New Rapid Diagnostic Testing for Bloodstream Infections….Coming soon for UC Davis Health System

Raymond Gong, M.D., Pathology Resident
Anna Maria Romanelli, Ph.D., Medical Director of Clinical Microbiology Laboratory

Background:

Bloodstream infections are a leading cause of morbidity and mortality in the United States [1].  The timely identification of blood borne pathogens and the selection of appropriate antimicrobial therapy can significantly improve clinical outcomes.

At the UC Davis Clinical Microbiology Laboratory, blood cultures are continuously monitored by an automated BACTEC FX blood culture instrument.  Blood culture bottles are incubated for a total of 5 days and continuously checked by the instrument every 10 minutes for the growth of organisms.  If growth is detected, a Gram stain will be performed from the positive blood culture and the clinician will be notified by a Clinical Laboratory Scientist of the results.  Our current practice for organism identification from positive blood cultures relies on the sub-culturing of isolates followed by identification and susceptibility testing via MALDI-TOF and BD Phoenix systems, respectively.  Blood culture identification by our current method is reported within in 48-72 hours or potentially longer, depending on the organism’s growth characteristics, from the initial positive Gram stain.

Laboratory Best Practice:

The UC Davis Clinical Microbiology Laboratory is in the final stages of validation for the BioFire FilmArray Blood Culture Identification (BCID) Panel. The BCID Panel is a qualitative nucleic acid-based PCR test that can identify a panel of bacterial and fungal pathogens commonly associated with bloodstream infections, as well as detect antimicrobial resistance genes from positive blood culture samples [2]. The performance characteristics of the BCID Panel show an overall sensitivity of 98% and specificity of 99.9% [3]. The test’s high clinical sensitivity and specificity have been supported by several additional studies [4-6].

The following 27 targets will be tested by the BCID Panel:

Gram-Positive Bacteria Gram-Negative Bacteria
Enterococcus Acinetobacter baumannii
Listeria monocytogenes Haemophilus influenza
Staphylococcus Neisseria meningitides
Staphylococcus aureus Enterobacteriaceae
Streptococcus Enterobacter cloacae complex
Streptococcus agalactiae Escherichia coli
Streptococcus pyogenes Klebsiella oxytoca
Streptococcus pneumoniae Klebsiella pneumoniae
Proteus
Serratia marcescens
Pseudomonas aeruginosa
Yeast Antimicrobial Resistance Genes
Candida albicans  mecA – methicillin resistance
Candida glabrata  vanA/B – vancomycin resistance
Candida krusei  KPC – carbapenem resistance
Candida parapsilosis
Candida tropicalis

[/fusion_table}

The BCID Panel will improve our practice for blood culture identification. The test will be integrated into the current workflow at the point when new positive blood cultures are detected. After being flagged as positive by the blood culture instrument and examined on Gram stain by a Clinical Laboratory Scientist, a sample will be drawn directly from the blood culture bottle and tested with the BCID panel on a BioFire FilmArray Torch instrument. The BCID Panel will provide results within 2 hours of a new positive blood culture, in advance of confirmatory identification and susceptibility testing of sub-cultured isolates. The rapid identification of organisms and antimicrobial resistance genes by the BCID Panel will decrease turnaround time to diagnosis and allow for earlier, targeted antimicrobial therapy. Antimicrobial stewardship intervention will be built in through the laboratory’s result reporting. Reports for the BCID panel will provide comments that will aid interpretation of results for antimicrobial resistance genes if detected.

As shown in prior studies, rapid diagnosis with the BCID Panel in combination with antimicrobial stewardship has shown shorter times from blood culture collection to organism identification and shorter times to effective, narrowed therapy when compared to control groups [7, 8]. In addition, this approach has resulted in shorter times to antimicrobial de-escalation and higher rates of de-escalation. Given the demonstrated success of the test, our goal with incorporating the BCID Panel is to follow suit and improve upon bloodstream infection testing and management for our patients. By providing rapid identification and enabling earlier optimization of antimicrobial therapy, we may see benefits such as shortened hospital length of stay and lower healthcare costs overall.

