Kuliah Blok 11




Bacteremia and Sepsis

dr. I Gede Yasa Asmara, SpPD, MMed, DTMH

Department of Internal Medicine

Faculty of Medicine University of Mataram
West Nusa Tenggara General Hospital
 Outline
• Definition
• Epidemiology
• Pathophysiology
• Clinical manifestations
• Management
• Prevention
• Summary
DEFINITIONS
 Definition

Infection= microbial phenomenon characterized by

an inflammatory response to the presence of
microorganisms or the invasion of normally sterile
host tissue by those organisms.

Bacteremia = the presence of viable bacteria in the

blood.

Crit Care Med 1992; 20:864

Clinical Spectrum of Infection
Infection

Bacteremia

Sepsis

Severe Sepsis

Septic Shock
Infection and septic shock is along a spectrum
Infection/

Trauma SIRS Sepsis Severe Sepsis

A clinical response arising from SIRS with a presumed or

a nonspecific insult, including ≥ confirmed infectious
2 of the following: process
• Temperature >38oC or <36oC
• HR >90 beats/min
• Respirations >20/min SIRS = Systemic Inflammatory Response Syndrome
• WBC count >12,000/mm3 or

<4,000/mm3 or >10% immature
neutrophils
Infection and septic shock is along a spectrum
Infection/

Trauma SIRS Sepsis Severe Sepsis

Sepsis with ≥1 sign of organ

failure
Cardiovascular (refractory
hypotension)
Renal
Respiratory
Hepatic Shock
Hematology
CNS
Metabolic acidosis
Relationship of Infection, SIRS, Sepsis,
Severe Sepsis and Septic Shock

SEPSIS PANCREATITIS

SEVERE
SEPSIS

INFECTION SIRS BURNS

SEPTIC

SHOCK

TRAUMA

OTHER
 Diagnostic criteria for sepsis
Infection, documented or suspected, and some of the following:
General variables
• Fever (> 38.3°C)
• Hypothermia (core temperature < 36°C)
• Heart rate > 90/min–1 or more than two sd above the
normal value for age
• Tachypnea
• Altered mental status
• Significant edema or positive fluid balance (> 20 mL/kg
over 24 hr)
• Hyperglycemia (plasma glucose > 140 mg/dL or 7.7
mmol/L) in the absence of diabetes
Inflammatory variables
• Leukocytosis (WBC count > 12,000 µL–1)
• Leukopenia (WBC count < 4000 µL–1)
• Normal WBC count with greater than 10%
immature forms
• Plasma C-reactive protein more than two sd above
the normal value
• Plasma procalcitonin more than two sd above the
normal value

Hemodynamic variables
• Arterial hypotension (SBP < 90 mm Hg, MAP < 70
mm Hg, or an SBP decrease > 40 mm Hg in adults
or less than two sd below normal for age)
Organ dysfunction variables
• Arterial hypoxemia (Pao2/Fio2 < 300)
• Acute oliguria (urine output < 0.5 mL/kg/hr for at least 2
hrs despite adequate fluid resuscitation)
• Creatinine increase > 0.5 mg/dL or 44.2 µmol/L
• Coagulation abnormalities (INR > 1.5 or aPTT > 60 s)
• Ileus (absent bowel sounds)
• Thrombocytopenia (platelet count < 100,000 µL–1)
• Hyperbilirubinemia (plasma total bilirubin > 4 mg/dL or
70 µmol/L)

Tissue perfusion variables

• Hyperlactatemia (> 1 mmol/L)
• Decreased capillary refill or mottling
 Severe sepsis: sepsis-induced tissue
hypoperfusion or organ dysfunction)
• Sepsis-induced hypotension
• Lactate above upper limits laboratory normal
• Urine output < 0.5 mL/kg/hr for more than 2 hrs
despite adequate fluid resuscitation
• Acute lung injury with Pao2/Fio2 < 250 in the
absence of pneumonia as infection source
• Acute lung injury with Pao2/Fio2 < 200 in the
presence of pneumonia as infection source
• Creatinine > 2.0 mg/dL (176.8 µmol/L)
• Bilirubin > 2 mg/dL (34.2 µmol/L)
• Platelet count < 100,000 µL
• Coagulopathy (international normalized ratio > 1.5)
 Diagnostic criteria for Sepsis

