Sepsis and septic shock refer to systemic inflammatory response syndrome caused by infection. In 1992, terminology was standardized to classify patients based on severity from systemic inflammatory response syndrome to septic shock and multiple organ dysfunction syndrome. Bacteria are the most common cause, and symptoms may include fever, changes in mental status, and hypotension. Diagnosis involves blood tests showing signs of infection as well as identifying the pathogen through blood and other cultures. Treatment goals are timely diagnosis, eliminating the infection source, and early broad-spectrum antibiotics while preventing organ failure through other supportive measures.

1. Sepsis and septic
shock
By - Money Kalash
Pharm.D

2. Definition
In past ,sepsis was considered as Severe, systemic
infection due to bacteria getting into the bloodstream from
an infectiousfocusin thebody .
But In 1992 , terminology for sepsis was standardized
by ACCP& SCCM.
It became clear that non-infectious diseases also can give
rise to the same clinical syndrome that is caused by
bacteria(burns, pancreatitisetc.)
According to new terms patients can be categorized as
having bacteraemia, SIRS, sepsis, severesepsis, MODS.

3. By definition -
SIRS – Systemic Inflammatory Response
Syndrome
By definition: at least 2 criteria
Temperatureabove38˚C or below 360
C
Heart rateabove90/min.
Respiratory rateabove20/min
Pa(CO2) < 32 torr
Leukocyte count above 12000 or below 4000 or
morethan 10 % immatureforms

4. SIRS – Non-infectious systemic
inflammatory responsesyndrome
Sepsis – Infectious systemic inflammatory
responsesyndrome
Infection – Invasion of microbes that
provokes a controlled, local
inflammatory response
Severe Sepsis – sepsis associated with organ
dysfunction , hypoperfusion or hypotension .

5. Septic shock – Sepsis with hypotension ,
despite fluid resuscitation , along with the
presenceof perfusion abnormalities.
Multiple – organ dysfunction syndrome
(MODS) - presence of altered organ function
to maintain homeostasis.
Compensatory anti-inflammatory response
syndrome (CARS) – Compensatory
physiologic response to systemic
inflammation.

8. Etiology
Causativeorganism vary and dependsupon siteof infection.
Bacteria , viruses , fungi , protozoa , spirochetes and
ricketssiae can cause sepsis or septic shock. However , bacteria
themost common causeof sepsis.
Community acquired infections
Gram- negative bacteria – E.co li ,Klebsiella pnuemo niae
,Pseudo monas aerugino sa , N. meningitidis, L. pneumophilaetc.
Gram- positive bacteria – Staphylo co ccus aureus , S.
pyogenes, S. pneumoniae, S. aureus Entero co cci ,Strepto cocci
etc.

9. Etiology
Nosocomial infections
Gram-positive bacteria - S. aureus (MRSA),
S. epidermidis (MRSE), Entero co ccus spp
Gram-negative bacteria - E. co li, K. pneumo niae,
P. aerugino sa, A. baumannii
Fungi - Candida spp, Aspergillus spp

10. Infection site Prevalence
Respiratory tract 21%-68%
Intra-abdominal space 14%-22%
Urinary tract 14%-18%
Primary Infectionssitesarelisted below:
Pathogen Incidence
Gram –negativeBacteria 38% of patients
Gram-positiveBacteria 40% of patients
Fungi 17% of patients
Leading causeof sepsis:

11. Sepsis is an extremely complex
response syndrome evoked by
microbial agents.
Endothelium damage, micro vascular
dysfunction, impaired tissue oxygen uptake
with consecutiveorgan damage.
The sepsis is an auto destructive process
that precipitates the dysfunction of multiple
organs: MODS (multiple organ dysfunction
syndrome)

12. Mediators of sepsis
Cytokines (morethan 150)
Pro-inflammatory cytokines
TNF – Tumour necrosisfactor
Interleukins1, 2, 6, 12
PAF – Thrombocyteactivating factor
Anti-inflammatory cytokines
Interleukin 4, 10, 11, 13

13. The sepsis syndrome is the response of the human
organism to microbe invasion: the outcome depends
on theinter-relationship of pro- and anti-inflammatory
cytokines.
If the infectious source can be controlled and the
function of pro- and anti-inflammatory cytokines is
balanced, thepatient survives.
If the function of pro-inflammatory cytokines – for
any reason-outweighs the anti-inflammatory system,
the developing organ damage becomes irreversible
and it may lead to death.

