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
Passive immunization
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
Passive immunization
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
Passive immunization
S. aureus (Immunotherapy)
1. Que Y, Moreillon P. Staphylococcus aureus (Including Staphylococcal Toxic Shock). In: Mandell
GL, Bennett JE, Dolin R, editors. Mandell, Douglas,
and Bennetts Principles and Practice of Infectious
Diseases. 7th ed. Philadelphia: Elsevier Inc.; 2010. p.
2543-78.
2. Nickerson EK, Wuthiekanun V, Wongsuvan
G, Limmathurosakul D, Srisomang P, Mahavanakul
W, et al. Factor predicting and reducing mortality in
patients with invasive Staphylococcus aureus Disease in a developing country. PLoS ONE. 2009;4:e6512.
3. Nickerson EK, Wuthiekanun V, Day NP,
Chaowagul W, Peacock SJ. Meticillin-resistant
Staphylococcus aureus in rural Asia. Lancet Infect
Dis. 2006;6:70-1.
4. Nickerson EK, Hongsuwan M, Limmathu-
rosakul D, Wuthiekanun V, Shah KR, Srisomang P,
et al. Staphylococcus aureus bacteraemia in a tropi-cal setting: patient outcome and impact of antibiotic
resistance. PloS ONE. 2009;4:e4308.
5. Diekema DJ, Pfaller MA, Schmitz FJ,
Smayevsky J, Bell J, Jones RN, et al. Survey of in-
fections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates
collected in the United States, Canada, Latin America,
Europe, and the Western Pacific region for the SEN-
TRY Antimicrobial Surveillance Program, 19971999.
Clin Infect Dis. 2001;32(suppl 2):S114-32.
6. Tishyadhigama P, Dejsirilert S, Thongmali
O, Sawanpanyalert P, Aswapokee N, Piboonbanakit
D. Antimicrobial Resistance among Clinical Isolates
of Staphylococcus aureus in Thailand from 2000 to 2005. J Med Assoc Thai. 2009;92(Suppl 4):S8-18.
7. Mekviwattanawong S, Srifuengfung S,
Chokepaibulkit K, Lohsiriwat D, Thamlikitkul V. Epide-
miology of Staphylococcus aureus infections and the prevalence of infection caused by community-acquired
Methicillin-Resistant Staphylococcus aureus in hospi-talized patients at Siriraj Hospital. J Med Assoc Thai.
2006;89(Suppl 5):S106-17.
8. Lulitanond A, Chanawong A, Sribenjalux
P, Khewkes W, Vorachit M, Chongtrakool P, et al.
Detection of heterogenous, intermediate-vancomycin-
resistant Staphylococcus aureus (hVISA) using low-concentration vancomycin disks. Southeast Asian J
Trop Med Public Health. 2006;37:761-7.
9. Phongsamart W, Srifeungfung S, Tiensasi-
torn C, Vanprapar N, Chearskul S, Chokephaibulkit K.
The first pediatric case of Staphylococcus aureus with
627 47
heterogenous resistant to vancomycin endocarditis
in Thailand. J Med Assoc Thai. 2005; 88(Suppl 8):
S264-8.
10. Kaplan SL, Hulten KG, Mason EO. Sta-
phylococcus aureus infections (Coagulase-positive
Staphylococci). In: Feigin RD, Cherry JD, Demmler-Harrison GL, Kaplan SL editors. Feigin and Cherrys
Textbook of Infectious Diseases. 6th ed. Philadelphia:
Elsevier Inc.; 2009. p. 1197-212.
11. Committee on Infectious Diseases, Ameri-
can Academy of Pediatrics. Staphylococcal infections. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS,
eds. Red Book: 2009 Report of the Committee on
Infectious Diseases. 28th ed. Elk Grove Village, IL:
American Academy of Pediatrics; 2009. p. 601-15.
12. Laupland KB, Church DL, Mucenski M,
Sutherland LR, Davies HD. Population-Based Study
of the Epidemiology of and the Risk Factors for Inva-
sive Staphylococcus aureus Infections. J Infect Dis. 2003;187:14529.
13. Jacobsson G, Dashti S, Wahlberg T, An-
dersson R. The epidemiology of and risk factors for
invasive Staphylococcus aureus infections in western Sweden. Scand J Infect Dis. 2007; 39: 6-13.
