Disclosures:

No relevant disclosures

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.

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?

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

www.robertreeveslaw.com

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

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

-γδ Tcell

TLR2

MRSA

IL-17R

NF- Bκ

IL-17

DC

Keratinocyte

β-DefCath

MC/MΦ

IL-1βIL-23

IL-1R

Fe Fe

FeT-cell

IL-17IFNg

B-cell

IL-1βIL-23

IL-17

-γδ Tcell

TLR2

MRSA

IL-17R

NF- BκDC

Keratinocyte

MC/MΦ

IL-1R

Fe

Fe Fe

T-cell

IL-17IFNg

B-cell

Siderophores

α-hemolysin

Anti-PMN

PVL

Enterotoxins

Toxic ShockProtein

Protein A

Vitamin D

β-DefCath

Anti-Burst

qacA/B/C

100% Colonized with Staph species ~10% Colonized with MRSA

www.genome.gov/pressDisplay.cfm?photoID=20169

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)

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

Current Staph Burden:

19,000 American deaths per year

Skin infections: 10 million outpatient visits per year 500,000 hospital admissions per year

Slide courtesy of John Bartlett

Current Staph Burden:

Invasive Infections: #1 risk factor is breach of skin barrier

(Trauma, central line placement, medical procedure)

Endocarditis Pneumonia (often post influenza)

Slide courtesy of John Bartlett

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

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

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.

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)

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

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

Eradication Strategies:

Batra R, et al. CID 2010 Jan 15;50(2):210-7

qacA/B positive strain

Chlorhexadine washes

Eradication Strategies:

NEJM 2011;364:1407

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.

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:

Shame Method:

JAHCO Hand Hygiene Guidelines:

Spartanburg – rates from 63.8% to 83.6%

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:

High Tech Enforcement:

Armellino D. CID 2012;54:1

Cost $3,000/room to install, 3000 per ICU to maintain

Reminder Method:

JAHCO Hand Hygiene Guidelines:

POLITE AGGRESSIVE

I find your lack of hand hygiene disappointing

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!

Baltimore Sun

(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

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

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