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Systemic Inflammatory  Response Syndrome  (SIRS) PRANEE SITAPOSA, MD.
SEPSIS and It’s Disease spectrum <ul><li>Various stages of disease </li></ul><ul><ul><li>Bacteremia </li></ul></ul><ul><ul...
Definition <ul><li>Infection   </li></ul><ul><ul><li>Presence of microorganisms in a normally sterile site.  </li></ul></u...
SIRS  (Systemic Inflammatory Response Syndrome) <ul><li>The systemic response to a wide range of stresses. </li></ul><ul><...
Severe Sepsis <ul><li>Sepsis with organ hypoperfusion      one of the followings : </li></ul><ul><ul><li>SBP < 90 mmHg </l...
MODS (Multiple Organ Dysfunction Syndrome) <ul><li>Sepsis with multiorgan hypoperfusion  </li></ul><ul><li>Two or more of ...
Relationship between SIRS and Sepsis Bone RC et al, Chest1992;101:164-55.
The Sepsis Continuum <ul><li>A clinical response arising from a nonspecific insult, with   2 of the following: </li></ul>...
Mortality rate in SIRS   Rangel - Frausto, et al. JAMA 273:117-123, 1995.
The Response to Pathogens  “Cross-Talk” NEJM 2003;348:138-150.
Inflammatory Response to Sepsis NEJM 2006;355:1699-1713.
Procoagulant Response in Sepsis NEJM 2006;355:1699-1713.
Pathogenesis of sepsis and septic shock Angus DC, et al .  Crit Care Med 2001, 29:1303-1310.
Pathogenesis of Severe Sepsis Infection Microbial Products (exotoxin/endotoxin) Cellular Responses Oxidases Platelet Activ...
Normal Systemic Response to Infection and Injury   (1) <ul><li>Leukocytosis Mobilizes neutrophils into the circulation </l...
Normal Systemic Response to Infection and Injury   (2) <ul><li>Acute-Phase Responses   </li></ul><ul><ul><li>Anti-infectiv...
Normal Systemic Response to Infection and Injury   (3) <ul><li>Anti-inflammatory </li></ul><ul><ul><li>Releases anti-infla...
Normal Systemic Response to Infection and Injury   (4) <ul><li>Procoagulant </li></ul><ul><ul><li>Walls off infection, pre...
Risk factors of sepsis   <ul><li>aggressive oncological chemotherapy and radiation therapy  </li></ul><ul><li>use of corti...
Patients at increased risks of developing sepsis <ul><li>Underlying diseases :  neutropenia, solid tumors, leukemia, dyspr...
Source   ( usually an endogenous source of infection ) <ul><li>intestinal tract  </li></ul><ul><li>oropharynx  </li></ul><...
Diagnosis <ul><li>History   </li></ul><ul><ul><li>community or nosocomially acquired  infection </li></ul></ul><ul><ul><li...
Specific Infectious agents <ul><li>Splenectomy   (traumatic or functional) </li></ul><ul><ul><li>S pneumoniae, H influenza...
Specific Infectious agents <ul><li>Aids </li></ul><ul><ul><li>P aeuginosa  (if neutropenic),  S aureus , PCP pneumonia </l...
Diagnosis <ul><li>Physical Examination </li></ul><ul><ul><li>essential  </li></ul></ul><ul><ul><li>In all neutropenic pati...
Signs and Symptoms <ul><li>Nonspecific symptoms of sepsis : not pathognomonic </li></ul><ul><ul><li>fever </li></ul></ul><...
Complications   <ul><li>Adult respiratory distress syndrome ( ARDS ) </li></ul><ul><li>Disseminated Intravascular Coagulat...
Surviving Sepsis Campaign Guidelines for Management of  Severe Sepsis and Septic Shock Dellinger RP, et al. Crit Care Med ...
<ul><li>Before the initiation of antimicrobial therapy, at least two blood cultures should be obtained </li></ul><ul><ul><...
