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Detection of bacteremia: Blood cultures and other diagnostic tests

Detection of bacteremia: Blood cultures and other diagnostic tests
Author:
Gary V Doern, MD
Section Editor:
Denis Spelman, MBBS, FRACP, FRCPA, MPH
Deputy Editor:
Elinor L Baron, MD, DTMH
Literature review current through: Aug 2021. | This topic last updated: Apr 28, 2021.

INTRODUCTION — The diagnosis of bacteremia is based on blood culture results [1-5]. Issues related to indications, collection technique, number of cultures, volume of blood, timing of collection, and interpretation of results will be reviewed here.

The management of bacteremia is discussed separately. (See "Gram-negative bacillary bacteremia in adults" and "Clinical approach to Staphylococcus aureus bacteremia in adults" and "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of bacteremia" and "Staphylococcus aureus bacteremia in children: Management and outcome".)

GENERAL CONSIDERATIONS

Indications for blood cultures — Routine blood cultures are warranted from patients with syndromes associated with a high likelihood of bacteremia (table 1). These include [2,6-8]:

Sepsis (see "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis")

Endovascular infection:

Infective endocarditis (IE) (see "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis" and "Prosthetic valve endocarditis: Epidemiology, clinical manifestations, and diagnosis")

Implantable cardioverter defibrillator (ICD)/pacemaker infection (see "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis")

Intravascular catheter infection (see "Intravascular non-hemodialysis catheter-related infection: Clinical manifestations and diagnosis")

Vascular graft infection

Septic thrombophlebitis (see "Catheter-related septic thrombophlebitis")

Vertebral osteomyelitis and/or discitis (see "Vertebral osteomyelitis and discitis in adults")

Meningitis (see "Clinical features and diagnosis of acute bacterial meningitis in adults")

Epidural abscess (see "Intracranial epidural abscess" and "Spinal epidural abscess")

Septic arthritis (native joint, nontraumatic) (see "Septic arthritis in adults")

Ventriculoatrial shunt infection (see "Infections of cerebrospinal fluid shunts and other devices")

For patients with syndromes associated with moderate likelihood of bacteremia (table 1) (these include pyelonephritis, cholangitis, pyogenic liver abscess, severe community-acquired pneumonia [CAP], ventilator-associated pneumonia, ventriculoperitoneal shunt infection, and cellulitis in the setting of immunosuppression), blood cultures are warranted when cultures from the primary source of infection are not available prior to initiation of antibiotics. In addition, blood cultures are warranted for patients with moderate likelihood of bacteremia who are at risk of endovascular infection (these include patients with an ICD/pacemaker, vascular graft, prosthetic valve, history of IE, heart transplant recipient with valvulopathy, unrepaired congenital heart disease, repaired congenital heart disease with residual shunt or valvular regurgitation, or repaired congenital heart disease within the first six months postrepair).

For patients with syndromes associated with low likelihood of bacteremia (table 1) (these include nonsevere cellulitis, cystitis, prostatitis, nonsevere CAP, nonsevere healthcare acquired pneumonia, postoperative fever within 48 hours of surgery), routine blood cultures are not necessary. For patients with isolated fever and/or leukocytosis, the decision to obtain blood cultures should be guided by careful history and physical examination to assess the potential benefit added by blood cultures.

Blood cultures are often collected in patients with fever and leukocytosis or leukopenia; however, bacteremia may be present in the setting of normothermia and/or a normal white blood cell count [6-8].

The above approach is supported by a review including 50 studies and more than 28,000 blood cultures from non-neutropenic adults, infectious disease syndromes were categorized into low, moderate, and high pretest probability of bacteremia (table 1) [2]. Similarly, in another review including 35 studies and more than 4500 episodes of bacteremia in immunocompetent adults, the likelihood of bacteremia was highest in the setting of sepsis, septic shock, or acute bacterial meningitis [6]. The likelihood of bacteremia was moderate in the setting of pyelonephritis, and low in the setting of community-onset fever requiring hospitalization, CAP, ambulatory outpatients, and cellulitis.

Collecting blood cultures — Prior to initiation of antimicrobial therapy, at least two sets of blood cultures taken from separate venipuncture sites should be obtained; administration of antimicrobials prior to blood culture collection may lead to false-negative results [9]. A blood culture set should consist of both an aerobic and anaerobic blood culture bottle whenever possible.

Site selection — When possible, blood cultures should be obtained via venipuncture, given the lower likelihood of contamination compared with blood cultures collected through vascular catheters (even if obtained at the time of catheter insertion). In one meta-analysis including nine studies and more than 13,000 blood cultures, the likelihood of contamination was higher for blood cultures collected through an intravascular catheter than blood cultures collected by venipuncture (odds ratio 2.69, 95% CI 2.03-3.57) [10].

