615

47

Vancomycin-resistance S. aureus VRSA S. aureus

Staphylococcus aureus


S. aureus 300,000

S. aureus
3
S. aureus
5 1
S. aureus (Invasive S. aureus genus Staphylococci
infection) 19-341
Staphy S. aureus lococcus S. aureus
262
Staphylococci S. aureus
44-483,4
coagulase clumping factor
S. aureus
cloxa- adhesin toxin 20
cillin methicillin (Methicillin-resistance S. aureus 30 Coagulase-negative staphylococci
MRSA) adhesin 10
72-73 toxin1
( 1)10
S. aureus 5
1. Cell wall peptidoglycan
MRSA 23-423,4,6,7
( 1) peptidoglycan
glycopeptides vancomycin endotoxin
(Vancomycin-intermediate resistance S. Cytokines Disaureus - VISA) 8,9 seminated intravascular clotting (DIC)

616

1 S. aureus
( 10)

S. aureus capsular
polysaccharide (CP)
S. aureus
12 CP5 CP8
85
CP5 CP8
10
2. Surface protein
Protein A (Antiphagocytic) S. aureus ( 1)
(Adhesin)
Microbial Surface Components Recognizing
Adhesive Matrix Molecules (MSCRAMM)


passive
immunization S. aureus 10
3. (Extracellular
products) ( 1) 1,10
3.1 Superantigens Enterotoxins
Epidemiolytic toxins (Exfoliatin
A B) Scalded skin syndrome Toxic
shock toxin-1
3.2 Cytotoxin Hemolysin

Hemolysin
S. aureus
Leukocidin Panton-Valentine
leukocidin (PVL)
S. aureus PVL

PVL
3.3 S. aureus
Coagulase, Hyaluronidase

S. aureus
(Colonization) 30 50
S. aureus 11




MRSA1,11

S. aureus

 47 617
1 (Extracellular Factors) S. aureus 1

Surface proteins
Protein A
Collagen BP
Fibronectin BPA and B
Clumping factor A and B
Capsular polysaccharides
Polysaccharide capsule type 5
Polysaccharide capsule type 8
Cytotoxins
, , , and -hemolysin
Panton-Valentine leukocidin (PVL)
Superantigens
Enterotoxin A-D
Exfoliatin A, B
Toxic shock syndrome toxin-1 (TSST-1)
Enzymes
V8 protease, Hyaluronidase, Coagulase,
Staphylokinase, etc.

Anti-immune, anti-PMN
Collagen binding
Fibronectin binding
Fibrinogen binding
Anti-phagocytosis?
Anti-phagocytosis?
Hemolysin, cytotoxin
Leucolysin
Food poisoning, Toxic shock syndrome
Scaled skin syndrome
Toxic shock syndrome
Spreading factor, Clotting, Clot digestion, Plasminogen
activator, etc.

S. aureus
28-35 12,13
1 65 12
hemodialysis
peritoneal dialysis


COPD Rhumotoid
arthritis12,13

S. aureus 38

60 MRSA
20 14 S.
aureus sterile site
( 19
15 )15 S. aureus

S. aureus

Hemophilus influenzae type
B Streptococcus pneumoniae
16-18

S. aureus
3

26


(Healthcare-associated infection) MRSA
2-4
MRSA

618
MRSA

MRSA .. 1997-1999
MRSA
Western-Pacific 46
34 26
MRSA MRSA
5 .. 2000
(Nosocomial) (Healthcareassociated) (Communityacquired) MRSA 61, 52 14

19

MRSA
(CA-MRSA HA-MRSA)
MRSA
MRSA 26 67
S. aureus

MRSA
CA-MRSA HA-MRSA20
CA-MRSA


MRSA
2,7,21

S. aureus toxin-mediated
virulence
toxin-mediated
S. aureus

1,10,11
1. Exfoliative toxin A B

epidermis Scalded skin syndrome
Bullous impetigo
2. Toxic shock syndrome toxin -1 (TSST-1)
Superantigen
T-lymphocyte
cytokines

endotoxin

hemodynamic

3. Enterotoxin S. aureus enterotoxin



2-6

S. aureus






(Liquefaction necrosis)
S. aureus

 47 619

1,10,11

S. aureus

1.





cellulitis pyomyositis
S. aureus
S. aureus
necrotizing fasciitis


1
2.
S. aureus



systemic
inflammatory response

DIC
S. aureus
2.1 (Infective endocarditis-IE)
S. aureus (Acute IE)

pulmonary
emboli
cardiac murmur

2 Oslers node Janeway lesion S. aureus

septicemia with acute IE

septic emboli ( 2)
hemiplegia
septic emboli 1,22
2.2 (Purulent pericarditis) precordial
friction rub

cardiac tamponade pericardiocenthesis
surgical drainage1,22
2.3
S. aureus pneumonia
(Necrotizing pneumonia)

1
2.4 S. aureus

620



23

2.5
(Acute or Chronic osteomyelitis)

S. aureus systemic

2-3
systemic

fistula tract
S. aureus
brain abscess, epidural
abscess, discitis cavernous sinus thrombosis

venticuloperitoneum shunt11
3.
3.1 Staphylococcal scalded skin syndrome
(SSSS) epidermolytic toxin S. aureus

anti-toxin
antibody
Bullous impetigo
( 3, 4)
3.2 Staphylococcal toxic shock syndrome
TSST-1
1-2
S. aureus

3 Bullous impetigo
epidermolytic toxin S. aureus
( )

4 SSSS S. aureus

( )

