MAUDE Adverse Event Report: BIOFIRE DIAGNOSTICS LLC BIOFIRE® BLOOD CULTURE IDENTIFICATION 2 (BCID2) PANEL

Model Number RFIT-ASY-0147

Device Problem False Negative Result (1225)

Patient Problems Renal Failure (2041); Sepsis (2067)

Event Date 03/10/2023

Event Type  Death  

Manufacturer Narrative

Investigation: on (b)(6) 2023, a 76-year-old, female patient was admitted to the hospital with symptoms of altered mental status and possible urinary tract infection (uti).At 10:47 p.M., a blood culture sample was collected for testing.On (b)(6) 2023, the patient was admitted to intensive care unit (icu) due to septic shock.The patient had hydronephrosis and pyelonephritis.A ureteral stent was placed successfully.A second blood culture sample was collected for testing at 1:47 a.M.At 2:54 p.M., the first blood culture sample was tested on the biofire bcid2 panel.The biofire bcid2 panel reported enterobacterales and klebsiella pneumoniae as detected.Gram stain observed gram-negative rods.The patient was on piperacillin/tazobactam, metronidazole, and vancomycin before the biofire bcid2 panel testing (unknown if this treatment was initiated on (b)(6) 2023).On (b)(6) 2023, culture of the first and second samples identified k.Pneumoniae via vitek® ms.At 2:52 pm, the patient died.The final diagnosis of the patient was sepsis/septic shock, acute renal failure, lactic acidosis, and uti.The day after the patient died, on (b)(6) 2023, extended spectrum beta-lactamase (esbl) was identified via vitek® 2 for the k.Pneumoniae isolates culture from both the first and second samples.Two days after the patient died, on (b)(6) 2023, two more biofire bcid2 panel tests were performed - one using the first blood culture sample and one using the second blood culture sample.Both biofire bcid2 panel tests reported enterobacterales, klebsiella pneumoniae, and ctx-m as detected.The customer reported that due to the false negative ctx-m biofire bcid2 panel result on (b)(6) 2023, the patient did not receive carbapenem (which would have been used if it was known that the k.Pneumoniae was esbl producing).The laboratory supervisor stated that because the patient did not receive carbapenems, the biofire bcid2 panel result contributed to the patient's death.Biofire was informed that both blood culture samples were still available and requested to receive them for in-house testing.Biofire received the samples on (b)(6)2023 and is in the testing process.Quality control (qc) records for pouch lot# 2nv022 (kit lot# 2246322) were reviewed.This pouch lot passed qc criteria and was found within specifications.No run malfunction occurred and the filmarray instrument (serial number# (b)(4) was working within designed specifications.Biofire's investigation into this event is ongoing and further information has been requested from the customer.The full investigation, in-house testing results, and associated conclusions will be provided in the final report.No remedial action, corrective action, preventive action, or fsca has been deemed necessary at this time.Conclusion: investigation ongoing.

Event Description

Summary: (b)(6) reported a potential false negative ctx-m result on the biofire blood culture identification 2 (bcid2) panel after testing a patient blood culture sample.Due to the biofire bcid2 panel result, the patient was not treated with carbapenem.The patient ultimately passed away and the laboratory supervisor stated that they believe the biofire bcid2 panel result contributed to the patient's death.Biofire has requested further information from the customer and is currently investigating this event.No remedial action, corrective action, preventive action, or field safety corrective action (fsca) has been deemed necessary at this time.

