Blood Culture Identification Panel Research Articles

Impact of Multiplex Polymerase Chain Reaction Technology with Antimicrobial Stewardship Interventions in the Management of Patients with Positive Blood Cultures

BackgroundTraditional blood culture identification methods often lead to delayed time to optimal antimicrobial agents. This delay may increase morbidity and mortality. Rapid diagnostic tests decrease time to organism identification. The BioFire FilmArray®, a multiplex Polymerase Chain Reaction (mPCR) technology, was implemented at CHI Memorial in October 2016. We aimed to evaluate the tool’s blood culture identification panel in conjunction with antimicrobial stewardship (AS) on improving the management of patients with blood stream infections.MethodsDuring the post-mPCR period, the AS team received real-time notifications of blood culture results via a pager system, reviewed available patient data, and made recommendations to the primary service as necessary. A retrospective chart review was conducted in adult inpatients with positive blood cultures from November 1, 2015 to December 31, 2015 (pre-mPCR period) and November 1, 2016 to January 31, 2017 (post-mPCR period). The primary endpoint was the time to effective and de-escalated antimicrobial therapy in the pre- and post-mPCR periods. Secondary endpoints included differences in pre- and post-mPCR periods in the time to pathogen identification, adverse drug reactions, Clostridium difficile infections, length of stay, in-hospital mortality, 30-day readmission and antimicrobial costs.ResultsA total of 149 patients were included; 77 in the pre-mPCR and 72 in the post-mPCR period. The median age was 70 years, 30% of patients were admitted to ICU, most common source of infection was urinary tract and most common organisms were Escherichia coli and Staphylococcus aureus. There were more patients with sepsis in the post-mPCR group. Time to pathogen identification was significantly reduced from 68.7 to 34.1 hours (P < 0.01). Median times to effective and de-escalated therapy were also significantly reduced from 5.8 to 3.8 hours (P = 0.04) and 73.6 to 36.3 hours (P < 0.01), respectively. No significant differences in secondary outcomes were noted between groups.ConclusionmPCR blood culture identification tool combined with antimicrobial stewardship leads to faster time to effective and de-escalated antimicrobial therapy.Disclosures All authors: No reported disclosures.

Impact of a Rapid Diagnostic for Bloodstream Infections with Antimicrobial Stewardship Intervention at a Comprehensive Cancer Center

BackgroundMolecular based assays reduce time to organism identification for bloodstream infections (BSI) but have limited impact without Antimicrobial Stewardship (AS) intervention. The benefit of pairing molecular based assays with AS in immunocompromised hosts is unknown. Immunocompromised patients present unique challenges to AS efforts and evaluations of traditional AS interventions are needed in this patient population. The purpose of this analysis was to evaluate the utility of a molecular based assay for BSI with and without AS intervention at a cancer hospital.MethodsA retrospective quasi-experimental pre-post study was performed to evaluate the impact of the FilmArray© Blood Culture Identification (BCID) panel with and without AS intervention on time to appropriate antimicrobial therapy defined as de-escalation to the narrowest spectrum agent taking into account need to cover concomitant infections and antibiotic allergies or intolerances. We included inpatients with positive blood cultures between 2014 and 2016 in three separate 100-day cohorts: prior to BCID implementation (pre); after BCID implementation without AS intervention (post); after BCID implementation with AS intervention (ASP) involving blood culture review and antimicrobial treatment recommendations.Results130 of 155 subjects with a BSI during the study period were included. The pre (n = 52), post (n = 43), and ASP (n = 35) cohorts were balanced with the exception of more immunocompromised patients in the ASP compared with pre (91% vs 65%; P < 0.01) and post cohorts (91% vs 72%; P = 0.04). Time to appropriate antimicrobial therapy, although not statistically different, was shorter in the post and ASP groups as compared with the pre-BCID group [40.2 hours (pre) vs 24.6 hours (post) vs 25.9 hours (ASP); P = 0.46].ConclusionImplementation of the BCID in a cancer hospital was associated with reduced time to appropriate antimicrobial therapy; however, additional reductions were not seen when coupled with AS intervention. Further large-scale evaluation is warranted due to unbalanced study groups and small study size to understand the role of rapid diagnostics and AS interventions for BSIs in immunocompromised populations.Disclosures R. Benefield, Merck: Grant Investigator, Research grant

Performance of the FilmArray Blood culture identification panel in positive blood culture bottles and cerebrospinal fluid for the diagnosis of sepsis and meningitis.