Sepsis resuscitation bundle <ul><li>Serum lactate measured </li></ul><ul><li>Blood cultures obtained before antibiotics ad...
Sepsis management bundle <ul><li>Fluid resuscitation </li></ul><ul><li>Appropriate cultures prior to antibiotic administra...
Sepsis management bundle <ul><li>Evaluation for adrenal insufficiency </li></ul><ul><li>Stress dose corticosteroid adminis...
Infection Control <ul><li>Appropriate cultures prior to antibiotic  </li></ul><ul><li>administration </li></ul><ul><li>Ear...
Early Goal-Directed Therapy CVP  : central  venous  pressure MAP  : mean  arterial  pressure ScvO 2 : central  venous  oxy...
Early Goal-Directed Therapy Results 49.2% 33.3% 0 10 20 30 40 50 60 Standard Therapy n=133 EGDT n=130 P = 0.01* *Key diffe...
Antibiotic use in Sepsis (1) <ul><li>The drugs used depends on the source of the sepsis   </li></ul><ul><li>Community acqu...
Antibiotic use in Sepsis (2) <ul><li>Nosocomial abdominal infection  </li></ul><ul><ul><li>Imipenem-cilastatin and aminogl...
Antibiotic use in Sepsis (3) <ul><li>Nosocomial urinary tract infection:  </li></ul><ul><ul><li>Vancomycin and Cefipime  <...
New Drug in Treating Severe Sepsis   <ul><li>It is the first agent  approved by the FDA  effective in the treatment of  se...
NEJM;355:1699-1723.
Sepsis Cascade
Activated Protein C  ( Xigris ) NEJM;355:1640, October 19, 2006.
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Sirs present

  1. 1. Systemic Inflammatory Response Syndrome (SIRS) PRANEE SITAPOSA, MD.
  2. 2. SEPSIS and It’s Disease spectrum <ul><li>Various stages of disease </li></ul><ul><ul><li>Bacteremia </li></ul></ul><ul><ul><li>SIRS </li></ul></ul><ul><ul><li>Sepsis syndrome </li></ul></ul><ul><ul><li>Sepsis shock : early and refractory </li></ul></ul>
  3. 3. Definition <ul><li>Infection </li></ul><ul><ul><li>Presence of microorganisms in a normally sterile site. </li></ul></ul><ul><li>Bacteremia </li></ul><ul><ul><li>Cultivatable bacteria in the blood stream. </li></ul></ul><ul><li>Sepsis </li></ul><ul><ul><li>The systemic response to infection. If associated with proven or clinically suspected infection, SIRS is called “sepsis”. </li></ul></ul>American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee. Crit Care Med. 1992;20:864-874.
  4. 4. SIRS (Systemic Inflammatory Response Syndrome) <ul><li>The systemic response to a wide range of stresses. </li></ul><ul><ul><li>Temperature >38 °C (100.4°) or <36°C (96.8°F). </li></ul></ul><ul><ul><li>Heart rate >90 beats/min. </li></ul></ul><ul><ul><li>Respiratory rate >20 breaths/min or PaCO 2 <32 mmHg. </li></ul></ul><ul><ul><li>White blood cells > 12,000 cells/ml or < 4,000 cells/ml or >10% immature (band) forms. </li></ul></ul><ul><li>Note </li></ul><ul><ul><li>Two or more of the following must be present. </li></ul></ul><ul><ul><li>These changes should be represent acute alterations from baseline in the absence of other known cause for the abnormalities. </li></ul></ul>American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee. Crit Care Med. 1992;20:864-874.
