Staphylococcal infection

BS. Phuøng Nguyeãn Theá

Nguyeân
 Objectives
 Learners will be able to:
– list patterns of diseases due to staph.
– Apply in diagnosis diseases of staphy
 Staphylococci
– Recognize species & structure of staphylococci.
 Gram positive cocci

 staphylococcus  streptococcus
 Staphylococci
 27 species
 Three Important Species

– Staphylococcus aureus: Important human pathogen

– Staphylococcus epidermidis: Normal skin flora, disease

under special circumstances

– Staphylococcus saprophyticus: UTI’s in young females

 Different Staphylococci species

S. aureus S. epidermidis S. saprophyticus

Catalase positive positive positive

Coagulase positive negative negative

Novobiocin negative negative positive

Resistance
 Staphylococci - enzyme
 Coagulase:
– Converts fibrinogen into insoluble fibrin  deposit a layer of fibrin
around S. aureus site of infection
– Promotes abscess formation (wall)
 Staphylokinase
 Hyaluronidase
 Lipase: hydrolize lipid so help and developt S. aureus survive in
subcutaneous.
 Nuclease
 Hemolysin, leukocidine
 Staphylococci - Cell Wall
 Main component of the cell wall: Peptidoglycan (90%)
• [Less in Gram negative organism]
 Staphylococci - Cell Wall
Teichoic acid is responsible for the antigenic determinant of the organism
 Staphylococci - Cell Wall
3) Protein A
– Bind the Fc component of antibodies

4) Coagulase
– Bound and soluble forms
– Activates the coagulation cascade
• Fibrin meshwork  abscess formation

5) Capsule
– Variable
 S. aureus - epidemiology

 Asymptomatic Carriage Sites:

– Nares
– Rectum
– Perineum
– Pharynx

 Skin Colonization - Brief, Repeated

 Transmission - Person to Person

 Staphylococcal Infections - Risk Factors

Healthy people don’t get serious Staph infections

 Skin Disease  Diabetes

– Increased colonization  Renal Failure
 Trauma  Leukocyte & Immunoglobulin
Defects
– Expose binding sites
 Elevated Serum IgE Levels
 Viral Respiratory Tract Infection
(Influenza)  Narcotics Addiction
– Expose binding sites  Broad Spectrum Antibiotic
– Decreased clearance Therapy
 Foreign Body
 Liver disease
 Neoplasia
 Staphylococcal Infections
 Spread
 can spread hematogenously ANYWHERE to cause abscesses or
osteomyelitis or septic arthritis
 can also cause toxigenic infections --- toxin spreads

 Multiplication
 grows well anywhere

 Avoid Host Immune Response

 coagulase, catalase, leukotoxins, Fc binding protein, adhesins

 Damage
 inflammation, superantigens, degradative enzymes

 Transmission
 contact from fomites or direct person-person contact
 Patterns of Disease - S. aureus

 Invasion with Tissue Destruction

 Toxin Mediated
– Toxic Shock Syndrome
– Scalded Skin Syndrome
– Staphylococcal Food Poisoning
 S. aureus - Invasive Infections
A Two Step Process:
1. Binding (adherence) to host tissues
2. Invasion
 Staphylococcal Virulence Factors -
Adherence
 Nasal Mucosa: Teichoic Acid

 Traumatized Skin and Foreign Surfaces

Breech in normal barrier of mucosa or skin  Unmasked host proteins that S. aureus
has specific receptors
• Fibronectin
• Fibrinogen
• Laminin
• Type IV collagen
 Endothelial Cell
S. aureus has a unique affinity for the vascular tree
• Attach to Fibronectin, Laminin and Endothelium Itself
 Furuncle (nhoït)
 Often starts Folliculitis
 Firm, tender red, painful node
 Fluctuant with time
 Carbuncle

Larger than furuncle

 Extends into subcutaneous fat
 Interconnected
 Firm, inelastic skin
 Impetigo
 Superficial infection of skin
 Usually
– S. aureus
– Streptococcus pyogenes

 Children
 Hot Weather
 Minor Trauma
 Initially  vesicles
 Impetigo
 Later: Crusted with
yellow  dark brown
material
 Erysipelas
 Strep pyogenes or S.
aureus
 Sharp, raised borders
 Cellulitis
 Acute, spreading
Infection
 Involves both skin and
subcutaneous tissues
 Prior trauma to skin
 Warm and erethematous
 Invasive infection
 Pneumonia, arthritis…
 TSST-1: toxic shock syndrome toxin -1:
– Stimulus Il1, TNF -,  interferon from macrophages
&lymphomcytes

 Staphylococcal Enterotoxins A, B,C, D, E

 Pneumonia
 Onset: skin infection, cellulitis…

 Pneumonia:
– Progress quickly  respiratory failure
– Bilateral pneumonia.
– Necrotizing pneumonia abcesses
– Complication: pneumothorax
 TOXIC SHOCK SYNDROME

1978 - Todd and coworkers reported a group of children:

 Acute Febrile Illness
 Subsequent Development of Hypotension and Shock.
 Noted association with S. aureus phage group I
 Named the illness "Toxic Shock Syndrome“

