Infectious Diseases I

Sepsis I & II
 Sepsis I & II
Infectious Diseases I-MIC 643
Microbiology Division
Nilda J. Zapata Molina, MD
School of behavioral and brain sciences
Sepsis-Related-Terminology and Definitions

• Infection: A 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.

Sepsis:
• The systemic response to infection; this response is
identical to SIRS, except that it must result from infection.

Septic shock:
• Sepsis with hypotension (systolic blood pressure <90 mm
Hg, or a reduction of >40 mm Hg from baseline) despite
adequate fluid resuscitation, in conjunction with organ
dysfunction and perfusion abnormalities (e.g., lactic
acidosis, oliguria, obtundation),in the absence of other
known causes for the abnormalities.
SIRS:
• The systemic inflammatory response to a variety of severe
clinical insults, including infection, pancreatitis, ischemia,
multiple trauma and tissue injury, hemorrhagic shock,
immune-mediated organ injury, and exogenous
administration of inflammatory mediators, such as tumor
necrosis factor alpha(TNF-) an other cytokines.
Numeric Criteria for SIRS
Two or more of the following must be present:

• Temperature>38C (100.4F) or <36 C (96.8F).

• Heart rate >90 beats/min.
• Respiratory rate>20 breaths/min or Paco2<32 mm
Hg.
• White blood cells>12,000 cells/l or >10% immature
(band) forms.
Sepsis: A Complex Disease
• This Venn diagram
provides a conceptual
framework to view the
relationships between
various components
of sepsis.
• The inflammatory
changes of sepsis are
tightly linked to disturbed
hemostasis.
JAMA Feb 23, 2016

The Third International Consensus

Definitions for Sepsis and Septic Shock.
Sepsis: life threatening organ dysfunction caused by a
dysregulated host response to infection.
Organ dysfunction: acute change in total SOFA
score≥ 2 points secondary to infection.
SOFA-Sepsis Organ Failure Assessment Score.
qSOFA score≥ 2 mortality 10%
Resp rate
Altered cognition
Systolic BP < 100mm/Hg
Septic Shock: sepsis in which underlying
circulatory and cellular/metabolic
abnormalities are profound enough to
increase mortality.
Sepsis

• A systemic response to infection

• Mortality 50-90%
• Bacteria, viruses, rickettsiae, fungi
Gram negative sepsis
• Usually results in metabolic complications and
shock
• Most common cause of septic shock
• Endotoxin on cell wall
-Is the lipopolysaccharide outer layer
-“lipid A” – biologic activity of endotoxin
Gram positive sepsis

• 10% develops septic shock

• Higher incidence of suppurative complications
• Higher capability of adhesing to endothelial cells
Pathogenesis
• Endotoxin – lipopolysaccharide outer layer of Gram neg.
bacilli cell wall.
- Activates Hageman factor

• Hageman factor – activates the alternate complement

pathway
- C3A. C5A are generated acting as vasodilatory
anaphylotoxing
Sepsis cascade
1. Release of intracellular or extracellular bacterial activators
(lipid A, etc.).
2. Activation of macrophages by bacterial products.
3. Release of active molecules (cytokines, TNF-, IL-1).
4. Release of stress hormones (interleukins 2, 6, 8, 10 and
other mediators).
5. Changes in multiple organ systems (endothelium, pulmonary
alveolar cells, liver cells).
Selected Biological and Clinical Manifestations Seen in the Sepsis
Syndrome
Substance Selected Biological Manifestations Selected Clinical manifestations
Endotoxin Activation of macrophages Clinical effect is mediated by the
Release of TNF- release of TNF and the other
Release of IL-1 mediators
TNF  IL-1 Fever
 IL-6  Catabolic state
 IL-8 Microthrombi
 Nitric oxide (NO) Mental status changes
 Myocardial depressant factor  Cortisol level
Activate arachidonic metabolism
PMN activation
IL-1 Virtually identical to TNF- effects, Same as TNF-
except less effect on PMN function
and chemotaxsis
Selected Biological and Clinical Manifestations Seen in the Sepsis Syndrome (cont.)
Nitric oxide  Myocardial performance  Tissue oxygen supply
 Vascular smooth muscle tone Hypotension
Ileus and abdominal distension
Hypoxemia from increased shunting

High levels suppress TH1 T-cell

function
Thromboxanes Platelet and PMN adhesiveness Regional hypoperfusion
Increased PMN adhesiveness ARDS
Vasoconstriction of regional blood vessels Pulmonary shunting
Enhanced capillary permeability Edema
Increased airway resistance Wheezing

Prostaglandins Vasodilation (PGI2 , PGE1) Hypotension

Vasoconstriction (PGI2)  Systemic and pulmonary shunting

Antiagrregatory effects on platelets Arterial hypoxemia
Enhanced capillary permeability  Edema
Identifying Acute Organ Dysfunction as a Marker of Severe Sepsis
Tachycardia
Hypotension
Altered  CVP
Consciousness  PAOP
Confusion
Psychosis

