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Bloodstream infections (BSIs), which include bacteremias when the infections are bacterial and fungemias when the infections are fungal, are infections present in the
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
. Blood is normally a sterile environment, so the detection of microbes in the blood (most commonly accomplished by
blood culture A blood culture is a medical laboratory test used to detect bacteria or fungi in a person's blood. Under normal conditions, the blood does not contain microorganisms: their presence can indicate a bloodstream infection such as bacteremia or ...
s) is always abnormal. A bloodstream infection is different from
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
, which is the host response to bacteria. Bacteria can enter the bloodstream as a severe complication of
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dis ...
s (like
pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severi ...
or meningitis), during surgery (especially when involving
mucous membranes A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...
such as the gastrointestinal tract), or due to
catheters In medicine, a catheter (/ˈkæθətər/) is a thin tube made from medical grade materials serving a broad range of functions. Catheters are medical devices that can be inserted in the body to treat diseases or perform a surgical procedure. Cat ...
and other foreign bodies entering the
arteries An artery (plural arteries) () is a blood vessel in humans and most animals that takes blood away from the heart to one or more parts of the body (tissues, lungs, brain etc.). Most arteries carry oxygenated blood; the two exceptions are the pu ...
or
veins Veins are blood vessels in humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated b ...
(including during intravenous drug abuse). Transient bacteremia can result after dental procedures or brushing of teeth. Bacteremia can have several important health consequences. The
immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...
to the bacteria can cause
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
and septic shock, which has a high
mortality rate Mortality rate, or death rate, is a measure of the number of deaths (in general, or due to a specific cause) in a particular population, scaled to the size of that population, per unit of time. Mortality rate is typically expressed in units of d ...
. Bacteria can also spread via the blood to other parts of the body (which is called hematogenous spread), causing infections away from the original site of infection, such as
endocarditis Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or the ...
or
osteomyelitis Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children e.g. the femur and humerus, while the ...
. Treatment for bacteremia is with
antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...
, and prevention with antibiotic prophylaxis can be given in high risk situations.


Presentation

Bacteremia is typically transient and is quickly removed from the blood by the
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splint ...
. Bacteremia frequently evokes a response from the immune system called
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
, which consists of symptoms such as
fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
, chills, and
hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...
. Severe immune responses to bacteremia may result in septic shock and ''
multiple organ dysfunction syndrome Multiple organ dysfunction syndrome (MODS) is altered organ function in an acutely ill patient requiring medical intervention to achieve homeostasis. Although Irwin and Rippe cautioned in 2005 that the use of "multiple organ failure" or "multisy ...
'', which are potentially fatal.


Causes

Bacteria can enter the bloodstream in a number of different ways. However, for each major classification of bacteria (gram negative, gram positive, or anaerobic) there are characteristic sources or routes of entry into the bloodstream that lead to bacteremia. Causes of bacteremia can additionally be divided into healthcare-associated (acquired during the process of receiving care in a healthcare facility) or community-acquired (acquired outside of a health facility, often prior to hospitalization).


Gram positive bacteremia

Gram positive bacteria In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bacte ...
are an increasingly important cause of bacteremia. Staphylococcus, streptococcus, and enterococcus species are the most important and most common species of gram-positive bacteria that can enter the bloodstream. These bacteria are normally found on the skin or in the gastrointestinal tract. '' Staphylococcus aureus'' is the most common cause of healthcare-associated bacteremia in North and South America and is also an important cause of community-acquired bacteremia. Skin ulceration or wounds, respiratory tract infections, and IV drug use are the most important causes of community-acquired staph aureus bacteremia. In healthcare settings, intravenous catheters, urinary tract catheters, and surgical procedures are the most common causes of staph aureus bacteremia. There are many different types of streptococcal species that can cause bacteremia. ''Group A streptococcus'' (GAS) typically causes bacteremia from skin and soft tissue infections. ''Group B streptococcus'' is an important cause of bacteremia in
neonates An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...
, often immediately following birth. ''
Viridans streptococci The viridans streptococci are a large group of commensal streptococcal Gram-positive bacteria species that are α-hemolytic, producing a green coloration on blood agar plates (hence the name "viridans", from Latin "vĭrĭdis", green), although ...
'' species are normal bacterial flora of the mouth. Viridans strep can cause temporary bacteremia after eating, toothbrushing, or flossing. More severe bacteremia can occur following dental procedures or in patients receiving chemotherapy. Finally, '' Streptococcus bovis'' is a common cause of bacteremia in patients with colon cancer. ''Enterococci'' are an important cause of healthcare-associated bacteremia. These bacteria commonly live in the gastrointestinal tract and female genital tract. Intravenous catheters,
urinary tract infection A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidne ...
s and surgical wounds are all risk factors for developing bacteremia from enterococcal species. Resistant enterococcal species can cause bacteremia in patients who have had long hospital stays or frequent antibiotic use in the past (see antibiotic misuse).