Sepsis Severe Sepsis Septic Shock

SIRS
•Sepsis plus •Sepsis-induced
•Infectious & non •SIRS plus
•Sepsis-induced hypo-perfusion or
infectious causes •Presumed or hypotension
•Clinical response confirmed organ
dysfunction or persisting despite
arising from a infection 30 mls/kg fluid
non specific tissue
hypoperfusion rescusitation
insult
 Definition Changes in 2016
• A task force of 19 leaders in the field of sepsis was convened by
SCCM and the European Society of Intensive Care Medicine (ESICM)
• Changes categories to sepsis and septic shock
• The new diagnostic tool for sepsis : quickSOFA qSOFA, 2 of 3
indicators below
– An alteration in mental status
– A decrease in systolic blood pressure of less than 100 mm Hg
– A respiration rate greater than 22 breaths/min
• Septic Shock Definitions
– Persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg
– Blood lactate >2 mmol/L despite adequate volume resuscitation

Singer M, Deutschman CS, Seymour C, et al. The Third International

Consensus Definitions for Sepsis and Septic Shock
(Sepsis-3). JAMA. 2016;315(8):801-810. doi:10.1001/jama.2016.0287
 Sepsis-3: A life threatening organ dysfunction
caused by a dysregulated host response to infection

• SOFA score
– Respiration: PaO2/FiO2 or SaO2/FiO2
– Coagulation: Platelets
– Liver: Bilirubin
– Cardiovascular: Hypotension or vasopressor
– CNS: GCS
– Renal: Creatinine or urinary output
• qSOFA
– RR> 22, Altered Mental status, SBP <100
1o outcome: increased specificity in predicting
Mortality > 10%; ICU LOS > 3 days
EPIDEMIOLOGY
 The Burden
• Common

• Sepsis: 330 per 100,000 per annum

• AMI: 208 per 100,000 per annum

• Mortality: 20 - 55%
Mortality Increases in Septic Shock Patients
Incidence Mortality

Sepsis
400,000 7-17%

Severe Sepsis 20-53%

300,000

Septic
Approximately 200,000 53-63%
patients including 70,000 Shock
Medicare patients have
septic shock annually
Septic shock and mortality

Chest 2003;123:1615–1624
Changes of Pathogens pattern in Sepsis
 Main Pathogens in Septic Shock
• Gram-positive bacteria (30-50%)
– staphylococci, Staphylococcus
aureus, Streptococcus pneumoniae,
enterococci, other
• Gram-negative bacteria (25-30%)
– E. coli, Ps. aeruginosa, K.
pneumoniae, other
• Fungi (1-3%)
– Candida albicans, other
• Parasites (1-3%)
• Viruses (2-4%)

Lancet 2005;365:63-78
 Common origins of sepsis
• Lung
– bacteremia associated with nosocomial
pneumonia
• Abdomen (Intraabdominal infections)
• Genitourinary tract
• Postoperative wound infections
• Primary bloodstream infection via intravascular
lines
PATHOPHYSIOLOGY
Natural history of infection

Canadian Journal of Anaesthesia

2001;159:502-509
NEJM 1993;328:1471-1478
Sequential events in septic shock
Infection inflammation
Bacteria coagulation
Fungi fibrinolysis
Viruses

microvascular thrombosis
neutrophil rolling
endothelial dysfunctions

Acute organ dysfunction Hypoxemia

CLINICAL MANIFESTATIONS
 Cardiovascular system
• Systemic vasodilation and hypotension (Systolic <100 mmHg)

• Tachycardia (>100 beats/min)

• Increased cardiac output (hyperdynamic), although contractility is

depressed; hypodynamic in late shock

• Ventricular dilation; decreased ejection fraction

• Loss of sympathetic responsiveness

• Hypovolemia due to vascular leakage

• Compromised nutrient blood flow to organs; decreased organ

oxygen extraction
 Respiratory and Renal system
• Hyperventilation
• Pulmonary hypertension and oedema
• Hypoxemia (arterial pO2 <50 mmHg)
• Respiratory muscle failure

• Renal hypoperfusion; oliguria

• Acute tubular necrosis and renal failure
• Increase serum creatinine
 Other systems
• Disseminated intravascular coagulation (DIC)
• Blood dyscrasias
– leukopenia
– thrombocytopenia
– polycythemia
• Central and peripheral nervous dysfunction
• Increased ALT, ALP, bilirubin and lactate
• GIT manifestations
• Skin manifestations
MANAGEMENT
 Basic principles of management
1. Immediate stabilise patient (ABC)

