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Repeating blood cultures after initial bacteremia: When and how often?
Author(s)
Ammara Mushtaq, MD
Bryce X. Bredell, MS
Ayman O. Soubani, MD

Repeat cultures are indicated in specific scenarios, but for most patients, frequent and indiscriminate repetition after an initial positive culture is unnecessary and may be associated with excessive use of resources. Prospective studies and practice guidelines are needed to help further define the indications.

See related editorial

THE TENDENCY TO REPEAT CULTURES

Current literature lacks strong evidence for repeating previously positive blood cultures collected appropriately—ie, 10 mL of blood for aerobic culture and 10 mL for anaerobic culture from 2 different sites, and a positive result from both sets. However, because of the risk of serious complications of bacteremia, particularly in critically ill patients, many clinicians order multiple, repeated sets of blood cultures.

Tabriz et al1 found that one-third of hospitalized patients got repeat cultures after an initial set, regardless of the result of the first set. Most (83.4%) of those cultures yielded no growth, 9.1% grew the same pathogen, and 5.0% were contaminated. Finding a new pathogen was rare, occurring in only 2.5% of repeated cultures.

Wiggers et al2 reported an even higher number of repeat cultures ordered for patients who had an initially positive culture: 38.9%.2 And in another study,3 half of the patients received more than 2 consecutive cultures.

Drawbacks

Unrestrained ordering of repeat blood cultures can increase the risk of a false-positive result, leading to more cultures, echocardiography, other imaging tests, and unnecessary antimicrobial therapy, all of which puts patients at risk of adverse effects of treatment and missed alternative diagnoses and increases the length and cost of hospitalization.4

Advantages

On the other hand, repeat blood cultures  may increase the diagnostic yield for conditions such as infective endocarditis and may have implications for the duration of antibiotic therapy.1 The duration of therapy for bacteremia is usually determined from the last negative culture; hence, documenting clearance of bacteremia can determine a precise end-date for antibiotic therapy.

Bacteremia due to Staphylococcus aureus and to endovascular and epidural sources has been found to be independently associated with persistent bacteremia, detected in 6.6% of 1,801 index cases of bacteremia in a retrospective cohort study.2 An endovascular source (adjusted odds ratio [OR] 7.66, 95% confidence interval [CI] 2.30–25.48), an epidural source (adjusted OR 26.99, 95% CI, 1.91–391.08), and S aureus bacteremia (adjusted OR 4.49, 95% CI 1.88–10.73) were independently associated with persistent bacteremia. Escherichia coli (5.1%, P =  .006), viridans group streptococci (1.7%, P =  .035), and beta-hemolytic streptococci (0%, P = .028) were associated with a lower likelihood of persistent bacteremia. Patients with persistent bacteremia were less likely to have achieved source control within 48 hours of the index event (29.7% vs 52.5%, P < .001).2

 

 

WHEN REPEATING CULTURES IS APPROPRIATE

Repeating blood cultures after an initial positive result is superfluous, except in certain situations.

Suspected endovascular infection

Patients with endocarditis, thrombophlebitis, an indwelling device for epidural access, or a cardiovascular implantable electronic device should have repeat cultures after an initial positive culture. Implantable electronic device infection is suspected in the following cases: sustained positive blood culture (> 24 hours); relapsing bacteremia despite a course of appropriate antibiotic therapy; presence of an implantable cardioverter defibrillator; presence of a prosthetic cardiac valve; and an episode of bacteremia within 3 months of device placement.5

S aureus bacteremia

Repeat blood culture is warranted for S aureus bacteremia regardless of methicillin susceptibility.1 But persistent methicillin-resistant S aureus (MRSA) bacteremia changes the management of these patients.6 For example, the source of infection should be identified, followed by debridement or drainage, and then either high-dose or combination antimicrobial therapy.6 Infective endocarditis from persistent MRSA bacteremia is an indication for surgery.6

Persistent S aureus bacteremia may change the duration of therapy, as the common practice is to continue treating uncomplicated gram-positive bacteremia for 14 days from the date of the first negative culture. Infection leading to infective endocarditis increases the duration of antibiotic therapy to at least 4 weeks.

Candidemia

Candidemia is an absolute indication for repeat blood culture.7 Patients with persistent candidemia should undergo imaging of the genitourinary tract, liver, and spleen as part of the evaluation for a deep-tissue source of infection.7 Also, if the patient is initially treated with an echinocandin, therapy can be transitioned to fluconazole if the isolate is azole-susceptible, the patient’s condition is clinically stable, and repeat cultures are negative.7 Therefore, repeating cultures has therapeutic implications.

Confirming response to therapy

In patients with infective endocarditis or other endovascular infection caused by S aureus, Enterococcus species, or gram-negative bacilli,1 repeat blood culture should be done to confirm therapeutic response. Patients with infective endocarditis whose condition is stable can be discharged to receive outpatient parenteral antibiotic therapy. However, patients with uncontrolled heart failure, systemic emboli, abscess, persistent fever, or persistently positive cultures are not candidates for outpatient therapy and require repeat cultures.8

Multidrug-resistant gram-negative bacilli

Bacteremia due to multidrug-resistant gram-negative bacilli requires repeat blood cultures to document clearance of bacteremia and to ensure the efficacy of antibiotics, as these organisms pose a higher risk of treatment failure, and combination synergistic regimens may be needed if bacteremia does not clear.