Preferred venipuncture sites include the antecubital veins or other upper extremity blood vessels; these sites are less likely to be associated with blood culture contamination than femoral vessels or sites affected by dermatologic disease [4]. Venous and arterial blood cultures have comparable yield [11,12].

Skin antisepsis and collection technique — When collecting blood for culture, care must be exercised to avoid contamination with normal skin flora. This is important because skin flora can cause true infection, particularly intravascular infections (eg, IE, infected mycotic aneurisms, vascular graft infections, and septic thrombophlebitis), and it can be difficult to distinguish between true-positive and false-positive blood culture results. In addition, false-positive blood cultures are associated with unnecessary antibiotic use and follow-up laboratory testing [1].

Principles of technique for blood culture collection include:

Ideally, blood cultures should be obtained by phlebotomists with training in blood culture collection [1,13].

A tourniquet should be applied and the vein should be palpated before disinfection of the venipuncture site.

The venipuncture site should be disinfected with 2% alcoholic chlorhexidine or an alcoholic iodine-containing preparation; tincture of iodine or povidone iodine preparations that do not contain alcohol should not be used [1,14,15].

In one meta-analysis including six randomized trials evaluating the efficacy of skin disinfectants for prevention of blood culture contamination, use of alcoholic chlorhexidine was associated with a lower blood culture contamination rate than povidone iodine (<2 percent versus >3 percent) [15].

The septa of blood culture bottles should be disinfected with 70% isopropyl alcohol [16].

Both the skin disinfectant and the alcohol used to disinfect the blood culture bottles should be allowed to dry for 30 to 60 seconds prior to inoculation.

If further vein palpation is necessary after skin preparation, a sterile glove should be worn [17,18].

Issues related to blood volume are discussed below. (See 'Blood volume' below.)

Blood should be inoculated directly into culture bottles during the venipuncture procedure, rather than into tubes sent to the laboratory for subsequent transfer into the culture bottles.

If blood is collected with a butterfly needle apparatus, the aerobic bottle should be inoculated first, since air may be trapped in the cannula.

If blood is collected with a syringe and needle, and sufficient volume has been obtained to inoculate both an aerobic and anaerobic blood culture bottle (see 'Blood volume' below), the anaerobic bottle should be inoculated first, without changing the needle between bottles; this is because the final aliquot of blood typically contains free air. If the volume is insufficient to inoculate both bottles, all of the specimen should be inoculated into the aerobic bottle.

As noted above, blood cultures should be obtained via venipuncture whenever possible. If blood for culture must be obtained through an intravenous catheter, the line port should be carefully disinfected with 2% alcoholic chlorhexidine or an alcoholic iodine-containing preparation prior to specimen collection. In the setting of a multilumen catheter, blood for culture should be obtained through all catheter hubs [19,20]. In addition, a second set of blood cultures should be obtained via peripheral venipuncture if possible. The blood culture bottles should be labeled to reflect the collection sites.

Use of an initial specimen diversion device has been proposed as a tool for reducing rates of blood culture contamination [21-24]. Such devices sequester the initial 1.5 to 2 mL of blood collected, with transfer of the remaining aliquot of blood specimen into blood culture bottles. This approach is based on the observation that most blood culture contaminants emanate from the skin plug through which the collection needle traverses during phlebotomy. These bacteria are thus sequestered within the initial aliquot of blood; diversion of the initial portion of blood thus reduces the likelihood of blood culture contamination. In three investigations, blood culture contamination rates of less than 1 percent were achieved without compromising the yield of true positive cultures [21-23].

For circumstances in which intravascular catheter-related infection is suspected, the approach to blood culture collection and diagnostic criteria are discussed in detail separately. (See "Intravascular non-hemodialysis catheter-related infection: Clinical manifestations and diagnosis", section on 'Blood cultures'.)

Blood volume — Drawing the correct volume of blood is the most important factor in maximizing the yield of true pathogens [3-5]:

For adults, some data suggest that the optimal blood volume for each culture may be 30 mL bottle [25]; however, in practice, 20 mL is most often collected, with inoculation of 10 mL into an aerobic bottle and 10 mL into an anaerobic bottle. If ≤10 mL of blood is obtained, the anaerobic bottle should not be inoculated. Rather, all of the specimen should be inoculated into the aerobic culture bottle.

Bacteremia in adults is generally intermittent and frequently low grade, with colony count of ≤1 colony forming units (CFU)/mL. Therefore, blood culture yield is influenced by the volume of blood cultured [26-29]. In one study including more than 516,000 blood cultures, the positivity rate was higher for standard volume blood cultures than for low volume blood cultures (mean 8.6 mL versus 2.3 mL; 8.8 versus 7.4 percent), with no change in the contamination rate [29].

For children, blood culture volumes should be guided by body weight, as summarized in the table (table 2) [26,30-34]. Among children, the magnitude of bacteremia is generally greater than in adults, often >100 CFU/mL [3].

