Transcript Edward L. Goodman, MD Core Faculty Hospital Epidemiologist June 27, 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
Terminology
Systemic Inflammatory Response Syndrome (SIRS)
Temp > 38 or < 36
HR > 90
RR > 20 or PaCO2 < 32
WBC > 12 or < 4 or Bands > 10%
TWO out of four criteria
acute change from baseline
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.
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.
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.
Sepsis Pathogenesis
Unbalanced Immune Reaction
Tissue Factor
Mediators of
Inflammation
Procoagulant State
ROS
Microvascular
Thrombosis
Vasodilation
Capillary
Leak
Organ failure in sepsis
P/F
Platelets
Bili
BP
GCS
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.
Critical Care Medicine 2013;41:580
Grading of Recommendations, Assessment,
Development and Evaluation
 GRADE SYSTEM
 Strength of Evidence (A – D)
 Level of Recommendation (1 or 2)
Management
 Initial Resuscitation
 Fluids
 Pressors
 Microbial Diagnosis
 Antimicrobial Therapy
 Primer on Antibiotics
 Source Control
 Infection Prevention
Summary
Other Supportive Measures
Other Supportive
Other Supportive
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
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
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
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!
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
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
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
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
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
When to Cover for MRSA
 Severe purulent SSTI
 Necrotizing pneumonia/empyema
 Central line associated
 (Known MRSA carriers?)
 Go To Drug = Vancomycin
When to Cover for Pseudomonas
 Severe COBPD/bronchiectasis
 Frequent ABX
 Steroid dependent
 Known airway colonization
 Neutropenic septic leukemic
 (Burn patients)
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
Cefepime
Ceftazidime
P/T
66.67%
CPM
54.67%
CTZ
57.33%
P/T + FQ
73.34%
CPM + FQ
61.33%
CTZ + FQ
64.00%
P/T + Gent
89.34%
CPM + G
82.67%
CTZ + G
84.00%
P/T + Tobra
96.00 %
CPM + T
89.33%
CTZ + T
90.67%
P/T + Amik
97.30%
CPM + A
93.34%
CTZ + A
93.33%
Sepsis is “always” a secondary
diagnosis: where is it coming from?
Septic Patients are not Immune to Hospital
Acquired Infections!
 “Bundles”
 Guidelines
 Recent literature
Prevent CLABSI
Prevent Ventilator Adverse Events
Prevent CAUTI
Sepsis Guidelines 2013
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
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