Febrile neutropenia

Blood cultures are important in the management of febrile neutropenia. In a study by Rosenblum et al,9 repeat cultures were positive in 10.9% of patients with febrile neutropenia after an initial negative culture, but many of those organisms were of low pathogenicity, and a significant proportion were coagulase-negative staphylococci.10 Another study showed that the frequency of detecting new pathogens by repeat culture in recurrent febrile neutropenia was higher than that in persistent febrile neutropenia (8% vs 2%) (P = .0491); a history of recent bacteremia was identified as a significant predictor of positive culture in recurrent febrile neutropenia.11

Persistent or new infection

Persistence of fever, leukocytosis, or other signs of infection 72 hours after appropriate antibiotic therapy is started requires follow-up blood cultures.

New episode of sepsis. A new episode of sepsis should be confirmed12 using the systemic inflammatory response syndrome criteria, the newer definition of Sepsis-related Organ Failure Assessment (SOFA) in the intensive-care unit, or the quick SOFA in general units. If the patient develops new signs of sepsis after response to treatment for initial bacteremia, repeat blood cultures should be considered.

Central line-associated bloodstream infection requires repeat cultures.13 Persistence of bacteremia in this type of infection extends the duration of therapy, as most clinicians determine treatment duration from the last negative culture. Persistent bacteremia also influences the decision to salvage or remove the catheter. Microbiologic clearance of bacteremia on blood culture can also guide the time of reinsertion if the catheter was removed.

Concern for an unresolved focus of infection such as abscess, joint infection, or retained catheter is an indication for repeat blood cultures.

Bacteremia of unknown source. In clinical practice, we encounter scenarios in which blood cultures are positive but no source can be identified. In those situations, it is important to repeat blood cultures to document clearance. If bacteremia persists, we need to continue searching for the source.

 

 

WHEN ROUTINELY REPEATING CULTURES IS NOT INDICATED

Repeat blood cultures are not routinely indicated in patients with streptococcal bacteremia, uncomplicated gram-negative bacteremia, and bacteremia associated with localized infection such as cellulitis, community-acquired pneumonia, or pyelonephritis.2,4 A study of patients with gram-negative bacteremia found that 17 repeated cultures needed to be drawn to yield 1 positive culture.14

Isolated fever or leukocytosis does not accurately predict bacteremia.4 A study that excluded neutropenic and intensive-care patients reported none of the initially negative cultures to be positive when repeated.15

Ordering repeat cultures in response to persistent fever is a common practice, even though fever is typical in the first 72 hours of antibiotic therapy. Such cultures rarely if ever reveal new pathogens, and results can be predicted based on cultures before the start of antibiotics.15 For patients on antibiotics, physicians should therefore wait for results of the preantibiotic cultures rather than order new cultures in response to persistent fever.15

WOULD WE MISS PERSISTENT BACTEREMIA?

In theory, not repeating blood cultures could miss persistent bacteremia, but this is unlikely if the concerns discussed above are considered. Further, persistent bacteremia would result in clinical signs and symptoms that should prompt repeat cultures.

FREQUENCY OF REPEAT BLOOD CULTURES

There are no evidence-based guidelines for the frequency of repeating cultures. The Infectious Diseases Society of America recommends repeating blood cultures 2 to 4 days after the index positive culture in the case of multidrug-resistant S aureus bacteremia, and every day or every other day for candidemia.6,7,9

A study evaluating the practice patterns of repeating cultures after an initial bacteremia showed that 34.7% were done within 24 hours and 44.7% were done in 2 to 4 days.1 There is no evidence that repeating blood cultures daily is necessary in these patients. As a general rule, it should be done 48 to 72 hours after a positive culture.

