy. However, truly infection-specific antibiotic treatment cannot be prescribed until results from AST are available — at least 48 hours after sample submission. The new technologies in development have the potential to expedite this process and transform the clinical microbiology workflow (depicted in blue boxes). Urine samples collected in clinic can be analysed at the point of care. In this setting, integrated platforms can determine both pathogen identity and AST enabling precise, infection-specific treatment in a matter of hours from presentation. For complex samples or those collected from clinics without access to point-of-care testing, integrated platforms can provide similarly robust and efficient information in a clinical laboratory. MALDI-TOF, matrix-assisted laser desorption ionization–time of flight.
Davenport, M. et al. (2017) New and developing diagnostic technologies for urinary tract infections
Nat. Rev. Urol. doi: /nrurol

30. Table 1 Approved technologies for pathogen detection
Davenport, M. et al. (2017) New and developing diagnostic technologies for urinary tract infections
Nat. Rev. Urol. doi: /nrurol

31. “Stewardship of Culturing”
Opportunities and Challenges to Safely Reduce Test Use
Ref: Madden G, Weinstein R. ICHE 2018, vol. 39, no. 2

32. Wound Infections
In the US, chronic wounds affect 6.5 million patients with more than $25 billion spent on treating wound-related complications
Delayed initiation of appropriate antimicrobial therapy is an independent risk factor for treatment failure in skin and soft tissue infections (SSTI).
Ref: Sen CK. Wound Repair Regen. 2009;17(6):
Amin AH et al .Mayo Clin Proc. 2014;89(10):

33. New Test: DxWound Report

34. Improving Antibiotic Stewardship in the ED: What Will It Take?
Because patient turnover in the ED is rapid, reducing antibiotic use will require faster and better diagnosis and treatment of infection
Rapid results of a diagnostic test can alleviate fear of missing a subtle bacterial infection
Limit the use of "just-in-case" antibiotics
Avoid unintended consequences of C. difficile and multidrug-resistant organisms.
Antibiotic Stewardship in the Emergency Department: Raising the Bar for Antibiotic Use - Medscape - May 01, 

35. Assessments of Opportunities to Improve Antibiotic Prescribing in an Emergency Department
A Period Prevalence Survey
Approximately 30% of all outpatient antimicrobials are inappropriately prescribed.
Inappropriate antibiotic prescribing in the ED occurred in 39% of cases with the highest rates observed among patients with bronchitis, URTI, and SSTI.
URTI= Upper Respiratory Tract Infection
SSTI= Skin and Soft Tissue Infection
Timbrook, Tristan T. et al. “Assessments of Opportunities to Improve Antibiotic Prescribing in an Emergency Department: A Period Prevalence Survey.” Infectious Diseases and Therapy 6.4 (2017): 497–505. PMC. Web. 26 Jan

36. What do patient’s want? Fast AND accurate Look on Amazon
IT + ID = 2 publications!
Accuracy matters
Ref:

37. Xpert® Xpress Strep A Performed on the GeneXpert® System
Qualitative in vitro diagnostic test for the detection of Streptococcus pyogenes (group A β-hemolytic streptococcus, strep A) in throat swab specimens from patients with signs and symptoms of pharyngitis.
Utilizes an automated real-time polymerase chain reaction (PCR) to detect Streptococcus pyogenes DNA.

38. Strep A Tests Available in the Market
MDx
MDx Batch
EIA Readers
GeneXpert
Alere i
Roche Liat
Focus Simplexa
Illumigene
Quidel Solana
BD Veritor
Quidel Sofia
Method
RT-PCR
Isothermal Molecular
EIA
TAT (min)
18-24^ 8
~20
~60
<60 35 5
Market Average Cost $$
$$$ $
Sensitivity
100%
95.9%
98.3%
94.7%
98.0%
98.2%
96.6%
90.6%
Specificity
94.1%
94.6%
94.2%
95%
97.7%
97.2%
95.5%
96.1%
Storage Requirements
Room Temp
Refrigerator
Frozen
Culture Confirmation Req. No
Yes
LIS Connectivity
CLIA Waiver
Acquisition Method
Purchase/Placement/RRA
Placement/RRA
Purchase
Purchase/RRA

39. RDT
Fungal infections

40. T2 nanodiagnostic panel that uses T2 magnetic resonance
Does not depend on recovery of viable organisms
14 U.S. hospitals enrolled 152 patients diagnosed with candidemia through a blood culture
It took nearly two days for the culture to identify that the patient had candidemia, and another day-and-a-half to specify which strain of Candida.
The T2 Candida Panel was significantly more likely to be positive than blood cultures in patients with recent candidemia, in particular those patients who were being treated with antifungal drugs or had neutropenia.
The study didn’t assess whether T2Candida shortens time to starting antifungal treatment or improves patient outcomes. 
Ref CID 2018 Feb early release

41. RDT
Viral infections

42. Molecular viral diagnostic tests.
are in their infancy
It is time to increase the awareness of the viral etiology in RTIs and implement mRDT in clinical practice
Studies using molecular rapid test (mRDT) The impact of mRDT on antibiotic use was investigated. Antibiotics were still continued in about 75% of the patients, despite the detection of virus. This finding was explained by being a new test*
*Am J Infect Control 44(11):1396–1398

43. Molecular viral diagnostic tests Hospitalized patients
children
adults
Decreased 45% to 29% p<0.009
Decreased 72% to 63% p=0.36
Keske, et al. Eur J Clin Microbiol Infect Dis (2018).

44. Ref: Tokarz et al. Nature SCIENTIFIC REPORTS | (2018) 8:3158 | DOI:10
Ref: Tokarz et al. Nature SCIENTIFIC REPORTS | (2018) 8:3158 | DOI: /s

45. Question
Tick-borne diseases (TBDs) are the most common vector-borne diseases in the US1 Borrelia burgdorferi, the causative agent of Lyme disease, alone accounts for an estimated 300,000 annual cases of TBDs .
Q. How many specimens are tested for TBD in the US each year?
500,000
1 million
2 million
3 million
> 4 million

46. Tick-borne diseases (TBDs) are the most common vector-borne diseases in the US1 Borrelia burgdorferi, the causative agent of Lyme disease, alone accounts for an estimated 300,000 annual cases of TBDs .
Q. How many specimens are tested for TBD in the US each year?
Each year, approximately 3 million clinical specimens are tested for TBDs in the US with serology being the mainstay of TBD diagnosis

47. Question
How can ASPs assist in helping microbiology labs acquire RDT? A. voice your support and hope for the best B. co-develop a business plan C. meet with hospital COO and medical director D. B and C

48. The mentors provided a strategy to help justify the cost of a rapid diagnostic test to be used in ASP interventions for Staphylococcus aureus bacteremia. As a result, the hospital administrators at three hospitals approved additional funding for the microbiology laboratory.
Am J Health-Syst Pharm. 2017; 74:e34-41

49. The key to successful RDT: is the twinning of these technologies to ASP team that can notify & guide clinicians about test results to initiate or modify therapy without this link between microbiologists and ASP, the rapid results run the risk of floating adrift at sea