disclosures: no relevant disclosures objectives: understand the rates and impact of staph aureus...
TRANSCRIPT
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