References
  1. Tabriz MS, Riederer K, Baran J Jr, Khatib R. Repeating blood cultures during hospital stay: practice pattern at a teaching hospital and a proposal for guidelines. Clin Microbiol Infect 2004; 10(7):624–627. doi:10.1111/j.1469-0691.2004.00893.x
  2. Wiggers JB, Xiong W, Daneman N. Sending repeat cultures: is there a role in the management of bacteremic episodes? (SCRIBE study). BMC Infect Dis 2016; 16:286. doi:10.1186/s12879-016-1622-z
  3. Kang CK, Kim ES, Song KH, et al. Can a routine follow-up blood culture be justified in Klebsiella pneumoniae bacteremia? A retrospective case–control study. BMC Infect Dis 2013; 13:365. doi:10.1186/1471-2334-13-365
  4. Coburn B, Morris AM, Tomlinson G, Detsky AS. Does this adult patient with suspected bacteremia require blood cultures? JAMA 2012; 308(5):502–511. doi:10.1001/jama.2012.8262
  5. Baddour LM, Epstein AE, Erickson CC, et al; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee; Council on Cardiovascular Disease in Young; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Nursing; Council on Clinical Cardiology; Interdisciplinary Council on Quality of Care; American Heart Association. Update on cardiovascular implantable electronic device infections and their management: a scientific statement from the American Heart Association. Circulation 2010; 121(3):458–477. doi:10.1161/CIRCULATIONAHA.109.192665
  6. Liu C, Bayer A, Cosgrove SE, et al; Infectious Diseases Society of America. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52(3):e18–e55. doi:10.1093/cid/ciq146
  7. Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2016; 62(4):e1–e50. doi:10.1093/cid/civ933
  8. Baddour LM, Wilson WR, Bayer AS, et al; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation 2015; 132(15):1435–1486. doi:10.1161/CIR.0000000000000296
  9. Rosenblum J, Lin J, Kim M, Levy AS. Repeating blood cultures in neutropenic children with persistent fevers when the initial blood culture is negative. Pediatr Blood Cancer 2013; 60(6):923–927. doi:10.1002/pbc.24358
  10. Thomas MW, Chauvenet AR, O'Suoji C. Repeating blood cultures in neutropenic children with persistent fevers when the initial blood culture is negative. Pediatr Blood Cancer 2014; 61(2):194. doi:10.1002/pbc.24834
  11. Kimura SI, Gomyo A, Hayakawa J, et al. Clinical significance of repeat blood cultures during febrile neutropenia in adult acute myeloid leukaemia patients undergoing intensive chemotherapy. Infect Dis (Lond) 2017; 49(10):748–757. doi:10.1080/23744235.2017.1340665
  12. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016; 315(8):801–810. doi:10.1001/jama.2016.0287
  13. Shah H, Bosch W, Thompson KM, Hellinger WC. Intravascular catheter-related bloodstream infection. Neurohospitalist 2013; 3(3):144–151. doi:10.1177/1941874413476043
  14. Canzoneri CN, Akhavan BJ, Tosur Z, Andrade PEA, Aisenberg GM. Follow-up blood cultures in gram-negative bacteremia: are they needed? Clin Infect Dis 2017; 65(11):1776–1779. doi:10.1093/cid/cix648
  15. Grace CJ, Lieberman J, Pierce K, Littenberg B. Usefulness of blood culture for hospitalized patients who are receiving antibiotic therapy. Clin Infect Dis 2001; 32(11):1651–1655. doi:10.1086/320527
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Author and Disclosure Information

Ammara Mushtaq, MD
Department of Medicine, Detroit Medical Center; Wayne State University, School of Medicine, Detroit, MI

Bryce X. Bredell, MS
Wayne State University, School of Medicine, and Department of Medicine, Sinai-Grace Hospital, Detroit, MI

Ayman O. Soubani, MD
Department of Medicine, Detroit Medical Center; Wayne State University, School of Medicine, Detroit, MI

Address: Ammara Mushtaq, MD, Wayne State University, School of Medicine, 4201 St. Antoine Street, Suite 2E, Detroit, MI 48201; [email protected]

Issue
Cleveland Clinic Journal of Medicine - 86(2)
Publications
Cleveland Clinic Journal of Medicine
Topics
Infectious Diseases
Hospital Medicine
Vascular
Cardiology
Page Number
89-92
Legacy Keywords
bacteremia, blood cultures, hospital medicine, testing, Staphylococcus aureus, endovascular infection, endocarditis, Ammara Mushtaq, Bryce Bredell, Ayman Soubani
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1-Minute Consult
Author(s)
Ammara Mushtaq, MD
Bryce X. Bredell, MS
Ayman O. Soubani, MD
Author(s)
Ammara Mushtaq, MD
Bryce X. Bredell, MS
Ayman O. Soubani, MD
Author and Disclosure Information

Ammara Mushtaq, MD
Department of Medicine, Detroit Medical Center; Wayne State University, School of Medicine, Detroit, MI

Bryce X. Bredell, MS
Wayne State University, School of Medicine, and Department of Medicine, Sinai-Grace Hospital, Detroit, MI

Ayman O. Soubani, MD
Department of Medicine, Detroit Medical Center; Wayne State University, School of Medicine, Detroit, MI

Address: Ammara Mushtaq, MD, Wayne State University, School of Medicine, 4201 St. Antoine Street, Suite 2E, Detroit, MI 48201; [email protected]

Author and Disclosure Information

Ammara Mushtaq, MD
Department of Medicine, Detroit Medical Center; Wayne State University, School of Medicine, Detroit, MI

Bryce X. Bredell, MS
Wayne State University, School of Medicine, and Department of Medicine, Sinai-Grace Hospital, Detroit, MI

Ayman O. Soubani, MD
Department of Medicine, Detroit Medical Center; Wayne State University, School of Medicine, Detroit, MI

Address: Ammara Mushtaq, MD, Wayne State University, School of Medicine, 4201 St. Antoine Street, Suite 2E, Detroit, MI 48201; [email protected]

Article PDF
mushtaq_repeatingbloodcultures.pdf
Article PDF
mushtaq_repeatingbloodcultures.pdf
Related Articles
Follow-up blood cultures are often needed after bacteremia
When does S aureus bacteremia require transesophageal echocardiography?

