FILMARRAY® MENINGITIS/ENCEPHALITIS (ME) PANEL
Report
- Report Number
- 3002773840-2025-00013
- Event Type
- Death
- Date Received
- March 12, 2025
- Date of Event
- January 2, 2025
- Report Date
- April 4, 2025
- Manufacturer
- BIOFIRE DIAGNOSTICS, LLC
- Product Code
- PLO
- UDI-DI
- 00815381020123
- PMA / PMN Number
- K160462
- Adverse Event
- Yes
- Report Source
- Manufacturer report
- Reporter Location
- CA
- Reporter Occupation
- OTHER HEALTH CARE PROFESSIONAL
- Health Professional
- Yes
Narratives
INVESTIGATION: (B)(6) CANADA) REPORTED A POTENTIAL FALSE NEGATIVE CRYPTOCOCCUS NEOFORMANS/GATTII RESULT ON THE FILMARRAY MENINGITIS/ENCEPHALITIS (ME) PANEL AFTER TESTING A PATIENT'S CEREBROSPINAL FLUID (CSF) SAMPLE. DUE TO THE FILMARRAY ME PANEL RESULT, THE PATIENT'S DIAGNOSIS AND TREATMENT WERE DELAYED. THE PATIENT PASSED AWAY AND THE CUSTOMER REPORTED THAT THE PATIENT'S DEATH APPEARED TO BE MULTIFACTORIAL, BUT THE DIAGNOSTIC DELAY POSSIBLY CONTRIBUTED TO THE UNFAVORABLE OUTCOME FOR THE PATIENT. BIOFIRE'S INVESTIGATION INTO THIS EVENT IS ONGOING AND FURTHER INFORMATION HAS BEEN REQUESTED FROM THE CUSTOMER. THE FULL INVESTIGATION 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.
INVESTIGATION: THE PATIENT WAS A 71-YEAR-OLD MALE WHO WAS ADMITTED TO THE HOSPITAL ON (B)(6) 2024, WITH NONSPECIFIC SYMPTOMS. ON (B)(6) 2025, MORE PRONOUNCED NEUROLOGICAL SYMPTOMS APPEARED, LEADING TO CSF COLLECTION BY LUMBAR PUNCTURE. ON (B)(6) 2025, THE CSF SAMPLE WAS TESTED ON THE FILMARRAY ME PANEL. THE FILMARRAY ME PANEL REPORTED ALL ANALYTES AS NOT DETECTED. ON (B)(6) 2025, THE CSF CULTURE WAS POSITIVE FOR CRYPTOCOCCUS, WHICH PROMPTED THE CUSTOMER TO PERFORM CRYPTOCOCCAL ANTIGEN (CRAG) TEST ON THE CSF SAMPLE, CONFIRMING CRYPTOCOCCUS. TREATMENT WAS INITIATED FOLLOWING THE POSITIVE CRYPTOCOCCUS RESULT. THE CUSTOMER REPORTED THAT THIS RESULTED IN A PROCESSING DELAY OF 9 DAYS ((B)(6) 2024 TO (B)(6) 2025). PLEASE NOTE THAT THE DELAY ASSOCIATED WITH THE FILMARRAY ME PANEL RESULT WAS 4 DAYS AS THE TEST WAS PERFORMED ON (B)(6) 2025. ACCORDING TO THE CUSTOMER, CRYPTOCOCCUS WAS INITIALLY RULED OUT DUE TO THE NEGATIVE FILMARRAY ME PANEL RESULT, THE ABSENCE OF RISK FACTORS, AND A NON-SUGGESTIVE CLINICAL PICTURE. THE CUSTOMER REPORTED THAT DUE TO THE COMPLEXITY OF THE CASE, THE PATIENT WAS TRANSFERRED TO A TERTIARY CENTER ON (B)(6) 2025, AND DIED ON (B)(6) 2025. WHEN ASKED IF THE PATIENT WAS AFFECTED BY THE FILMARRAY ME PANEL RESULT, THE CUSTOMER STATED THAT IT WAS DIFFICULT TO ASSESS WITH CERTAINTY WHETHER THE PATIENT WAS DIRECTLY HARMED BY THE DIAGNOSTIC DELAY, HOWEVER, A DELAY IN TREATMENT IN A SERIOUS INFECTION SUCH AS