Oliguria
Anuria
Tachypnea
 Creatinine
PaO2 <70 mm Hg
SaO2 <90%
PaO2/FiO2 300

 Platelets
Jaundice  PT/APTT
 Enzymes  Protein C
 Albumin  D-dimer
 PT
Risk factors
• Elderly
• Diabetic
• Debilitated
• Alcoholic
• Immunocompromised
Clinical manifestations
• Fever • Hypotension
• Chills • Bleeding
• Hyperventilation • Leukopenia
• Hypothermia • Throbocytopenia
• Skin lesions • Organ failure
• Change in mental status
Non-specific presentations
• Concurrent fever, chills, hypotension
• Fever alone (granulocytopenia)
• Unexplained hypotension, Tachypnea, Oliguria,
Hypothermia, Impairment of sensorium,
Coagulation disorders, Hypoglycemia
Skin
• Cellulitis
• Bullous lesions
• Diffuse erythroderma (erythrogenic toxins)
• Echymosis
• Pethechia
Pulmonary
• Tachypnea (respiratory alkalosis)
• ARDS in 40%,  mortality
•  Alveolar capillary permeability
Hematologic
• Leukocytosis
• Neutropenia -mortality
• Thrombocytopenia
• DIC – consumption of platelets and clotting
factors
• Hemolytic anemia – Clostridia, Mycoplasma
Renal
• Insufficiency is multifactorial
• Acute tubular necrosis 2 to:
- Hypotension
- Volume depletion inflammatory
- Activated inflammatory mediators
- Antibiotics
Gastrointestinal
• Liver dysfunction
• Hypoglycemia
 Gluconeogenesis
 Hepatic glycogen stores
Cardiovascular
• Warm shock – (CO, SVR)
 Kinins C3a and CSA (anaphylotoxins), histamine, prostaglandins,
endorphins.
 Cardiac index to compensate inadequate 02 consumption
Patients are vasodilated (warm shock).
• Cold shock – (CO, SVR)
 catecholamine activity –
 C0 because of  stroke volume and  preload from splanchnic
blood pooling
Patients are vasoconstricted (cold shock)
Severe Sepsis: A Complex and unpredictable
Clinical Syndrome
Systemic
• High mortality rate Inflammation
Coagulation
(28%-50%)
• Heterogeneous
patient population
Impaired
• Unpredictable Fibrinolysis
disease progression
• Unclear etiology and
pathogenesis
Diagnostic principles

• High index of suspicion

• Blood, urine, sputum, CSF cultures
• Gram stains
 Special Circumstances in Septic Patients

Circumstance Possible Pathogens

• Splenectomy Streptococcus pneumoniae, Haemophilus influenzae,
(traumatic or functional) Neisseria meningitides

• Neutropenia Gram-negatives, including Pseudomonas aeruginosa,

(<500 neutrophils/l) gram-positives, including
Staphylococcus aureus
Fungi, especially Candida species

• Hypogammaglobulinemia Streptococcus pneumoniae, Escherichia coli (e.g., CLL)

 Special Circumstances in Septic Patients (cont.)
• Burns Staphylococcus aureus (methicillin
resistant), Pseudomonas aeruginosa,
resistant gram-negatives

• AIDS Pseudomonas aeruginosa (if neutropenic),

Staphylococcus aureus, Pneumocystis
carinii (pneumonia)

• Intravascular devices Staphylococcus aureus, Staphylococcus

epidermidis

• Nosocomial infections Staphylococcus aureus (methicillin

resistant), Enterococcus species, resistant
gram-negatives, Candida species.
 General Principles in the Management of Sepsis
1. Control of infection:
- Provide appropriate antibiotics.
- Initiate surgical or invasive management of the infection if appropriate (drain any
abscesses, correct a perforated viscous, remove infected device if appropriate).

2. Optimize tissue perfusion and oxygenation:

- Optimize arterial oxygen saturation.
- Optimize fluid status (crystalloids are preferred).
- Optimize cardiac output and oxygen delivery (note that supernormal values have not
been proven to be beneficial and may be harmful).
- Transfuse blood only if patient is symptomatic and hemoglobin is <8 g/dl.
General Principles in Management of Sepsis (cont.)

3. Consider active nutritional support:

- If the patient has malnutrition or is expected to be without nutrition for more than 3 days.
- Gut feeding is preferable to parenteral feeding
4. Optimal management of organ failure:
- Use PEEP and low tidal volume in the management of ARDS complicating sepsis.
5. Prevent nosocomial complications:
- DVT prophylaxis.
- Stress ulcer prophylaxis.
- Judicious use of antibiotics to avoid nosocomial infections by resistant organisms.
 Antimicrobial Regimens for Empirical Therapy

Community acquired infection

• UTI – 3rd generation cephalosporin, quinolone, broad
spectrum penicillin.
• Other – 3rd generation Cephalosporin + metronidazole
or broad spectrum penicillin+ aminoglycoside.
Nosocomial infection – 3rd or 4th generation
Cephalosporin + aminoglycoside or
Inipenem  aminoglycoside.
Sympathomimetics to support circulation

After volume replacement and hemodynamic

monitoring:
• Dopamine
• Dometamine
• Isopartenol
• Norepinephrine
Factors Affecting the Choice of Antibiotics in Sepsis
• Antibiotic penetration into infected site
- Pyelonephritis
- Biliary infection
- Central nervous system infection
• Underlying medical problems that affect antibiotic metabolism or safety
- Renal dysfunction
- Hepatic dysfunction
- Seizure disorders
• Identification of the organism
- Enterobacter species
- Staphylococcus aureus
• Allergies
Contact Information:

Nilda J. Zapata Molina, MD

Microbiology Course Coordinator & Assistant Professor
e-mail: [email protected], or [email protected]

Office: Microbiology Department

Phone: 787-840-2575, ext. 4225 (office)

Office hours: call or e-mail to make an appointment

Microbiology Textbook:
Mandell, Douglas, and Bennett's. Principles and Practice of Infectious Diseases.
Edition 8. 2014. John E. Bennett, Raphael Dolin, Martin J. Blaser. Elsevier
Health Sciences- Editor.

Reference Book:

1.Gorbach, Infectious Diseases 3rd Ed. 2004.

3.Sherris, Medical Microbiology 5th Ed

2023