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document : Blood Culture BPA Supplement

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    Problem: UVA blood culture utilization data reveal that follow-up cultures (ordered following a prior positive) are frequently ordered in low-yield situations (e.g. gram-negative bacteremia) and when indicated, are often ordered earlier than current guidelines recommend (i.e. after 48 hours of active antimicrobial therapy to assess for clearance). Similarly, repeated daily blood cultures are often performed with episodes of continued fever despite prior negative cultures and patient stability.

    Impact: In addition to unnecessary testing, blood culture over-utilization has been associated with increased antimicrobial exposure, longer lengths of stay, unnecessary removal of vascular catheters, and increased healthcare costs [1–8].

    Goal: The UVA Repeat Blood Culture Best Practice Alert will prompt LIPs when ordering new blood cultures within 48 hours of prior pending cultures and provide general recommendations for best practice. This document provides further details regarding these best practices and supporting evidence.

     

    When are repeat blood cultures indicated after an initial POSITIVE blood culture?

    Infectious Disease Society of America (IDSA) clinical practice guidelines recommend repeat blood cultures to document clearance of bacteremia 2-4 days after initial positive blood cultures in Staphylococcus aureus bacteremia [9], and in candidemia [10]. Since Staphylococcus lugdunensis is considered similarly virulent and associated with endovascular infection, follow-up blood cultures should also be routinely obtained [11]. For Staphylococcus aureus, recent data suggest persistent bacteremia should be defined as two days or more despite active antimicrobial therapy [12] – obtaining follow-up blood cultures at 48 hours is often most informative in identifying patients at increased risk of metastatic infection and death.

    Formal guidelines do not exist regarding bacteremia secondary to other organisms; however, supporting data for Enterobacterales [13–15], Pseudomonas [16,17] and streptococci [13,18] demonstrate follow-up blood cultures are unlikely to be positive outside of an endovascular source or inadequate source control. While infective endocarditis due to gram-negative organisms is rare [19], nontyphoidal Salmonella bacteremia has a higher predilection for vascular infection [20]. For streptococci, the propensity for causing infective endocarditis varies by species [21], with B-hemolytic streptococci, Streptococcus pneumoniae and Streptococcus anginosus demonstrating low prevalence of positive follow-up blood cultures [13,18] and infective endocarditis [21] .

    There are no studies or guidelines to specifically address the need to repeat blood cultures prior to replacing a catheter in catheter-associated bacteremia; however, this is generally recommended.

    When are repeat blood cultures indicated after an initial NEGATIVE blood culture?

    For patients with initial negative blood cultures and no change in clinical stability, repeat cultures are low yield following initiation of antimicrobials [22–24]. The Clinical & Laboratory Standards Institute (CLSI) M-47A Principle and Procedures for Blood Cultures guideline recommends that “collection of another two or three blood culture sets may be indicated after 48 or 72 hours if the initial culture sets were non-informative”[25].

    In febrile neutropenia, current National Comprehensive Cancer Network (NCCN) clinical practice guidelines state: “although some experts recommend daily blood cultures until the patient becomes afebrile, increasing evidence suggests that daily blood cultures are unnecessary in stable neutropenic patients with persistent fever of unknown etiology” [26]. Current UVA expected practice is to obtain daily blood cultures for the initial 72 hours of consecutive neutropenic fever. If the patient remains persistently febrile but clinically stable with negative prior blood cultures, further blood cultures can be withheld.

     

    Supporting Literature:

    1. Fabre V, Sharara SL, Salinas AB, Carroll KC, Desai S, Cosgrove SE. Does This Patient Need Blood Cultures? A Scoping Review of Indications for Blood Cultures in Adult Nonneutropenic Inpatients. Clinical Infectious Diseases 2020; :ciaa039.
    2. Fabre V, Carroll KC, Cosgrove SE. Blood Culture Utilization in the Hospital Setting: A Call for Diagnostic Stewardship. J Clin Microbiol 2021; :JCM0100521.
    3. Dempsey C, Skoglund E, Muldrew KL, Garey KW. Economic health care costs of blood culture contamination: A systematic review. American Journal of Infection Control 2019; 47:963–967.
    4. Bates DW, Goldman L, Lee TH. Contaminant blood cultures and resource utilization. The true consequences of false-positive results. JAMA 1991; 265:365–369.
    5. Alahmadi YM, Aldeyab MA, McElnay JC, et al. Clinical and economic impact of contaminated blood cultures within the hospital setting. Journal of Hospital Infection 2011; 77:233–236.
    6. Doern GV, Carroll KC, Diekema DJ, et al. 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. Clinical Microbiology Reviews 2019; 33. Available at: https://cmr.asm.org/content/33/1/e00009-19. Accessed 28 October 2020.
    7. Zwang O, Albert RK. Analysis of strategies to improve cost effectiveness of blood cultures. J Hosp Med 2006; 1:272–276.
    8. Dunagan WC, Woodward RS, Medoff G, et al. Antimicrobial misuse in patients with positive blood cultures. Am J Med 1989; 87:253–259.
    9. Liu C, Bayer A, Cosgrove SE, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children. Clinical Infectious Diseases 2011; 52:e18–e55.
    10. 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. Clinical Infectious Diseases 2016; 62:e1–e50.
    11. Zinkernagel AS, Zinkernagel MS, Elzi MV, et al. Significance of Staphylococcus lugdunensis Bacteremia: Report of 28 Cases and Review of the Literature. Infection 2008; 36:314–321.
    12. Kuehl R, Morata L, Boeing C, et al. Defining persistent Staphylococcus aureus bacteraemia: secondary analysis of a prospective cohort study. The Lancet Infectious Diseases 2020; 20:1409–1417.
    13. 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. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4906775/. Accessed 1 April 2020.
    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; 65:1776–1779.
    15. Jung J, Song K-H, Jun KIl, et al. Predictive scoring models for persistent gram-negative bacteremia that reduce the need for follow-up blood cultures: a retrospective observational cohort study. BMC Infect Dis 2020; 20. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499917/. Accessed 26 October 2020.
    16. Green AL, Liang Y, O’Hara LM, et al. Follow-up blood cultures in Pseudomonas aeruginosa bacteremia: A potential target for diagnostic stewardship. ASHE 2021; 1:e23.
    17. Fabre V, Amoah J, Cosgrove SE, Tamma PD. Antibiotic Therapy for Pseudomonas aeruginosa Bloodstream Infections: How Long Is Long Enough? Clinical Infectious Diseases 2019; 69:2011–2014.
    18. Siegrist EA, Wungwattana M, Azis L, Stogsdill P, Craig WY, Rokas KE. Limited Clinical Utility of Follow-up Blood Cultures in Patients With Streptococcal Bacteremia: An Opportunity for Blood Culture Stewardship. Open Forum Infectious Diseases 2020; 7:ofaa541.
    19. Morpeth S, Murdoch D, Cabell CH, et al. Non-HACEK gram-negative bacillus endocarditis. Ann Intern Med 2007; 147:829–835.
    20. Benenson S, Raveh D, Schlesinger Y, et al. The risk of vascular infection in adult patients with nontyphi Salmonella bacteremia. Am J Med 2001; 110:60–63.
    21. Chamat-Hedemand S, Dahl A, Østergaard L, et al. Prevalence of Infective Endocarditis in Streptococcal Bloodstream Infections Is Dependent on Streptococcal Species. Circulation 2020; 142:720–730.
    22. Cheng MP, Stenstrom R, Paquette K, et al. Blood Culture Results Before and After Antimicrobial Administration in Patients With Severe Manifestations of Sepsis: A Diagnostic Study. Ann Intern Med 2019; 171:547.
    23. Grace CJ, Lieberman J, Pierce K, Littenberg B. Usefulness of Blood Culture for Hospitalized Patients Who Are Receiving Antibiotic Therapy. Clinical Infectious Diseases 2001; 32:1651–1655.
    24. Tabriz MS, Riederer K, Baran J, Khatib R. Repeating blood cultures during hospital stay: practice pattern at a teaching hospital and a proposal for guidelines. Clin Microbiol Infect 2004; 10:624–627.
    25. Clinical and Laboratory Standards Institute. M47-A: Principles and Procedures for Blood Cultures; Approved Guideline. 2007;
    26. Baden LR, Swaminathan S, Angarone M, et al. Prevention and Treatment of Cancer-Related Infections, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2016; 14:882–913.

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