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Diagnosis and Management of Sepsis 2013

Diagnosis and Management of Sepsis 2013. Edward L. Goodman, MD Core Faculty Hospital Epidemiologist June 27, 2013. Outline. Recognition and Impact Grades of recommendations Non-antimicrobial management Antimicrobial management Infection Prevention Antibiotic Stewardship.

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Diagnosis and Management of Sepsis 2013

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  1. Diagnosis and Management of Sepsis 2013 Edward L. Goodman, MD Core Faculty Hospital Epidemiologist June 27, 2013

  2. Outline • Recognition and Impact • Grades of recommendations • Non-antimicrobial management • Antimicrobial management • Infection Prevention • Antibiotic Stewardship

  3. Recognizing Sepsis

  4. Terminology • Systemic Inflammatory Response Syndrome (SIRS) • Temp > 38 or < 36 • HR > 90 • RR > 20 or PaCO2 < 32 • WBC > 12 or < 4 or Bands > 10% • Sepsis • The systemic inflammatory response to infection. • Severe Sepsis • Organ dysfunction secondary to Sepsis. • e.g. hypoperfusion, hypotension, acute lung injury, encephalopathy, acute kidney injury, coagulopathy. • Septic Shock • Hypotension secondary to Sepsis that is resistant to adequate fluid administration and associated with hypoperfusion. TWO out of four criteria acute change from baseline Bone, R., Balk, R., Cerra, F., Dellinger, R., Fein, A., Knaus, W., Schein, R., et al. (1992). Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest, 101(6), 1644–1655.

  5. Infection, SiRS, Sepsis Bone, R., Balk, R., Cerra, F., Dellinger, R., Fein, A., Knaus, W., Schein, R., et al. (1992). Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest, 101(6), 1644–1655.

  6. Sepsis Pathogenesis Unbalanced Immune Reaction Mediators of Inflammation Tissue Factor Procoagulant State ROS Microvascular Thrombosis Capillary Leak Vasodilation

  7. Organ failure in sepsis P/F Platelets Bili BPGCS Cr/UOP Vincent, J.-L., Sakr, Y., Sprung, C. L., Ranieri, V. M., Reinhart, K., Gerlach, H., Moreno, R., et al. (2006). Sepsis in European intensive care units: results of the SOAP study. Critical Care Medicine, 34(2), 344–353.

  8. Critical Care Medicine 2013;41:580

  9. Grading of Recommendations, Assessment, Development and Evaluation • GRADE SYSTEM • Strength of Evidence (A – D) • Level of Recommendation (1 or 2)

  10. Management • Initial Resuscitation • Fluids • Pressors • Microbial Diagnosis • Antimicrobial Therapy • Primer on Antibiotics • Source Control • Infection Prevention

  11. Summary

  12. Other Supportive Measures

  13. Other Supportive

  14. Other Supportive

  15. Antimicrobial Therapy

  16. Microbiology and Antibiotic Primer 101 • Three classes of major bacterial pathogens that need to be considered in septic patients • Gram Positive Cocci • Gram Negative Rods • Strict Anaerobes

  17. Gram Positive Cocci • Staphylococcus aureus • 50% are MRSA • Beta hemolytic streptococci • Always penicillin susceptible • Viridans streptococci • Usually penicillin or ceftriaxone susceptible • Enterococcus species • E faecium is always penicillin resistant, often vancomycin resistant

  18. Facultative Gram Negative Rods (Enterobacteraciae) • Most common pathogens are E coli and Klebsiella • Increasing resistance includes ESBL, Kpc • SPICE Organisms (Serratia, Indole Positive Proteus, Citrobacter, Enterobacter) • Possess Amp C resistance genes which can be induced or selected

  19. Strictly Aerobic Gram Negatives • Pseudomonas aeruginosa • Inherently resistant to many classes of drugs • Possess Amp C genes (also SPICE organism), many other beta lactamases, efflux pumps and altered porin channels • Can become even more resistant • Even to carbapenemases! • Acinetobacter species • Inherently MDR • Can become totally resistant, even to colistin!

  20. Strict Anaerobes • Most common pathogens are Bacteroides fragilis and fusobacterium species • Produce beta lactamases • Resistant to penicillins and older cephalosporins • Susceptible to BL/BLI, cefoxitin, carbapenems, metronidazole, clindamycin

  21. Classes of Antibiotics to Use Initially in Sepsis • Beta Lactams* • Broad Spectrum Penicillins = piperacillin/tazobactam • 3 or 4th Generation Cephalosporins • Non anti-pseudomonal = ceftriaxone or cefotaxime • Anti-pseudomonal = ceftazidime or cefepime • Carbapenems • Non anti-pseudomonal = ertapenem • Anti-pseudomonal = meropenem • Monobactams = aztreonam • Only for “beta lactam” allergic • No gram positive or anaerobic activity • Anti-pseudomonas activity comparable to ceftazidime * Avoid combinations of beta lactams

  22. Aminoglycosides • Gentamicin/tobramycin (7 mg/kg/day) • Cover most enterobacteraciae and pseudomonas • Not as resistant to aminoglycoside modifying enzymes • Amikacin (20 mg/kg/day) • More resistant to aminoglycoside modifying enzymes • Should be the “Go To AG” • Once MIC’s available, can de-escalate to other class (BL, FQ) • Rarely need more than 1-2 days of AG • Nephro/oto-toxicity are unlikely

  23. Vancomycin • Only active against GPC • Slowly bactericidal • Pharmacodynamic parameter = AUC/MIC • Goal of >=400 • Need loading dose for serious infections: 25 mg/kg AW • Trough >15 achieves AUC/MIC of >400 when MIC <2 • For OSSA, less effective than beta lactams

  24. What is Missing? • Fluoroquinolones • Only empiric indication in sepsis would be as part of combination therapy for severe CAP • Not empirically for UTI, intra-abdominal or SSTI • Why not? • 25-30+% of E coli in ICU are resistant! • 35% of Pseudomonas in ICU are resistant

  25. When to Cover for MRSA • Severe purulent SSTI • Necrotizing pneumonia/empyema • Central line associated • (Known MRSA carriers?) • Go To Drug = Vancomycin

  26. When to Cover for Pseudomonas • Severe COBPD/bronchiectasis • Frequent ABX • Steroid dependent • Known airway colonization • Neutropenic septic leukemic • (Burn patients)

  27. Combination Rx for Pseudomonas?(Andrew Faust, PharmD) • Only indicated to ensure coverage until MICs are available • Does not prevent resistance from developing • Synergy is not clinically relevant • What combinations are optimal in ICU isolates 2012?

  28. Sepsis is “always” a secondary diagnosis: where is it coming from?

  29. Septic Patients are not Immune to Hospital Acquired Infections! • “Bundles” • Guidelines • Recent literature

  30. Prevent CLABSI

  31. Prevent Ventilator Adverse Events

  32. Prevent CAUTI

  33. Sepsis Guidelines 2013

  34. Antibiotic Stewardship • Get appropriate cultures before starting ABX • Pick empiric therapy based on likely source and organism(s) • Once meaningful cultures are available, use susceptibilities to de-escalate therapy • Limit duration of therapy to evidence based recommendations when possible

  35. Thanks to • Andrew Faust, PharmD • Terri Smith, PharmD, Sharon Williamson, MT(ASCP), CIC • Michael H. Hooper, MD, Eastern Virginia Medical School • Surviving Sepsis Campaign. Dellinger et al. Critical Care Medicine 2013;41;580-637

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