47_ วัคซีนป้องกันโรคติดเชื้อสแตฟฟิลโลคอคคัส

615

Staphylococcus aureus

S. aureus 300,000

S. aureus 3

5 1

S. aureus (Invasive S. aureus infection) 19-341

S. aureus 262

44-483,4

cloxa-

cillin methicillin (Methicillin-resistance S. aureus MRSA)

72-73

S. aureus 5

MRSA 23-423,4,6,7

glycopeptides vancomycin

(Vancomycin-intermediate resistance S. aureus - VISA) 8,9

Vancomycin-resistance S. au-reus VRSA S. aureus

S. aureus genus Staphylococci

Staphy-

lococcus S. aureus

Staphylococci S. aureus coagulase clumping factor

S. aureus adhesin toxin 20

30 Coagulase-negative staphylococci

adhesin 10

toxin1

( 1)10 1. Cell wall peptidoglycan

( 1) peptidoglycan

endotoxin

Cytokines Dis-

seminated intravascular clotting (DIC)

47

616 47

S. aureus capsular polysaccharide (CP)

S. aureus 12 CP5 CP8

85

CP5 CP8

10

2. Surface protein

Protein A (Anti-

phagocytic) 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

1 S. aureus( 10)

617 47

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

(Health-

care-associated infection) MRSA

2-4

MRSA

1 (Extracellular Factors) S. aureus 1

Surface proteinsProtein A Anti-immune, anti-PMNCollagen BP Collagen bindingFibronectin BPA and B Fibronectin bindingClumping factor A and B Fibrinogen bindingCapsular polysaccharidesPolysaccharide capsule type 5 Anti-phagocytosis?Polysaccharide capsule type 8 Anti-phagocytosis?Cytotoxins, , , and -hemolysin Hemolysin, cytotoxinPanton-Valentine leukocidin (PVL) LeucolysinSuperantigensEnterotoxin A-D Food poisoning, Toxic shock syndromeExfoliatin A, B Scaled skin syndromeToxic shock syndrome toxin-1 (TSST-1) Toxic shock syndromeEnzymesV8 protease, Hyaluronidase, Coagulase,Staphylokinase, etc.

Spreading factor, Clotting, Clot digestion, Plasminogen activator, etc.

618 47

MRSA

MRSA .. 1997-1999

MRSA

Western-Pacific 46

34 26

MRSA MRSA

5 .. 2000

(Nosoco-

mial) (Healthcare-

associated) (Community-

acquired) 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

619 47

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

septic emboli ( 2)

hemiplegia

septic emboli 1,22

2.2 (Purulent peri-

carditis) precordial

friction rub

cardiac tamponade pericardiocen-

thesis

surgical drainage1,22

2.3

S. aureus pneu-monia

(Necrotizing pneumonia)

1

2.4 S. aureus

2 Oslers node Janeway lesion S. aureus septicemia with acute IE

620 47

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

1

3 Bullous impetigo

epidermolytic toxin S. aureus( )

4 SSSS S. aureus

( )

621 47

1,11

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

S. aureus 65 MSSA MRSA 47 18 23

Agar diffusion Kirby-Bauer E-test1

(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 tetra-

cycline Glycopeptides

vancomycin CA-MRSA

MRSA 2

vancomycin MRSA

622 47

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

S. aureus

MRSA HA-MRSA

CA-MRSA

cloxacillin

(Skin

and soft tissue infection, SSTIs)

2 HA-MRSA CA-MRSA25

HA-MRSA CA-MRSA

()

PVL

SCCmec I-IIIPVL

SCCmec IV-V

5 Clindamycin-inducible resistance

D-zone test

( 10)

623 47

11,26

cellulitis

(septic

phlebitis)

clindamycin, trimethoprim-

sulfamethoxazole (TMP/SMX), doxycycline

7 linezolid

Streptococcus group A clindamycin linezolid TMP/SMX doxy-

cycline 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

S. aureus

()

Passive immunization

Passive immunization 27

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 47

S. aureus adjunctive therapy 27

3. Paglibaximab

Lipoteichoic acid

( 1)

1/2

S. aureus sepsis

2/3 27,29 Surface proteins

S. aureus Tefibazumab MSCRAMM ( 1)

S. aureus adjunctive therapy


S. aureus 30

27

3 S. aureus11

Susceptibility Antimicrobial Agents Comments1. Initial empiric therapy (unknown susceptibility)

Vancomycin + Cloxacillin + Gentamicin

Life-threatening infections

Cloxacillin Nonlife-threatening infection when rate of MRSA are lowClindamycin Nonlife-threatening infection when rate of MRSA are substantial AND

prevalence of clindamycin resistance is lowVancomycin Nonlife-threatening infection when rate of MRSA are substantial AND

prevalence of clindamycin resistance is high2. Methicillin-susceptible S. aureus

CloxacillinCefazolinClindamycin Serious penicillin allergy AND clindamycin susceptible strain AND

nonlife-threatening infectionVancomycin Serious penicillin allergy AND clindamycin resistant strain

3. MRSA (Oxacillin MIC 4 ./. )HA-MRSA VancomycinAlternatives TMP/SMX, Linezolid

Fluoroquinolone(If susceptible)

CA-MRSA Vancomycin Life-threatening infectionsClindamycin(If susceptible)

Pneumonia, septic arthritis, osteomyelitis, SSTIs

4. VISA (MIC 4-16 ./.)Choices Linezolid, daptomycin

TigecyclineOptimal therapy is not known, depend on susceptibility test results

625 47

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 Staphypen

Component Protein or Capsule

Conjugated CP5 and CP8 StaphyVAX (Nabi) 3

IsdB

(Iron surface determinant B)

V710 (Merck)

2

Multi-components

(IsdA, IsdB, SdrE, SdrD)

-

Exotoxin

Mutant of -hemolysin -

Mutant of TSST-1 -

626 47

S. aureus

S. aureus Biofilm neutralize toxin


S. aureus (Immunotherapy)

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