  5. 5. Severe Sepsis <ul><li>Sepsis with organ hypoperfusion one of the followings : </li></ul><ul><ul><li>SBP < 90 mmHg </li></ul></ul><ul><ul><li>Acute mental status change </li></ul></ul><ul><ul><li>PaO 2 < 60 mmHg on RA (PaO 2 /FiO2 < 250) </li></ul></ul><ul><ul><li>Increased lactic acid/acidosis </li></ul></ul><ul><ul><li>Oliguria </li></ul></ul><ul><ul><li>DIC or Platelet < 80,000 /mm 3 </li></ul></ul><ul><ul><li>Liver enzymes > 2 x normal </li></ul></ul>American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee. Crit Care Med. 1992;20:864-874.
  6. 6. MODS (Multiple Organ Dysfunction Syndrome) <ul><li>Sepsis with multiorgan hypoperfusion </li></ul><ul><li>Two or more of the followings: </li></ul><ul><ul><li>SBP < 90 mmHg </li></ul></ul><ul><ul><li>Acute mental status change </li></ul></ul><ul><ul><li>PaO 2 < 60 mmHg on RA (PaO 2 /FiO 2 < 250) </li></ul></ul><ul><ul><li>Increased lactic acid/acidosis </li></ul></ul><ul><ul><li>Oliguria </li></ul></ul><ul><ul><li>DIC or Platelet < 80,000 /mm 3 </li></ul></ul><ul><ul><li>Liver enzymes > 2 x normal </li></ul></ul>American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee. Crit Care Med. 1992;20:864-874.
  7. 7. Relationship between SIRS and Sepsis Bone RC et al, Chest1992;101:164-55.
  8. 8. The Sepsis Continuum <ul><li>A clinical response arising from a nonspecific insult, with  2 of the following: </li></ul><ul><ul><li>T >38 o C or <36 o C </li></ul></ul><ul><ul><li>HR >90 beats/min </li></ul></ul><ul><ul><li>RR >20/min </li></ul></ul><ul><ul><li>WBC >12,000/mm 3 or <4,000/mm 3 or >10% bands </li></ul></ul>SIRS = systemic inflammatory response syndrome SIRS with a presumed or confirmed infectious process Chest 1992;101:1644. Sepsis with organ failure Refractory hypotension Sepsis SIRS Severe Sepsis Septic Shock
  9. 9. Mortality rate in SIRS Rangel - Frausto, et al. JAMA 273:117-123, 1995.
  10. 10. The Response to Pathogens “Cross-Talk” NEJM 2003;348:138-150.
  11. 11. Inflammatory Response to Sepsis NEJM 2006;355:1699-1713.
  12. 12. Procoagulant Response in Sepsis NEJM 2006;355:1699-1713.
  13. 13. Pathogenesis of sepsis and septic shock Angus DC, et al . Crit Care Med 2001, 29:1303-1310.
  14. 14. Pathogenesis of Severe Sepsis Infection Microbial Products (exotoxin/endotoxin) Cellular Responses Oxidases Platelet Activation Kinins Complement Coagulopathy/DIC Vascular/Organ System Injury Multi-Organ Failure Death Endothelial damage Endothelial damage Coagulation Activation Cytokines TNF, IL-1, IL-6
  15. 15. Normal Systemic Response to Infection and Injury (1) <ul><li>Leukocytosis Mobilizes neutrophils into the circulation </li></ul><ul><li>Tachycardia Increases cardiac output, blood flow to injuried tissue </li></ul><ul><li>Fever Raises core temperature; peripheral vasoconstriction shunts blood flow to injuried tissue. Occurs much more often when infection is the trigger for systemic responses </li></ul>Mandell et al. Principals and Practice of Infectious Diseases6th ed;906:906-926.
  16. 16. Normal Systemic Response to Infection and Injury (2) <ul><li>Acute-Phase Responses </li></ul><ul><ul><li>Anti-infective </li></ul></ul><ul><ul><ul><li>Increases synthesis of complement factors, microbe pattern-recognition molecules(mannose-binding lectin, LBP, CRP, CD14, Others) </li></ul></ul></ul><ul><ul><ul><li>Sequesters iron (lactoferrin) and zinc (metallothionein) </li></ul></ul></ul>Mandell et al. Principals and Practice of Infectious Diseases6th ed;906:906-926.
