1. International Epidemics Lecture November 4, 2015 B. W. Cue, Jr
International Epidemics Lecture November 4, 2015 B.W. Cue, Jr. (UMB 1969)
Outline: An overview of infectious microbes (excluding fungii)
Bacteria vs. viruses
An overview of antimicrobial therapy
Cidal vs. static drugs
What is drug resistance?
Green chemistry implications
Treatment approaches
New drugs and approaches

2. Bacteria or Virus?
Source: Wikipedia

3. Bacteria or Virus?
Source: Wikipedia

4. Cidal vs. Static Drugs Bacteriocidal Bacteriostatic
This kind of drug kills all susceptible bacteria
Bacteriostatic
This kind of drug inhibits/slows the growth of bacteria until host’s immune system takes over

6. What causes antibiotic resistance?
The more antibiotics are used, the more chances bacteria have to become resistant to them.
Major causes of antibiotic resistance include using antibiotics when they are not needed. Defensive medicine.
Over-the-counter availability in some regions of the world.
not taking antibiotics at the doses and times that a doctor prescribes — this allows time for the bacteria in your system to become resistant.
Antibiotics are also often overused in animals (in veterinary medicine and in agriculture).
Improper disposal of unused antibiotics. Hospital waste.
Discharge of waste containing antibiotics from manufacturing plants.

7. You can help prevent antibiotic resistance
understanding that most people don’t need antibiotics for colds and flu because they are caused by viruses
telling your doctor you only want an antibiotic if it is really necessary
taking the right dose of your antibiotic at the right time, as prescribed by your doctor
taking your antibiotics for as long as your doctor tells you to taking simple steps to avoid infections and prevent them from spreading
Properly disposing of unused/unwanted antibiotics

12. Source: CDC Report, Antibiotic Resistance Threats in the United States, 2013

14. Green Chemistry
“…the utilization of a set of principles that reduces or eliminates the use or generation of hazardous substances in the design, manufacture and application of chemical products.”
*Source: Paul T. Anastas and John C. Warner, Green Chemistry: Theory and Practice (New York, NY: Oxford University Press Inc., 1998). ISBN

15. Green chemistry has become associated with a quick way to eliminate bad actor chemicals
Origins
Of Materials
Manufacturing
Distribution
Use
End of Life
Waste Prevention
Less Hazardous
Reagents
Atom Economy
Renewable Feedstocks
Design For
Degradation
Benign Solvent Systems
Green Analytical
Methods
Use of Catalysis
Benign Product Design
Design for Safety and Security
Unnecessary
Derivatives
Energy Considerations
Green chemistry applies across the product lifecycle

16. Meeting Both Quality and Environmental Requirements Is a Big Challenge

17. Top Generic Companies by Sales (88% of 2014 Rx’s)
Company & Sales (2012)1
Our Perception of Their Green Chemistry Activity (Max +++++)2
Teva $10.2 B
Sandoz (Novartis) $8.7B
Actavis $5.9 B
Mylan $5.8 B
Hospira $4.1 B
Sanofi $2.5 B
Ranbaxy $2.3 B
Aspen Pharmacare $1.5B
STADA Arzneimittel $1.3B ++
+++ -
1. Source 2012 Sales:
2. Benchmarking green chemistry adoption by “big pharma” and generics manufacturers: Drivers, Barriers and Opportunities, Veleva and Cue, submitted.

18. Concerns about Manufacturing Waste in China and India
A consumer advocacy group, SumOfUs, reports one of XXX’s antibiotics suppliers in China, NCPC, discharges pharmaceutical waste into the environment. Generic drug company YYY contracts with an Indian company, AAA, which in turn gets drug supplies from four polluting Chinese factories. And ZZZ deals with three Chinese companies that “have been in the Chinese media spotlight for various offenses including improper waste management and the release of noxious chemicals,” the study says
Researchers from Sweden studying the water supplies around the pharmaceutical center of Hyderabad, India, found them contaminated with various kinds of drugs that had been released by manufacturing plants there.
Sweden has proposed adding environmental considerations to global ICH cGMP’s.
The ACS Green Chemistry Institute’s Pharmaceutical Roundtable has begun to consider how to spread green chemistry throughout the pharmaceutical supply chain

19. Contract Research Sites in India
Source:

20. Antibiotic Manufacturing Waste near Hyderabad, India
Source:

21. Figure 1. Multi-drug resistance observed among 93 bacterial strains isolated from the PETL WWTP.
Marathe NP, Regina VR, Walujkar SA, Charan SS, Moore ERB, et al. (2013) A Treatment Plant Receiving Waste Water from Multiple Bulk Drug Manufacturers Is a Reservoir for Highly Multi-Drug Resistant Integron-Bearing Bacteria. PLoS ONE 8(10): e doi: /journal.pone

22. New drugs and approaches

23. New systemic antibacterial agents approved by the US Food and Drug Administration per 5-year period, through 2012.
New systemic antibacterial agents approved by the US Food and Drug Administration per 5-year period, through Modified from Spellberg 2004 [23].
Boucher H W et al. Clin Infect Dis. 2013;cid.cit152
© The Author Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please

25. GAIN legislation

30. The first new beta lactamase inhibitor in 30 years

31. Beta Lacatmase Inhibitors
Sulbactam CP-45899
MK-7665 Relebactam
NDA Approval 2015?

33. Bacteriophages

36. Questions?? b.cue@comcast.net
Thank You
Questions??