PPDS 1 Orthopaedi dan Traumatologi 1.Aryo Budiyogo A 2.Hidayat KW 3.Seti Aji Hadinoto 4.Sinung BawonoPembimbing : Prof. DR. Dr. Priyambodo, M.Sc

Introducing Came from greece words that means: golden grape-

cluster berry Coccus shape Positive gram staining Anaerob fakultatif Dangerous strain : MRSA

Genom Involved of circulair chromosome ( 2800 bp), dan

prophages, plasmids, and transposons Gen that works on virulens resistence on AB laid on chromosome and extra chromosome elements Can be transfered to another strains

Ciri dasar S aureus Non-motile Spherical Growth on chain grapes shapes Golden-yellow Hemolytic pattern on blood agarouseimg/staph_em.jpg

product koagulase dan katalase can changes H2O2

H2O and O2www.aic.cuhk.edu.hk/ web8/mrsa.htm

Summary of Virulence Determinants Of Staphylococcus aureus http://textbookofbacteriology.net/staph.html

http://textbookofbacteriology.net/staph. html

Factor Virulensi

Cell Wall Citoplasmic membran and osmotic barier regulate on ion

concentrations gradient in order to the cell is more stable and not easy to lysis. Polysacaryde and adhesin alter fagositosis. Petidoglikan make bacterial adhesion at the host cell

membrane Protein A- Immunological disguise.

Invasive enzymes Coagulase Complex-Seals off infection, preventing phagocytic

engulfment

Protease, lipase, & DNase provide nourishment for MRSA bacterium FAME-(Fatty acid modifying enzyme) modifies the anti-bacterial lipids side chain-inactivating antibiotic action

Staphylokinase-Fibrinolysisn aids the in spreading factor Hyaluronidase- Destroys connective tissue

Damage To The Host: Extracellular Products Leukocidins-Kills White blood cells (WBCS) Alpha, Beta, Delta toxins-These damaging toxins

bid to to cell wall surface, forms a pore, and cellular machinery of host cell leak out

Genetic Regulation of VirulenceDeterminant Expression- Surface proteins are predominantly synthesized during the exponential growth phase, and the secreted proteins are synthesized during the stationary phase

- During the initial stages of infection, the expression of surface proteins that bind extracellular-matrix molecules favors successful colonization of host tissues, whereas the synthesis of exoproteins favors the spread to adjacent tissues

EPIDEMIOLOGY OF STAPHYLOCOCCAL DISEASE Humans are a natural reservoir of S. Aureus (30-50%) type 1 diabetes intravenous drug users patients undergoing hemodialysis surgical patients patients with the acquired immunodeficiency

syndrome

Transmission nosocomial infection -->exposure to the hands of

health care workers . Outbreaks may also result from exposure to a single long-term carrier or environmental sources,

PATHOGENESIS OF STAPHYLOCOCCAL DISEASE infections the skin or mucosal barrier allows

staphylococci access to adjoining tissues or the bloodstream. (host -defense mechanism) The risk of infection is increased by the presence of foreign material :intravenous cathetersthrombusbacterial adherencenosocomial endocarditis

Invasive InfectionsA. The endothelial cell is central to these pathogenic processes : target for injury Staphylococci avidly adhere to endothelial cells and bind through adhesinreceptor interactions

B.monocytes and macrophages (same as infection of gram bacteria) The monocytes release TNF and interleukin-1, interleukin-6, and interleukin-8 after contact with intact staphylococci.

Sepsis cytokine and cellular activation the complement and

coagulation pathways are activated, arachidonic acid is metabolized, and platelet-activating factor is releasedcause fever, hypotension, capillary leak, disseminated intravascular coagulopathy, depression of myocardial function, and multiorgan dysfunctionseptic syndrome

Toxin-Mediated Disease Pyrogenic-toxin superantigenshigh fever, shock,

capillary leak, and multiorgan dysfunction massive release of cytokines by both macrophages and T cells shock syndrome (endotoxin shock) tissue damage

Host Response to Infection abscess formation:

adhesion molecules on endothelial cells migration of leukocytes to the site of infection - After infection, cytokines are first demonstrable within vessels, extending into tissues as inflammatory cells migrate to the sites of infection

S. aureusinfected endothelial cells also express

intercellular adhesion molecule 1 (CD54), vascular-cell adhesion molecule 1 (CD106), and MHC class I

DISEASES CAUSED BY S. AUREUS skin, soft-tissue, respiratory, bone, joint, and

endovascular disorders. Bacteremia Mortality: 11 to 43 percent. age of more than 50 years, nonremovable foci of infection, serious underlying cardiac, neurologic, or respiratory disease

Endocarditis 25 to 35 percent of cases intravenous drug users, elderly patients, patients with prosthetic valves

Metastatic Infections tends to bones, joints, kidneys, and lungs Suppurative collections at these sites serve as potential

foci for recurrent infections

Sepsis advanced age, immunosuppression, chemotherapy,

and invasive procedures. similar to that of gram-negative sepsis, with fever, hypotension, tachycardia, and tachypnea the most common gram-positive pathogens in cases of sepsis.

Severe cases progress to multiorgan dysfunction,

disseminated intravascular coagulation, lactic acidosis, and death both gram-positive and gram-negative sepsis, the levels of circulating tumor necrosis factor , interleukin-1, and interleukin-6 are predictive of the outcome.

Toxic Shock Syndrome superabsorbent tampons for use during menstruation high fever, erythematous rash with subsequent

desquamation, hypotension, and multiorgan damage toxic shock syndrome toxin 1(>90%) associated with menstruation, other enterotoxins account for 50 percent of cases unrelated to menstruation ( localized infections, surgery, or insect bites) Mortality rate:nonmenstrual toxic shock syndrome>menstrual

-laktamase penicillin (serin protease that hidrolyze lactamase ring Inaktive

Less than 5 % remain sensitive to penicillin

Mechanism Of Resistance http://www.jci.org/cgi/content/full/114/12/1693/F1

http://www.jci.org/cgi/content/full/114/12/1693/F1

Resisten cephalosporin

Resisten penicillin

Resisten Meticilin

high level of resistance requires the presence of the mec gene that encodes penicillin-binding protein 2a

suggesting the horizontal transfer of mec DNA The enterococcal plasmid-bearing gene for resistance to vancomycin has been transferred by conjugation to S. aureus in vitro.

Horizontal Gene Transfer-Another Mechanism For Resistance

http://www.bioteach.ubc.ca/Biodiversity/AttackO fTheSuperbugs

Treatment on Staphylococcus aureus infectionssensitive

Penicillin is drug of choice

Nafcillin

Staphylococcus aureus with laktamase

Oxacillin

Cefazolin Pasien with penicillin allergy

Cephalothin

VancomycinAllergy patient: fluoroquinolones, Drug of choice for isolated MRSA trimethoprim sulfamethoxazole, clindamycin, or minocycline If resisstent : quinolon, quinupristin dalfopristin, a new carbapenem, and a new family of antimicrobial drugs, oxzolidinones

VancomycinCombination -lactams and aminoglycosides increases invitro bacterial killing and in animal models with endocarditis.

RifampicinPotent Easy become enough for resistent in S. aureus single use

Pencegahan terhadap infeksi staphylococcusTopycal agent (mupirocin) vaccinations Spread preventions Inhibition of RNA and protein synthesis Elimination on nasal colonisations Reduce of wound infections.

A capsular polysaccharideprotein conjugate antistaphylococcal vaccine has produced improved phagocytosis in vitro and improved survival in experimental models of staphylococcal infection

Universal precaution