Improving Patient Outcomes: 5 Essential Tips for Ordering Blood Cultures

For instance, I only learned when to order blood cultures during my residency years, based on rules like draw blood cultures when CRP is high or when a patient has a new fever. However, these common rules aren’t based on the current evidence. In what follows, I want to create some new ones that are.

1. The threshold for ordering blood cultures should remain low in a clinically deteriorating patient.

   The true positive ratio of blood cultures is generally low and varies between 4 to 13% across the different studies (1-3). Some studies proposed ways to increase this ratio (2,5), although these initiatives could ultimately result in a too restricted drawing of blood cultures. In my opinion, blood cultures should remain part of the workup in a clinically deteriorating patient for two reasons.

   1. Clinicians are overall not very good in recognizing sepsis. In one study, a sample of practicing intensive care specialists was asked if they would categorize five case vignettes as sepsis or septic shock. Their responses were extremely variable and the authors of this study could only conclude that diagnosing sepsis is extremely subjective (4).

   2. Blood cultures can contribute greatly to antibiotic stewardships. On the one hand, positive blood cultures with a true pathogen can be used to downgrade antibiotics according to susceptibility data. On the other hand, negative blood cultures, whether or not in combination with an alternative diagnosis, can lead to a faster cessation of antibiotics.

      
      

2. If ordering blood cultures, order at least 2 sets (and preferably 3) with every bottle adequately filled

   
   

3. If ordering blood cultures, one shouldn’t wait for fever.

   Traditionally, blood cultures were taken intermittently over a certain period, preferably when the patient had fever. The hypothesis was that the chance of growing something in culture was higher at the moments of fever. Supposedly, the bacteria were only periodically present in the blood, releasing cytokines and resulting in fever (6). This hypothesis has been debunked by a few studies (most famously by one of Riedel et al) (7), which didn’t find any correlation between the body temperature and the probability of positive blood cultures. Also, the length of the interval in which blood cultures are taken, doesn’t seem to influence their positivity ratio (6).

   
   

   The current microbiological techniques can detect very low concentrations of bacteria (1) with as main limitation the amount of blood drawn. Therefore, ordering blood cultures shouldn’t depend on fever or not.

   
   

   In a quite old study already, increasing the blood volume from 20 to 40 ml increased the amount of bacteremia detected by 19%, with an additional 10% if blood volume was increased from 40 to 60 ml (8).

   
   

   Currently, different guidelines recommend that at least 2 sets are taken (so in total 4 bottles) when blood cultures are drawn (1). Each bottle should be filled appropriately, with 8 to 10 milliliters of blood for optimal detection. However, real life data of Spain showed that on average 5 ml of blood was collected per bottle (9).

    

   In general, drawing a solitary blood culture set should be avoided due to the lack of sensitivity (too little blood volume drawn) and the difficulties of distinguishing contamination from true positive blood cultures. One possible exception might be to check for clearance of bacteremia: in one study, a single culture taken after 4 days had a sensitivity of more than 95% to exclude ongoing S. aureus bacteremia (10).

   
   

4. If ordering blood cultures, multiple sets can ben taken from one draw.

   Traditionally, it is recommended that every set of blood cultures is taken from a different draw (multi-sampling strategy). Old data even seemed to indicate that multiple draws are more sensitive, although this result was more likely due to small total blood volume inoculated (1). Moreover, pathogens can easily be distinguished from contaminants with a multi-sampling strategy.

   
   

   However, some recently published data are in favor of taking all sets of blood cultures from a single draw (single-sampling strategy). Especially, one prospective study showed that overall single-sampling was superior compared to multi-sampling (11).

    

   Apart from the promising results, there are some additional arguments to implement (at least partly) a single-sampling strategy:

   1. Like mentioned before, the main determinant of finding a positive blood culture is the total blood volume drawn. This is a solid finding in a multitude of studies.

   2. Some patients are difficult to bleed. Sticking to multi-sampling strategy in these cases, will only lead to discomfort, time loss and more solitary blood cultures.

   3. The second set is sometimes forgotten (1). Single-sampling strategy can also lead to a reduction of solitary blood cultures.

   
   

   Nevertheless, the way of medical reasoning still needs to adapt to a single-sampling strategy.

   1. Contamination should be defined differently in case of a single-sampling strategy. The main determinant should become the number of positive blood cultures and the type of micro-organism (1).