1980 - Illness had been identified in 941 patients in the USA

1990 - More than 3,300 cases have been reported

 95% in women
 90% occurred during menstruation in women who were using tampons
1989 - 61 cases of TSS reported
 TSST – A Superantigen
 Able to activate large
number of Tcells
– Up to 20% at one time  Massive
Cytokine Release
 Interacts directly with invariable
region of Class II MHC molecule
 Activated T Cells Release
– IL-1: pyrogen, muscle proteolysis
– IL-2
– TNF: inhibit PMN function
– IFN-
 Physicochemical Factors that
Promote TSST-1 Production

1) Protein (or amino acid) containing

environment
2) Temperature 37oC - 40oC
3) Ph range 6.5 - 8
4) Presence of Oxygen
 Toxic Shock Syndrome
- Clinical Manifestations
1. High Fever (38.9oC)
2. Rash: diffuse macular erythroma
3. Hypotension.
4. Desquamation during convalescence:
1-2 weeks ater onset illness.
 Manifestations of Specific Organ
Involvement
Involvement of 3 or more the following system:
1. Mucous Membranes: hyperemia
2. Gastrointestinal Tract: vomiting and diarrhea at onset
3. Muscle: severe myalgias or CPK > 2 normal
4. Central Nervous System: disorientation alterations in
consciousness.
5. Kidney: azotemia, pyuria urinary tract infection
6. Liver: elevation of serum total bilirubin and SGOT or
SGPT > 2 upper limit of normal.
7. Blood: Thrombocytopenia
Toxic Shock Syndrome –laboratory findings

 Blood count:
– leukocytosis (90% imature and mature neutrophins)
– Toxic granulations: neutrophil cytoplasmic granules due to
immature or abnormally azurophil granules.
– Doehle bodies: fragments of ribosome-rich endoplasmic
reticulum.
– Vacuoles: pinocytosed membrane

 CRP.
Toxic Shock Syndrome -Diagnosis

 Isolation of toxin producing S. aureus from

a patient with a compatible clinical illness.
 Toxic Shock Syndrome -
Treatment
1. Treatment of Hypotension and Shock
– Vigorous Fluid Replacement

2. Attention to the Site of S. aureus Colonization

– Removal of Tampons
– Drainage of Staphylococcal Abscess

3. Anti-Staphylococcal Antibiotic Therapy

 Staphylococcal scalded skin syndrome
 A Disease of Infants
– Localized Infection with Diffuse Skin Rash

 S. aureus (Phage group II) recovered from:

– Nose
– Pustules
– Eye
– Umbilicus

 Exfoliative Toxin
– Two Serologically and Biologically Distinct Proteins
• Exfoliatin A
• Exfoliatin B
– Inter-Epithelial Splitting of Stratum Granulosum Layer
– No cytolysis or inflamattion
 Staphylococcal Scalded Skin Syndrome -
Clinical Features

 Starts Abruptly
– Perioral erythema
– Sunburn like, tender rash 
spreads over entire body
 Exfoliated Areas Eventually Dry
– Flaky desquamation lasting 3-5
days
 Within 10 days After Onset
Complete Recovery
– New epidermis has replaced the
denuded areas
 Staphylococcal Food Poisoning
 Commonly implicated foods
– Custard filled bakery good
– Canned food
– Potato salad
– Ice cream

 Toxigenic Strain of S. aureus growing in contaminated

food (enterotoxin A – E)
 Person to Person Transmission
 Food appears normal in appearance, odor and taste
 Staphylococcal Food Poisoning -
Clinical Features
 Incubation period 2-6 hours
 Enterotoxin stimulates intestinal
peristalsis and CNS
– Abrupt onset:
• Salivation
• Nausea and vomiting
• Abdominal cramps
• Watery diarrhea without bloody

 Afebrile
 Self limited, symptoms disappear in 8 hours
Staphylococcal Food Poisoning - treatment
 Decrease symptoms
 No antibiotic (toxin cause not bacteria)
 S. aureus Treatment
1941 – Penicillin available
1945 – Penicillin resistance reported
– Plasmid mediated
– 2o to beta-lactamase (penicillinase)
1960-64 Semi-synthetic pencillins produced
– Methacillin, oxacillin, nafcillin
1961 Methacillin resistant S. aureus (MRSA) reported
– Resistant to all beta-lactam antibiotics
Methacillin Resistant S. aureus (MRSA)

 2 Penicillin binding proteins (PBPs) normally

have enzymatic activity responsible for cross
linking peptidoglycan wall
 MRSA have acquired a chromosomal gene MecA
 code for alternate PBP (“PBP 2a”)
– Low affinity for beta lactam
– Enzymatically active  generate peptidoglycan

 Treatment  Vancomycin (glycopeptide AB)

 Glycopeptide
 Prevent wall synthesis by binding pentapeptide (a precursor of cell
wall).

 Resistant: fisrt 2002 in Michigan & pennsylvania

 Mechanism of resistant: (vancomycin –resistant strains have abnormal,

thickened cell wall)
– Change in structure or metabolism of teichoic acid
– Affinity trapping of vancomycin by cell wall monomers