Number of blood culture sets — A blood culture set, as noted above, usually consists of one aerobic bottle and one anaerobic bottle. At least two, preferably three, blood culture sets should be obtained [1,3-5]. In studies evaluating the yield of four or more blood cultures, the cumulative yield of true pathogens increased with the number of cultures collected (one culture; 73 to 80 percent, two cultures: 80 to 89 percent, three cultures: 95 to 98 percent, and four cultures: 99 to 100 percent) [35,36].

A total of two blood culture sets is usually adequate when continuous bacteremia is suspected and the pretest probability of bacteremia is high (as in patients with suspected IE who have not received prior antimicrobial therapy). (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Blood cultures'.)

A total of three blood culture sets is appropriate for circumstances in which bacteremia due to a pathogen not likely to be a contaminant is anticipated (as in intra-abdominal sepsis or pneumonia) and when the pretest probability of bacteremia is low to moderate. The first two blood cultures, obtained with separate venipunctures, may be obtained in sequence, with collection of the third blood culture four to six hours later.

A total of four blood culture sets are rarely needed; collection may be considered when the pretest probability of bacteremia is high and the anticipated pathogen is likely to be a common contaminant, such coagulase-negative staphylococci. Clinical examples include prosthetic valve endocarditis or endovascular infections due to infected devices, such as pacemakers or grafts. As many as four blood culture sets may also be necessary to diagnose endocarditis in patients who have received antimicrobial therapy in the preceding two weeks.

Additional blood cultures are rarely useful in patients who have been evaluated by the above criteria unless there has been a significant change in the patient's condition or a new focus of infection is suspected. Furthermore, the likelihood of obtaining a false-positive test (ie, a positive blood culture due to a contaminant) increases as more blood cultures are obtained.

Single blood cultures should always be avoided as they lack sensitivity and preclude the ability to distinguish true bacteremia from contaminants such as most species of coagulase-negative staphylococci, most species of Corynebacterium spp and related genera, Bacillus spp (other than Bacillus anthracis), Micrococcus spp, and Cutibacterium (formerly Propionibacterium) acnes and related species [37].

In pediatric patients, it may be advisable to inoculate two aerobic bottles (rather than one aerobic and one anaerobic bottle), since anaerobic bacteria are less common than aerobes as causes of bacteremia in children. Furthermore, in children, it may not be possible to obtain sufficient blood to inoculate more than a single blood culture bottle; in such cases, all of the blood should be inoculated into an aerobic bottle.

Timing of collection — Blood cultures should be obtained prior to initiating antimicrobial therapy. In one study including 325 adults with severe manifestations of sepsis, blood culture collection prior to initiation of antimicrobial therapy was associated with positive results in 31 percent of cases [9]. Among these patients, additional blood cultures collected after initiation of antimicrobial therapy were positive in only 19 percent of cases.

The optimal time for collection of blood cultures is just before onset of fever [38]; since it is not possible to anticipate this, it is common practice to draw blood cultures when fever is detected. However, fever at the time of blood culture collection is neither a sensitive nor specific predictor of bacteremia. In one retrospective study evaluating the timing of blood culture collection in relation to temperature elevations among more than 1400 patients with bacteremia and fungemia, no relationship was observed between timing of specimen collection and likelihood of a positive blood culture [39].

Laboratory blood culture systems — Most modern clinical microbiology laboratories worldwide employ automated continuous monitoring blood culture systems for detecting bacteremia. Such systems are based on instrument detection of carbon dioxide in blood culture bottles as an indication of growth [4]. Continuous monitoring blood culture systems permit detection of positive blood cultures 1 to 3 days faster than older manual systems (which were based on visual inspection, blind Gram stains, and blind subcultures of blood culture bottles).

Specialized blood culture techniques may be helpful in some settings:

For patients receiving antimicrobial therapy at the time blood cultures are obtained, use of blood culture bottles containing media with resins, charcoal, lytic agents, or other neutralizing substances to inhibit the activity of antimicrobial agents may useful for increasing blood culture yield [4]. Many institutions use such media routinely. When that is not the case, such media can be employed selectively for blood cultures from patients receiving antimicrobial therapy at the time blood cultures are obtained.

In the setting of a clinical suspicion for bloodstream infection due to fungi or Bartonella, blood culture yield may be increased by use of the Isolator lysis-centrifugation blood culture system. With this system, blood is aseptically collected into a vacutainer tube containing the lytic agent, saponin, and an anticoagulant, sodium polyanetholsulfonate. Saponin lyses the cellular material present in the blood specimen. Upon receipt in the laboratory, the tube is centrifuged, and the supernatant, free of lysed cellular debris, is subcultured onto appropriate solid media which is then incubated for recovery of target pathogens [4].

Detection of Mycobacteria species in blood is best accomplished by use of specialized blood culture media in conjunction with a continuous monitoring blood culture system.

