Although a common practice, follow-up blood cultures (FUBCs) may not be necessary in otherwise clinically stable or improving patients with aerobic gram-negative bacteremia. This is probably due to the often-transient nature of gram-negative bloodstream infections and less propensity of these organisms to cause intravascular infections (eg, endocarditis) compared to gram-positives. 1
A 2017 study addressing the value of FUBCs in gram-negative bacteremia found that repeat positive blood cultures were uncommon with positive results not associated with mortality or higher ICU admissions. 1 Specifically, 17 FUBCs had to be drawn to yield 1 positive result. Although the numbers of positive FUBCs were too low for in-depth analysis, it was concluded that FUBCs added little value in the management of gram-negative bacteremias.
In contrast, FUBCs are recommended in the following situations: 1-3
- Staphylocccus aureus bacteremia given the propensity of this organism to cause intravascular (eg, endocarditis) and metastatic infections.
- Presumed or documented endocarditis or intravascular device infections (eg, intravenous catheters and pacemakers) to document timely clearance of bacteremia
- Infections involving organisms that may be difficult to clear such as fungemia or multi-drug resistant pathogens.
As with many things in medicine, clinical context is important before ordering tests and blood cultures are no different. The urge to order FUBCs should also be balanced with the possibility of having to deal with contaminants.
- Canzoneri CN, Akhavan BJ, Tosur Z et al. Follow-up blood cultures in gram-negative bacteremia: Are they needed? Clin Infect Dis 2017;65:1776-9. https://www.ncbi.nlm.nih.gov/pubmed/29020307
- Tabriz MS, Riederer K, Baran J, et al. Repeating blood cultures during hospital stay: Practice pattern at a teaching hospital and a proposal for guidelines. Clin Microbiol Infect 2004;10:624-27. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1469-0691.2004.00893.x
- Mylotte JM, Tayara A. Blood cultures: Clinical aspects and controversies. Eur J Clin Microbiol Infect Dis 200;19:157-63. https://www.ncbi.nlm.nih.gov/pubmed/10795587
For great majority of patients, more than 2 sets of blood culture obtained closely apart is not likely to significantly improve the yield of detecting bacteremia.
Although a 2004 report suggested that 2 sets of blood cultures over 24 h period had a sensitivity of only 80% for bacteremia, several other studies have found much higher sensitivities, ranging from ~90%- 99% 2-3. When broken down by organism, sensitivity of 2 sets of blood cultures may be highest for Staphylococcus aureus (97%), followed by E. coli (91%), and Klebsiella pneumoniae (90%) 2. The Clinical and Laboratory Standards Institute guidelines recommend paired blood culture sets (each set with 2 bottles, 10 ml of blood in each) to detect about 90-95% of patients with documented bacteremia, and 3 sets for 95-99% detection rate 4.
It seems prudent to strike a balance between drawing more than 2 sets of blood cultures—with its attendant risk of picking up contaminants— and what may be a definite but small incremental increase in the rate of detection of true bacteremia.
If you are concerned about “continuous” bacteremia (eg, in endocarditis) or a common blood culture contaminant causing true disease (eg, Staphylococcus epidermidis prosthetic valve infection), you may consider a 3rd or 4th set of blood cultures drawn 4-6 hrs after the initial sets.
Whatever you do, please don’t order only 1 set of blood cultures! Aside from its generally low yield, when positive it may be difficult to distinguish contaminants from true invaders.
- Cockerill FR, Reed GS, Hughes JG, et al. Clinical comparison of BACTEC 9240 Plus Aerobic/F resin bottles and the Isolator aerobic cultures. Clin Infect Dis 2004;38:1724-30. https://www.ncbi.nlm.nih.gov/pubmed/9163464
- Lee A, Mirrett S, Reller LB, et al. Detection of bloodstream infections in adults: how many cultures are needed? J Clin Microbiol 2007; 45:3546-48. http://jcm.asm.org/content/45/11/3546
- Towns ML, Jarvis WR, Hsueh PR. Guidelines on blood cultures. J Microbiol Immunol Infect 2010;43:347-49. https://www.ncbi.nlm.nih.gov/pubmed/20688297
- Weinstein MP, Reller LB, Murphy JR, et al. The clinical significance of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. I. Laboratory and eipidemiologic observations. Rev Infect Dis 1982;5:35-53. https://www.ncbi.nlm.nih.gov/pubmed/6828811
A common medical myth is that the yield of BCs is highest when obtained around the time of a fever spike. In 1989, an abstract reported a non-significant trend toward higher frequency of positive BCs in the period immediately before a fever spike1. In 1994, another study found no significant difference between the yield of simultaneous and serial (separated by a few hrs) BCs2, supporting the current practice of collecting ≥2 sets of BCs simultaneously.
In 2008, a multicenter retrospective study found that the likelihood of detecting bacteremia was not significantly enhanced by collecting BCs at the time of fever3. Instead, obtaining an adequate blood volume (~40 – 60mL for each episode), and collecting ≥2 sets of BCs under strict aseptic technique were emphasized4. BCs should be obtained prior to antibiotic administration.
So in our patient, BCs should be obtained if sepsis is suspected, irrespective of fever.
- Thomson RB, et al. Timing of blood culture collection from febrile patients. Abstr. C-227. 89th Annual Meeting American Society of Microbiology, Washington, DC, 1989.
- Li J, et al. Effects of volume and periodicity on blood cultures. J Clin Microbiol. 1994; 32:2829-2831.
- Riedel S, et al. Timing of specimen collection for blood cultures from febrile patients with bacteremia. J Clin Microbiol. 2008;46:1381-1385.
- Clinical and Laboratory Standards Institute (CLSI). Principles and Procedures for Blood Cultures: Approved Guideline. 2007. CLSI document M47-A. Clinical and Laboratory Standards Institute, Wayne, PA
Contributed by Henrietta Afari, MD, Mass General Hospital, Boston, MA