2. Control source of infection

3. Reverse inflammation and coagulation cascades

Give 3
1.OXYGEN: Titrate O2 to saturations of
94 -98% or 88-92% in chronic lung
disease.
2. FLUIDS: Start IV fluid resuscitation if
evidence of hypovolaemia. 500ml bolus
of isotonic crystalloid over 15mins & give
up to 30ml/kg, reassessing for signs of
hypovolaemia, euvolaemia, or fluid
overload.
3. ANTIMICROBIALS: Give IV
antimicrobials according to local
antimicrobial guidelines.
Take 3
1. CULTURES: Take blood cultures before
giving antimicrobials (if no significant delay
i.e. >45 minutes) and consider source
control. 
2.BLOODS: Check point of care lactate
& full blood count. Other tests and
investigations as per history and
examination.
3. URINE OUTPUT: Assess urine
output and consider urinary catheterisation
for accurate measurement in patients with
severe sepsis/septic shock.
SURVIVING SEPSIS CAMPAIGN BUNDLES

TO BE COMPLETED WITHIN 3 HOURS:

1. Measure lactate level
2. Obtain blood cultures prior to administration of antibiotics
3. Administer broad spectrum antibiotics
4. Administer 30 mL/kg crystalloid for hypotension or lactate 4mmol/L
TO BE COMPLETED WITHIN 6 HOURS:
1. Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation)
to maintain a mean arterial pressure (MAP) 65 mm Hg
2. In the event of persistent arterial hypotension despite volume resuscitation (septic
shock) or initial lactate 4 mmol/L (36 mg/dL):
– Measure central venous pressure (CVP)*
– Measure central venous oxygen saturation (ScvO2)*
3. Remeasure lactate if initial lactate was elevated*
Targets for quantitative resuscitation included in the guidelines are CVP of 8 mm Hg,
ScvO2 of 70%, and normalization of lactate.
Fluid Resuscitation
Vasopressor in septic shock

NEJM 1999;340:207-214
 Underlying, comorbidity
Immune status
Severity/sepsis
Organ disfunctions

Antibiotic spectrum Gram positive/negative

Availability Community/HCAI/HAI
Cost Sensitive/Resistance
 Principles in antibiotic therapy
• AB should be started within the first hour
• The choice of AB should be guided by the susceptibility
patterns of micro organisms in the community and in the
hospital
• 3rd of 4th cephalosporin or Carbapenem ! 1st choice
• Glycopeptide AB ! 2nd choice
• AB regimen should be reassessed after 24-72 hr on the basis of
microbiological and clinical data
• AB should be given 7-10 days
• Empirical antifungal therapy is only considered in patient with
high risk of invasive candidiasis
 Antibiotic therapy

Antibiotics that DO NOT worsen sepsis include:

- Carbapenems
- Ceftriaxone
- Cefepine
- Glycopeptides
- Aminoglycosides
- Quinolones
 De-escalation approach to antimicrobial utilization
Serious hospital acquired infection suspected
Obtain appropriate microbial
sample for culture and special stain

Begin empirical antibacterial treatment with

a combination agents targeting the most
common pathogen based on local data

Follow clinical parameter : Temp, WBC, CXR

PaO2/FiO2, haemodynamic, organ function

De-escalating antibacterial based on

results of clinical microbiology data
Search for superinfection
Abscess formation No Significant clinical improvement
Non infectious caused after 48-96 hours
of fever
Y

Discontinue antibacterial after 7-14 days course based

on site of infection and clinical response

Kollef, Drugs 2003;63 (20): 2157

 Corticosteroids
We suggest against using intravenous
hydrocortisone to treat septic shock patients
if adequate fluid resuscitation and
vasopressor therapy are able to restore
hemodynamic stability. If this is not
achievable, we suggest intravenous
hydrocortisone at a dose of 200 mg per day.
(Weak recommendation; low quality of evidence) 
PREVENTION
Early detection is
crucial in the
prevention

source: www.xigris.com
 Basic principles in prevention
• Keep surface mucosa intact

• Aseptic technique in every medical

procedures

• Antibiotics prophylaxis
Preventive measures

Lancet
 Summary
• Sepsis has a high rate of mortality
• Understanding the pathophysiology of
bacteremia and sepsis is crucial in its
management and prevention
• Antibiotics alone is not enough in treatment of
sepsis
• Prevention is important to reduce morbidity and
mortality of sepsis
Questions???