Duration of incubation — In most instrument-based continuous-monitoring blood culture systems, a five-day incubation period is sufficient for detecting the majority of pathogens. Most episodes of clinically significant bacteremia are detected within 48 hours; detection of fungemia may require an additional 24 to 48 hours of incubation [40]. In general, modern automated blood culture detection systems allow detection of common as well as fastidious pathogens such as members of the HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) group, within five days of incubation [41,42].

An extended incubation period may be required for recovery of certain fastidious organisms [3,4]. For suspected Legionella or Francisella, up to 7 days is reasonable. For suspected fungal infection, some laboratories hold cultures for 14 days; for suspected Bartonella or Brucella, some laboratories hold cultures for 21 days. For detection of mycobacteria, blood cultures should be incubated for 28 days. (See 'Laboratory blood culture systems' above.)

Organisms that are difficult to cultivate may be better diagnosed by molecular and/or immunologic methods.

Organism identification — Conventional methods for organism identification utilize Gram stain morphology and biochemical reactions to establish an organism's identification. Biochemical identification tests, usually performed on instruments, typically provide results 16 to 24 hours following recovery of organisms in blood culture bottles. This approach to organism identification is based on detection of pH changes, enzymatic reactions, indicators of metabolic activity in the presence of a variety of carbon sources, and detection of volatile or nonvolatile acids [43].

Molecular methods such as nucleic acid amplification, matrix-assisted laser desorption ionization-time of flight mass spectrometry, nucleic acid sequencing, and peptide nucleic acid fluorescence in situ hybridization can be used for the rapid identification of organisms recovered from blood culture bottles [28,39,40,44,45]. In some circumstances, molecular methods can be used for rapid identification directly in blood culture broth, obviating the need for subculture. In addition, molecular methods have the potential for the direct assessment of antimicrobial resistance determinants [46-48]. Numerous studies have demonstrated the value of these rapid methods in the diagnosis and management of patients with bloodstream infections [49-51].

Antimicrobial susceptibility testing — Antimicrobial susceptibility testing should be performed on clinically significant blood culture isolates using reference standard methods. The antimicrobial agents tested should be determined based on the organism recovered, the nature of the infection and the formulary availability of specific agents. When possible, tests for minimum inhibitory concentrations (MICs) should be performed and MIC results reported along with category interpretations.

In addition, when available, direct detection of antimicrobial resistance determinants using molecular methods may be performed. This is particularly useful in instances of bacteremia due to methicillin-resistant Staphylococcus aureus or multidrug-resistant gram-negative bacilli including carbapenem-resistant Enterobacteriaceae. In some circumstances, use of direct molecular detection may provide susceptibility information to facilitate antibiotic selection sooner than would be possible with reference standard methods.

APPROACH TO POSITIVE BLOOD CULTURES

Patterns of bacteremia — Bacteremia may be intermittent or continuous.

Intermittent bacteremia refers to the presence of bacteria in the blood for defined periods of time, followed by non-bacteremic intervals; it typically reflects infection outside of the bloodstream, with seeding of the blood via the lymphatics. Causes of intermittent bacteremia include infections involving the skin, soft tissue, bone, joints, lungs, gastrointestinal tract, genitourinary tract, and central nervous system. In addition, intermittent bacteremia can occur following manipulation of infected tissues (such as surgical abscess drainage) or following instrumentation of mucosal surfaces (such as dental work or procedures involving the respiratory, genitourinary, or gastrointestinal tracts).

Continuous bacteremia usually reflects the presence of a persistent endovascular focus of infection such as endocarditis, suppurative thrombophlebitis, an infected aneurysm, or infection of an intravascular foreign body such as an intravascular catheter or vascular graft. In addition, continuous bacteremia occurs during the first two weeks of infection due to typhoid fever and brucellosis; in these conditions, relatively low numbers of bacteria are present in blood.

Interpretation of findings

Common organisms — The interpretation of blood culture results should be guided by the organism(s) identified.

The presence of the following organisms in blood cultures should always be considered clinically significant [1,52,53]:

S. aureus

Streptococcus pneumoniae

Group A Streptococcus

Enterobacteriaceae

Haemophilus influenzae

Pseudomonas aeruginosa

Bacteroidaceae

Candida species

The presence of the following organisms in blood cultures may be clinically significant or may reflect contamination; clinical correlation is required [1,52,53]:

Enterococci

Viridans streptococci

In one study of positive blood cultures, enterococci (93 isolates) and viridans streptococci (71 isolates) represented true pathogens in 70 and 38 percent of cases, respectively [53]. Clostridium spp may also fall into this category.

