MRSA “The Bacteria – Fight Back!” A 2009 Literature Review

1. MRSA “The Bacteria – Fight Back!”A 2009 Literature Review Jim Turner, D.O. Medical Director, Lugar Center for Rural Health Deputy Commissioner of Vigo County Health Department Member, Infection Control Committee, Union Hospital

2. MRSA History • Uncommon before 1975 • 1975-1980 – spread to hospitals and cases increased rapidly • 1980s-1990s – healthcare associated (HA-) MRSA continued to increase dramatically. • 1998 – alarming increase in Community Associated (CA) MRSA in young children with risk factors • Recent study of invasive MRSA – • 25% onset in hospital • 58% (CA) MRSA with previous healthcare exposure, 16% CA only.

3. How do MRSA infections present?

4. Hospital Infections • 1.7 million patients per year • 100,000 deaths • Additional $6.5 billion cost • 1.5% U.S. residents—4 million people—carry MRSA • 25% of these colonized in hospital have subsequent infection.

5. CDC Reports • 100,000 MRSA infections/year • 19,000 related fatalities • (Greater than the death toll from HIV-AIDS) • Virtually all bacteria capable of causing serious infections, especially if immunocompromised. • Many arise from our own bacterial flora

6. Oral pneumococcus>lungs • E Coli gut>diverticulitis>UTI • Staph aureus>skin>abscess • Staph epidermidis>skin

7. COST – Surgical Site Infection • $29,000 – control • $52,000 – MSSA • $92,000 MRSA • In one study, cost for surgical procedure $31,000 with hospital infection, $185,000

8. (CA) Versus (HA) MRSA • Genetic difference • CA – more likely to have PVL toxin • Associated with severe pneumonia • More likely to be susceptible to common antibiotics

9. Food for Thought If we calculate all the cells in the human body, we are only 10% Human. Researchers think there are more bacteria in our body than stars in the milky way galaxy The colors look like paint, but they’re bacteria The Milky-Way Galaxy

10. Back to the Basic Sciences • Plasmids • Quorum Sensing • Exotoxin Production • Intracellular Persistence • Biofilm Formation • Adhesions

11. Back to the Basic Sciences • Plasmids

12. Quorum Sensing • Allows the bacteria to detect the density of their own species and alter their genetic expression. • Adhesion to skin less important, other genes allow for transcription producing toxins that are activated for deeper penetration into tissue and eventually the bloodstream, allowing the bacteria additional sites to perpetuate themselves.

13. EXOTOXIN • Panton-Valentine Levcocidin (PVL) toxin linked as virulence factor for CA-MRSA. Found in necrotizing pneumonia with mortality rate of 75%. • Staphylococcal Exotoxin more virulent by presence of B-lactam antiobiotics.

14. Intracellular Persistence • MRSA may survive within host cells such as phagocytes. May be found in chronic infections such as osteomyelitis, prosthetic joints, and skin infections.

15. Biofilm • A structured community of micro organisms encapsulated within a self-developed matrix and adherent to a living on inert surface found 80% of infections. Bacteria may survive in biofilms that protect them from antibiotics and adverse environmental factors. Biofilm on endotracheal and tracheostomy tubes may prove an excellent and relataively protected growth medium for the lung and act as the lung as a resovoir of MRSA. Biofilm quickly coat catheters that support MRSA.

16. ADHESIONS • MRSA adheres to plasma proteins such as fibrogen, which coat implanted bio materials such as catheters and orthopedic devices.

17. From 1 bacteria to 300,000,000,000,000 in 24 HOURS

18. Future Pharmaceutical Challenges • 15 major pharmaceutical companies, 10 have left the field of antibiotic discovery programs.

19. Pharmaceutical Industry • Antibiotic sales at $25 billion per year • Antidepressant and antihypertensives taken for years, not 7-10 days. • Resistance could mean a drug that cost $2 billion to R&D and 14 years to approve, only useful for a few years.

20. Pharmaceutical Industry • Provided semi-synthetic penicillin, e.g. methicillin, in 1959. Within two years – resistance via a new gene – MECA, first MRSA strains.

21. GENOMICS • 650 bacteria genes sequenced, thought would reveal a treasure trove of new targets for antibiotics to attack, has been a dismal failure.

22. 7 years, $70 million, evaluated 300 genes thought to be essential for bacterial viability, no drugs found to render bacteria unfit for survival.

23. Who Is At Risk? – 5”C” • Skin Contact • Compromised Skin-Cuts/Abrasions • Contaminated Items and Surfaces • Crowding • Lack of Cleanliness

24. “Bettineski started out with a small red mark on his calf. A week later surgery staved off amputation of his leg.” Phil Taylor, “A Menace in the Locker Room,” SI.com, February 23, 2005. 9.

25. Prisoners • Incarcerated persons transferred to acute care facilities are high risk for MRSA colonization and should be targeted for surveillance and culture nose and wounds.

26. Patients at Risk • Previous admission to long-term care facility/hospital in past year and advanced age.

28. TREATMENT • Index of suspicion • Culture of wound • Incision and drainage more important than antibiotics • Appropriate antibiotic therapy • P.O. or I.V. Keep wound covered

29. VancomycinBactrimDoxycyclineClindamycincCubicinZyvoxTygacilMerremInvazVancomycinBactrimDoxycyclineClindamycincCubicinZyvoxTygacilMerremInvaz

30. You now must report Staphylococcus Aureus Infections

31. Prevention • 57% of patients receive inappropriate antiobiotic treatment of the index MRSA infection • “Good judgment comes from experience, and a lot of that comes from bad judgment.” Will Rogers

32. Inappropriate Use of Antibiotics • Encourage over growth of resistant organisms – now have access to nutrients and space • MRSA infections associated with B-lactam and quinolones allow rapid proliferation of an organism that may have been merely colonizing

33. Changes In Practice • Must rein in use of antibiotics • 55% of all RX for URI in US unnecessary • Avoid broad spectrum antibiotics • How long to treat? • Decrease antibiotic use in agricultural industry.

34. Prevention • Surveillance cultures • Barrier precautions • Hand washing • Single bed facilities • Isolation of infected patients

36. America Learns About MRSA

37. Preventable and Unacceptable • On July 30, a jury awarded over $2.5 million to James Klotz and his wife Mary in a medical malpractice lawsuit against a heart surgeon, his group practice and St. Anthony’s Medical Center in St. Louis, MO. • In 2004 Mr. Klotz, now 68, was rushed to the hospital with a heart attack and a pacemaker was surgically implanted.

38. Preventable and Unacceptable • He developed a drug-resistant staph infection called methicillin-resistant Staphylococcus aureus (MRSA). It was so severe that he underwent 15 additional operations, spent 84 days in the hospital and lost his right leg, part of his left foot, and a kidney..

39. Preventable and Unacceptable • This verdict should send a warning to physicians, hospitals and hospital board members. Until recently, infection was considered an unavoidable risk. But now, there is proof that nearly all hospital infections are avoidable when doctors and staff clean their hands and rigorously practice proper hygiene and other preventive measure. Hospital infections will cause the next wave of class-action lawsuits, even bigger than litigation over asbestos.

40. “When meditating over a disease, I never think of finding a remedy for it, but, instead, a means of preventing it.” Meditating…. • Louis Pasteur 1822-1895