3er curso latino americano de cicatrización avanzada en heridas (i)
TRANSCRIPT
Tammy Luttrell MSPT, PhD, CWS , FACCWS
Profesora AdjuntoColorado Univerisity, Anschutz Medical Campus
National Jewish Health
3 Comunes Invasores
3 Comunes invasores
CU DPT Lecture SeriesSpring 2012
Columbia June 2012
Innate (First Response) Immune System
• Present from birth (Inbuilt Immunity)• NOT Antigen specific• No Memory--(No enhanced response with second
exposure)
• Uses cellular and humoral components• Decreased effectiveness in the absence of
Adaptive Immunity• Responsible for Adaptive Immune response
– Initiation– Amplification
• Cytotoxic T Cells – CTL’s – • Generally Th1Columbia June 2012
Basic Humoral/Adaptive Immunology
• AntiGen- Antibody Generator (Ag)• Recognized by Antibodies (Ab)
• Immunoglobulin (IgA, IgG…)
• Made by B Lymphocytes • T- Lymphocytes HELP B cells
• T helper cells (Th)
• Dendritic Cells (DC)• “present” Antigen (Ag)
• Generally Th2
Columbia June 2012
Origin of Immune System Cells: Innate & Adaptive
Columbia June 2012
WBC’s: Who are they?
Columbia June 2012
General Strategies for Aversion
• Prevent Recognition– Alter the charge associated with the outer cell
membrane (from negative to neutral)• Cationic AMP’s don’t bind
– Binding to the Fc (wrong end) of IgG• Prevents opsonization• Complement cascade does not initiate
• Protection from HOST defenses– Secretion of cytotoxic molecules to damage
HOST immune cells– Secretion of enzymes that disable HOST
defenses
3 Virulence Factors/Strategies Used….
CU DPT Lecture SeriesSpring 2012
Streptococci
• Group A Streptococcus S. pyogenes– necrotising fasciitis– toxic shock syndrome– 1574 cases in England, Wales & NI
(2010)
• Group B Streptococcus • S. agalactiae
– Wound infections & septicaemia in adults– 1610 cases in England, Wales & NI
(2010)
Classified into Lancefield groups (1938)
What does group B Strep do?
• Colonisation– Asymptomatic and intermittent– Intestinal (<30% of adults)– Vaginal (<25% of women)
• Infection– Newborn babies– Adults: the elderly,
pregnant/postpartum women, others with underlying disease
Group A Streptococcus (GAS) S.pyogenes
Diseases:•Strep Throat•Toxic Shock•Necrotizing Fascitis•Endocarditis•Nephritis
A Few of the Virulence Factors:•M protein•Hemolysins•Extracellular enzymes•Gene encoding SpyCEP
Mortality10% to 15% of people with invasive GAS25% of those with necrotizing fascitis 35% of those with toxic shock syndrome
L.A. Times:Flesh-eating bacteria: Scientists identify the perpetratorAugust 13, 2008 | 4:39 pm
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Dividing streptococci (12,000X). Electron micrograph of Streptococcus pyogenes by Maria Fazio and Vincent A. Fischetti, Ph.D. with permission. The Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University.
Spr
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2012
Group A Streptococcus
CU DPT Lecture SeriesSpring 2012
NETS – Neutrophil Extracellular Traps
• Unbound Chromatin (DNA)• Histones• Azurophilic granules
– Pore forming peptides– Proteases– Cytotoxic AMP’s (Antimicrobial
Peptides)
• Cytosolic proteins
Neutrophil “Nets”DNA based traps for Pathogenic Bacteria
CU DPT Lecture SeriesSpring 2012
Group A Streptococcus
CU DPT Lecture SeriesSpring 2012
Sda 1 – Breakdown of NETSS.Pyogenes RELEASED!Neutrophil Apoptosis
Group A Streptococcus: SLS Cytotoxcity
CU DPT Lecture SeriesSpring 2012
Facilitates penetration of S. corneum =INVASION
Spring 2012 CU DPT Lecture Series
Group B Strep – Virulence Factors
[Frontiers in Bioscience 9, 1794-1802, May 1, 2004]
Virulence FactorGBS Surface Polysaccharide Capsule
• Antiphagocytic properties • Capsule-deficient mutants diminished virulence in animal models• Sialic acid residues on capsule inhibit the binding of opsonically-active C3
component of complement to the cell surface– blocking activation of the alternative pathway
• Transplacental passage of type-specific anticapsular IgG antibody from mother to infant is an important protective factor against invasive disease
http://medicine.ucsd.edu/NizetLab
Virulence FactorGBS β-hemolysin
• Cytotoxic to pulmonary epithelial and endothelial cells– Pulmonary injury and alveolar protein exudate in
early-onset pneumonia
• Activity is blocked by surfactant phospholipid– Increased risk of premature, surfactant-deficient
neonates for severe pneumonia
• Induces cytokine release and nitric oxide production in macrophages– Stimulate elements of the sepsis cascade
S. Aureus : Pigmentation
Dangerous GOLDAureus =
“golden” Latin
CU DPT Lecture Series
Senecio aureus Golden Groundsel
Octavian Aureus, 30 BCE
Amblyglyphidodon aureus (Cuvier, 1830) Golden damselfish
Spring 2012
Staphlococcus ‘Aureus’
CU DPT Lecture SeriesSpring 2012
Staphyloxanthin = GOLD pigmentProtects against ROS
Host Unsuccessfu
l Evading S. Aureus
Semin Immunopathol. 2012 March; 34(2): 237–259.
