Optimizing antibiotic therapy in icu setting

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Optimizing antibiotic therapy in icu setting

  1. 1. Optimizing AntimicrobialTherapy in the ICU settingDr. Mahen Kothalawala MBBS, Dip in Micro, MD, MPH(NZ)Consultant Clinical MicrobiologistTeaching Hospital KandyKandy
  2. 2. Introduction• Severe sepsis & Septic Shock – are majorchallenges in critical care practice• A condition with ↑ mortality• Published data in US,– mortality of 28.6%– 215,000 deaths from 750,000 diagnosed Ref 2 page 30
  3. 3. Severe sepsis….• Brings up many PK/PD changes– Distribution & protein binding– Clearance– Metabolism– Spectrum– Target site concentration– Activity and interactions• If not addressed properly → MAY CAUSETREATMENT FAILURE
  4. 4. Adjustment of antimicrobial therapyAccording to PK/PD changes in orderto achieve maximum benefit withouttoxicity
  5. 5. Objective of Optimization of antibiotictherapy …• To achieve rapid bacterial clearing• before irreversible state sets in
  6. 6. How to achieve optimization– 1. Application of De-escalation Strategy followed by stream lining of antibiotics– 2. Point of Care Testing– 3. Directed/Targeted Therapy– 4. Guiding Therapy objectively using inflammatory Markers– 5. Monitoring for therapeutic response – Target attainment at site of infection– 6. Monitoring for side effects and adverse drug reactions– 7. Adjusting dose according to the changes in PK/PD properties– 8. Source control– 9. Proper Infection Control Practices– 10. Antibiotic stewardship program
  7. 7. 1. Application of De-escalation Strategy followed by streamlining of antibiotics• De-escalation Therapy – Provision of most effectiveantibiotics specially in initial period of severe sepsis– Initial inadequate therapy ≡ Delaying to commencement of Rx– Initial adequate therapy – Save lives• De-escalation encompasses two key features– A. Intent to narrow the spectrum of coverage with• Clinical response or• Lab reports or• With availability of susceptibilities of the identified pathogens– B. Commitment to stop antibiotics if no evidence of infectionpresent• To “clear” microbes before effects of cytokine storm sets in• Subsequent Streamlining with Laboratory inputs
  8. 8. Advantages ofDe-escalation Strategy• Effective & Rapid response• Reduction of antibiotic related side effects oradverse effects• Reduction of overall antibiotic cost (notalways)
  9. 9. 2. Point of Care Testing• Point of Care – First place where pt comes in to contact,– OPD,– Primary Care Units (PCU),– Emergency Departments (ER/EU)• Limited set of Tests, which are not costly Easy to performwhich will identify sepsis/severe sepsis very early– Serum Lactate– Blood Culture– CRP• Objective –– Early identification of septic insult– timely action, without any delay
  10. 10. POCT…..• bring the test conveniently and immediatelyto the patient• increases the likelihood of physician, and careteam will receive the results quicker,→allows making quick management decisions
  11. 11. New clinical tools to identify sepsisearly ….. For early action• Without laboratory input or with minimalinput from laboratory• Only with few clinical parameters• Diagnostic as well as prognostics
  12. 12. 3. Directed/Targeted Therapy• Identify the most probable pathogen/s and usingdirected/targeted therapy (Minimize The CollateralDamage)• Initial empiric convert to targeted Tx later• The most cost effective way of treatment and reduceantibiotic resistance• Requires 24/7 availability of Microbiology Facilities• Making Antibiotics Available 24/7
  13. 13. Availability of antibiotics 24/724 hr Microbiology Help
  14. 14. 4. Guiding Therapy objectively usinginflammatory Markers• Serial Assessment of Bio-Markers of sepsis to assesresponse or no response– CRP– PCT• CRP and PCT- These can be used as prognosticMarkers as well• Blood Counts- Not a good indicator or not reflectiveof disease progression/response
  15. 15. 5. Monitoring for therapeutic response – Target attainmentat site of infection• Drug Levels to check for PD target attainment at site– Can detect antimicrobial adequacy very early• PD Targets – Depend on type of antibiotics– %T> MIC– CMAX/MIC– AUC0→24hrs /MIC• Clinical response to therapy – often delayed• Fever Response – occur 48 hrs or later• Initial Evidence of response– ↓ Inotroph requirement,– Improvement of Oxygenation
  16. 16. 6. Monitoring for side effects and adverse drug reactions• Side Effects– Clinically Apparent SE– Laboratory SE• Clinically apparent side effects – appear very late due toreserve capacity of the internal organs• Lab side effects – May appear early and reflective of organdamage earlier than clinical side effects• Best- Monitoring of SE using Drug Levels -– Levels done specially for• antibiotics with narrow therapeutic Index• potentially toxic antimicrobial co-administered with known toxic drugs
  17. 17. 7. Source control• Treatment will not effective without source control– Limb in Necrotizing Fasciitis or in myonecrosis– Non functional organs– Leaking Viscera– Retained Infected Products of conception– Foreign bodies-, CVP, other lines, urinary catheters ETC– Un-drained Abscesses• Reduce Microbial burden/Toxin production• Allows penetration of antibiotics deep in to source• ↓ Bio Film
  18. 18. 8. Adjusting dose according to the changes in PK/PDproperties• Use appropriate drugs on selected sites– Daptomycin may not effective in lung– Usage of Bacteristatic drugs for septicemia– Inadequate dosages- Meropenem in VAP, Conventional dose wouldachieve 15% only– Pip-Taz – TDS dose (May not sufficient to achieve the desirable levels@ site of infection• Gross edema- ↓ [] of polar/hydrophillic antibiotics• Intracellular pathogens- need non polar drugs- which to go intoICF• Drugs which cross-BBB to treat meningitis• Consider changes in Vd, Clearance etc and correct the dosesaccordingly
  19. 19. 9 .Proper Infection Control Practices• Usage of Disinfectants and Antiseptics whenindicated –– To Disrupt biofilm– Use antibiotic/antiseptic Impregnated devices• Prevent Spread- Hospital outbreaks• Proper care of invasive devices• Use of AHR
  20. 20. 10. Antibiotic Stewardship Programs• (1) prospective auditing of antimicrobial utilization withdirect interaction and feedback to the prescriber,• (2) formulary restriction and pre-authorizationrequirements to immediately reduce antimicrobial use andcost.• (3) other methods– education,– antimicrobial cycling,– antimicrobial order– forms,– parenteral-to-oral conversion plans
  21. 21. In Management of Severe Sepsis…

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