Sepsis and meningitis are life threatening medical conditions. Culture-based methods are used for identification of the causative pathogens, but they can be improved by implementation of additional test systems. We evaluated the performance of the novel FilmArray blood culture identification (BCID; Biofire Diagnostics) panel for rapid and accurate identification of microorganisms in positive blood cultures and additionally, in this cerebrospinal fluid (CSF) pilot study for direct testing of CSF. A total of 107 positive blood cultures and 20 CSF samples (positive and negative) were investigated and compared to the routine procedures. Of the 107 positive blood cultures, 90.7% (97/107) showed monomicrobial growth and 9.3% (10/107) polymicrobial growth. The FilmArray BCID panel covered 89.3% (25/28) of the bacteria and 100% (2/2) of the yeasts found in this study and accurately identified all of them.From the 20 retrospective analyzed CSF, in 9 positive specimens 6 different bacterial species were identified. Discrepant identification results were found in 25% (5/20) and a low sensitivity of 50% (95% CI of 15.7% to 84.3%) was detected.Our study confirms the FilmArray BCID panel as a rapid, easy to handle PCR system with a good performance in positive blood cultures without Gram-staining result. However, our results additionally suggest that the system is not useful for direct CSF testing due to poor sensitivity.

Clinical Impact and Provider Acceptability of Real-Time Antimicrobial Stewardship Decision Support for Rapid Diagnostics in Children With Positive Blood Culture Results.

Rapid diagnostic technologies for infectious diseases have the potential to improve clinical outcomes, but guideline-recommended antimicrobial stewardship (AS) strategies are not currently optimized for rapid intervention. We evaluated the clinical impact and provider acceptability of implementing real-time AS decision support for children with positive blood culture results according to the FilmArray blood culture identification panel (BCID [BioFire Diagnostics]) at Children's Hospital Colorado. A pre-post quasi-experimental design was used to compare the outcomes of 100 postintervention children with positive blood culture results matched with 200 preintervention control children. Causative organisms in the preintervention group were identified using conventional microbiologic techniques and communicated to providers by a microbiology technologist. Postintervention organisms were identified by the BCID and communicated by an AS provider in real time with interpretation and antimicrobial recommendations. The primary outcome was time to optimal antimicrobial therapy (time from blood culture collection to start of predetermined pathogen-specific regimen or antimicrobial discontinuation for contaminants) compared by a log-rank test and Kaplan-Meier analysis. Provider acceptability of the intervention was assessed via E-mailed surveys. The median time to optimal therapy decreased from 60.2 hours before intervention to 26.7 hours after intervention (P = .001). Among children with blood cultures that contained true pathogens, the time to effective antimicrobial therapy decreased from 6.9 to 3.4 hours (P = .03). Unnecessary antibiotic initiation for children with a culture that contained organisms considered to be contaminants decreased from 76% to 26% (P < .001). Providers reported a change in management as a result of BCID results in 73% of the cases and a mean overall satisfaction rating of 4.8 on a 5-point Likert scale. Real-time AS decision support for rapid diagnostics is associated with improved antimicrobial use and high satisfaction ratings by providers.

Benefits of Adding a Rapid PCR-Based Blood Culture Identification Panel to an Established Antimicrobial Stewardship Program.

