Staph Infection: Current impacts and intervention strategies

1. Staph Infection: Current impacts and intervention strategies LCDR Ian A. Myles, MD National Institutes of Health National Institute of Allergy and Infectious Disease

2. Disclosures: • No relevant disclosures

3. Objectives: • Understand the rates and impact of Staph aureus mediated disease. • Understand the potential underlying disorders associated with Staph aureus infections. • Understand intervention strategies for Staph aureus disease.

4. Outline: • Historical Information • How do we fight off Staph? • How does Staph fight back? • Who is at risk? • How big of a problem is this? • How do we treat Staph infections? • Controversy • How can we eradicate Staph?

5. Historical Information: • Sir Alexander Ogston • Aberdeen Undergrad • Observed 88 wound infections under the microscope • Named the organism “Staphylococcus aureus” for small bunches of yellow grapes www.abdn.ac.uk

6. Rev Infect Dis Jan 1984. 6(1):122-8 www.robertreeveslaw.com

7. History Continued: • 1880—1940: Treatment limited to topical Carbolic Acid (phenol) • 1940: Discovery of penicillin • 1942: First reports of resistance • 1950: Penicillin use discouraged for Staph treatment • 1961: Methicillin resistance described

8. β-Def Cath MRSA IL-1R IL-17R Keratinocyte IL-17 IFNg TLR2 IL-1β IL-23 MC/MΦ IL-17 DC Fe T-cell γδ-Tcell B-cell NF-κB Fe Fe

9. β-Def Cath MRSA IL-1R IL-17R Keratinocyte IL-17 IFNg TLR2 IL-1β IL-23 MC/MΦ IL-17 DC Fe B-cell γδ-Tcell T-cell Toxic Shock Protein PVL Anti-Burst Siderophores α-hemolysin Anti-PMN Vitamin D Protein A qacA/B/C Enterotoxins NF-κB Fe Fe

10. 100% Colonized with Staph species • ~10% Colonized with MRSA www.genome.gov/pressDisplay.cfm?photoID=20169

11. At Risk Populations: • Too few functional neutrophils: • Low numbers (congenital, auto-immune,chemotherapy) • Weak oxidation (CGD, MPO, Specific Granule Def) • Poor chemotaxis (LAD) • Both poor burst and chemotaxis (Diabetes and renal disease) • Abnormal TLR/IL-1 pathway (IRAK4, MyD88 mutations)

12. At Risk Populations: • Disrupted Skin Function: • Trauma • Atopic Dermatitis • Abnormal T-cell responses: • APOCED • STAT3 mutations (Job’s syndrome) • DOCK8 mutations • Mucocutaneous Candidiasis • HIV/AIDS

13. How bad is this problem?

14. Current Staph Burden: • 19,000 American deaths per year • Skin infections: • 10 million outpatient visits per year • 500,000 hospital admissions per year

15. Slide courtesy of John Bartlett

16. Current Staph Burden: • Invasive Infections: • #1 risk factor is breach of skin barrier (Trauma, central line placement, medical procedure) • Endocarditis • Pneumonia (often post influenza)

17. Slide courtesy of John Bartlett

18. Current Staph Burden: • Skin infections: • 10 million outpatient visits per year • 500,000 hospital admissions per year • 19,000 deaths per year • Invasive Infections: • #1 risk factor is breach of skin barrier (Trauma, central line placement, medical procedure) • Endocarditis • Pneumonia (often post influenza) • Food-borne: US meat and poultry, Brazilian meat products tested positive for MRSA Myles and Datta. Semin Immunopathol. 2012 Mar;34(2):181-4

19. Treatment Options: • Topical: • Mupirocin (nasal gel) and Chlorhexadine (topical wash) • Identical mechanism of action to Carbolic acid • Oral: • Clindamycin (300-450 mg q8h) – skin infection only • Also MRSA may quickly develop resistance to clinda if already resistant to erythromycin • Trimethoprim-sulfamethoxazole (2 DS tablets BID) – for emperic Tx, typically combined Amoxicillin (500 mg TID) or Rifampin • Doxycycline (100mg BID) – for emperic combine with amoxicillin or Rifampin • Linezolid (600mg BID) – okay in isolation but $$$$ and high toxicity potential Liu, C et al. CID 2011; 52:e18