Gram negative bacteremia

Gram negative bacterial species are responsible for approximately 24% of all cases of healthcare-associated bacteremia and 45% of all cases of community-acquired bacteremia. In general, gram negative bacteria enter the bloodstream from infections in the respiratory tract,
genitourinary tract The genitourinary system, or urogenital system, are the organs of the reproductive system and the urinary system. These are grouped together because of their proximity to each other, their common embryological origin and the use of common pathw ...
, gastrointestinal tract, or
hepatobiliary system The biliary tract, (biliary tree or biliary system) refers to the liver, gallbladder and bile ducts, and how they work together to make, store and secrete bile. Bile consists of water, electrolytes, bile acids, cholesterol, phospholipids and ...
. Gram-negative bacteremia occurs more frequently in elderly populations (65 years or older) and is associated with higher
morbidity A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
and mortality in this population. ''E.coli'' is the most common cause of community-acquired bacteremia accounting for approximately 75% of cases. E.coli bacteremia is usually the result of a urinary tract infection. Other organisms that can cause community-acquired bacteremia include ''
Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. aerug ...
'', ''
Klebsiella pneumoniae ''Klebsiella pneumoniae'' is a Gram-negative, non-motile, encapsulated, lactose- fermenting, facultative anaerobic, rod-shaped bacterium. It appears as a mucoid lactose fermenter on MacConkey agar. Although found in the normal flora of the mo ...
'', and '' Proteus mirabilis''. '' Salmonella'' infection, despite mainly only resulting in gastroenteritis in the developed world, is a common cause of bacteremia in Africa. It principally affects children who lack antibodies to Salmonella and HIV+ patients of all ages. Among healthcare-associated cases of bacteremia, gram negative organisms are an important cause of bacteremia in the ICU. Catheters in the veins, arteries, or urinary tract can all create a way for gram negative bacteria to enter the bloodstream. Surgical procedures of the genitourinary tract, intestinal tract, or hepatobiliary tract can also lead to gram negative bacteremia. ''Pseudomonas'' and ''Enterobacter'' species are the most important causes of gram negative bacteremia in the ICU.


Bacteremia risk factors

There are several risk factors that increase the likelihood of developing bacteremia from any type of bacteria. These include: *
HIV infection Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ma ...
*
Diabetes Mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
* Chronic
hemodialysis Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatinin ...
* Solid
organ transplant Organ transplantation is a medical procedure in which an organ (anatomy), organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organ ...
*
Stem cell transplant Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce ...
* Treatment with
glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every verteb ...
s * Liver failure *
Asplenia Asplenia refers to the absence of normal spleen function and is associated with some serious infection risks. Hyposplenism is used to describe reduced ('hypo-') splenic functioning, but not as severely affected as with asplenism. ''Functional'' a ...


Mechanism

Bacteremia can travel through the blood stream to distant sites in the body and cause infection (hematogenous spread). Hematogenous spread of bacteria is part of the pathophysiology of certain infections of the heart (
endocarditis Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or the ...
), structures around the brain ( meningitis), and tuberculosis of the spine ( Pott's disease). Hematogenous spread of bacteria is responsible for many bone infections (
osteomyelitis Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children e.g. the femur and humerus, while the ...
). Prosthetic cardiac implants (for example artificial heart valves) are especially vulnerable to infection from bacteremia. Prior to widespread use of vaccines, occult bacteremia was an important consideration in febrile children that appeared otherwise well.