14. El Atrouni WI, Knoll BM, Lahr BD, Eckel-
Passow JE, Sia IG, Baddour LM. Temporal Trends in
the Incidence of Staphylococcus aureus Bacteremia in Olmsted County, Minnesota, 1998 to 2005: A Pop-
ulation-Based Study. Clin Infect Dis. 2009;49:e130-8.
15. Styers D, Sheehan DJ, Hogan P, Sahm DF.
Laboratory-based surveillance of current antimicrobial
resistance patterns and trends among Staphylococ-cus aureus: 2005 status in the United States. Ann Clin Microbiol Antimicrob. 2006;5:2.
16. Henderson KL, Johnson AP, Muller-Pe-
body B, Charlett A, Gilbert R, Sharland M. The chang-
ing aetiology of paediatric bacteraemia in England and
Wales, 1998-2007. J Med Microbiol. 2010;59: 213-9.
17. Laupland KB, Gregson DB, Vanderkooi
OG, Ross T, Kellner JD. The changing burden of
pediatric bloodstream infections in Calgary, Canada,
2000-2006. Pediatr Infect Dis J. 2009;28:114-7.
18. Grijalva CG, Nuorti JP, Zhu Y, Griffin MR.
Increasing incidence of empyema complicating child-
hood community-acquired pneumonia in the United
States. Clin Infect Dis. 2010;50:805-13.
19. Friedman ND, Kaye KS, Stout JE, McGarry
SA, Trivette SL, Briggs JP, et al. Health care-asso-
ciated bloodstream infections in adults: a reason to
change the accepted definition of community-acquired
infections. Ann Intern Med. 2002;137:791-7.
20. Song JH, Hsueh PR, Chung DR, Ko KS,
Kang CI, Peck KR, et al. Spread of methicillin-resistant
Staphylococcus aureus between the community and the hospitals in Asian countries: an ANSORP study. J
Antimicrob Chemother. 2011; 66: Epub February 20,
2011.
21. Nickerson EK, West TE, Day NP, Peacock
SJ. Staphylococcus aureus disease and drug resist-ance in resource-limited countries in South and East
Asia. Lancet Infect Dis. 2009;9:130-5.
22. Starke JR. Infective endocarditis. In: Fei-
gin RD, Cherry JD, Demmler-Harrison GL, Kaplan SL
editors. Feigin and Cherrys Textbook of Infectious
Diseases. 6th ed. Philadelphia: Elsevier Inc.; 2009. p.
365-89.
23. Sukswai P, Kovitvanitcha D, Jeerathan-
yasakun Y, Thumkunanon V, Chotpitayasunondh T,
Sangtawesin V. Acute hematogenous osteomyelitis
and septic arthritis in children: Clinical characteristics
628
and outcomes study. J Med Assoc Thai 2011 (In
Press).
24. Woodford N, Livermore DM. Infections
caused by Gram-positive bacteria: a review of the
global challenge. J Infect. 2009;59(Suppl 1):S4-16.
25. Matouskova I, Janout V.Current knowledge
of Methicillin-resistant Staphylococcus aureus and community-associated methicillin-resistant Staphy-
lococcus aureus. Biomed Pap Med Fac Univ Palacky
Olomouc Czech Repub. 2008;152:191-202.
26. Liu C, Bayer A, Cosgrove SE, Daum RS,
Fridkin SK, Gorwitz RJ, et al. Clinical Practice Guide-
lines by the Infectious Diseases Society of America for
the treatment of Methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:e18-55.
27. Schaffer AC, Lee JC. Staphylococcal
vaccines and immunotherapies. Infect Dis Clin N Am.
2009;23:153-71.
28. DeJonge M, Burchfield D, Bloom B, et
al. Clinical trial of safety and efficacy of INH-A21 for
the prevention of nosocomial staphylococcal blood-
stream infection in premature infants. J Pediatr. 2007;
151:260-5.
29. Shinefield HR. Use of a conjugate polysac-
charide vaccine in the prevention of invasive staphy-
lococcal disease: Is an additional vaccine needed or
possible? Vaccine. 2006;24 (suppl 2):S65-9.
30. Shah PS, Kaufman DA. Antistaphylococcal
immunoglobulins to prevent staphylococcal infection
in very low birth weight infants. Cochrane Database
Syst Rev. 2009;15:CD006449.
31. Robert S. Daum. Staphylococcus aureus vaccines. In: Plotkin SA, Orenstein WA, Offit PA. eds.
Vaccines. 5th ed. Philadelphia: Elsevier Inc.; 2008. p.
1307-15.