  17. 17. Normal Systemic Response to Infection and Injury (3) <ul><li>Anti-inflammatory </li></ul><ul><ul><li>Releases anti-inflammatory neuroendocrine hormones (cortisol, ACTH, epinephrine, α -MSH) </li></ul></ul><ul><ul><ul><li>Increases synthesis of proteins that help prevent inflammation within the systemic compartment </li></ul></ul></ul><ul><ul><ul><li>Cytokine antagonists (IL-1Ra, sTNF-Rs) </li></ul></ul></ul><ul><ul><ul><li>Anti-inflammatory mediators (e.g.,IL-4, IL-6, IL-6R, IL-10, IL-13, TGF- β ) </li></ul></ul></ul><ul><ul><ul><li>Protease inhibitors (e.g., α 1-antiprotease) </li></ul></ul></ul><ul><ul><ul><li>Antioxidants (haptoglobin) </li></ul></ul></ul><ul><ul><li>Reprograms circulating leukocytes (epinephrine, cortisol, PGE 2 , ?other) </li></ul></ul>Mandell et al. Principals and Practice of Infectious Diseases6th ed;906:906-926.
  18. 18. Normal Systemic Response to Infection and Injury (4) <ul><li>Procoagulant </li></ul><ul><ul><li>Walls off infection, prevents systemic spread </li></ul></ul><ul><li>Increases synthesis or release of fibrinogen, PAI-1, C4b </li></ul><ul><li>Decreases synthesis of protein C, anti-thrombin III </li></ul><ul><li>Metabolic </li></ul><ul><ul><li>Preserves euglycemia, mobilizes fatty acids, amino acids </li></ul></ul><ul><ul><ul><li>Epinephrine, cortisol, glucagon, cytokines </li></ul></ul></ul><ul><li>Thermoregulatory </li></ul><ul><ul><li>Inhibits microbial growth </li></ul></ul><ul><ul><ul><li>Fever </li></ul></ul></ul>Mandell et al. Principals and Practice of Infectious Diseases6th ed;906:906-926.
  19. 19. Risk factors of sepsis <ul><li>aggressive oncological chemotherapy and radiation therapy </li></ul><ul><li>use of corticosteroid and immunosuppressive therapies for organ transplants and inflammatory diseases </li></ul><ul><li>longer lives of patients predisposed to sepsis, the elderly, diabetics, cancer patients, patients with major organ failure, and with granulocyopenia. </li></ul><ul><li>Neonates are more likely to develop sepsis ( ex . group B Streptococcal infections ). </li></ul><ul><li>increased use of invasive devices such as surgical protheses, inhalation equipment, and intravenous and urinary catheters. </li></ul><ul><li>indiscriminate use of antimicrobial drugs that create conditions of overgrowth, colonization, and subsequent infection by aggressive, antimicrobial - resistant organisms . </li></ul>Angus DC, et al . Crit Care Med 2001, 29:1303-1310.
  20. 20. Patients at increased risks of developing sepsis <ul><li>Underlying diseases : neutropenia, solid tumors, leukemia, dysproteinemias, cirrhosis of the liver, diabetes, AIDS, serious chronic conditions. </li></ul><ul><li>Surgery or instrumentation : catheters . </li></ul><ul><li>Prior drug therapy : Immuno-suppressive drugs, especially with broad-spectrum antibiotics. </li></ul><ul><li>Age : males, above 40 y; females, 20-45 y . </li></ul><ul><li>Miscellaneous conditions : childbirth, septic abortion, trauma and widespread burns, intestinal ulceration. </li></ul>Angus DC, et al . Crit Care Med 2001, 29:1303-1310.