Manufacturer Narrative

Investigation: on (b)(6), 2023, a 76-year-old, female patient was admitted to the hospital with symptoms of altered mental status and possible urinary tract infection (uti).At 10:47 p.M., a blood culture sample was collected for testing due to a clinical indication of septic shock.On (b)(6), 2023, the patient was admitted to intensive care unit (icu) due to septic shock.The patient had hydronephrosis and pyelonephritis.A ureteral stent was placed successfully.A second blood culture sample was collected for testing at 1:47 a.M.At 2:54 p.M., the first blood culture sample was tested on the biofire bcid2 panel 20 minutes after the blood culture bottle signaled positive.The biofire bcid2 panel reported enterobacterales and k.Pneumoniae as detected.Gram-negative rods were observed on the gram stain.The patient was on piperacillin/tazobactam, metronidazole, and vancomycin before the biofire bcid2 panel testing (unknown if this treatment was initiated on (b)(6), 2023, or (b)(6), 2023).On (b)(6), 2023, culture of the first sample identified k.Pneumoniae via vitek® ms at 9:58 am.At 2:52 pm, the patient died.The final diagnosis of the patient was sepsis/septic shock, acute renal failure, lactic acidosis, and uti.The patient's cause of death was determined to be sepsis.At 7:18 pm, vitek® ms identified k.Pneumoniae in the culture of the second sample.The day after the patient died, on (b)(6), 2023, extended spectrum beta-lactamase (esbl) resistance phenotype was identified via vitek® 2 for the k.Pneumoniae isolates culture from both the first and second samples.Two days after the patient died, on (b)(6), 2023, two more biofire bcid2 panel tests were performed - one using the first blood culture sample and one using the second blood culture sample.Both biofire bcid2 panel tests reported enterobacterales, klebsiella pneumoniae, and ctx-m as detected.The customer reported that due to the false negative ctx-m biofire bcid2 panel result on (b)(6), 2023, the patient did not receive carbapenem (which would have been used if it was known that the k.Pneumoniae was esbl producing).The laboratory supervisor stated that because the patient did not receive carbapenems, the biofire bcid2 panel result contributed to the patient's death.Biofire requested the patient samples for in-house testing.The results of that investigation are as follows: the customer provided biofire with four samples from the patient that were shipped refrigerated.Biofire received two aerobic and two anaerobic blood culture bottles, labeled aer1/aer2 and ana1/ana2 respectively, where aer2 was the initial bottle that was tested on the biofire bcid2 panel at the customer site and aer1 appeared to be the second bottle tested.(ana1/ana2 were collected at the same time as the aerobic bottles but were not tested via the biofire bcid2 panel at the customer site).Biofire tested each bottle in triplicate on the biofire bcid2 panel.Aer2, aer1, and ana2 were all positive for ctx-m, however, ana1 was negative for ctx-m.To confirm the customer's vitek® results each sample was plated on blood, macconkey, hardychrom¿ uti, and hardychrom¿ esbl agar plates in duplicate with/without antibiotic disk and incubated for a day at 37°c.The colony morphology was consistent across all the culture plates.Vitek® ms determined the isolates as k.Pneumoniae (99.9% confidence); whereas vitek® 2 antimicrobial susceptibility testing (ast) determined ana2 and aer1 to be esbl positive and ana1 and aer2 were determined to be esbl negative.Isolates were used to create pbst suspensions, which were also tested on the biofire bcid2 panel.All samples were id'd as k.Pneumoniae with both aer1 and ana2 positive for ctx-m, and aer2 negative for ctx-m.Isolates from ana1 bottle that were cultured with an antibiotic disk on the plate demonstrated an esbl phenotype (suggestive of ctx-m), while isolates from ana1 that did not have an antibiotic disk on the culture plate were negative for the esbl phenotype (suggestive ctx-m was absent).All of these isolates were also determined to be k.Pneumoniae by vitek® 2 & vitek® ms.From the above testing, biofire determined that samples aer1 and ana2 demonstrated consistent positivity for ctx-m both on biofire bcid2 panel and vitek® testing.However, aer2 (the initial bottle tested for the patient) and ana1 demonstrated a mixture of positive and negative esbl results.Because both positive and negative esbl results were observed for isolated strains of k.Pneumoniae, it is likely that a mixed population of k.Pneumoniae was present; both an esbl-producing strain (through the ctx-m mechanism), and a strain that does not express the ctx-m gene or demonstrate the same esbl activity.The discordance between the customer's biofire bcid2 panel run files can be reasonably equated to the initial dominance of a non-esbl k.Pneumoniae strain that likely outgrew the esbl expressing strain.Biofire suspects that over time, the gradual increase of the esbl expressing k.Pneumoniae strain was able to grow to concentration the ctx-m target was able to be detected by the biofire bcid2 panel.Quality control (qc) records for pouch lot# 2nv022 (kit lot# 2246322) were reviewed.This pouch lot passed qc criteria and was found within specifications.No run malfunction occurred and the filmarray instrument (serial number# (b)(6)) was working within designed specifications.Conclusion: based on the information provided, the investigation concluded that the most likely cause for the discrepant result was a mixed culture of esbl negative (ctx-m negative) and esbl-producing (ctx-m positive) k.Pneumoniae.Biofire internally investigated four blood culture bottles from the patient (2 aerobic and 2 anaerobic), where it was determined there were likely mixed cultures of k.Pneumoniae species.One strain produced esbl susceptibilities via the ctx-m mechanism, and another strain that did not demonstrate the same antibiotic resistance.It is proposed during the initial biofire bcid2 panel test of the aerobic blood culture bottle on (b)(6), 2023, the esbl sensitive k.Pneumoniae strain was growing at a concentration that likely drove the bottle to positivity and was at a high enough titer to be detected by the biofire bcid2 panel.The same sample was tested 3 days later, and it is suspected the k.Pneumoniae strain producing the ctx-m mechanism for antibiotic resistance was able to proliferate to a level where the antibiotic resistance gene was detectable by the biofire bcid2 panel.The suspicion of a mixed-culture was further confirmed during in-house testing where agar plates from one of the anaerobic bottles was planted in duplicate with/without antibiotic disk, and biofire was able to produce organism strains that had dissimilarity in the ctx-m detection when tested on the biofire bcid2 panel.The biofire bcid2 panel is a highly sensitive, multiplexed, nucleic-acid-based test designed to detect multiple bacterial, yeast, and antimicrobial resistant nucleic acids.While rare, discrepancies between biofire bcid2 panel and other identification methods are part of the normal performance of the product observed in the field.These discrepancies can be caused by differences in genotypic and phenotypic expression, specifically regarding expression of certain means of antimicrobial resistance displayed by any organism or organisms in a mixed culture.According to the biofire bcid2 panel instruction for use (ifu) (www.Online-ifu.Com/iti0048), antimicrobial resistance can occur via multiple mechanisms; & a 'not detected' result for any antimicrobial resistance gene assays does not indicate antimicrobial susceptibility.Subculturing and standard susceptibility testing of isolates is required to determine antimicrobial susceptibility.Discrepancies between the biofire bcid2 panel test result and other microbial identification methods may be caused by the inability to reliably differentiate closely related species based on standard phenotypic microbial identification methods or the design of other molecular assays.The results for the antimicrobial resistance gene assays do not specifically link the resistance gene to other applicable bacteria detected.In mixed cultures, the resistance gene may be associated with other strains of an organism carrying these gene targets, any other applicable bacteria that maybe detected, or an organism that was not detected by the biofire bcid2 panel.The biofire bcid2 panel results must be correlated with the clinical history, epidemiological data, and other data available to the clinician evaluating the patient.Performance data: according to table 44.Biofire bcid2 panel clinical performance summary, ctx-m of the biofire bcid2 panel's ifu, the performance of the ctx-m assays compared to pcr/sequencing with any associated organism showed an overall positive percent agreement (ppa) of 99.1 % (95% ci 95.0-99.8%) and an overall negative percent agreement (npa) of 100% (95% ci 99.3-100%).