Repeat cultures are indicated in specific scenarios, but for most patients, frequent and indiscriminate repetition after an initial positive culture is unnecessary and may be associated with excessive use of resources. Prospective studies and practice guidelines are needed to help further define the indications.

See related editorial

THE TENDENCY TO REPEAT CULTURES

Current literature lacks strong evidence for repeating previously positive blood cultures collected appropriately—ie, 10 mL of blood for aerobic culture and 10 mL for anaerobic culture from 2 different sites, and a positive result from both sets. However, because of the risk of serious complications of bacteremia, particularly in critically ill patients, many clinicians order multiple, repeated sets of blood cultures.

Tabriz et al1 found that one-third of hospitalized patients got repeat cultures after an initial set, regardless of the result of the first set. Most (83.4%) of those cultures yielded no growth, 9.1% grew the same pathogen, and 5.0% were contaminated. Finding a new pathogen was rare, occurring in only 2.5% of repeated cultures.

Wiggers et al2 reported an even higher number of repeat cultures ordered for patients who had an initially positive culture: 38.9%.2 And in another study,3 half of the patients received more than 2 consecutive cultures.

Drawbacks

Unrestrained ordering of repeat blood cultures can increase the risk of a false-positive result, leading to more cultures, echocardiography, other imaging tests, and unnecessary antimicrobial therapy, all of which puts patients at risk of adverse effects of treatment and missed alternative diagnoses and increases the length and cost of hospitalization.4

Advantages

On the other hand, repeat blood cultures  may increase the diagnostic yield for conditions such as infective endocarditis and may have implications for the duration of antibiotic therapy.1 The duration of therapy for bacteremia is usually determined from the last negative culture; hence, documenting clearance of bacteremia can determine a precise end-date for antibiotic therapy.

Bacteremia due to Staphylococcus aureus and to endovascular and epidural sources has been found to be independently associated with persistent bacteremia, detected in 6.6% of 1,801 index cases of bacteremia in a retrospective cohort study.2 An endovascular source (adjusted odds ratio [OR] 7.66, 95% confidence interval [CI] 2.30–25.48), an epidural source (adjusted OR 26.99, 95% CI, 1.91–391.08), and S aureus bacteremia (adjusted OR 4.49, 95% CI 1.88–10.73) were independently associated with persistent bacteremia. Escherichia coli (5.1%, P =  .006), viridans group streptococci (1.7%, P =  .035), and beta-hemolytic streptococci (0%, P = .028) were associated with a lower likelihood of persistent bacteremia. Patients with persistent bacteremia were less likely to have achieved source control within 48 hours of the index event (29.7% vs 52.5%, P < .001).2

 

 

WHEN REPEATING CULTURES IS APPROPRIATE

Repeating blood cultures after an initial positive result is superfluous, except in certain situations.

Suspected endovascular infection

Patients with endocarditis, thrombophlebitis, an indwelling device for epidural access, or a cardiovascular implantable electronic device should have repeat cultures after an initial positive culture. Implantable electronic device infection is suspected in the following cases: sustained positive blood culture (> 24 hours); relapsing bacteremia despite a course of appropriate antibiotic therapy; presence of an implantable cardioverter defibrillator; presence of a prosthetic cardiac valve; and an episode of bacteremia within 3 months of device placement.5

S aureus bacteremia

Repeat blood culture is warranted for S aureus bacteremia regardless of methicillin susceptibility.1 But persistent methicillin-resistant S aureus (MRSA) bacteremia changes the management of these patients.6 For example, the source of infection should be identified, followed by debridement or drainage, and then either high-dose or combination antimicrobial therapy.6 Infective endocarditis from persistent MRSA bacteremia is an indication for surgery.6

Persistent S aureus bacteremia may change the duration of therapy, as the common practice is to continue treating uncomplicated gram-positive bacteremia for 14 days from the date of the first negative culture. Infection leading to infective endocarditis increases the duration of antibiotic therapy to at least 4 weeks.

Candidemia

Candidemia is an absolute indication for repeat blood culture.7 Patients with persistent candidemia should undergo imaging of the genitourinary tract, liver, and spleen as part of the evaluation for a deep-tissue source of infection.7 Also, if the patient is initially treated with an echinocandin, therapy can be transitioned to fluconazole if the isolate is azole-susceptible, the patient’s condition is clinically stable, and repeat cultures are negative.7 Therefore, repeating cultures has therapeutic implications.

Confirming response to therapy

In patients with infective endocarditis or other endovascular infection caused by S aureus, Enterococcus species, or gram-negative bacilli,1 repeat blood culture should be done to confirm therapeutic response. Patients with infective endocarditis whose condition is stable can be discharged to receive outpatient parenteral antibiotic therapy. However, patients with uncontrolled heart failure, systemic emboli, abscess, persistent fever, or persistently positive cultures are not candidates for outpatient therapy and require repeat cultures.8

Multidrug-resistant gram-negative bacilli

Bacteremia due to multidrug-resistant gram-negative bacilli requires repeat blood cultures to document clearance of bacteremia and to ensure the efficacy of antibiotics, as these organisms pose a higher risk of treatment failure, and combination synergistic regimens may be needed if bacteremia does not clear.