20. Treatment Options: • Intravenous: • Tigecycline (100mg IV xT, then 50mg IV q12h) • Daptomycin: • Skin: 4mg/kg IV daily • Bacteremia: 6mg/kg daily • Vancomycin: 30mg/kg IV daily, max 2g/24hr • However… Figueroa DA, et al. CID 2009; 49:177-80. Benvenuto M, et al. Antimicrob Ther Chemother 2006; 50:3245-9.

21. Vanco Controversy: • Guidelines state: • If MIC >2 the report will state “sensitive” but alternative treatment is advised (Liu C, CID 2011; 52:969) • Treat to trough level of 15-20mcg/mL(Rybak MJ, et al. CID 2009;49:325) • However, 15-20mcg/mL carries 20% risk of severe nephrotoxicity (Lodise TP, et al. CID 2009;49:507)

22. Other Options if Not Using Vancomycin? • Linezolid is not inferior to Vancomycin for Staph Pneumonia (Wunderink RC. CID 2012;54:621 ) or skin infection • Vaccination: TBA

23. Eradication Strategies: • Screen all patients with nasal swabs • All positives go on contact isolation and have mupirocin nasal gel applied for several days NEJM 2011;364:1425

24. Eradication Strategies: Chlorhexadine washes qacA/B positive strain Batra R, et al. CID 2010 Jan 15;50(2):210-7

25. Eradication Strategies: NEJM 2011;364:1407

26. Difference in study may have been: VA Study – “Aggressive enforcement of hand hygiene through positive deviance” Univ study – observation only, no change in hand hygiene.

27. Reward Method: • Denver Hospital, CO: • Each time staff member “caught” washing hands they got a raffle ticket – monthly drawings • Spartanburg Regional, SC: • Each staff member received a “Caught You Caring” certificate JAHCO Hand Hygiene Guidelines:

28. Shame Method: Spartanburg – rates from 63.8% to 83.6% JAHCO Hand Hygiene Guidelines:

29. Intimidation Method: • Greenview Regional Hospital in Bowling Green Kentucky • People hired to observe hand washing • Non-adherent staff received letters • 1st went only to staff member • 2nd went to staff member and department chair • 3rd went to staff member, department chair, and credentialing committee JAHCO Hand Hygiene Guidelines:

30. High Tech Enforcement: Cost $3,000/room to install, 3000 per ICU to maintain Armellino D. CID 2012;54:1

31. Reminder Method: JAHCO Hand Hygiene Guidelines:

32. I find your lack of hand hygiene disappointing AGGRESSIVE POLITE

33. Eradication in Outpatient: • Oral medication to treat any active infection • Chlorhexadine washes and mupirocin nasal gel to reduce colonization (5 days) • Family members as well • Chlorhexadine wipe-down of all surfaces in home/office. Wash all sheets, pillows, etc. • Treat the #1 enemy of clearing MRSA from a home!

35. Baltimore Sun

36. (Unofficial) Eradication in Outpatient: Bleach Baths • Pre-treatment with antibiotics • Cephalexin for 2 weeks (MSSA!!!) • Bathe 5-10min 2x/week • Follow with emollient • Reduces burden, but does not clear Staph Huang, et al. Pediatrics. 2009;123:e808-814

38. Conclusions: • MRSA is a significant pathogen in the US • Staph aureus has many mechanisms for evading normal immune responses • Immunity complicated by beneficial effects • Oral and IV options are available, but the treatments of today may not persist • Screening may not be of benefit • Hand washing and aggressive cleansing needed for eradication

39. Shameless Self Promotion: • Any patients with recurrent Staph infections despite adequate eradication strategies • Any patients with invasive Staph infections • Clinicaltrials.gov • “Host Factors in Invasive and Recurrent Staphylococcus Aureus Infections” • PROTOCOL# NCT00911430