Studies have demonstrated that the combination of antimicrobial stewardship programs (ASP) and rapid organism identification improves outcomes in bloodstream infections (BSI) but have not controlled for the incremental contribution of the individual components. Hospitalized adult patients with blood culture pathogens on a rapid, multiplex PCR-based blood culture identification panel (BCID) that included 19 bacterial species, 5 Candida spp., and 4 antimicrobial resistance genes were studied over sequential time periods in a pre-post quasiexperimental study in 3 groups in the following categories: conventional organism identification (controls), conventional organism identification with ASP (AS), and BCID with ASP (BCID). Clinical and economic outcomes were compared between groups. There were 783 patients with positive blood cultures; of those patients, 364 (115 control, 104 AS, and 145 BCID) met inclusion criteria. The time from blood culture collection to organism identification was shorter in the BCID group (17 h; P < 0.001) than in the control group (57 h) or the AS group (54 h). The BCID group had a shorter time to effective therapy (5 h; P < 0.001) than the control group (15 h) or AS group (13 h). The AS (57%) and BCID (52%) groups had higher rates of antimicrobial de-escalation than the control group (34%), with de-escalation occurring sooner in the BCID group (48 h; P = 0.034) than in the AS group (61 h) or the control group (63 h). No difference between the control group, AS group, and BCID group was seen with respect to mortality, 30-day readmission, intensive care unit length of stay (LOS), postculture LOS, or costs. In patients with BSI, ASP alone improved antimicrobial utilization. Addition of BCID to an established ASP shortened the time to effective therapy and further improved antimicrobial use compared to ASP alone, even in a setting of low antimicrobial resistance rates.

Impact of a rapid multiplex polymerase chain reaction blood culture identification technology on outcomes in patients with vancomycin-resistant Enterococcal bacteremia

Background: Early appropriate antibiotic selection is associated with favorable clinical outcomes. We evaluated the clinical impact of rapid detection of vancomycin-resistant Enterococcal bacteremia (VREB) by the FilmArray blood culture identification (BCID) panel coupled with antimicrobial stewardship program (ASP) interventions.Methods: Hospitalized adult patients with VREB identified by conventional methods (CM) were compared to patients with VREB identified by BCID. Real time alerts of BCID results were provided to the ASP for intervention. Outcomes were compared between groups.Results: Sixty-eight patients with VREB were included (CM, n = 45; BCID, n = 23). No significant differences in demographics, pre-existing conditions, or clinical characteristics were observed. Significant reductions were demonstrated between CM and BCID groups in median hours to organism identification (47.7 versus 18.2, p < 0.001), to identification of vancomycin resistance from time of culture positivity (50.1 versus 1.2, p < 0.001), and time to effective therapy (50.3 versus 20.8, p < 0.001). Differences between CM and BCID did not reach statistical significance for mortality (35.6% versus 26.1%), 30-day readmission rate (31.0% versus 17.6%), intensive care length of stay [LOS] (8.0 versus 7.0 days), post-culture LOS (14.6 versus 14.1 days) or median hospital costs per patient ($95,826 versus $53,195).Conclusions: In patients with VREB, rapid organism and resistance detection by the BCID panel with ASP intervention significantly reduced time to initiation of effective therapy by over 24 hours. Non-significant improvements in clinical outcomes were observed. Additional studies are needed to determine the full implications of BCID technology on patient outcome.

Rapid Identification of Microorganisms by FilmArray Blood Culture Identification Panel Improves Clinical Management in Children.

Blood cultures are a common investigation for children admitted to hospital. In routine practice, it takes at least 24 hours to identify an organism as a contaminant or clinically significant. FilmArray Blood Culture Identification Panel (FA-BCIP) is a multiplex polymerase chain reaction that can detect 24 pathogens within 1 hour. We assessed whether results from FA-BCIP lead to changes in clinical management in a tertiary referral paediatric hospital. We prospectively studied children having blood cultures taken at our tertiary children's hospital. Blood cultures were monitored and organisms identified using standard methods. FA-BCIP was performed when growth was initially detected in first positive blood cultures per episode, between January 1 and June 30, 2014. Assessment of whether the FA-BCIP result altered clinical management was made, specifically focused on antimicrobial stewardship and length of stay. FA-BCIP was done on 117 positive blood cultures; 74 (63%) grew clinically significant organisms, 43 (37%) grew contaminants. FA-BCIP results were judged to alter clinical management in 63 of the 117 episodes (54%). Antimicrobials were started/altered in 23 (19%) episodes and de-escalated/withheld/stopped in 29 (25%) episodes. Ten children were discharged from hospital earlier, which saved a cumulative total of 14 bed days. Rapid identification of microorganisms in pediatric blood cultures by FA-BCIP, led to changes in clinical management for half of the episodes. This improved antimicrobial stewardship and allowed early discharge from hospital for 10% of children. Future studies should focus on how best to use this technology in a cost-effective manner.