However, as with all laboratory tests, the BCID Panel will carry certain limitations and a brief overview is provided in the following discussion [2]. As a test that is not all-inclusive, the BCID panel will not detect organisms outside of the BCID panel of 27 targets (see above table for test targets. Finally, a negative result does not exclude the possibility of a bloodstream infection, as it may be due to causes including sequence variation in targeted regions, the presence of inhibitors and interfering substances, organism levels below the test’s limit of detection, or an infection caused by an organism not detected by the panel. Results from this test will need to be correlated with standard identification and susceptibility testing of sub-cultured isolates in addition to the clinical history, epidemiological data, and other data available to the clinician.

Prior to its implementation, the performance characteristics of the BCID Panel must be verified to confirm the new test’s suitability for use within the UCD Health System. This ongoing process has entailed extensive testing of non-clinical control organisms and clinical patient specimens in comparison to reference methods. Following the completion of validation, the next steps include developing standard operating procedures and training personnel for use.

The UC Davis Clinical Microbiology Laboratory is also currently validating the BioFire FilmArray Gastrointestinal (GI) Panel, which, like the BCID panel, is run on the BioFire FilmArray Torch system and will test for 22 total targets of enteric infection including bacteria, viruses, and parasites [9]. The GI panel will similarly provide rapid identification within 2 hours and stands to offer clinical benefits such as decreased number of tests per patient, turnaround time to diagnosis, and hospital length of stay.

Bottom Line:

As it nears completion of validation, the BCID panel will improve upon our current practice for blood culture identification. The BCID panel will rapidly test for 27 targets within hours of detection of positive blood cultures. The test allows for decreased turnaround time to identification and susceptibility results, which, together with antimicrobial stewardship, will lead to more rapid implementation of targeted treatment for patients, shortened hospital length of stay, and lower healthcare costs overall.

The BioFire FilmArray Gastrointestinal (GI) Panel is also currently being validated by our laboratory. Like the BCID panel, the GI panel will be run on the BioFire FilmArray Torch system and will also be implemented in the near future.

References:

  1. Bearman GM, Wenzel RP. Bacteremias: a leading cause of death. Arch Med Res. 2005;36:646–659.
  2. FilmArray Blood Culture Identification Panel (BCID) Instruction Booklet (RFIT-PRT-0369-02). BioFire Diagnostics.
  3. Aggregated Prospective Performance from the FilmArray® Blood Culture Identification Panel Clinical Trial. Data on File, BioFire Diagnostics.
  4. Blaschke AJ, Heyrend C, Byington CL, Fisher MA, Barker E, Garrone NF, Thatcher SA, Pavia AT, Barney T, Alger GD, Daly JA, Ririe KM, Ota I, Poritz MA. Rapid identification of pathogens from positive blood cultures by multiplex polymerase chain reaction using the FilmArray system. Diagn Microbiol Infect Dis. 2012;74:349–355.
  5. Altun O, Almuhayawi M, Ullberg M, Ozenci V. Clinical evaluation of the FilmArray blood culture identification panel in identification of bacteria and yeasts from positive blood culture bottles. J Clin Microbiol. 2013;51:4130-4136.
  6. Salimnia H, Fairfax MR, Lephart PR, Schreckenberger P, DesJarlais SM, Johnson JK, Robinson G, Carroll KC, Greer A, Morgan M, Chan R, Loeffelholz M, Valencia-Shelton F, Jenkins S, Schuetz AN, Daly JA, Barney T, Hemmert A, Kanack KJ. Evaluation of the Filmarray blood culture identification panel: results of a multicenter controlled trial. J Clin Microbiol 2016;54:687–698.
  7. Banerjee R, Teng CB, Cunningham SA, Ihde SM, Steckelberg JM, Moriarty JP, Shah ND, Mandrekar JN, Patel R. Randomized trial of rapid multiplex polymerase chain reaction–based blood culture identification and susceptibility testing. Clin Infect Dis 2015;61:1071–1080.
  8. MacVane SH, Nolte FS. Benefits of adding a rapid PCR-based blood culture identification panel to an established antimicrobial stewardship program. J Clin Microbiol 2016;54:2455–2463.
  9. FilmArray Gastrointestinal Panel (GI) Instruction Booklet (RFIT-PRT-0143-04). BioFire Diagnostics.
By | 2019-02-21T10:10:27+00:00 February 15, 2019|0 Comments

Leave A Comment