The following organisms are usually found to be blood culture contaminants. In some circumstances, however, these bacteria may be clinically significant; thus, clinical correlation is required to establish significance [1,52,53]:

Coagulase negative staphylococci

Corynebacterium species (also referred to as 'diphtheroids')

C. (formerly Propionibacterium) acnes

Bacillus species

Micrococcus species

Assessing clinical significance — Information pertinent to assessing the significance of a blood culture result includes [4,54-58]:

The number of positive cultures and the total number of cultures obtained

The organism(s) recovered

The length of time for blood cultures to become positive

The site of culture collection (eg, venipuncture versus catheter)

The likelihood of bacteremia based on clinical assessment (including white blood cell count, the presence of fever, hemodynamic status, etc.)

Blood culture contamination rates should be tracked routinely by clinical microbiology laboratories. Through use of appropriate specimen collection techniques, contamination rates of <1 percent are achievable. For rates >1 percent, specimen collection technique should be reviewed and educational efforts undertaken [1,58]. (See 'Collecting blood cultures' above.)

False positive due to laboratory instrument — In rare cases, continuous monitoring blood culture instruments signal a positive culture but no organisms are seen on Gram stain of blood culture broth, direct tests for microorganisms are negative, and subcultures do not yield an isolate. This may be attributable to the blood culture instrument; such results may be observed in the setting of leukocytosis or when vials are overfilled [59]. Such results should be communicated to clinicians with appropriate explanation and blood cultures should be repeated.

In the specific setting of pneumococcal bacteremia, the organism may grow in blood culture broth (with a positive culture signaled by the instrument), however, as a result of autolysis, Gram stains of blood culture broth may be confusing and viable organisms may not be recovered on subculture. In such cases, the organism may be identified by an antigen detection procedure or a molecular identification test applied directly to blood culture broth.

Follow-up blood cultures — In patients noted to have true bacteremia, follow-up blood cultures (within one to two days of initiating antimicrobial therapy) should be obtained in the following circumstances [2]:

Bacteremia due to S. aureus (see "Clinical approach to Staphylococcus aureus bacteremia in adults")

Bacteremia due to Staphylococcus lugdunensis (see "Staphylococcus lugdunensis")

Presence of known or suspected endovascular infection:

Infective endocarditis (IE)

Implantable cardioverter defibrillator (ICD)/pacemaker infection

Intravascular catheter infection

Vascular graft infection

Septic thrombophlebitis

Bacteremia in patient at risk for endovascular infection (these include patients with an ICD/pacemaker, vascular graft, prosthetic valve, history of IE, heart transplant recipient with valvulopathy, unrepaired congenital heart disease, repaired congenital heart disease with residual shunt or valvular regurgitation, or repaired congenital heart disease within the first six months postrepair)

Presence of fever, leukocytosis, or other signs of infection more than 72 hours after initiation of antimicrobial therapy

Known or suspected site of infection with limited antimicrobial penetration, such as an abscess or joint space infection

Presumed source of infection in the abdomen or central nervous system

Presence of pathogens that are known or suspected to be multiply resistant to standard antimicrobial agents

An unknown source for initial bacteremia

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Sepsis in adults (The Basics)")

SUMMARY

Indications for blood culture collection depend on the clinical presentation (table 1) (see 'Indications for blood cultures' above):

For patients with syndromes associated with a high likelihood of bacteremia, routine blood cultures are warranted. These include sepsis, endovascular infection, vertebral osteomyelitis and/or discitis, meningitis, epidural abscess, septic arthritis, and ventriculoatrial shunt infection.

For patients with syndromes associated with moderate likelihood of bacteremia (table 1), blood cultures are warranted when cultures from the primary source of infection are not available prior to initiation of antibiotics, and/or for patients at risk of endovascular infection (these include patients with an implantable cardioverter defibrillator /pacemaker, vascular graft, prosthetic valve, history of infective endocarditis, heart transplant recipient with valvulopathy, unrepaired congenital heart disease, repaired congenital heart disease with residual shunt or valvular regurgitation, or repaired congenital heart disease within the first six months postrepair).

For patients with syndromes associated with low likelihood of bacteremia (table 1), routine blood cultures are not necessary. For patients with isolated fever and/or leukocytosis, the decision to obtain blood cultures should be guided by careful history and physical examination to assess the potential benefit added by blood cultures.

Prior to initiation of antimicrobial therapy in adults, at least two, preferably three, sets of blood cultures taken from separate venipuncture sites should be obtained. The technique, number of cultures, and volume of blood are more important factors for detection of bacteremia than timing of culture collection. (See 'Collecting blood cultures' above.)

Care should be taken to avoid introducing contaminants into blood culture bottles at the time of collection. This includes effective disinfection of the venipuncture site and avoiding blood culture collection through existing intravenous lines. For adults, the optimal blood volume may be 30 mL; however, in practice, 20 mL is often collected, with inoculation of 10 mL into an aerobic bottle and 10 mL into an anaerobic bottle. For children, blood volumes are summarized in the table (table 2). (See 'Collecting blood cultures' above.)