Evaluation of the BioFire® FilmArray® Blood Culture Identification Panel on positive blood cultures in a regional hospital laboratory in KwaZulu-Natal.

BackgroundThere are presently many non-culture-based methods commercially available to identify organisms and antimicrobial susceptibility from blood culture bottles. Each platform has its benefits and limitations. However, there is a need for an improved system with minimal hands-on requirements and short run times.ObjectivesIn this study, the performance characteristics of the FilmArray® BCID Panel kit were evaluated to assess the efficiency of the kit against an existing system used for identification and antimicrobial susceptibility of organisms from blood cultures.MethodsPositive blood cultures that had initially been received from hospitalised patients of a large quaternary referral hospital in Durban, South Africa were processed as per routine protocol at its Medical Microbiology Laboratory. Positive blood cultures were processed on the FilmArray BCID Panel kit in parallel with the routine sample processing. Inferences were then drawn from results obtained.ResultsOrganism detection by the FilmArray BCID panel was accurate at 92.6% when organisms that were on the repertoire of the kit were considered, compared to the combination methods (reference method used in the study laboratory). Detection of the antimicrobial resistance markers provided by the panel and reference method demonstrated 100% consistency. Blood cultures with a single organism were accurately identified at 93.8% by FilmArray, while blood cultures with more than one organism were identified at 85.7%.ConclusionThe FilmArray BCID Panel kit is valuable for detection of organisms and markers of antibiotic resistance for an extensive range of organisms.

Evaluation of the FilmArray Blood Culture Identification Panel: Results of a Multicenter Controlled Trial.

Sepsis is a major cause of morbidity, mortality, and increased medical expense. Rapid diagnosis improves outcomes and reduces costs. The FilmArray blood culture identification panel (BioFire Diagnostics LLC, Salt Lake City, UT), a highly multiplexed PCR assay, can identify 24 etiologic agents of sepsis (8 Gram-positive, 11 Gram-negative, and 5 yeast species) and three antimicrobial resistance genes (mecA, vanA/B, and blaKPC) from positive blood culture bottles. It provides results in about 1 h with 2 min for assay setup. We present the results of an eight-center trial comparing the sensitivity and specificity of the panel with those of the laboratories' standard phenotypic identification techniques, as well as with molecular methods used to distinguish Acinetobacter baumannii from other members of the A. calcoaceticus-A. baumannii complex and to detect antimicrobial resistance genes. Testing included 2,207 positive aerobic blood culture samples, 1,568 clinical and 639 seeded. Samples were tested fresh or were frozen for later testing within 8 h after the bottles were flagged as positive by an automated blood culture system. At least one organism was detected by the panel in 1,382 (88.1%) of the positive clinical specimens. The others contained primarily off-panel organisms. The panel reported multiple organisms in 81 (5.86%) positive clinical specimens. The unresolved blood culture identification sensitivity for all target detections exceeded 96%, except for Klebsiella oxytoca (92.2%), which achieved 98.3% sensitivity after resolution of an unavoidable phenotypic error. The sensitivity and specificity for vanA/B and blaKPC were 100%; those for mecA were 98.4 and 98.3%, respectively.

Emergency management in bacterial meningitis and sepsis: application of real time-polymerase chain reaction and FilmArray technology performed directly on cerebrospinal fluid and blood samples