  21. 21. Source ( usually an endogenous source of infection ) <ul><li>intestinal tract </li></ul><ul><li>oropharynx </li></ul><ul><li>instrumentation sites </li></ul><ul><li>contaminated inhalation therapy equipment </li></ul><ul><li>IV fluids. </li></ul><ul><li>Most frequent sites of infection : Lungs, abdomen, and urinary tract. </li></ul><ul><li>Other sources include the skin/soft tissue and the CNS. </li></ul>Angus DC, et al . Crit Care Med 2001, 29:1303-1310.
  22. 22. Diagnosis <ul><li>History </li></ul><ul><ul><li>community or nosocomially acquired infection </li></ul></ul><ul><ul><li>immunocompromised patient </li></ul></ul><ul><ul><li>exposure to animals, travel, tick bites, occupational hazards, alcohol use, seizures, loss of consciousness, medications </li></ul></ul><ul><ul><li>underlying diseases ; specific infectious agents </li></ul></ul><ul><ul><li>Some clues to a septic event include </li></ul></ul><ul><ul><ul><li>Fever or unexplained signs with malignancy or instrumentation </li></ul></ul></ul><ul><ul><ul><li>Hypotension </li></ul></ul></ul><ul><ul><ul><li>Oliguria or anuria </li></ul></ul></ul><ul><ul><ul><li>Tachypnea or hyperpnea </li></ul></ul></ul><ul><ul><ul><li>Hypothermia without obvious cause </li></ul></ul></ul><ul><ul><ul><li>Bleeding </li></ul></ul></ul>Angus DC, et al . Crit Care Med 2001, 29:1303-1310.
  23. 23. Specific Infectious agents <ul><li>Splenectomy (traumatic or functional) </li></ul><ul><ul><li>S pneumoniae, H influenzae, N meningitidis </li></ul></ul><ul><li>Neutropenia (<500 neutrophil/ml) </li></ul><ul><ul><li>Gram-negative, including P aeruginosa , gram-positives, including S aureus </li></ul></ul><ul><ul><li>Fungi, especially Candida species </li></ul></ul><ul><li>Hypogammaglobulinemia (e.g.,CLL) </li></ul><ul><ul><li>S pneumoniae, E coli </li></ul></ul><ul><li>Burns </li></ul><ul><ul><li>MRSA, P aeruginosa , resistant gram-negatives </li></ul></ul>MacArthur RD, et al. Mosby, 2001:3-10. Wheeler AP, et al. NEJM 1999;340:207-214. Chaowagul W, et al. J Infect Dis 1989;159:890-899.
  24. 24. Specific Infectious agents <ul><li>Aids </li></ul><ul><ul><li>P aeuginosa (if neutropenic), S aureus , PCP pneumonia </li></ul></ul><ul><li>Intravascular devices </li></ul><ul><ul><li>S aureus , S epidermidis </li></ul></ul><ul><li>Nosocomial infections </li></ul><ul><ul><li>MRSA, Enterococcus species, resistant gram-negative, Candida species </li></ul></ul><ul><li>Septic patients in NE of Thailand </li></ul><ul><ul><li>Burkholderia pseudomallei </li></ul></ul>MacArthur RD, et al. Mosby, 2001:3-10. Wheeler AP, et al. NEJM 1999;340:207-214. Chaowagul W, et al. J Infect Dis 1989;159:890-899.
  25. 25. Diagnosis <ul><li>Physical Examination </li></ul><ul><ul><li>essential </li></ul></ul><ul><ul><li>In all neutropenic patients and in patients with as suspected pelvic infection the physical exam should include rectal, pelvic, and genital examinations </li></ul></ul><ul><ul><ul><li>perirectal, and/or perineal abscesses </li></ul></ul></ul><ul><ul><ul><li>pelvic inflammatory disease and/or abscesses, or prostatitis </li></ul></ul></ul>Angus DC, et al . Crit Care Med 2001, 29:1303-1310.