Diagnosis

Bacteremia is most commonly diagnosed by
blood culture A blood culture is a medical laboratory test used to detect bacteria or fungi in a person's blood. Under normal conditions, the blood does not contain microorganisms: their presence can indicate a bloodstream infection such as bacteremia or ...
, in which a sample of blood drawn from the vein by needle puncture is allowed to incubate with a
medium Medium may refer to: Science and technology Aviation *Medium bomber, a class of war plane *Tecma Medium, a French hang glider design Communication * Media (communication), tools used to store and deliver information or data * Medium of ...
that promotes bacterial growth. If bacteria are present in the bloodstream at the time the sample is obtained, the bacteria will multiply and can thereby be detected. Any bacteria that incidentally find their way to the culture medium will also multiply. For example, if the skin is not adequately cleaned before needle puncture, contamination of the blood sample with normal bacteria that live on the surface of the skin can occur. For this reason, blood cultures must be drawn with great attention to sterile process. The presence of certain bacteria in the blood culture, such as S''taphylococcus aureus'', ''
Streptococcus pneumoniae ''Streptococcus pneumoniae'', or pneumococcus, is a Gram-positive, spherical bacteria, alpha-hemolytic (under aerobic conditions) or beta-hemolytic (under anaerobic conditions), aerotolerant anaerobic member of the genus Streptococcus. They ar ...
'', and ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
'' almost never represent a contamination of the sample. On the other hand, contamination may be more highly suspected if organisms like '' Staphylococcus epidermidis'' or ''
Cutibacterium acnes ''Cutibacterium acnes'' (formerly ''Propionibacterium acnes'') is the relatively slow-growing, typically aerotolerant anaerobic, gram-positive bacterium (rod) linked to the skin condition of acne; it can also cause chronic blepharitis and endopht ...
'' grow in the blood culture. Two blood cultures drawn from separate sites of the body are often sufficient to diagnose bacteremia. Two out of two cultures growing the same type of bacteria usually represents a real bacteremia, particularly if the organism that grows is not a common contaminant. One out of two positive cultures will usually prompt a repeat set of blood cultures to be drawn to confirm whether a contaminant or a real bacteremia is present. The patient's skin is typically cleaned with an alcohol-based product prior to drawing blood to prevent contamination. Blood cultures may be repeated at intervals to determine if persistent — rather than transient — bacteremia is present. Prior to drawing blood cultures, a thorough patient history should be taken with particular regard to presence of both fevers and chills, other focal signs of infection such as in the skin or soft tissue, a state of immunosuppression, or any recent invasive procedures. Ultrasound of the heart is recommended in all those with bacteremia due to '' Staphylococcus aureus'' to rule out infectious endocarditis.


Definition

Bacteremia is the presence of
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...
in the bloodstream that are alive and capable of reproducing. It is a type of bloodstream infection. Bacteremia is defined as either a primary or secondary process. In primary bacteremia, bacteria have been directly introduced into the bloodstream.
Injection drug use Drug injection is a method of introducing a drug into the bloodstream via a hollow hypodermic needle, which is pierced through the skin into the body (usually intravenously, but also at an intramuscular or subcutaneous location). Intravenous t ...
may lead to primary bacteremia. In the hospital setting, use of blood vessel
catheter In medicine, a catheter (/ˈkæθətər/) is a thin tubing (material), tube made from medical grade materials serving a broad range of functions. Catheters are medical devices that can be inserted in the body to treat diseases or perform a surgi ...
s contaminated with bacteria may also lead to primary bacteremia. Secondary bacteremia occurs when bacteria have entered the body at another site, such as the cuts in the skin, or the mucous membranes of the lungs (
respiratory The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies gre ...
tract), mouth or intestines (
gastrointestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
tract), bladder (urinary tract), or genitals. Bacteria that have infected the body at these sites may then spread into the lymphatic system and gain access to the bloodstream, where further spread can occur. Bacteremia may also be defined by the timing of bacteria presence in the bloodstream: transient, intermittent, or persistent. In transient bacteremia, bacteria are present in the bloodstream for minutes to a few hours before being cleared from the body, and the result is typically harmless in healthy people. This can occur after manipulation of parts of the body normally colonized by bacteria, such as the mucosal surfaces of the mouth during tooth brushing, flossing, or dental procedures, or instrumentation of the bladder or colon. Intermittent bacteremia is characterized by periodic seeding of the same bacteria into the bloodstream by an existing infection elsewhere in the body, such as an abscess,
pneumonia Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severi ...
, or bone infection, followed by clearing of that bacteria from the bloodstream. This cycle will often repeat until the existing infection is successfully treated. Persistent bacteremia is characterized by the continuous presence of bacteria in the bloodstream. It is usually the result of an infected heart valve, a central line-associated bloodstream infection (CLABSI), an infected blood clot (suppurative thrombophlebitis), or an infected blood vessel graft. Persistent bacteremia can also occur as part of the infection process of
typhoid fever Typhoid fever, also known as typhoid, is a disease caused by '' Salmonella'' serotype Typhi bacteria. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often there is a gradual onset of a high fever over several ...
,
brucellosis Brucellosis is a highly contagious zoonosis caused by ingestion of unpasteurized milk or undercooked meat from infected animals, or close contact with their secretions. It is also known as undulant fever, Malta fever, and Mediterranean fever. The ...
, and bacterial meningitis. Left untreated, conditions causing persistent bacteremia can be potentially fatal. Bacteremia is clinically distinct from
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
, which is a condition where the blood stream infection is associated with an inflammatory response from the body, often causing abnormalities in
body temperature Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when the surrounding temperature is very different. A thermoconforming organism, by contrast, simply adopts the surrounding temperature ...
, heart rate, breathing rate, blood pressure, and
white blood cell count A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cells and p ...
.