Biofilm
Biofilm – What is it? And why do we care?
• Biofilm – What is it?–Polysaccharide coating “protective
covering” for bacteria–Self contained, micro environment
for bacterial colonies
Spring 2012 CU DPT Lecture Series
Biofilm- Why is it a problem?
• Human phagocytes do not recognize that:–Biofilm = Bacteria–Biofilm goes “undetected”
• Impermeable to external Antibiotic therapy
• Bacteria are under the PS coating and “protected”
• Rapid emergence of AB resistance to even the very newest AB (CDC 2001)
Spring 2012 CU DPT Lecture Series
Occurrence of Resistance
CU DPT Lecture SeriesSpring 2012
Biofilm Formation
Biofilms usually occur when one bacterial species attaches specifically or non specifically to a surface, and then secretes carbohydrate slime (exopolymer) that imbeds the bacteria and attracts other microbes to the biofilm for protection or nutritional advantages.
http://textbookofbacteriology.net/themicrobialworld/NormalFlora.html
Biofilm
So What???
• Management of wounds
• Contamination versus Disease and Infection
• Techniques supporting HOST defense mechanisms
• Judicious use of antibiotics
• Kick the BUGS OUT!!!
Successful Host Immunity
Semin Immunopathol. 2012 March; 34(2): 237–259.
Macrophage Ingesting S.pyogenes
Spring 2012 CU DPT Lecture Series
Neutrophil Ingesting S.pyogenes
Spring 2012 CU DPT Lecture Series
Accurately Discern and Characterize Bacterial Bioburden
Spring 2012 CU DPT Lecture Series
Terminology: Definitions and concepts
Disease - damage caused by presence of microorganisms or their products (can be unapparent or without observable symptoms at a point in time).
Colonization - presence of microorganisms without disease at that point. This term applies to surfaces only, i.e., the blood cannot be colonized and host cells with intracellular infection are not colonized.
Columbia June 2012
Contamination vs. Infection
• All wounds are have bacteria • Clinically infected wounds may or
may not have local and systemic changes
• What you may observe:– Normal inflammatory response– Mild erythema– Cellulitis– S/S systemic infection
Columbia June 2012
Basics of Wound Care
• Cleanse• Debride• Maintain moisture• Assessment and Re-assessment
Spring 2012 CU DPT Lecture Series
Cleansing of LIVING tissue
• Cautious use of:– Antiseptics
• Providone iodine• Sodium Hypochlorite (Dakins)• Iodophor• H2O2• Acetic acid (vinegar)
Spring 2012 CU DPT Lecture Series
Cleansing of LIVING tissue
• Create a healing environment – Move beyond chronic inflammatory
phase• Accomplish removal of bacteria –
– IF impeding the normal progression of healing
– Do NOT eradicate bacteria at the expense of • Fibroblasts• Keratinocytes• NeutrophilsSpring 2012 CU DPT Lecture Series
Reducing Bacterial Bioburden
• Irrigation with Normal Saline– 19 gauge needle = 4 to 15 psi pressure; 8 psi
optimal– 50+ cc of irrigant
• UVC– Bacterial cannot replicate or mutate to UVC; – UVC stimulates vasodilitation– Not painful
• Ultrasound – Facilitates liquification of slough/fibrin– US stimulates vasodilitation– Not painful
Spring 2012 CU DPT Lecture Series
Wound Cleansing
• Goal– Remove bacteria and surface
contaminates• Allow the wound to move more
rapidly from inflammation to proliferation
– Protect the healing wound• Minimize risk of infection
– Minimize chemical and mechanical trauma
Spring 2012 CU DPT Lecture Series
Debridement
• Mechanical• Conservative Sharp• Enzymatic• Autolytic• Surgical• Biological - Sterile Maggots
Spring 2012 CU DPT Lecture Series
Dressing Selection
• Thin Film• Occlusive / Semi permeable• Hydrocolloid• Hydrogel• Foam• Alginate• Silver
– Ionic or nanocrystalline
Spring 2012 CU DPT Lecture Series
Dressing Selection Based on 5 key Questions
• Is the Wound Healing• Is the Tissue Viable or Necrotic• Does the wound have an Optimal
amount of moisture – (DRY CELL = DEAD CELL)
• Is there dead space• What does the peri wound tissue
look like?Spring 2012 CU DPT Lecture Series
Conclusions
• Bacterial Evasion Strategies– Multiple and complex– Antibiotic resistance- REAL and present threat– Gene Sharing
• Share critical survival mechanisms – Cassettes– Phage
• Core genes • Mobile genes (SCCmec)
• Best Defense is a good HOST OFFENSE!– HOST immune system
• Facilitate and Support!
– Advanced Wound care
¿Preguntas?
Behold the turtle. He makes progress only when he sticks his neck out. - James B. Conant (1893-1978)