&lt;em&gt;Background&lt;/em&gt; &lt;em&gt;and&lt;/em&gt; &lt;em&gt;Aims&lt;/em&gt;. Bacterial meningitis and sepsis are medical emergencies where tests with a high sensitivity and short turn around time (TAT) are crucial for an early targeted therapy. Aim of this study was the evaluation of an optimal diagnostic strategy for infectious meningitis/sepsis management, assessing seven methods: cerebrospinal fluid (CSF) physical-chemical examination, CSF cultural tests (CCT), Gram stained smears (GSS), CSF latex agglutination test (CLAT), blood culture (BC), Real-Time (RT)-PCR and FilmArray Technology (FAT) performed directly on CSF/blood. &lt;br /&gt;&lt;em&gt;Materials&lt;/em&gt; &lt;em&gt;and&lt;/em&gt; &lt;em&gt;Methods&lt;/em&gt;. Samples of CSF (240), blood (180) and cavitary fluids (9) were tested by commercial RT-PCR (Eurospital and Liferiver kits) and traditional methods. Positive samples (BC and RT-PCR) were tested by FAT (Blood Culture Identification Panel, Biofire, Salt Lake City, UT, USA) performed directly on CSF, blood and cavitary fluids. &lt;br /&gt;&lt;em&gt;Results&lt;/em&gt;. In CSF, GSS, CLAT, CCT, RT-PCR and FAT sensitivity was 41%, 35%, 41%, 100% and 62,5%, respectively. In blood, BC, RT-PCR and FAT sensitivity was 96%, 70% and 44%, respectively. TAT was 48-96 hrs, 3 hrs and 1 hr and NPV was 98%, 89% and 57%, respectively. &lt;br /&gt;&lt;em&gt;Conclusions&lt;/em&gt;. For sepsis management, RT-PCR is faster than BC (3 hrs vs 24-72 hrs), but limited by a low overall sensitivity (70%), due to the low number of detectable pathogens; FAT, performed directly on positive BC should replace biochemical identification (Vitek 2, Biomérieux Marcy-l’Étoile, France) reducing TAT (1 hr &lt;em&gt;vs&lt;/em&gt; 12 hrs). For meningitis management, RT-PCR is the most sensitive and rapid method used in routine and emergency regimen. It is cost effective and it represents the gold standard for diagnosis and follow-up of patients under treatment. For meningitis management, FAT, with a higher sensitivity and rapidity and an easier and objective interpretation, should replace CLAT and GSS in emergency regimen.

Clinical and economic impact of antimicrobial stewardship interventions with the FilmArray blood culture identification panel

The purpose of this study was to evaluate the impact of the FilmArray Blood Culture Identification (BCID) Panel on the management of patients with blood cultures growing gram positive cocci and Candida. We retrospectively compared clinical and economic outcomes between patients during the BCID testing period and a matched historical control group before BCID testing was introduced. A total of 84 BCID patients were matched to 252 historical controls. BCID identification of coagulase negative staphylococci contaminants resulted in shorter post-culture length of stay (P < 0.008) and saved roughly $30,000 per 100 patients tested. The BCID led to shorter duration of empirical vancomycin for patients with contaminated blood cultures (P = 0.005) and methicillin-susceptible Staphylococcus aureus bacteremia (P < 0.001). Patients with vancomycin-resistant enterococcal bacteremia received active therapy earlier than historical controls (P = 0.047). The BCID, coupled with antimicrobial stewardship intervention, was a cost effective tool to improve patient care.

Efficacy of the FilmArray blood culture identification panel for direct molecular diagnosis of infectious diseases from samples other than blood.

Molecular-based techniques reduce the delay in diagnosing infectious diseases and therefore contribute to better patient outcomes. We assessed the FilmArray blood culture identification (BCID) panel (Biofire Diagnostics/bioMérieux) directly on clinical specimens other than blood: cerebrospinal, joint, pleural and ascitic fluids, bronchoscopy samples and abscesses. We compared the results from 88 samples obtained by culture-based techniques. The percentage of agreement between the two methods was 75 % with a Cohen κ value of 0.51. Global sensitivity and specificity using the FilmArray BCID panel were 71 and 97 %, respectively. Sensitivity was poorer in samples with a low bacterial load, such as ascitic and pleural fluids (25 %), whereas the sensitivity for abscess samples was high (89 %). These findings suggest that the FilmArray BCID panel could be useful to perform microbiological diagnosis directly from samples other than positive blood cultures, as it offers acceptable sensitivity and moderate agreement with conventional microbiological methods. Nevertheless, cost-benefit studies should be performed before introducing this method into algorithms for microbiological diagnostics.