14. Microbial factors in sepsis
Gram-negative bacteria
Endotoxins: Constituents of the outer membrane of
Gram-negativebacteria(lipopolysaccharides– LPS)
Exotoxins: Actively produced and secreted proteins
(V. cholera)

15. Microbial factors in sepsisMicrobial factors in sepsis
Gram-positivebacteria:
Exotoxins(C. difficile)
Pyrogen exotoxins (super antigens): S.aureus ,
S.pyo genes =
Toxic shock syndrome

16. Cascadeof sepsis

17. Complications of sepsisComplications of sepsis
Disseminated intravascular coagulation (DIC)
Pulmonary dysfunction
Acuterespiratory distresssyndrome(ARDS)
Renal failure

18. Clinical presentationClinical presentation
Fever
Chills
Change in mental status
Fatigue
Sometimes hypothermia instead of fever
Hypotension
Oliguria
Gastrointestinal hemorrhage

19. DIAGNOSIS OF
SEPSIS

20. LABORATORY TESTSLABORATORY TESTS
COMPLETE BLOOD PICTURE
Leukopeniaor Neutrophil leukocytosis
Toxic granulation of neutrophils
Increased band forms
Low platelet count – DIC
COAGULATION SCREEN – For Evidenceof DIC
PT – Prolonged
Fibrinogen – Low levels
Markersof fibrinolysis(D-Dimer) - Elevated

21. LABORATORY TESTSLABORATORY TESTS
Electrolytesand Renal function tests
Liver function tests
Plasmaalbumin – acutefall
C-ReactiveProtein
Procalcitonin levels
Blood glucose
Plasmalactate
Arterial blood gases
Endotoxin or Cytokinelevels(TNF-alpha, IL-6)

22. LABORATORY TESTSLABORATORY TESTS
MICROBIOLOGY TESTS
Blood Culture
Sputum Culture
UrineCulture

23. Treatment goalsTreatment goals
The primary goals for treatment of sepsis are as
follows:
Timely diagnosisand identification of thepathogen.
Rapid elimination of thesourceof infection.
Early initiation of aggressiveantimicrobial therapy.
Interruption of the pathogenic sequence leading to
septic shock.
Avoidanceof organ failure.

24. Principles of antimicrobial therapy in sepsisPrinciples of antimicrobial therapy in sepsis
For the optimum treatment of sepsis one has to have
some imagination about the focus and the type of
pathogen according to thesiteof infection.
Samples have to be taken for culture before the
administration of antibiotics.
Bactericidal antibioticsshould bechosen.
The probability of effectiveness of antimicrobial
therapy should be at least 90-95 % in severe
infections.
Early antimicrobial therapy is helpful in management
of sepsis.

25. Vallés et al. Chest 2003 123:1615–1624

26. Factors to be considered forthe choiceFactors to be considered forthe choice
of antibioticsof antibiotics
1. Community versushospital-acquired infections
 The pathogens are different in term of spectrum and
antibiotic sensitivity.
 The pathogens of the nosocomial infections are more
resistant or even multiply resistant.
2. Theanatomical siteof thefocusof sepsis
 The anatomical site determines the types of possible
pathogens, especially in community-acquired
infections

27. Factors to be considered forthe choiceFactors to be considered forthe choice
of antibioticsof antibiotics
3. Thepresenceof
underlying diseases
 Diabetesmellitus
 Alcoholism
 Splenectomy
 Neutropenia
 Myeloma
 Immunosuppression
4. Diagnostic or surgical
intervention in the
recent past
 IV lines
 Indwelling catheter
 Implantations
 Operation

