1. Presentation

Bacteremia is typically transient and is quickly removed from the blood by the immune system.^[1]

Bacteremia frequently evokes a response from the immune system called Sepsis, which consists of symptoms such as fever, chills, and hypotension.^[2] Severe immune responses to bacteremia may result in septic shock and multiple organ dysfunction syndrome,^[2] which are potentially fatal.

2. 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).

2.1. Gram pPositive bBacteremia

Gram positive bacteria are an increasingly important cause of bacteremia.^[3] 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.^[4] 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.^[5]

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.^[6] Group B streptococcus is an important cause of bacteremia in neonates, often immediately following birth.^[7] Viridans streptococci species are normal bacterial flora of the mouth. Viridans strep can cause temporary bacteremia after eating, toothbrushing, or flossing.^[7] More severe bacteremia can occur following dental procedures or in patients receiving chemotherapy.^[7] Finally, streptococcus bovis is a common cause of bacteremia in patients with colon cancer.^[8]

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 infections and surgical wounds are all risk factors for developing bacteremia from enterococcal species.^[9] Resistant enterococcal species can cause bacteremia in patients who have had long hospital stays or frequent antibiotic use in the past.^[10]

2.2. Gram nNegative bBacteremia

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.^[11][12] In general, gram negative bacteria enter the bloodstream from infections in the respiratory tract, genitourinary tract, gastrointestinal tract, or hepatobiliary system. Gram-negative bacteremia occurs more frequently in elderly populations (65 years or older) and is associated with higher morbidity and mortality in this population.^[13]

E.coli is the most common cause of community-acquired bacteremia accounting for approximately 75% of cases.^[14] E.coli bacteremia is usually the result of a urinary tract infection. Other organisms that can cause community-acquired bacteremia include Pseudomonas aeruginosa, Klebsiella pneumoniae, and Proteus mirabilis. Salmonella infection, despite mainly only resulting in gastroenteritis in the developed world, is a common cause of bacteremia in Africa.^[15] 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.^[16] Catheters in the veins, arteries, or urinary tract can all create a way for gram negative bacteria to enter the bloodstream.^[6] Surgical procedures of the genitourinary tract, intestinal tract, or hepatobiliary tract can also lead to gram negative bacteremia.^[6] Pseudomonas and Enterobacter species are the most important causes of gram negative bacteremia in the ICU.^[16]

2.3. Bacteremia rRisk fFactors

There are several risk factors that increase the likelihood of developing bacteremia from any type of bacteria.^[3][17] These include:

• HIV infection
• Diabetes Mellitus
• Chronic hemodialysis
• Solid organ transplant
• Stem cell transplant
• Treatment with glucocorticoids
• Liver failure
• Asplenia^[18]

3. 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), structures around the brain (meningitis), and tuberculosis of the spine (Pott's disease). Hematogenous spread of bacteria is responsible for many bone infections (osteomyelitis).^[19]

Prosthetic cardiac implants (for example artificial heart valves) are especially vulnerable to infection from bacteremia.^[20]

Prior to widespread use of vaccines, occult bacteremia was an important consideration in febrile children that appeared otherwise well.^[21]

4. Diagnosis

Bacteremia is most commonly diagnosed by blood culture, in which a sample of blood drawn from the vein by needle puncture is allowed to incubate with a medium that promotes bacterial growth.^[22] 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.^[23] 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 Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli 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 grow in the blood culture.

Two blood cultures drawn from separate sites of the body are often sufficient to diagnose bacteremia.^[23] 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.^[23] 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.^[23] The patient's skin is typically cleaned with an alcohol-based product prior to drawing blood to prevent contamination.^[23] Blood cultures may be repeated at intervals to determine if persistent — rather than transient — bacteremia is present.^[23]

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.^[22]

Ultrasound of the heart is recommended in all those with bacteremia due to Staphylococcus aureus to rule out infectious endocarditis.^[24]

4.1. Definition

Bacteremia is the presence of bacteria in the bloodstream that are alive and capable of reproducing. It is a type of bloodstream infection.^[25] Bacteremia is defined as either a primary or secondary process. In primary bacteremia, bacteria have been directly introduced into the bloodstream.^[26] Injection drug use may lead to primary bacteremia. In the hospital setting, use of blood vessel catheters contaminated with bacteria may also lead to primary bacteremia.^[27] 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 tract), mouth or intestines (gastrointestinal tract), bladder (urinary tract), or genitals.^[28] 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.^[29]

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.^[30] This can occur after manipulation of parts of the body normally colonized by bacteria, such as the mucosal surfaces of the mouth during teeth brushing, flossing, or dental procedures,^[31] or instrumentation of the bladder or colon.^[25] 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, or bone infection, followed by clearing of that bacteria from the bloodstream. This cycle will often repeat until the existing infection is successfully treated.^[25] Persistent bacteremia is characterized by the continuous presence of bacteria in the bloodstream.^[25] 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.^[25] Persistent bacteremia can also occur as part of the infection process of typhoid fever, brucellosis, and bacterial meningitis. Left untreated, conditions causing persistent bacteremia can be potentially fatal.^[7]

Bacteremia is clinically distinct from sepsis, which is a condition where the blood stream infection is associated with an inflammatory response from the body, often causing abnormalities in body temperature, heart rate, breathing rate, blood pressure, and white blood cell count.^[32]

5. Treatment

The presence of bacteria in the blood almost always requires treatment with antibiotics. This is because there are high mortality rates from progression to sepsis if antibiotics are delayed.^[16]

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.^[13] 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 past history of antibiotic use, the severity of the presenting symptoms, and any allergies to antibiotics.^[33] Empiric antibiotics should be narrowed, preferably to a single antibiotic, once the blood culture returns with a particular bacteria that has been isolated.^[33]

5.1. Gram pPositive bBacteremia

The Infectious Disease Society of America (IDSA) recommends treating uncomplicated methicillin resistant staph aureus (MRSA) bacteremia with a 14-day course of intravenous vancomycin.^[34] Uncomplicated bacteremia is defined as having positive blood cultures for MRSA, but having no evidence of endocarditis, no implanted prostheses, negative blood cultures after 2–4 days of treatment, and signs of clinical improvement after 72 hrs.^[34]

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.^[3]

5.2. Gram nNegative bBacteremia

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.^[35] In particular, a recent history of exposure to a healthcare setting may necessitate the need for antibiotics with pseudomonas aeruginosa coverage or broader coverage for resistant organisms.^[35] Extended generation cephalosporins such as ceftriaxone or beta lactam/beta lactamase inhibitor antibiotics such as piperacillin-tazobactam are frequently used for the treatment of gram negative bacteremia.^[35]

5.3. Catheter-aAssociated iInfections

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.^[36] 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.^[36]