edward l. goodman, md core faculty hospital epidemiologist june 27, 2013
TRANSCRIPT
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Edward L. Goodman, MDCore Faculty
Hospital EpidemiologistJune 27, 2013
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OutlineRecognition and ImpactGrades of recommendationsNon-antimicrobial managementAntimicrobial managementInfection PreventionAntibiotic Stewardship
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TerminologySystemic Inflammatory Response Syndrome (SIRS)
Temp > 38 or < 36HR > 90RR > 20 or PaCO2 < 32WBC > 12 or < 4 or Bands > 10%
SepsisThe systemic inflammatory response to infection.
Severe SepsisOrgan dysfunction secondary to Sepsis.e.g. hypoperfusion, hypotension, acute lung injury, encephalopathy, acute kidney injury, coagulopathy.
Septic ShockHypotension secondary to Sepsis that is resistant to adequate fluid administration and associated with hypoperfusion.
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.
TWO out of four criteriaacute change from baseline
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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.
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Sepsis PathogenesisUnbalanced Immune Reaction
Tissue Factor
Procoagulant State
MicrovascularThrombosis
Mediators of Inflammation
ROS
Vasodilation CapillaryLeak
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Organ failure in sepsis
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.
P/FPlateletsBiliBPGCSCr/UOP
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Critical Care Medicine 2013;41:580
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Grading of Recommendations, Assessment, Development and EvaluationGRADE SYSTEM
Strength of Evidence (A – D)Level of Recommendation (1 or 2)
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ManagementInitial Resuscitation
FluidsPressors
Microbial DiagnosisAntimicrobial Therapy
Primer on AntibioticsSource ControlInfection Prevention
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Summary
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Other Supportive Measures
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Other Supportive
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Other Supportive
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Microbiology and Antibiotic Primer 101Three classes of major bacterial pathogens
that need to be considered in septic patientsGram Positive CocciGram Negative RodsStrict Anaerobes
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Gram Positive CocciStaphylococcus aureus
50% are MRSABeta hemolytic streptococci
Always penicillin susceptibleViridans streptococci
Usually penicillin or ceftriaxone susceptibleEnterococcus species
E faecium is always penicillin resistant, often vancomycin resistant
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Facultative Gram Negative Rods (Enterobacteraciae)Most common pathogens are E coli and
KlebsiellaIncreasing resistance includes ESBL, Kpc
SPICE Organisms (Serratia, Indole Positive Proteus, Citrobacter, Enterobacter)Possess Amp C resistance genes which can be
induced or selected
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Strictly Aerobic Gram NegativesPseudomonas 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 speciesInherently MDRCan become totally resistant, even to colistin!
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Strict AnaerobesMost common pathogens are Bacteroides
fragilis and fusobacterium speciesProduce beta lactamases
Resistant to penicillins and older cephalosporins Susceptible to BL/BLI, cefoxitin, carbapenems,
metronidazole, clindamycin
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Classes of Antibiotics to Use Initially in SepsisBeta Lactams*
Broad Spectrum Penicillins = piperacillin/tazobactam3 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
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AminoglycosidesGentamicin/tobramycin (7 mg/kg/day)
Cover most enterobacteraciae and pseudomonasNot as resistant to aminoglycoside modifying
enzymesAmikacin (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 AGNephro/oto-toxicity are unlikely
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VancomycinOnly active against GPCSlowly bactericidalPharmacodynamic parameter = AUC/MIC
Goal of >=400Need loading dose for serious infections: 25
mg/kg AWTrough >15 achieves AUC/MIC of >400 when
MIC <2For OSSA, less effective than beta lactams
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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
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When to Cover for MRSASevere purulent SSTINecrotizing pneumonia/empyemaCentral line associated(Known MRSA carriers?)
Go To Drug = Vancomycin
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When to Cover for PseudomonasSevere COBPD/bronchiectasis
Frequent ABXSteroid dependentKnown airway colonization
Neutropenic septic leukemic(Burn patients)
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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?
Pip/Tazo
P/T 66.67%
P/T + FQ 73.34%
P/T + Gent
89.34%
P/T + Tobra
96.00 %
P/T + Amik
97.30%
Cefepime
CPM 54.67%
CPM + FQ
61.33%
CPM + G 82.67%
CPM + T 89.33%
CPM + A 93.34%
Ceftazidime
CTZ 57.33%
CTZ + FQ 64.00%
CTZ + G 84.00%
CTZ + T 90.67%
CTZ + A 93.33%
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Sepsis is “always” a secondary diagnosis: where is it coming from?
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Septic Patients are not Immune to Hospital Acquired Infections!“Bundles”GuidelinesRecent literature
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Prevent CLABSI
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Prevent Ventilator Adverse Events
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Prevent CAUTI
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Sepsis Guidelines 2013
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Antibiotic StewardshipGet appropriate cultures before starting ABXPick empiric therapy based on likely source
and organism(s)Once meaningful cultures are available, use
susceptibilities to de-escalate therapyLimit duration of therapy to evidence based
recommendations when possible
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Thanks toAndrew Faust, PharmDTerri Smith, PharmD, Sharon Williamson,
MT(ASCP), CICMichael H. Hooper, MD, Eastern Virginia
Medical SchoolSurviving Sepsis Campaign. Dellinger et al.
Critical Care Medicine 2013;41;580-637