   2. Some diagnostic criteria depend on the identification of the same micro-organism in different blood draws. For instance, endocarditis as defined by the modified Duke criteria requires two positive blood cultures from separate draws for the major microbiological criterion (12).

      
      

5. Not every fever requires blood cultures.

   One of the first practical rules I was taught as an internal medicine trainee was that every feverish patient required blood cultures. Especially during night shifts I was often called for this reason. And this seems a widespread phenomenon. An American prospective study showed that blood cultures were commonly considered an essential part of the diagnostic workup for fever (13), although the current literature agrees that fever alone is a poor predictor for bacteremia in hospitalized patients (1,3,7).

   
   

   Moreover, not every infection requires blood cultures. The latest update of Dutch guidelines on community-acquired pneumonia (CAP), for example, advises against the drawing of blood cultures in CAP because of their low added value in the diagnosis (14). The same reasoning could easily be applied in other infections like appendicitis, cholecystitis or prostatitis. Therefore, some algorithms have been developed to streamline when to order blood cultures, which resulted in one study in a 30% reduction in the total number of blood cultures taken on the ward (2). An example of such algorithm is shown below (15).

References:

1. 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 May 12;7:697.

2. Fabre V, Klein E, Salinas AB,et al. A Diagnostic Stewardship Intervention To Improve Blood Culture Use among Adult Nonneutropenic Inpatients: the DISTRIBUTE Study. J Clin Microbiol. 2020 Sep 22;58(10):e01053-20.

3. Foong KS, Munigala S, Kern-Allely S, et al. Blood culture utilization practices among febrile and/or hypothermic inpatients. BMC Infect Dis. 2022 Oct 10;22(1):779.

4. Rhee C, Kadri SS, Danner RL, et al. Diagnosing sepsis is subjective and highly variable: a survey of intensivists using case vignettes. Crit Care. 2016 Apr 6;20:89.

5. Ryder JH, Van Schooneveld TC, Diekema DJ, et al. Every Crisis Is an Opportunity: Advancing Blood Culture Stewardship During a Blood Culture Bottle Shortage. Open Forum Infect Dis. 2024 Aug 23;11(9):ofae479.

6. Fabre V, Jones GF, Hsu YJ, et al. To wait or not to wait: Optimal time interval between the first and second blood-culture sets to maximize blood-culture yield. Antimicrob Steward Healthc Epidemiol. 2022 Mar 25;2(1):e51.

7. Riedel S, Bourbeau P, Swartz B, et al. Timing of specimen collection for blood cultures from febrile patients with bacteremia. J Clin Microbiol. 2008 Apr;46(4):1381-5.

8. Li J, Plorde JJ, Carlson LG. Effects of volume and periodicity on blood cultures. J Clin Microbiol. 1994 Nov;32(11):2829-31. doi: 10.1128/jcm.32.11.2829-2831.1994.

9. Bouza E, Sousa D, Rodríguez-Créixems M, et al. Is the volume of blood cultured still a significant factor in the diagnosis of bloodstream infections? J Clin Microbiol. 2007 Sep;45(9):2765-9.

10. Stewart JD, Graham M, Kotsanas D, et al. Intermittent Negative Blood Cultures in Staphylococcus aureus Bacteremia; a Retrospective Study of 1071 Episodes. Open Forum Infect Dis. 2019 Nov 18;6(12):ofz494.

11. Dargère S, Parienti JJ, Roupie E, et al. Unique blood culture for diagnosis of bloodstream infections in emergency departments: a prospective multicentre study. Clin Microbiol Infect. 2014 Nov;20(11):O920-7.

12. Fowler VG, Durack DT, Selton-Suty C, et al. The 2023 Duke-International Society for Cardiovascular Infectious Diseases Criteria for Infective Endocarditis: Updating the Modified Duke Criteria. Clin Infect Dis. 2023 Aug 22;77(4):518-526.

13. Howard-Anderson J, Schwab KE, Chang S, et al. Internal medicine residents' evaluation of fevers overnight. Diagnosis (Berl). 2019 Jun 26;6(2):157-163.

14. van Daalen FV, Boersma WG, van de Garde EMW, et al. Management of Community-Acquired Pneumonia in Adults: the 2024 Practice Guideline from The Dutch Working Party on Antibiotic Policy (SWAB) and Dutch Association of Chest Physicians (NVALT). www.swab.nl

15. Siev A, Levy E, Chen JT, et al. Assessing a standardized decision-making algorithm for blood culture collection in the intensive care unit. J Crit Care. 2023 Jun;75:154255.