Bacterial Infections of the Circulatory System

Question 1

What are the most common sources of bacteremia (bacteria in the blood)?

Answer 1

UTI, respiratory tract infections, and skin/soft tissue infections

Question 2

Potential consequences of bacteremia

Answer 2

Transient and benign

Sepsis and septic shock (including toxic shock)

Endocarditis

Question 3

Sepsis

Answer 3

Systemic inflammatory response syndrome (SIRS) that has a proven or suspected microbial etiology
-Note that bacteremia is NOT required, the microbe may invade the bloodstream or release substances (toxins) into the bloodstream

Question 4

SIRS

Answer 4

Two or more of the following conditions:

• Fever or hypothermia
• Tachypnea
• Tachycardia
• Abnormal WBC count: leukocytosis (> 12,000/uL), or leukopenia (<4,000/uL) or 10% bands

Question 5

Severe Sepsis

Answer 5

Sepsis with one or more signs of organ dysfunction

e.g. reduced urine output, mental status changes, systemic acidosis, hypoxemia

Question 6

Septic Shock

Answer 6

Severe Sepsis + Hypotension (systolic BP < 90 mm Hg)

Question 7

Refractory Septic Shock

Answer 7

Septic shock that lasts for > 1 hour and does not respond to fluid and pharmacologic treatment

Question 8

Multiorgan Failure

Answer 8

Dysfunction of >1 organ [(may include kidneys, lungs and liver, as well as development of DISSEMINATED INTRAVASCULAR COAGULATION (DIC)]
-Associated with a high fatality rate

Question 9

Two key points of Sepsis and Septic Shock

Answer 9

Bacterial cause > Fungal cause

Bacteremia is NOT required

Question 10

Sepsis and Septic Shock (Epidemiology and other Risk Factors)

Answer 10

Mortality rates increase with INCREASING AGE

Risk Factors:
-Indwelling catheters, mechanical devices, immunosuppression

Question 11

Sepsis and Septic Shock (Pathophysiology: Gram Negative vs Gram Positive)

Answer 11

Gram Negative Bacteria: induce septic shock in the bloodstream via ENDOTOXIN (LPS) and LIPID A

Gram Positive Bacteria: induce septic shock via PEPTIDOGLYCAN or EXOTOXINS (e.g. TSST-1 of Staph)

Polysaccharides of C. albicans, teichoic acid of Staph., capsule of S. pneumoniae can also initiate septic shock

Question 12

Mechanism of LPS/endotoxin causes of inflammation

Answer 12

1) Binds to CD14 and TLR4 on phagocytes/antigen presenting cells
2) Activates immune system

3) Causes inflammation/can cause SEPTIC SHOCK
- TNF, IL-1, IL-6

Question 13

Staphylococcus aureus

Answer 13

Catalase Positive
Coagulase Positive
Gram Positive Cocci arranged in CLUSTERS
Normal flora
Person-to-Person spread through direct contact or exposure to contaminated fomites (e.g. bed linenes or clothing)
***Facultative Intracellular***

Causes: skin infections, SEPSIS, ENDOCARDITIS, pneumonia, osteomyelitis, septic arthritis, purulent meningitis, food poisoning, TOXIC SHOCK

Question 14

Staphylococcus aureus (TSST-1)

Answer 14

22 kDa heat- and proteolysis-resistant EXOTOXIN

TSST-1 can penetrate the mucosal barrier and is responsible for systemic effects

• SUPERANTIGEN*
• Stimulates T-cell activation and release of cytokines

Question 15

Gram Positive Cocci: Staphylococcus vs Streptococcus

Answer 15

Staphylococcus:
Catalase Positive
CLUSTERS

Streptococcus:
Catalase Negative
PAIRS or CHAINS

Question 16

Streptococcal Toxic Shock Syndrome

Answer 16

Pain, fevers, chills, malaise, nausea, vomiting, diarrhea, SHOCK, and ORGAN FAILURE (e.g. kidney, lungs, liver, heart)

In contrast with staphylococcal disease, most patients with streptococcal disease are BACTEREMIC and many have NECROTIZING FASCIITIS

Production of PYROGENIC EXOTOXINS, particularly SpeA and SpeC, are responsible for clinical manifestations

Question 17

Streptococcal Pyrogenic Exotoxins (SpeA, SpeB, SpeC)

Answer 17

Superantigens

Stimulate T cells by binding to the class II major histocompatibility complex in the Vbeta of the T-cell receptor

Activated T cells release cytokines that mediate shock and tissue injury

Question 18

Sepsis and Septic Shock (Diagnosis)

Answer 18

Symptoms and…

• Blood cultures (Antibiotic susceptibility testing)
• Septic shock –> Blood cultures positive in 40-70% of patients
• > 95% of cases of INFECTIVE ENDOCARDITIS will yield (+) blood cultures
• Bacteremic patients without endocarditis:
  1) One culture = 80-90% positive
  2) Two cultures = 90-95% positive
  3) Three cultures = 99% positive

NOT USEFUL to collect blood cultures from patienst on antibiotic therapy

Question 19

Sepsis and Septic Shock (Treatment)

Answer 19

Hypotension: IV fluids

Hypoxia: ventilator therapy

DIC: transfusion of fresh-frozen plasma and platelets to stop bleeding OR heparin to prevent thrombi formation

Bacterial infection: antibiotics

Question 20

Sepsis and Septic Shock (Antimicrobial Therapy)

Answer 20

Unknown bacterium: Vancomycin and Gentamicin to cover both Gram Positive and Negative infections

Examples of Local Sites of Infections (knowing which organisms normally infect the site is helpful):

1) Staph aureus and Strep pyogenes: Generalized erythroderma in a septic patient suggests Toxic Shock Syndrome
2) Neisseria meningitidis: Sepsis accompanying petechiae in skin
3) Rocky Mountain Spotted fever (Rickettsia rickettsii): Petechial skin lesions in person who has been bitten by a tick in an endemic area
4) Vibrio vulnificus: Hemorrhagic skin lesions in a septic person who recently has eaten raw oysters

Question 21

Where do most infective Bacterial Endocarditis infections take place?