Febrile neutropenia

Blood cultures are important in the management of febrile neutropenia. In a study by Rosenblum et al,9 repeat cultures were positive in 10.9% of patients with febrile neutropenia after an initial negative culture, but many of those organisms were of low pathogenicity, and a significant proportion were coagulase-negative staphylococci.10 Another study showed that the frequency of detecting new pathogens by repeat culture in recurrent febrile neutropenia was higher than that in persistent febrile neutropenia (8% vs 2%) (P = .0491); a history of recent bacteremia was identified as a significant predictor of positive culture in recurrent febrile neutropenia.11

Persistent or new infection

Persistence of fever, leukocytosis, or other signs of infection 72 hours after appropriate antibiotic therapy is started requires follow-up blood cultures.

New episode of sepsis. A new episode of sepsis should be confirmed12 using the systemic inflammatory response syndrome criteria, the newer definition of Sepsis-related Organ Failure Assessment (SOFA) in the intensive-care unit, or the quick SOFA in general units. If the patient develops new signs of sepsis after response to treatment for initial bacteremia, repeat blood cultures should be considered.

Central line-associated bloodstream infection requires repeat cultures.13 Persistence of bacteremia in this type of infection extends the duration of therapy, as most clinicians determine treatment duration from the last negative culture. Persistent bacteremia also influences the decision to salvage or remove the catheter. Microbiologic clearance of bacteremia on blood culture can also guide the time of reinsertion if the catheter was removed.

Concern for an unresolved focus of infection such as abscess, joint infection, or retained catheter is an indication for repeat blood cultures.

Bacteremia of unknown source. In clinical practice, we encounter scenarios in which blood cultures are positive but no source can be identified. In those situations, it is important to repeat blood cultures to document clearance. If bacteremia persists, we need to continue searching for the source.

 

 

WHEN ROUTINELY REPEATING CULTURES IS NOT INDICATED

Repeat blood cultures are not routinely indicated in patients with streptococcal bacteremia, uncomplicated gram-negative bacteremia, and bacteremia associated with localized infection such as cellulitis, community-acquired pneumonia, or pyelonephritis.2,4 A study of patients with gram-negative bacteremia found that 17 repeated cultures needed to be drawn to yield 1 positive culture.14

Isolated fever or leukocytosis does not accurately predict bacteremia.4 A study that excluded neutropenic and intensive-care patients reported none of the initially negative cultures to be positive when repeated.15

Ordering repeat cultures in response to persistent fever is a common practice, even though fever is typical in the first 72 hours of antibiotic therapy. Such cultures rarely if ever reveal new pathogens, and results can be predicted based on cultures before the start of antibiotics.15 For patients on antibiotics, physicians should therefore wait for results of the preantibiotic cultures rather than order new cultures in response to persistent fever.15

WOULD WE MISS PERSISTENT BACTEREMIA?

In theory, not repeating blood cultures could miss persistent bacteremia, but this is unlikely if the concerns discussed above are considered. Further, persistent bacteremia would result in clinical signs and symptoms that should prompt repeat cultures.

FREQUENCY OF REPEAT BLOOD CULTURES

There are no evidence-based guidelines for the frequency of repeating cultures. The Infectious Diseases Society of America recommends repeating blood cultures 2 to 4 days after the index positive culture in the case of multidrug-resistant S aureus bacteremia, and every day or every other day for candidemia.6,7,9

A study evaluating the practice patterns of repeating cultures after an initial bacteremia showed that 34.7% were done within 24 hours and 44.7% were done in 2 to 4 days.1 There is no evidence that repeating blood cultures daily is necessary in these patients. As a general rule, it should be done 48 to 72 hours after a positive culture.

Repeat cultures are indicated in specific scenarios, but for most patients, frequent and indiscriminate repetition after an initial positive culture is unnecessary and may be associated with excessive use of resources. Prospective studies and practice guidelines are needed to help further define the indications.

See related editorial

THE TENDENCY TO REPEAT CULTURES

Current literature lacks strong evidence for repeating previously positive blood cultures collected appropriately—ie, 10 mL of blood for aerobic culture and 10 mL for anaerobic culture from 2 different sites, and a positive result from both sets. However, because of the risk of serious complications of bacteremia, particularly in critically ill patients, many clinicians order multiple, repeated sets of blood cultures.

Tabriz et al1 found that one-third of hospitalized patients got repeat cultures after an initial set, regardless of the result of the first set. Most (83.4%) of those cultures yielded no growth, 9.1% grew the same pathogen, and 5.0% were contaminated. Finding a new pathogen was rare, occurring in only 2.5% of repeated cultures.

Wiggers et al2 reported an even higher number of repeat cultures ordered for patients who had an initially positive culture: 38.9%.2 And in another study,3 half of the patients received more than 2 consecutive cultures.