In most instrument-based continuous-monitoring blood culture systems, a five-day incubation period is sufficient for detecting the majority of pathogens. Most episodes of clinically significant bacteremia are detected within 48 hours; detection of fungemia may require an additional 24 to 48 hours of incubation. An extended incubation period may be required for recovery of certain fastidious organisms. (See 'Duration of incubation' above.)

Conventional methods for organism identification utilize Gram stain morphology and biochemical reactions to establish an organism's identification. Biochemical identification tests (usually performed on instruments) typically provide results 16 to 24 hours following recovery of organisms in blood culture bottles. Molecular methods can be used for the rapid identification of organisms recovered from blood culture bottles. (See 'Organism identification' above.)

Bacteremia may be intermittent or continuous. Intermittent bacteremia refers to the presence of bacteria in the blood for defined periods of time, followed by non-bacteremic intervals; it typically reflects infection outside of the bloodstream. Continuous bacteremia usually reflects the presence of a persistent endovascular focus of infection. (See 'Patterns of bacteremia' above.)

The interpretation of blood culture results should be guided by the organism(s) identified (see 'Interpretation of findings' above):

The presence of the following organisms in blood cultures should always be considered clinically significant: Staphylococcus aureus, Streptococcus pneumoniae, Group A Streptococcus, Enterobacteriaceae, Haemophilus influenzae, Pseudomonas aeruginosa, Bacteroidaceae, and Candida species.

Blood culture isolates for which it may be difficult to distinguish between clinical significance and contamination include enterococci, viridans streptococci, coagulase-negative staphylococci, Corynebacterium species, Cutibacterium (formerly Propionibacterium) acnes, Bacillus species, and Micrococcus species. Clinical correlation is required to establish significance. (See 'Assessing clinical significance' above.)

Indications for follow-up blood cultures are summarized above. (See 'Follow-up blood cultures' above.)