Answer 21

Most infections occur on natural or prosthetic CARDIAC VALVES (primarily mitral or aortic)

Question 22

Acute vs Subacute Endocarditis (Clinical Features)

Answer 22

Acute:

• High fever (103-105 F), acutely ill
• Rapid damage to cardiac structures
• Untreated –> progresses to death within weeks
• Staph aureus is most common cause*

Subacute:

• Low grade fever
• Night sweats
• Weight loss
• Vague constitutional complaints
• Slower damage to heart
• Progresses to death over weeks to months
• Viridans Strep (less virulent) are most common cause*

Question 23

Endocarditis (Common Clinical Features)

Answer 23

New/unchanging heart murmur
Splenomegaly
Various skin lesions (petechiae, splinter hemorrhages, Osler's nodes, Janeway lesions)
Retinal lesions (Roth Spots)

Question 24

Splinter Hemorrhages

Answer 24

Red, linear streaks in the nail bed (seen in Bacterial Endocarditis)

Question 25

Roth Spots

Answer 25

Retinal hemorrhages (seen in Bacterial Endocarditis)

Question 26

Janeway Lesions

Answer 26

Painless lesions on palms or soles of feet (seen in Bacterial Endocarditis)

Question 27

Osler Node

Answer 27

Painful subcutaneous nodules in the pads of the digits (seen in Bacterial Endocarditis)

Question 28

Common Etiologic Agents in Infective Endocarditis

Answer 28

Viridans streptococci (several species): 30-40%

Staphylococcus aureus: 15-40%

Question 29

Streptococcus

Answer 29

Gram Positive Cocci in CHAINS or PAIRS
Aerobic and Facultative Anaerobic (i.e. can switch to anaerobic respiration)
Culture typically on blood agar to determine hemolysis
Catalase NEGATIVE (unlike Staph)

Question 30

Streptocci (Lancefield Groups)

Answer 30

A: S. pyogenes (Beta)
B: S. agalactiae (Beta)
D: Enterococcus (alpha, Beta, or gamma)

S. pneumoniae (alpha)
S. mutans (alpha or gamma)
S. mitis (alpha)

Question 31

Viridans Streptococci

Answer 31

• Large group of COMMENSAL (normal flora) streptococcal bacteria
• Associated with Subacute Bacterial Endocarditis (S. mitis and S. salivarius)
• Viridans are alpha-hemolytic or gamma-hemolytic
• Found in NORMAL ORAL FLORA

SBE: occurs over weeks to months, treat with PENICILLIN (+ aminoglycosidase)
-Vancomycin for resistant strains

Question 32

Viridans Streptococci (Optochin Testing)

Answer 32

RESISTANT to optochin

Question 33

Bacterial Endocarditis (Risk Factors)

Answer 33

1) Susceptible Cardiovascular Substrate

2) Source of Bacteremia (Prosthetic Valves, IV drug users, HIV, Immunosuppressed, Rheumatic Fever)

Question 34

Bacterial Endocarditis (Epidemiology)

Answer 34

More common in MEN
Average age has increased to 70 YEARS OLD
Incidence in IV drug users is 3 per 1000
Incidence in HIV-positive IV drug users is 13.8 per 1000

Seen in immunosuppressed patients with central venous catheters or hemodialysis patients

Prosthetic valve endocarditis = 10 to 15% of endocarditis cases

Question 35

Bacterial Endocarditis (Pathophysiology)

Answer 35

• Cardiac abnormalities create sites for attachment
• Blood contacts subendothelial factors, which promotes coagulation
• Pathogens bind and activate monocyte, cytokine, and tissue factor production, ENLARGING THE VEGETATION on the heart valves
• Vegetations damage heart valves and will lead to death if not treated
• Septic emboli can occur (most commonly in the BRAIN, SPLEEN, or KIDNEY)

Vegetations = platelets, fibrin, bacteria, and inflammatory cells

Question 36

Bacterial Endocarditis (Diagnosis and Treatment)

Answer 36

History and Physical Exam

Major Criteria:

• Positive blood culture w/ typical organism
• Evidence of endocardial involvement (positive echocardiogram, valvular regurgitation)

Minor Criteria:

• Predisposition (e.g. heart condition or IV drug use)
• Fever
• Vascular phenomena (e.g. emboli, Janeway lesions)
• Immunologic phenomena (e.g. Osler nodes, Roth spots)
• Microbiologic evidence (e.g. positive blood culture)

Definite Endocarditis: 2 major, 1 major and 3 minor, or 5 minor

Treatment:
-Aggressive antimicrobial therapy, as well as Prolonged antimicrobial therapy (usually longer than 4 weeks)