Drawbacks

Unrestrained ordering of repeat blood cultures can increase the risk of a false-positive result, leading to more cultures, echocardiography, other imaging tests, and unnecessary antimicrobial therapy, all of which puts patients at risk of adverse effects of treatment and missed alternative diagnoses and increases the length and cost of hospitalization.4

Advantages

On the other hand, repeat blood cultures  may increase the diagnostic yield for conditions such as infective endocarditis and may have implications for the duration of antibiotic therapy.1 The duration of therapy for bacteremia is usually determined from the last negative culture; hence, documenting clearance of bacteremia can determine a precise end-date for antibiotic therapy.

Bacteremia due to Staphylococcus aureus and to endovascular and epidural sources has been found to be independently associated with persistent bacteremia, detected in 6.6% of 1,801 index cases of bacteremia in a retrospective cohort study.2 An endovascular source (adjusted odds ratio [OR] 7.66, 95% confidence interval [CI] 2.30–25.48), an epidural source (adjusted OR 26.99, 95% CI, 1.91–391.08), and S aureus bacteremia (adjusted OR 4.49, 95% CI 1.88–10.73) were independently associated with persistent bacteremia. Escherichia coli (5.1%, P =  .006), viridans group streptococci (1.7%, P =  .035), and beta-hemolytic streptococci (0%, P = .028) were associated with a lower likelihood of persistent bacteremia. Patients with persistent bacteremia were less likely to have achieved source control within 48 hours of the index event (29.7% vs 52.5%, P < .001).2

 

 

WHEN REPEATING CULTURES IS APPROPRIATE

Repeating blood cultures after an initial positive result is superfluous, except in certain situations.

Suspected endovascular infection

Patients with endocarditis, thrombophlebitis, an indwelling device for epidural access, or a cardiovascular implantable electronic device should have repeat cultures after an initial positive culture. Implantable electronic device infection is suspected in the following cases: sustained positive blood culture (> 24 hours); relapsing bacteremia despite a course of appropriate antibiotic therapy; presence of an implantable cardioverter defibrillator; presence of a prosthetic cardiac valve; and an episode of bacteremia within 3 months of device placement.5

S aureus bacteremia

Repeat blood culture is warranted for S aureus bacteremia regardless of methicillin susceptibility.1 But persistent methicillin-resistant S aureus (MRSA) bacteremia changes the management of these patients.6 For example, the source of infection should be identified, followed by debridement or drainage, and then either high-dose or combination antimicrobial therapy.6 Infective endocarditis from persistent MRSA bacteremia is an indication for surgery.6

Persistent S aureus bacteremia may change the duration of therapy, as the common practice is to continue treating uncomplicated gram-positive bacteremia for 14 days from the date of the first negative culture. Infection leading to infective endocarditis increases the duration of antibiotic therapy to at least 4 weeks.

Candidemia

Candidemia is an absolute indication for repeat blood culture.7 Patients with persistent candidemia should undergo imaging of the genitourinary tract, liver, and spleen as part of the evaluation for a deep-tissue source of infection.7 Also, if the patient is initially treated with an echinocandin, therapy can be transitioned to fluconazole if the isolate is azole-susceptible, the patient’s condition is clinically stable, and repeat cultures are negative.7 Therefore, repeating cultures has therapeutic implications.

Confirming response to therapy

In patients with infective endocarditis or other endovascular infection caused by S aureus, Enterococcus species, or gram-negative bacilli,1 repeat blood culture should be done to confirm therapeutic response. Patients with infective endocarditis whose condition is stable can be discharged to receive outpatient parenteral antibiotic therapy. However, patients with uncontrolled heart failure, systemic emboli, abscess, persistent fever, or persistently positive cultures are not candidates for outpatient therapy and require repeat cultures.8

Multidrug-resistant gram-negative bacilli

Bacteremia due to multidrug-resistant gram-negative bacilli requires repeat blood cultures to document clearance of bacteremia and to ensure the efficacy of antibiotics, as these organisms pose a higher risk of treatment failure, and combination synergistic regimens may be needed if bacteremia does not clear.

Febrile neutropenia

Blood cultures are important in the management of febrile neutropenia. In a study by Rosenblum et al,9 repeat cultures were positive in 10.9% of patients with febrile neutropenia after an initial negative culture, but many of those organisms were of low pathogenicity, and a significant proportion were coagulase-negative staphylococci.10 Another study showed that the frequency of detecting new pathogens by repeat culture in recurrent febrile neutropenia was higher than that in persistent febrile neutropenia (8% vs 2%) (P = .0491); a history of recent bacteremia was identified as a significant predictor of positive culture in recurrent febrile neutropenia.11

Persistent or new infection

Persistence of fever, leukocytosis, or other signs of infection 72 hours after appropriate antibiotic therapy is started requires follow-up blood cultures.

New episode of sepsis. A new episode of sepsis should be confirmed12 using the systemic inflammatory response syndrome criteria, the newer definition of Sepsis-related Organ Failure Assessment (SOFA) in the intensive-care unit, or the quick SOFA in general units. If the patient develops new signs of sepsis after response to treatment for initial bacteremia, repeat blood cultures should be considered.

