1. Molecular Testing and Therapeutic Management in the Treatment of Infectious Disease
Leveraging the latest science and a team-based approach to improve outcomes in infectious disease

2. Bill W. Massey, Ph.D.

3. Antibiotics: History and Importance
In 1900, infectious disease was the leading cause of death
There was an explosion of antibiotic discovery between 1940 to 1970
1943 Penicillin, 1950 Tetracycline, 1953 Erythromycin, 1960 Methicillin, 1967 Gentamicin, 1972 Vancomycin
Antibiotic discovery is much slower now
Antibiotics played a big role in the increase in life expectancy: 47 years in 1900 to 78 years in 2000.

4. Antibiotic Classes

5. We are running out of options!

7. Beta Lactam Antibiotics

8. Ambler Classification: β-Lactamases

9. The Emerging Crisis of Antibiotic Resistance
Annually, two million Americans are infected with antibiotic-resistant bacteria and 23,000 will die from it.
As resistance to the newer antibiotics emerges, the available treatment options diminish.
Fewer new antibiotics are being developed.
Of the 18 largest pharmaceutical companies, 15 have abandoned the antibiotic field.

11. Causes of the Antibiotic Resistance Crisis
Over-Prescribing
e.g. antibiotic prescribed for cold virus
Inappropriate Prescribing
Wrong antibiotic for the causative pathogen
Ineffective treatment duration or dose
Empirically-guided choice of antibiotic or duration of therapy are incorrect in 30% to 50% of cases
Extensive Agricultural Use
Humans consume the antibiotics in food
Antibiotics induce resistance in the natural biome

12. Misuse of Antibiotics and Resistance

13. What can be done in clinical practice to combat the crisis?
Improve prescribing practices
Don’t use antibiotics unnecessarily (e.g. for a “cold”)
Antibiotics are prescribed for viral upper respiratory infections 40% to 75% of the time.
Optimize therapeutic regimens
Don’t treat for longer than recommended.
Use an appropriate dose.
Accurate diagnosis of infectious pathogens
You can’t ensure appropriate treatment if you don’t know the infectious pathogen.

14. Let’s focus on two things that we can do now!
Accurate pathogen identification
Use of diagnostics is key
Team-based therapeutic management
Can assist in providing optimal therapeutics by ensuring optimal drug selection, dose and duration of therapy

15. Pathogen Identification Methods
Microbial Culture and Antibiotic Sensitivity Testing
Growing bacteria in culture and testing antibiotics in the culture
Molecular Pathogen Identification and Resistance Gene Detection
PCR-based pathogen identification and characterization

16. Microbial Culture

17. Antibiotic Sensitivity Testing

18. Structure of DNA

20. Microbial Culture versus Molecular-Based Pathogen Identification
Issue
Culture-Based PathogenTesting
PCR-Based Pathogen Testing
Sample Collection Method
Cumbersome collection methods
Easy, fast collection methods
Turnaround Time
3-5 days up to over a week
8 hours
Accuracy
70% accurate pathogen identification
99.8% accurate pathogen identification
Completeness of Pathogen Detection
Some pathogens are slow to grow, or will not grow, in normal culture medium. In multi-pathogen infections, organisms can become symbiotic with other organisms (e.g. biofilms) and will not grow in culture once disrupted by removal from the site of infection. If they do not grow, they are not detected.
Captures all tested pathogens. Does not require the organism grow or even still be alive for detection.
Current Antibiotic Exposure
Current antibiotic treatment at time of sample collection can inhibit the ability of the pathogen to grow in culture, thereby delaying results or failure to grow. This can lead to detection failure.
Is not affected by antibiotic exposure. Will detect pathogen even if non-viable.

21. Culture-Based Sensitivity Testing versus Molecular-Based Resistance Characterization
Issue
Culture-Based Sensitivity Testing
PCR-Based Resistance Testing
Turnaround Time
Is performed after culture is grown, adding to the time to get results.
Is performed at the same time as pathogen identification and does not add to the time to get results.
Accuracy
Only shows the sensitivity at first exposure to antibiotics. This can lead to false positives since the pathogen may carry the gene for resistance but not express it until exposed to the antibiotic. Such latent resistance potential is not detected by sensitivity testing but could manifest during antibiotic treatment, adversely affecting treatment response.
Shows the ability (latent or expressed) for resistance to particular antibiotics. Much more comprehensive in its detection.
Minimum Inhibitory Concentration (MIC)
Sensitivity is measured by MIC, the concentration of antibiotic needed to inhibit growth. Concentration on an agar plate can be different than concentrations actually present in the body. Pharmacokinetics are different for different tissues. This can lead to mischaracterization.
Is not based on MIC.

22. Innovative Clinical Labs are moving beyond diagnostics and into providing therapeutic management services
Therapeutic Management is the integration, evaluation, and application of patient-specific information in the selection of the best possible therapeutic program for the particular patient.
TM is done by a team approach where outside experts in pharmacotherapy provide the treating physician with expert guidance.
Therapeutic management provides value by optimizing physician time and applying expertise at the point it is needed, resulting in precise, individualized treatment plans.

23. Therapeutic Management Services
Licensed pharmacists create a personalized medication regimen that integrates a patient’s physiological, genetic, diagnostic, and disease state information.
In addition to the patient-specific information, the personalized medication regimen takes into consideration drug-drug interactions, contraindications, drug allergies, and current medications (when provided).
The personalized therapeutic recommendations are then provided to the treating physician as part of an easy to use report.

24. TM is Changing the Paradigm in Personalized Medicine
Therapeutic management services provide for specialization of professional services in personalized medicine, enabling the implementation of advances in medical science to improve patient outcomes and promote excellence in medical care delivery.
Therapeutic management essentially changes the paradigm for personalized medicine from provision of impractical information via laboratory reports to provision of easy to use therapeutic recommendations by trained medical professionals (i.e., from laboratory services to a consultative coordinated care service).

25. TM is Changing the Paradigm in Personalized Medicine
Pharmacists provide a coordinated care plan for the physician to execute in a easy to use format, saving the physician precious time.
The health insurance industry has forced primary care physicians to treat a broad range of disease states that were previously treated by specialists. This situation imposes a burden on the physicians / nurse practitioners to provide the most appropriate treatment plans.
By providing therapeutic expertise, TM can fill in these knowledge gaps and enable confident optimal care, improving patient outcomes and promoting excellence in medical care delivery.

26. For any clinical solution to work, it must:
Practical Clinical Implementation of Molecular Pathogen Testing and Therapeutic Management
For any clinical solution to work, it must:
Save time;
Improve patient care;
Not require training;
Not require specialized software;
And not increase the cost of care.

29. Potential Benefits of Using Therapeutic Management Services
Reduced incidence of adverse drug events
Improved clinical outcomes
Improved safety
Improved patient satisfaction
Decreased hospitalizations
Reduced cost of care

30. Thank You!