  26. 26. Signs and Symptoms <ul><li>Nonspecific symptoms of sepsis : not pathognomonic </li></ul><ul><ul><li>fever </li></ul></ul><ul><ul><li>chills </li></ul></ul><ul><ul><li>constitutional symptoms of fatigue, malaise </li></ul></ul><ul><ul><li>anxiety or confusion </li></ul></ul><ul><li>absent symptoms in serious infections, especially in elderly individuals </li></ul>Angus DC, et al . Crit Care Med 2001, 29:1303-1310.
  27. 27. Complications <ul><li>Adult respiratory distress syndrome ( ARDS ) </li></ul><ul><li>Disseminated Intravascular Coagulation ( DIC ) </li></ul><ul><li>Acute Renal failure ( ARF ) </li></ul><ul><li>Intestinal bleeding </li></ul><ul><li>Liver failure </li></ul><ul><li>Central Nervous System dysfunction </li></ul><ul><li>Heart failure </li></ul><ul><li>Death </li></ul>Angus DC, et al . Crit Care Med 2001, 29:1303-1310.
  28. 28. Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock Dellinger RP, et al. Crit Care Med 2004; 32:858-873.
  29. 29. <ul><li>Before the initiation of antimicrobial therapy, at least two blood cultures should be obtained </li></ul><ul><ul><ul><li>At least one drawn percutaneously </li></ul></ul></ul><ul><ul><ul><li>At least one drawn through each vascular access device if inserted longer than 48 hours </li></ul></ul></ul><ul><li>Other cultures such as urine, cerebrospinal fluid, wounds, respiratory secretions or other body fluids should be obtained as the clinical situation dictates </li></ul><ul><li>Other diagnostic studies such as imaging and sampling should be performed promptly to determine the source and causative organism of the infection </li></ul><ul><ul><ul><li>may be limited by patient stability </li></ul></ul></ul>Weinstein MP. Rev Infect Dis 1983;5:35-53 Blot F. J Clin Microbiol 1999; 36: 105-109. Diagnosis Dellinger, et. al. Crit Care Med 2004, 32: 858-873.
  30. 30. Sepsis resuscitation bundle <ul><li>Serum lactate measured </li></ul><ul><li>Blood cultures obtained before antibiotics administered </li></ul><ul><li>Improve time to broad-spectrum antibiotics </li></ul><ul><li>In the event of hypotension or lactate > 4 mmol/L (36 mg/dL) </li></ul><ul><ul><li>a. Deliver an initial minimum of 20 mL/kg of crystaloid (or colloid equivalent) </li></ul></ul><ul><ul><li>b. apply vasopressors for ongoing hypotension </li></ul></ul><ul><li>In the event of persistent hypotension despite fluid resuscitation or lactate > 4 mmol/L (36 mg/dL) </li></ul><ul><ul><li>a. achieve central venous pressure of > 8 mmHg </li></ul></ul><ul><ul><li>b. achieve central venous oxygen saturation of > 70% </li></ul></ul>Hurtado FJ. et al. Crit Care Clin;2006; 22:521-9.
  31. 31. Sepsis management bundle <ul><li>Fluid resuscitation </li></ul><ul><li>Appropriate cultures prior to antibiotic administration </li></ul><ul><li>Early targeted antibiotics and source control </li></ul><ul><li>Use of vasopressors/inotropes when fluid </li></ul><ul><li>resuscitation optimized </li></ul>Surviving Sepsis Campaign Management Guidelines Committee. Crit Care Med 2004; 32:858-873.
  32. 32. Sepsis management bundle <ul><li>Evaluation for adrenal insufficiency </li></ul><ul><li>Stress dose corticosteroid administration </li></ul><ul><li>Recombinant human activated protein C (xigris) for severe sepsis </li></ul><ul><li>Low tidal volume mechanical ventilation for ARDS </li></ul><ul><li>Tight glucose control </li></ul>Surviving Sepsis Campaign Management Guidelines Committee. Crit Care Med 2004; 32:858-873.
