Bacteremia and Sepsis
last authored: Feb 2010, David LaPierre
last reviewed:
Introduction
Bacteremia references the presence of bacteria in the blood. In its most sinister form it is called sepsis.
Sepsis is the systemic response to infection, and is a common cause of death in hospitalized patients. Rates of sepsis have increased dramatically. It is now the 13th most common cause of death in the US, with approximately 600,000 cases per year. Disease of increasing severity includes:
- bacteremia: bacteria in bloodstrea; may be asymptomatic or transient
- sepsis syndrome: SIRS - altered organ perfusion, leading to hypoexia, decreased urine output, or altered mental status, or elevated lactate levels
- septic shock: hypotension, despite IV fluids
The Case of...
a simple case introducing clincial presentation and calling for a differential diagnosis to get students thinking.
Causes and Risk Factors
Gram negative bacteremia can begin in a number of sites, including:
- gastrointestinal system
- genitourinary system
- hepatobiliary tract
- lungs
Other sources can include:
- intravenous lines, surgical wounds, drains, pressure ulcers, and infusion fluids.
Common community-acquired organisms include:
- Escherichia coli
- Staphylococcus aureus
- Streptococcus pneumoniae
Common hospital-acquired organisms include:
- gram-negative aerobic bacilli
- coagulase negative Staph
- S aureus
- enterococci
- Candida
Risk factors, and commonly associated bacteria, include:
- neutropenia or immune dysfunction: Pseudomonas aeruginosa
- central lines: coagulase negative Staph
Pathophysiology
Disseminated intravascular coagulation occurs in 2-3% of patients.
Endotoxin leads to systemic inflammation and disaster.
Sepis is caused by the body's response to pathogenic material. Bacterial LPS is a common trigger for the inflammatory response. Other bacterial agents include teichoic acid and peptidoglycan. However, sepsis can also occur with viral, fungal, rickettsial, mycobacterial, or parasitic infections.
Pathogenic materials are taken up by macrophages, who respond by producing large amounts of pro-inflammatory cytokines such as TNF, IL-1, IL-6, IL-8, and G-CSF. Cytokines have multiple actions, inducing systemic response as well as stimulating T cells, B cells, and NK cells.
Coagulation can be induced by pro-inflammatory cytokines, tissue factor release, both through intrinsic and extrinsic pathways. Anticoagulants including proteins C and S, antithrombin III, and TFPI also become depleted, further inducing blot clot. Endotoxin stimulates membrane phospholipid production of platelet-activating factor (PAF), prostaglandins, and leukotrienes.
Resulting widespread microvascular thrombosis can act with disseminated intravascular coagulation to induce ischemia and mulitple organ failure.
Hormones such as cortisol, glucagon, and epinephrine can also be produced in response to endotoxin.
Signs and Symptoms
- history
- physical exam
History
Patients often describe abrupt onset of fever, chills, and malaise.
Physical Exam
Most patients have fever, though 15% of patients may be hypothermic (<36.4 C). Fever is less likely in the elderly and those with renal or liver failure.
Hyperventilation and changes in mental status can occur.
Signs of hypotension and shock suggest sepsis.
Signs and symptoms of sepsis are non-specific. They include:
- tachypnea and respiratory alkalosis (early sign)
- fever, chills
- hypothermia (poor prognosis)
- tachycardia
- hypotension
- mental status changes or delirium
- end-organ failure
Some organisms, especially gram-negatives, can cause ecthyma gangrenosum.
Assess underlying diseases, previous infections and antimicrobial therapy, and symptoms of local infection.
Inquire into travel, occupational exposure, or encounters with infectious sources.
Two or three sets of blood cultures have a sensitivity of 89% and 99%, respectively, in people with bacteremia.
Investigations
- lab investigations
- diagnostic imaging
Lab Investigations
The most common finding is either neutrophilia or neutropenia. A left shift may also be present. Neutropenia is common in overwhelming bacteremia, severe viral infections, alcoholics, and the elderly.
Thrombocytopenia is common; abnormal coagulation may be present.
Hyperventilation can lead to respiratory alkalosis.
Blood cultures should be drawn from three different sites before beginning antibiotic therapy. Optimally sampled cultures have a sensitivity of >95%. The false negative rate for a single culture of 5-10 ml is 30%.
Diagnostic Imaging
Differential Diagnosis
Treatments
Early recognition and initiation of treatment is of paramount importance. Patients are best served in the ICU, especially if hypotensive.
Treatment should be multi-pronged:
remove predisposing factors: stop immunosuppressants if possible
identify source: remove intravenous lines and drain abscesses as appropriate
supportive care: maintain hemodynamics and DIC as needed
antibiotics: provide antimicrobial therapy as soon as bacteremia is suspected. Use bacteriocidal, intravenous antibiotics as possible, ensuring good tissue penetration. Initially begin with coverage for both gram positive and gram negative bacteria.
corticosteroids:
biologics: blockade of TNF-alpha or IL-1 appears to show promise in reducing shock. Other options include binding endotoxin
recombinant activated protein C can reduce mortality, but leads to increased risk of bleeding.
Due to rates of false negatives, if a patient with a negative culture responds to antibiotics, and in the absence of other explanations, antibiotics should be continued.
Tissue perfusion can be maintained using crystalloid fluid recusitation, transfusion to kepp hematocrit >30%, and use of inotropes if necessary.
Antibiotics should be based on pathogen identified, local resistance patterns, and potential sites of infection. Early, broad-spectrum emperic therapy is necessary.
Glucose maintenance between 80-100 mg/dl can prevent death.
Activated protein C (drotrecogin-alpha) can reduce risk of mortality, but does increase risk of bleeding.
Consequences and Course
Patients who are otherwise healthy have a mortality rate of <5%. Those with serious conditions, such as cancer, cirrhosis, or aplastic anemia have a 15-20% chance of mortality, while patients with neutropenia or other immune dysfunction have a 40-60% mortality rate (McPhee and Papadakis, 2008).
Sepsis is more likely to be fatal with the following risk factors:
- severe disease
- delayed onset of treatment
- dangerous pathogen
- nosocomial infection
- organ failure (ARDS, anuria, DIC, bowel ischemia, coma)
The Case of...
Case #2 - a small story wrapping it all up and asking especially about management.
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