28. Infection
(Site orType)
Community-Acquired Hospital-Acquired
Urinary tract Ciprofloxacin or
levofloxacin
Ciprofloxacin,
levofloxacin or
ceftazidime, ceftriaxone
±gentamicin
Respiratory tract Newer fluoroquinolonea
or ceftriaxone +
clarithromycin/
azithromycin
Piperacillin, ceftazidime,
or cefepime
+ gentamicin or
ciprofloxacin
Intraabdominal β-Lactamase inhibitor
combob
or ciprofloxacin +
metronidazole
Piperacillin/tazobactam or
carbapenem
Skin/soft tissue Vancomycin or linezolid
or daptomycin
β−Lactamase inhibitor
combob or clindamycin
plus ciprofloxacin or
carbapenem
Catheter related Vancomycin + gentamicin
Unknown Piperacillin or
ceftazidime/cefepime or
imipenem/meropenem
± vancomycin

29. TreatmentTreatment
Antimicrobial therapy
Inotrope and vasoactive drug support (eg:-
dopamine , dobutamine , nor-epinephrine ,
epinephrine)
Hemodynamic support (increasecardiac output)
Adjunctive therapy (glucocorticoids)

30. EVIDENCEBASEDTREATMENTEVIDENCEBASEDTREATMENT
RECOMMENDATION FORSEPSIS ANDSEPTICRECOMMENDATION FORSEPSIS ANDSEPTIC
SHOCKSHOCK
Antibiotic therapy
 Use a broad initial empirical antibiotic regimen against all
likely pathogens
 There is no evidence of higher efficacy with combination
therapy
Fluid therapy
 Immediate initial resuscitation of a patient in severe sepsis or
sepsis-induced tissue hypoperfusion should be instituted to
achieve central venous pressure 8–12 mm Hg, mean arterial
pressure ≥65 mm Hg, urine output ≥0.5 mL/kg/h, central
venousor mixed venousoxygen saturation ≥70%

31. Vasopressors
 The advantages of norepinephrine and dopamine over epinephrine
(potential tachycardia, possibly disadvantageous effects on splanchnic
circulation) and phenylephrine (decrease in stroke volume) are not
supported by theliterature.
Inotropic therapy
 Dobutamine as the first-choice inotrope to increase cardiac output
combined with norepinephrine in the presence of low blood pressure is
not supported in theliterature.
Glucose control
There is minimal support for maintaining blood glucose <150 mg/dL
to improvesurvival
Steroids
 The value of intravenous hydrocortisone 200–300 mg/day for 7 days
in threeor four divided dosesin patientswith septic shock isnot clear.

32. Drotrecogin
Drotrecogin is effective in patients at high risk of death (Acute
Physiology and Chronic Health Evaluation II >25, sepsis induced
multiple organ failure, septic shock, or sepsis induced acute
respiratory distresssyndrome)
Deep vein thrombosis prophylaxis
Either low-dose heparin or low-molecular weight heparin are
effectivein preventing deep vein thrombosis.
Stress ulcerprophylaxis
H2 receptor inhibitorsaremoreefficaciousthan sucralfate.

33. MRSA
Methicillin-resistant Staphylococcusaureus.
Methicillin resistance implies resistance to all
penicillins, cephalosporins, carbapenems and beta
lactam/betalactamaseinhibitor combinations.

34. MRSA
Hospital associated MRSA isolates often are multiply
resistant to other commonly used antimicrobial
agents, including erythromycin, clindamycin and
tetracycline.
Community associated MRSA isolates are often
resistant only to betalactam agentsand erythromycin

35. TREATMENTOPTIONSTREATMENTOPTIONS
Carbapenems
Meropenem, Imipenem+Cilastatin, Ertapenem
Highly resistant to ESBLs – due to the trans-6 hydroxy
ethyl group.
They havesignificant PAE even against Pseudomonas
Resistance mechanisms
Production of Metallo carbapenamases (Class B beta-
lactamases) by some-Acinetobacter and Pseudomonas
strains
Efflux pumps
Changesin OMPs
Aztreonam is the drug of choice in treating
infections caused by carbapenamase producing
bacteria.

36. THANK
YOU