 47 621

1,11

S. aureus 65 MSSA MRSA

47 18 23

Agar diffusion Kirby-Bauer E-test1

S.
aureus blood agar liquid media
Mueller-Hinton broth 18-24 1


S. aureus

11

(Phenotypic tests)
Coagulase Agglutination
test surface
proteins agglutination
S. aureus Staphylococci 1
S. aureus
2
2
IE

50
1,10

.. 2539-2549
80
44

(Molecular diagnosis)

1
Staphylococcal Cassette Chromosome mec
(SCCmec) mecA
mecA Penicillin-Binding
Protein 2 (PBP2) PBP2a PBP2


SCCmec MRSA 8 24
MRSA
Pulsed Field Gel Electrophoresis
(PFGE), Multi-locus Sequence Typing (MLST)
SCCmec Typing MLST
sequencing
http://www.mlst.net
MRSA
ST30-MRSA-IV (ST30 Sequencing
type 30) Southwest Pacific clone ST30-MSSA
80/81 SCCmec type IV 24

HA-MRSA
aminoglycosides,
erythromycin, clindamycin, fluoroquinolone tetracycline Glycopeptides
vancomycin CA-MRSA

MRSA 2
vancomycin MRSA

622
2 HA-MRSA CA-MRSA25

HA-MRSA

PVL
SCCmec I-III

CA-MRSA
HA-MRSA CA-MRSA
225

Minimal Inhibitory
Concentration (MIC) S. aureus
MIC 4 ./. MRSA
CA-MRSA clindamycin
erythromycin clindamycin
Clindamycin-inducible resistance

D-zone test erythromycin

clindamycin
clindamycin
erythromycin zone D ( 5)10
MRSA S. aureus
vancomycin MRSA MIC
vancomycin 4 ./.

VRSA (MIC 16
./.) VRSA vanA
Enterococci
10,11

CA-MRSA

()

PVL
SCCmec IV-V

S. aureus

MRSA HA-MRSA
CA-MRSA
cloxacillin
(Skin
and soft tissue infection, SSTIs)

5 Clindamycin-inducible resistance
D-zone test
( 10)

 47 623

11,26

cellulitis

(septic
phlebitis)

clindamycin, trimethoprimsulfamethoxazole (TMP/SMX), doxycycline
7 linezolid
Streptococcus group A clindamycin
linezolid TMP/SMX doxycycline amoxicillin
impetigo
2% mupirocin ointment26
cloxacillin

SSTIs
CA-MRSA
vancomycin, linezolid clindamycin
clindamycin
1026

311

/
S. aureus 11,26

CA-MRSA cloxacillin

MSSA cloxacillin

S. aureus
vancomycin clindamycin11

S. aureus

Passive immunization

S. aureus

()
Passive immunization
Passive immunization 2 7
1. Veronate (INH-A21)

Clumping factor A (Clf A) surface protein
S. aureus fibrinogen Clf A

clot
2 Veronate
3
late-onset sepsis
S. aureus 28
2. AltaStaph
Capsular Polysaccharide
5 8

624
3 S. aureus11
Susceptibility
Antimicrobial Agents
Comments
1. Initial empiric therapy (unknown susceptibility)
Vancomycin +
Life-threatening infections
Cloxacillin + Gentamicin
Cloxacillin
Nonlife-threatening infection when rate of MRSA are low
Clindamycin
Nonlife-threatening infection when rate of MRSA are substantial AND
prevalence of clindamycin resistance is low
Vancomycin
Nonlife-threatening infection when rate of MRSA are substantial AND
prevalence of clindamycin resistance is high
2. Methicillin-susceptible S. aureus
Cloxacillin
Cefazolin
Clindamycin
Serious penicillin allergy AND clindamycin susceptible strain AND
nonlife-threatening infection
Vancomycin
Serious penicillin allergy AND clindamycin resistant strain
3. MRSA (Oxacillin MIC 4 ./. )
HA-MRSA
Vancomycin
Alternatives
TMP/SMX, Linezolid
Fluoroquinolone
(If susceptible)
CA-MRSA
Vancomycin
Life-threatening infections
Clindamycin
Pneumonia, septic arthritis, osteomyelitis, SSTIs
(If susceptible)
4. VISA (MIC 4-16 ./.)
Choices
Linezolid, daptomycin
Tigecycline

Optimal therapy is not known, depend on susceptibility test results

S. aureus
S. aureus adjunctive adjunctive therapy
Passive immunization
therapy 27
S. aureus 30

3. Paglibaximab
Lipoteichoic acid 27
( 1)
1/2
S. aureus sepsis


27,29
2/3

Surface proteins
S. aureus
Tefibazumab MSCRAMM ( 1)

 47 625

S. aureus
29,31
(
1, 2 3)
3 ( 4)27,29,31,32

Component
proteins
Conjugated capsular polysaccharide
(CP) 5 8 (StaphyVAX) 2
S. aureus
3
3,600
S. aureus


5 components CP5, CP8, Teichoic acid,
Non-toxic mutants -toxin PVL
PentaStaph 27
Component proteins

S. aureus
Heteropolymers, Lipoteichoic acid (LTA) conjugated
Autoinducing peptides (AIPs) Accessory
gene regulator (agr) 27,29
colonization

S. aureus S. aureus


Opsonization

27

4 27,29,31,32

Live whole-cell
Killed whole-cell
Component Protein or Capsule
Conjugated CP5 and CP8
IsdB
(Iron surface determinant B)
Multi-components
(IsdA, IsdB, SdrE, SdrD)
Exotoxin
Mutant of -hemolysin
Mutant of TSST-1

Staphypen

StaphyVAX (Nabi)
V710 (Merck)

3
2

626

S. aureus

S. aureus Biofilm neutralize

toxin




Passive immunization
S. aureus (Immunotherapy)

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