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  27. Ilstrup DM, Washington JA 2nd. The importance of volume of blood cultured in the detection of bacteremia and fungemia. Diagn Microbiol Infect Dis 1983; 1:107.
  28. Mermel LA, Maki DG. Detection of bacteremia in adults: consequences of culturing an inadequate volume of blood. Ann Intern Med 1993; 119:270.
  29. Khare R, Kothari T, Castagnaro J, et al. Active Monitoring and Feedback to Improve Blood Culture Fill Volumes and Positivity Across a Large Integrated Health System. Clin Infect Dis 2020; 70:262.
  30. Schelonka RL, Chai MK, Yoder BA, et al. Volume of blood required to detect common neonatal pathogens. J Pediatr 1996; 129:275.
  31. Isaacman DJ, Karasic RB, Reynolds EA, Kost SI. Effect of number of blood cultures and volume of blood on detection of bacteremia in children. J Pediatr 1996; 128:190.
  32. Brown DR, Kutler D, Rai B, et al. Bacterial concentration and blood volume required for a positive blood culture. J Perinatol 1995; 15:157.
  33. Kaditis AG, O'Marcaigh AS, Rhodes KH, et al. Yield of positive blood cultures in pediatric oncology patients by a new method of blood culture collection. Pediatr Infect Dis J 1996; 15:615.
  34. Miller JM, Binnicker MJ, Campbell S, et al. A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases Society of America and the American Society for Microbiology. Clin Infect Dis 2018; 67:e1.
  35. Lee A, Mirrett S, Reller LB, Weinstein MP. Detection of bloodstream infections in adults: how many blood cultures are needed? J Clin Microbiol 2007; 45:3546.
  36. Cockerill FR 3rd, Wilson JW, Vetter EA, et al. Optimal testing parameters for blood cultures. Clin Infect Dis 2004; 38:1724.
  37. Tafuro P, Colbourn D, Gurevich I, et al. Comparison of blood cultures obtained simultaneously by venepuncture and from vascular lines. J Hosp Infect 1986; 7:283.
  38. BENNETT IL Jr, BEESON PB. Bacteremia: a consideration of some experimental and clinical aspects. Yale J Biol Med 1954; 26:241.
  39. Riedel S, Bourbeau P, Swartz B, et al. Timing of specimen collection for blood cultures from febrile patients with bacteremia. J Clin Microbiol 2008; 46:1381.
  40. Doern GV, Brueggemann AB, Dunne WM, et al. Four-day incubation period for blood culture bottles processed with the Difco ESP blood culture system. J Clin Microbiol 1997; 35:1290.
  41. Petti CA, Bhally HS, Weinstein MP, et al. Utility of extended blood culture incubation for isolation of Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella organisms: a retrospective multicenter evaluation. J Clin Microbiol 2006; 44:257.
  42. Baron EJ, Scott JD, Tompkins LS. Prolonged incubation and extensive subculturing do not increase recovery of clinically significant microorganisms from standard automated blood cultures. Clin Infect Dis 2005; 41:1677.
  43. Karen C. Carroll, Melvin P. Weinstein. Manual and Automated Systems for Detection and Identification of Microorganisms. In: Manual of Clinical Microbiology, 9th, Patrick R. Murray (Ed), ASM Press, Washington, D.C. 2007. p.192.
  44. Krisher KK, Whyburn DR, Koepnick FE. Comparison of the BacT/Alert pediatric blood culture system, Pedi-BacT, with conventional culture using the 20-milliliter Becton-Dickinson supplemented peptone broth tube. J Clin Microbiol 1993; 31:793.
  45. Kennedy GT, Barr JG, Goldsmith C. Detection of bacteraemia by the continuously monitoring BacT/Alert system. J Clin Pathol 1995; 48:912.
  46. Banerjee R, Özenci V, Patel R. Individualized Approaches Are Needed for Optimized Blood Cultures. Clin Infect Dis 2016; 63:1332.
  47. Riedel S, Carroll KC. Early Identification and Treatment of Pathogens in Sepsis: Molecular Diagnostics and Antibiotic Choice. Clin Chest Med 2016; 37:191.
  48. Messacar K, Hurst AL, Child J, et al. Clinical Impact and Provider Acceptability of Real-Time Antimicrobial Stewardship Decision Support for Rapid Diagnostics in Children With Positive Blood Culture Results. J Pediatric Infect Dis Soc 2017; 6:267.
  49. Box MJ, Sullivan EL, Ortwine KN, et al. Outcomes of rapid identification for gram-positive bacteremia in combination with antibiotic stewardship at a community-based hospital system. Pharmacotherapy 2015; 35:269.
  50. Pliakos EE, Andreatos N, Shehadeh F, et al. The Cost-Effectiveness of Rapid Diagnostic Testing for the Diagnosis of Bloodstream Infections with or without Antimicrobial Stewardship. Clin Microbiol Rev 2018; 31.
  51. Lamy B, Dargère S, Arendrup MC, et al. How to Optimize the Use of Blood Cultures for the Diagnosis of Bloodstream Infections? A State-of-the Art. Front Microbiol 2016; 7:697.
  52. Pien BC, Sundaram P, Raoof N, et al. The clinical and prognostic importance of positive blood cultures in adults. Am J Med 2010; 123:819.
  53. Weinstein MP, Towns ML, Quartey SM, et al. The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin Infect Dis 1997; 24:584.
  54. Mirrett S, Weinstein MP, Reimer LG, et al. Relevance of the number of positive bottles in determining clinical significance of coagulase-negative staphylococci in blood cultures. J Clin Microbiol 2001; 39:3279.
  55. Weinstein MP. Current blood culture methods and systems: clinical concepts, technology, and interpretation of results. Clin Infect Dis 1996; 23:40.
  56. Strand CL, Wajsbort RR, Sturmann K. Effect of iodophor vs iodine tincture skin preparation on blood culture contamination rate. JAMA 1993; 269:1004.
  57. Beekmann SE, Diekema DJ, Doern GV. Determining the clinical significance of coagulase-negative staphylococci isolated from blood cultures. Infect Control Hosp Epidemiol 2005; 26:559.
  58. Richter SS, Beekmann SE, Croco JL, et al. Minimizing the workup of blood culture contaminants: implementation and evaluation of a laboratory-based algorithm. J Clin Microbiol 2002; 40:2437.
  59. Pitsch A, Ergani A, Vasse M, Farfour E. False-positive of blood culture instrument: leukocytosis, overfilled vials or defective position? Ann Biol Clin (Paris) 2019; 77:665.
Topic 2133 Version 39.0

References

1 : Practical Guidance for Clinical Microbiology Laboratories: A Comprehensive Update on the Problem of Blood Culture Contamination and a Discussion of Methods for Addressing the Problem

2 : Does This Patient Need Blood Cultures? A Scoping Review of Indications for Blood Cultures in Adult Nonneutropenic Inpatients.

3 : Blood cultures: key elements for best practices and future directions.

4 : Laboratory diagnosis of bacteremia and fungemia.

5 : Multidisciplinary team review of best practices for collection and handling of blood cultures to determine effective interventions for increasing the yield of true-positive bacteremias, reducing contamination, and eliminating false-positive central line-associated bloodstream infections.

6 : Does this adult patient with suspected bacteremia require blood cultures?

7 : Inadequacy of temperature and white blood cell count in predicting bacteremia in patients with suspected infection.

8 : Occult Staphylococcus aureus bacteremia in adult emergency department patients: rare but important.

9 : Blood Culture Results Before and After Antimicrobial Administration in Patients With Severe Manifestations of Sepsis: A Diagnostic Study.

10 : Effectiveness of practices to reduce blood culture contamination: a Laboratory Medicine Best Practices systematic review and meta-analysis.