Treatment

The presence of bacteria in the blood almost always requires treatment with
antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...
. This is because there are high
mortality rate Mortality rate, or death rate, is a measure of the number of deaths (in general, or due to a specific cause) in a particular population, scaled to the size of that population, per unit of time. Mortality rate is typically expressed in units of d ...
s from progression to
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
if antibiotics are delayed. The treatment of bacteremia should begin with empiric antibiotic coverage. Any patient presenting with signs or symptoms of bacteremia or a positive blood culture should be started on intravenous antibiotics. The choice of antibiotic is determined by the most likely source of infection and by the characteristic organisms that typically cause that infection. Other important considerations include the patient's history of antibiotic use, the severity of the presenting symptoms, and any allergies to antibiotics. Empiric antibiotics should be narrowed, preferably to a single antibiotic, once the blood culture returns with a particular bacteria that has been isolated.


Gram positive bacteremia

The Infectious Disease Society of America (IDSA) recommends treating uncomplicated methicillin resistant staph aureus (MRSA) bacteremia with a 14-day course of intravenous vancomycin. Uncomplicated bacteremia is defined as having positive blood cultures for MRSA, but having no evidence of endocarditis, no implanted
prostheses In medicine, a prosthesis (plural: prostheses; from grc, πρόσθεσις, prósthesis, addition, application, attachment), or a prosthetic implant, is an artificial device that replaces a missing body part, which may be lost through trau ...
, negative blood cultures after 2–4 days of treatment, and signs of clinical improvement after 72 hrs. The antibiotic treatment of choice for streptococcal and enteroccal infections differs by species. However, it is important to look at the antibiotic resistance pattern for each species from the blood culture to better treat infections caused by resistant organisms.


Gram negative bacteremia

The treatment of gram negative bacteremia is also highly dependent on the causative organism. Empiric antibiotic therapy should be guided by the most likely source of infection and the patient's past exposure to healthcare facilities. In particular, a recent history of exposure to a healthcare setting may necessitate the need for antibiotics with ''
pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. aerug ...
'' coverage or broader coverage for resistant organisms. Extended generation cephalosporins such as ceftriaxone or
beta lactam A beta-lactam (β-lactam) ring is a four-membered lactam. A ''lactam'' is a cyclic amide, and ''beta''-lactams are named so because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl. The simplest β-lactam possible is ...
/ beta lactamase inhibitor antibiotics such as piperacillin-tazobactam are frequently used for the treatment of gram negative bacteremia.


Catheter-associated infections

For healthcare-associated bacteremia due to intravenous catheters, the IDSA has published guidelines for catheter removal. Short term catheters (in place <14 days) should be removed if bacteremia is caused by any gram negative bacteria, staph aureus, enterococci or mycobacteria. Long term catheters (>14 days) should be removed if the patient is developing signs or symptoms of sepsis or endocarditis, or if blood cultures remain positive for more than 72 hours.


See also

* Antibiotic prophylaxis * Dental antibiotic prophylaxis * Fungemia *
Viremia Viremia is a medical condition where viruses enter the bloodstream and hence have access to the rest of the body. It is similar to ''bacteremia'', a condition where bacteria enter the bloodstream. The name comes from combining the word "virus" wit ...


References


External links


Bacteremia at Medscape eMedicine
{{Infectious blood tests Bacterial diseases Abnormal clinical and laboratory findings for blood Sepsis