  33. 33. Infection Control <ul><li>Appropriate cultures prior to antibiotic </li></ul><ul><li>administration </li></ul><ul><li>Early targeted antibiotics and source control </li></ul>Surviving Sepsis Campaign Management Guidelines Committee. Crit Care Med 2004; 32:858-873.
  34. 34. Early Goal-Directed Therapy CVP : central venous pressure MAP : mean arterial pressure ScvO 2 : central venous oxygen saturation NEJM 2001;345:1368-77 .
  35. 35. Early Goal-Directed Therapy Results 49.2% 33.3% 0 10 20 30 40 50 60 Standard Therapy n=133 EGDT n=130 P = 0.01* *Key difference was in sudden CV collapse, not MODS 28-day Mortality NEJM 2001;345:1368-77.
  36. 36. Antibiotic use in Sepsis (1) <ul><li>The drugs used depends on the source of the sepsis </li></ul><ul><li>Community acquired pneumonia </li></ul><ul><ul><li>third ( ceftriaxone ) or fourth ( cefepime ) generation cephalosporin is given with an aminoglycoside ( usually gentamicin ) </li></ul></ul><ul><li>Nosocomial pneumonia </li></ul><ul><ul><li>Cefipime or Imipenem-cilastatin and an aminoglycoside </li></ul></ul><ul><li>Abdominal infection </li></ul><ul><ul><li>Imipenem - cilastatin or Pipercillin - tazobactam and aminoglycoside </li></ul></ul>Angus DC, et al . Crit Care Med 2001, 29:1303-1310.
  37. 37. Antibiotic use in Sepsis (2) <ul><li>Nosocomial abdominal infection </li></ul><ul><ul><li>Imipenem-cilastatin and aminoglycoside or Pipercillin-tazobactam and Amphotericin B </li></ul></ul><ul><li>Skin / soft tissue </li></ul><ul><ul><li>Vancomycin and Imipenem - cilastatin or Piperacillin - tazobactam </li></ul></ul><ul><li>Nosocomial skin/soft tissue </li></ul><ul><ul><li>Vancomycin and Cefipime </li></ul></ul><ul><li>Urinary tract infection </li></ul><ul><ul><li>Ciprofloxacin and aminoglycoside </li></ul></ul>Angus DC, et al . Crit Care Med 2001, 29:1303-1310.
  38. 38. Antibiotic use in Sepsis (3) <ul><li>Nosocomial urinary tract infection: </li></ul><ul><ul><li>Vancomycin and Cefipime </li></ul></ul><ul><li>CNS infection : </li></ul><ul><ul><li>Vancomycin and third generation cephalosporin or Meropenem </li></ul></ul><ul><li>Nosocomial CNS infection: </li></ul><ul><ul><li>Meropenem and Vancomycin </li></ul></ul><ul><li>Drugs will change depending on the most likely cause of the patient's sepsis </li></ul><ul><li>Single drug regimens are usually only indicated when the organism causing sepsis has been identified and antibiotic sensitivity testing </li></ul>Angus DC, et al . Crit Care Med 2001, 29:1303-1310.
  39. 39. New Drug in Treating Severe Sepsis <ul><li>It is the first agent approved by the FDA effective in the treatment of severe sepsis proven to reduce mortality . Activated Protein C ( Xigris ) mediates many actions of body homeostasis . It is a potent agent for the : </li></ul><ul><ul><li>suppression of inflammation </li></ul></ul><ul><ul><li>prevention of microvascular coagulation </li></ul></ul><ul><ul><li>reversal of impaired fibrinolysis </li></ul></ul>Angus DC, et al . Crit Care Med 2001, 29:1303-1310.
  40. 40. NEJM;355:1699-1723.
  41. 41. Sepsis Cascade
  42. 42. Activated Protein C ( Xigris ) NEJM;355:1640, October 19, 2006.
  43. 43. Thank you

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