Event Description

Summary: (b)(6) (annapolis, md) reported a potential false negative ctx-m result on the biofire blood culture identification 2 (bcid2) panel after testing a patient blood culture sample.Due to the biofire bcid2 panel result, the patient was not treated with carbapenem.The patient ultimately passed away and the laboratory supervisor stated that they believe the biofire bcid2 panel result contributed to the patient's death.Upon investigation, no malfunction occurred, and the biofire bcid2 panel was working within specification.The investigation concluded that the most likely cause for the discrepant result was a mixed culture of esbl negative (ctx-m negative) and esbl-producing (ctx-m positive) klebsiella pneumoniae.

• Brand Name: BIOFIRE® BLOOD CULTURE IDENTIFICATION 2 (BCID2) PANEL
• Type of Device: BIOFIRE® BLOOD CULTURE IDENTIFICATION 2 (BCID2) PANEL
• Manufacturer (Section D): BIOFIRE DIAGNOSTICS LLC; 515 colorow dr; salt lake city UT 84108
• Manufacturer (Section G): BIOFIRE DIAGNOSTICS, LLC; 515 colorow dr; salt lake city UT 84108
• Manufacturer Contact: 515 colorow dr; salt lake city, UT 84108 ; 8017366354
• MDR Report Key: 16724847
• MDR Text Key: 313139605
• Report Number: 3002773840-2023-00001
• Device Sequence Number: 1
• Product Code: PAM
• UDI-Device Identifier: 00815381020338
• UDI-Public: 00815381020338
• Combination Product (y/n): N
• Reporter Country Code: US
• PMA/PMN Number: K193519
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: Health Professional
• Reporter Occupation: Other Health Care Professional
• Type of Report: Initial,Followup
• Report Date: 05/10/2023

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: No
• Device Operator: Health Professional
• Device Expiration Date: 12/11/2023
• Device Model Number: RFIT-ASY-0147
• Device Catalogue Number: RFIT-ASY-0147
• Device Lot Number: 2246322
• Was Device Available for Evaluation?: No
• Is the Reporter a Health Professional?: Yes
• Initial Date Manufacturer Received: 03/15/2023
• Initial Date FDA Received: 04/12/2023
• Supplement Dates Manufacturer Received: 03/15/2023
• Supplement Dates FDA Received: 05/11/2023
• Was Device Evaluated by Manufacturer?: Device Not Returned to Manufacturer
• Date Device Manufactured: 12/19/2022
• Is the Device Single Use?: Yes
• Is This a Reprocessed and Reused Single-Use Device?: No
• Type of Device Usage: Initial
• Patient Sequence Number: 1
• Patient Outcome(s): Death
• Patient Age: 76 YR
• Patient Sex: Female