Rapid Detection of Bloodstream Pathogens in Liver Transplantation Patients With FilmArray Multiplex Polymerase Chain Reaction Assays: Comparison With Conventional Methods

BackgroundBloodstream infection (BSI) is an important concern in transplant patients. Early intervention with appropriate antimicrobial therapy is critical to better clinical outcome; however, there is significant delay when conventional identification methods are used. MethodsWe aimed to determine the diagnostic performance of the FilmArray Blood Culture Identification Panel, a recently approved multiplex polymerase chain reaction assay detecting 24 BSI pathogens and 3 resistance genes, in comparison with the performances of conventional identification methods in liver transplant (LT) patients. A total of 52 defined sepsis episodes (signal-positive by blood culture systems) from 45 LT patients were prospectively studied. ResultsThe FilmArray successfully identified 37 of 39 (94.8%) bacterial and 3 of 3 (100%) yeast pathogens in a total of 42 samples with microbial growth, failing to detect only 2 of 39 (5.1%) bacterial pathogens that were not covered by the test panel. The FilmArray could also detect additional pathogens in 3 samples that had been reported as having monomicrobial growth, and it could detect Acinetobacter baumannii in 2 samples suspected of skin flora contamination. The remaining 8 blood cultures showing a positive signal but yielding no growth were also negative by this assay. Results of MecA, KPC, and VanA/B gene detection were in high accordance. The FilmArray produced results with significantly shorter turnaround times (1.33 versus 36.2, 23.6, and 19.5 h; P < .05) than standard identification methods, Vitek II, and Vitek MS, respectively. ConclusionsThis study showed that the FilmArray appeared as a reliable alternative diagnostic method with the potential to mitigate problems with protracted diagnosis of the BSI pathogens in LT patients.

Implementation and performance of the BioFire FilmArray® Blood Culture Identification panel with antimicrobial treatment recommendations for bloodstream infections at a midwestern academic tertiary hospital

The FilmArray® Blood Culture Identification (BCID) panel was recently implemented at a midwestern academic tertiary care hospital to provide rapid identification (ID) of common pathogens from positive blood cultures. This study evaluated the clinical performance of the BCID panel compared to culture-based ID methods. One hundred thirty-eight monomicrobial and 8 polymicrobial blood cultures were evaluated during the 30-day study resulting in the ID of 152 total organisms by culture with 115 organisms correctly identified using the BCID panel. The BCID panel had sensitivities of 80.4% (115/152) for all organisms identified during the study and 94.6% (115/122) when considering only on-panel organisms. BCID panel specificity was 100%. Implementation of the BCID panel was coupled with the development of empiric therapy recommendations for bloodstream infections by the antimicrobial stewardship team. Based on this study, the FilmArray® BCID panel is a rapid and reliable test for the detection of common bloodstream pathogens, and therapeutic decisions can be based upon panel results.

Comparison between MALDI-TOF MS and FilmArray Blood Culture Identification panel for rapid identification of yeast from positive blood culture

In this study we evaluated MALDI-TOF MS and FilmArray methods for the rapid identification of yeast from positive blood cultures. FilmArray correctly identified 20/22 of yeast species, while MALDI-TOF MS identified 9/22. FilmArray is a reliable and rapid identification system for the direct identification of yeasts from positive blood cultures.

Clinical Evaluation of the FilmArray Blood Culture Identification Panel in Identification of Bacteria and Yeasts from Positive Blood Culture Bottles

The FilmArray platform (FA; BioFire, Salt Lake City, UT) is a closed diagnostic system allowing high-order multiplex PCR analysis with automated readout of results directly from positive blood cultures in 1 h. In the present study, we evaluated the clinical performance of the FilmArray blood culture identification (BCID) panel, which includes 19 bacteria, five yeasts, and three antibiotic resistance genes. In total, 206 blood culture bottles were included in the study. The FilmArray could identify microorganisms in 153/167 (91.6%) samples with monomicrobial growth. Thirteen of the 167 (7.8%) microorganisms were not covered by the FilmArray BCID panel. In 6/167 (3.6%) samples, the FilmArray detected an additional microorganism compared to blood culture. When polymicrobial growth was analyzed, the FilmArray could detect all target microorganisms in 17/24 (71%) samples. Twelve blood culture bottles that yielded a positive signal but showed no growth were also negative by FilmArray. In 3/206 (1.5%) bottles, the FilmArray results were invalid. The results of the FilmArray were reproducible, as demonstrated by the testing and retesting of five bottles in the same day and a longitudinal follow-up of five other blood cultures up to 4 weeks. The present study shows that the FilmArray is a rapid identification method with high performance in direct identification of bacteria and yeasts from positive blood culture bottles.