11 : The use of the arterial line as a source for blood cultures.

12 : Blood Cultures Drawn From Arterial Catheters Are Reliable for the Detection of Bloodstream Infection in Critically Ill Children.

13 : Educational intervention as an effective step for reducing blood culture contamination: a prospective cohort study.

14 : Educational intervention as an effective step for reducing blood culture contamination: a prospective cohort study.

15 : Skin antiseptics in venous puncture-site disinfection for prevention of blood culture contamination: systematic review with meta-analysis.

16 : Skin antiseptics in venous puncture-site disinfection for prevention of blood culture contamination: systematic review with meta-analysis.

17 : Effect of routine sterile gloving on contamination rates in blood culture: a cluster randomized trial.

18 : Reducing blood culture contamination in community hospital emergency departments: a multicenter evaluation of a quality improvement intervention.

19 : How many lumens should be cultured in the conservative diagnosis of catheter-related bloodstream infections?

20 : In situ diagnosis of central venous catheter-related bloodstream infection without peripheral blood culture.

21 : Reduction in Blood Culture Contamination Through Use of Initial Specimen Diversion Device.

22 : Effectiveness of a Novel Specimen Collection System in Reducing Blood Culture Contamination Rates.

23 : Reducing blood culture contamination using an initial specimen diversion device.

24 : Modification of Blood Test Draw Order to Reduce Blood Culture Contamination: A Randomized Clinical Trial.

25 : Optimized pathogen detection with 30- compared to 20-milliliter blood culture draws.

26 : How reliable is a negative blood culture result? Volume of blood submitted for culture in routine practice in a children's hospital.

27 : The importance of volume of blood cultured in the detection of bacteremia and fungemia.

28 : Detection of bacteremia in adults: consequences of culturing an inadequate volume of blood.

29 : Active Monitoring and Feedback to Improve Blood Culture Fill Volumes and Positivity Across a Large Integrated Health System.

30 : Volume of blood required to detect common neonatal pathogens.

31 : Effect of number of blood cultures and volume of blood on detection of bacteremia in children.

32 : Bacterial concentration and blood volume required for a positive blood culture.

33 : Yield of positive blood cultures in pediatric oncology patients by a new method of blood culture collection.

34 : A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases Society of America and the American Society for Microbiology.

35 : Detection of bloodstream infections in adults: how many blood cultures are needed?

36 : Optimal testing parameters for blood cultures.

37 : Comparison of blood cultures obtained simultaneously by venepuncture and from vascular lines.

38 : Bacteremia: a consideration of some experimental and clinical aspects.

39 : Timing of specimen collection for blood cultures from febrile patients with bacteremia.

40 : Four-day incubation period for blood culture bottles processed with the Difco ESP blood culture system.

41 : Utility of extended blood culture incubation for isolation of Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella organisms: a retrospective multicenter evaluation.

42 : Prolonged incubation and extensive subculturing do not increase recovery of clinically significant microorganisms from standard automated blood cultures.

43 : Prolonged incubation and extensive subculturing do not increase recovery of clinically significant microorganisms from standard automated blood cultures.

44 : Comparison of the BacT/Alert pediatric blood culture system, Pedi-BacT, with conventional culture using the 20-milliliter Becton-Dickinson supplemented peptone broth tube.

45 : Detection of bacteraemia by the continuously monitoring BacT/Alert system.

46 : Individualized Approaches Are Needed for Optimized Blood Cultures.

47 : Early Identification and Treatment of Pathogens in Sepsis: Molecular Diagnostics and Antibiotic Choice.

48 : Clinical Impact and Provider Acceptability of Real-Time Antimicrobial Stewardship Decision Support for Rapid Diagnostics in Children With Positive Blood Culture Results.

49 : Outcomes of rapid identification for gram-positive bacteremia in combination with antibiotic stewardship at a community-based hospital system.

50 : The Cost-Effectiveness of Rapid Diagnostic Testing for the Diagnosis of Bloodstream Infections with or without Antimicrobial Stewardship.

51 : How to Optimize the Use of Blood Cultures for the Diagnosis of Bloodstream Infections? A State-of-the Art.

52 : The clinical and prognostic importance of positive blood cultures in adults.

53 : The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults.

54 : Relevance of the number of positive bottles in determining clinical significance of coagulase-negative staphylococci in blood cultures.

55 : Current blood culture methods and systems: clinical concepts, technology, and interpretation of results.

56 : Effect of iodophor vs iodine tincture skin preparation on blood culture contamination rate.

57 : Determining the clinical significance of coagulase-negative staphylococci isolated from blood cultures.

58 : Minimizing the workup of blood culture contaminants: implementation and evaluation of a laboratory-based algorithm.

59 : False-positive of blood culture instrument: leukocytosis, overfilled vials or defective position?