Central line-associated bloodstream infection requires repeat cultures.13 Persistence of bacteremia in this type of infection extends the duration of therapy, as most clinicians determine treatment duration from the last negative culture. Persistent bacteremia also influences the decision to salvage or remove the catheter. Microbiologic clearance of bacteremia on blood culture can also guide the time of reinsertion if the catheter was removed.

Concern for an unresolved focus of infection such as abscess, joint infection, or retained catheter is an indication for repeat blood cultures.

Bacteremia of unknown source. In clinical practice, we encounter scenarios in which blood cultures are positive but no source can be identified. In those situations, it is important to repeat blood cultures to document clearance. If bacteremia persists, we need to continue searching for the source.

 

 

WHEN ROUTINELY REPEATING CULTURES IS NOT INDICATED

Repeat blood cultures are not routinely indicated in patients with streptococcal bacteremia, uncomplicated gram-negative bacteremia, and bacteremia associated with localized infection such as cellulitis, community-acquired pneumonia, or pyelonephritis.2,4 A study of patients with gram-negative bacteremia found that 17 repeated cultures needed to be drawn to yield 1 positive culture.14

Isolated fever or leukocytosis does not accurately predict bacteremia.4 A study that excluded neutropenic and intensive-care patients reported none of the initially negative cultures to be positive when repeated.15

Ordering repeat cultures in response to persistent fever is a common practice, even though fever is typical in the first 72 hours of antibiotic therapy. Such cultures rarely if ever reveal new pathogens, and results can be predicted based on cultures before the start of antibiotics.15 For patients on antibiotics, physicians should therefore wait for results of the preantibiotic cultures rather than order new cultures in response to persistent fever.15

WOULD WE MISS PERSISTENT BACTEREMIA?

In theory, not repeating blood cultures could miss persistent bacteremia, but this is unlikely if the concerns discussed above are considered. Further, persistent bacteremia would result in clinical signs and symptoms that should prompt repeat cultures.

FREQUENCY OF REPEAT BLOOD CULTURES

There are no evidence-based guidelines for the frequency of repeating cultures. The Infectious Diseases Society of America recommends repeating blood cultures 2 to 4 days after the index positive culture in the case of multidrug-resistant S aureus bacteremia, and every day or every other day for candidemia.6,7,9

A study evaluating the practice patterns of repeating cultures after an initial bacteremia showed that 34.7% were done within 24 hours and 44.7% were done in 2 to 4 days.1 There is no evidence that repeating blood cultures daily is necessary in these patients. As a general rule, it should be done 48 to 72 hours after a positive culture.

References
  1. Tabriz MS, Riederer K, Baran J Jr, Khatib R. Repeating blood cultures during hospital stay: practice pattern at a teaching hospital and a proposal for guidelines. Clin Microbiol Infect 2004; 10(7):624–627. doi:10.1111/j.1469-0691.2004.00893.x
  2. Wiggers JB, Xiong W, Daneman N. Sending repeat cultures: is there a role in the management of bacteremic episodes? (SCRIBE study). BMC Infect Dis 2016; 16:286. doi:10.1186/s12879-016-1622-z
  3. Kang CK, Kim ES, Song KH, et al. Can a routine follow-up blood culture be justified in Klebsiella pneumoniae bacteremia? A retrospective case–control study. BMC Infect Dis 2013; 13:365. doi:10.1186/1471-2334-13-365
  4. Coburn B, Morris AM, Tomlinson G, Detsky AS. Does this adult patient with suspected bacteremia require blood cultures? JAMA 2012; 308(5):502–511. doi:10.1001/jama.2012.8262
  5. Baddour LM, Epstein AE, Erickson CC, et al; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee; Council on Cardiovascular Disease in Young; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Nursing; Council on Clinical Cardiology; Interdisciplinary Council on Quality of Care; American Heart Association. Update on cardiovascular implantable electronic device infections and their management: a scientific statement from the American Heart Association. Circulation 2010; 121(3):458–477. doi:10.1161/CIRCULATIONAHA.109.192665
  6. Liu C, Bayer A, Cosgrove SE, et al; Infectious Diseases Society of America. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52(3):e18–e55. doi:10.1093/cid/ciq146
  7. Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2016; 62(4):e1–e50. doi:10.1093/cid/civ933
  8. Baddour LM, Wilson WR, Bayer AS, et al; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation 2015; 132(15):1435–1486. doi:10.1161/CIR.0000000000000296
  9. Rosenblum J, Lin J, Kim M, Levy AS. Repeating blood cultures in neutropenic children with persistent fevers when the initial blood culture is negative. Pediatr Blood Cancer 2013; 60(6):923–927. doi:10.1002/pbc.24358
  10. Thomas MW, Chauvenet AR, O'Suoji C. Repeating blood cultures in neutropenic children with persistent fevers when the initial blood culture is negative. Pediatr Blood Cancer 2014; 61(2):194. doi:10.1002/pbc.24834
  11. Kimura SI, Gomyo A, Hayakawa J, et al. Clinical significance of repeat blood cultures during febrile neutropenia in adult acute myeloid leukaemia patients undergoing intensive chemotherapy. Infect Dis (Lond) 2017; 49(10):748–757. doi:10.1080/23744235.2017.1340665
  12. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016; 315(8):801–810. doi:10.1001/jama.2016.0287
  13. Shah H, Bosch W, Thompson KM, Hellinger WC. Intravascular catheter-related bloodstream infection. Neurohospitalist 2013; 3(3):144–151. doi:10.1177/1941874413476043
  14. Canzoneri CN, Akhavan BJ, Tosur Z, Andrade PEA, Aisenberg GM. Follow-up blood cultures in gram-negative bacteremia: are they needed? Clin Infect Dis 2017; 65(11):1776–1779. doi:10.1093/cid/cix648
  15. Grace CJ, Lieberman J, Pierce K, Littenberg B. Usefulness of blood culture for hospitalized patients who are receiving antibiotic therapy. Clin Infect Dis 2001; 32(11):1651–1655. doi:10.1086/320527
References
  1. Tabriz MS, Riederer K, Baran J Jr, Khatib R. Repeating blood cultures during hospital stay: practice pattern at a teaching hospital and a proposal for guidelines. Clin Microbiol Infect 2004; 10(7):624–627. doi:10.1111/j.1469-0691.2004.00893.x
  2. Wiggers JB, Xiong W, Daneman N. Sending repeat cultures: is there a role in the management of bacteremic episodes? (SCRIBE study). BMC Infect Dis 2016; 16:286. doi:10.1186/s12879-016-1622-z
  3. Kang CK, Kim ES, Song KH, et al. Can a routine follow-up blood culture be justified in Klebsiella pneumoniae bacteremia? A retrospective case–control study. BMC Infect Dis 2013; 13:365. doi:10.1186/1471-2334-13-365
  4. Coburn B, Morris AM, Tomlinson G, Detsky AS. Does this adult patient with suspected bacteremia require blood cultures? JAMA 2012; 308(5):502–511. doi:10.1001/jama.2012.8262
  5. Baddour LM, Epstein AE, Erickson CC, et al; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee; Council on Cardiovascular Disease in Young; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Nursing; Council on Clinical Cardiology; Interdisciplinary Council on Quality of Care; American Heart Association. Update on cardiovascular implantable electronic device infections and their management: a scientific statement from the American Heart Association. Circulation 2010; 121(3):458–477. doi:10.1161/CIRCULATIONAHA.109.192665
  6. Liu C, Bayer A, Cosgrove SE, et al; Infectious Diseases Society of America. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52(3):e18–e55. doi:10.1093/cid/ciq146
  7. Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2016; 62(4):e1–e50. doi:10.1093/cid/civ933
  8. Baddour LM, Wilson WR, Bayer AS, et al; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation 2015; 132(15):1435–1486. doi:10.1161/CIR.0000000000000296
  9. Rosenblum J, Lin J, Kim M, Levy AS. Repeating blood cultures in neutropenic children with persistent fevers when the initial blood culture is negative. Pediatr Blood Cancer 2013; 60(6):923–927. doi:10.1002/pbc.24358
  10. Thomas MW, Chauvenet AR, O'Suoji C. Repeating blood cultures in neutropenic children with persistent fevers when the initial blood culture is negative. Pediatr Blood Cancer 2014; 61(2):194. doi:10.1002/pbc.24834
  11. Kimura SI, Gomyo A, Hayakawa J, et al. Clinical significance of repeat blood cultures during febrile neutropenia in adult acute myeloid leukaemia patients undergoing intensive chemotherapy. Infect Dis (Lond) 2017; 49(10):748–757. doi:10.1080/23744235.2017.1340665
  12. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016; 315(8):801–810. doi:10.1001/jama.2016.0287
  13. Shah H, Bosch W, Thompson KM, Hellinger WC. Intravascular catheter-related bloodstream infection. Neurohospitalist 2013; 3(3):144–151. doi:10.1177/1941874413476043
  14. Canzoneri CN, Akhavan BJ, Tosur Z, Andrade PEA, Aisenberg GM. Follow-up blood cultures in gram-negative bacteremia: are they needed? Clin Infect Dis 2017; 65(11):1776–1779. doi:10.1093/cid/cix648
  15. Grace CJ, Lieberman J, Pierce K, Littenberg B. Usefulness of blood culture for hospitalized patients who are receiving antibiotic therapy. Clin Infect Dis 2001; 32(11):1651–1655. doi:10.1086/320527
Issue
Cleveland Clinic Journal of Medicine - 86(2)
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Cleveland Clinic Journal of Medicine - 86(2)
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89-92
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Cleveland Clinic Journal of Medicine
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Cleveland Clinic Journal of Medicine
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Repeating blood cultures after initial bacteremia: When and how often?
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Repeating blood cultures after initial bacteremia: When and how often?
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bacteremia, blood cultures, hospital medicine, testing, Staphylococcus aureus, endovascular infection, endocarditis, Ammara Mushtaq, Bryce Bredell, Ayman Soubani
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bacteremia, blood cultures, hospital medicine, testing, Staphylococcus aureus, endovascular infection, endocarditis, Ammara Mushtaq, Bryce Bredell, Ayman Soubani
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