CRYPTOCOCCOSIS, CLINICAL COURSE CAN BE INFLUENCED. THEY STATED, "IN THIS CASE, THE PATIENT'S DEATH APPEARS TO BE MULTIFACTORIAL, BUT THIS DIAGNOSTIC DELAY POSSIBLY CONTRIBUTED TO THE UNFAVORABLE OUTCOME." BIOFIRE MEDICAL AFFAIRS ALSO PROVIDED AN ASSESSMENT OF THE CASE. MEDICAL AFFAIRS STATED THAT THE GOLD STANDARD FOR DETECTING CRYPTOCOCCUS IS CULTURE AND CRYPTOCOCCAL ANTIGEN (CRAG). MOLECULAR METHODOLOGIES CAN PROVIDE VALUE IN ESTABLISHING THE ETIOLOGY OF DISEASE; HOWEVER, PERFORMANCE IS INSUFFICIENT TO RULE OUT INFECTION. A GLOBAL GUIDELINE FOR THE DIAGNOSIS OF CRYPTOCOCCOSIS RECOMMENDS THE DIAGNOSTIC WORKUP FOR A PATIENT WITH SUSPECTED INFECTION TO REQUIRE ASSESSMENT FOR CENTRAL NERVOUS SYSTEM (CNS), PULMONARY, AND OTHER SYSTEM INVOLVEMENT. SPECIFIC TO CNS INFECTION, THE RECOMMENDATIONS ARE FOR THE MEASUREMENT OF CSF OPENING PRESSURE, GLUCOSE, PROTEIN, CELL COUNTS, MICROSCOPY, CULTURE, AND QUANTIFICATION OF CSF CRAG.1 THE MAJOR CONTRIBUTING FACTORS FOR THE DIAGNOSTIC DELAY WAS: DEVIATION FROM CLINICAL GUIDELINES FOR EVALUATING PATIENTS SUSPECTED FOR CRYPTOCOCCAL INFECTION CUSTOMER MISCONCEPTION OF THE PERFORMANCE OF MOLECULAR METHODS FOR CRYPTOCOCCUS DETECTION. REFERENCE: 1. GLOBAL GUIDELINE FOR THE DIAGNOSIS AND MANAGEMENT OF CRYPTOCOCCOSIS: AN INITIATIVE OF THE ECMM AND ISHAM IN COOPERATION WITH THE ASM - THE LANCET INFECTIOUS DISEASES. ACCESSED (B)(6) 2025. HTTPS://WWW.THELANCET.COM/JOURNALS/LANINF/ARTICLE/PIIS1473-3099(23)00731-4/FULLTEXT. IN ADDITION TO THE CUSTOMER INFORMATION AND MEDICAL AFFAIRS ASSESSMENT, ANALYSIS OF THE FILMARRAY ME PANEL RUN FILE SHOWED NO AMPLIFICATION OR MELT SIGNATURE FOR THE C. NEOFORMANS/GATTII ASSAY. QUALITY CONTROL (QC) RECORDS FOR POUCH LOT# 3FBH24 (KIT LOT# 1625324) WERE REVIEWED. THIS POUCH LOT PASSED QC CRITERIA AND WAS FOUND WITHIN SPECIFICATIONS. NO RUN MALFUNCTION OCCURRED AT THE CUSTOMER SITE AND THE FILMARRAY INSTRUMENT (SERIAL NUMBER# (B)(6)) WAS WORKING WITHIN DESIGNED SPECIFICATIONS. CONCLUSION: THE INVESTIGATION CONCLUDED THAT THE MOST LIKELY CAUSE FOR THE DISCREPANT C. NEOFORMANS/GATTII RESULT WAS SENSITIVITY/SPECIFICITY DIFFERENCES BETWEEN THE FILMARRAY ME PANEL AND TRADITIONAL LABORATORY METHODS. ACCORDING TO THE FILMARRAY ME PANEL INSTRUCTIONS BOOKLET (WWW.ONLINE-IFU.COM/ITI0035), PATIENTS WITH A SUSPICION OF CRYPTOCOCCAL MENINGITIS AND A NEGATIVE CRYPTOCOCCAL PCR RESULT, SUCH AS BY THE FILMARRAY ME PANEL, SHOULD BE TESTED FOR CRYPTOCOCCAL ANTIGEN (CRAG). ACCORDING TO THE "CRYPTOCOCCUS DETECTION BY THE BIOFIRE® FILMARRAY® MENINGITIS/ENCEPHALITIS (ME) PANEL" TECHNICAL NOTE [FLM1-PRT-0278] , THERE HAVE BEEN REPORTS OF NEGATIVE RESULTS BY THE FILMARRAY ME PANEL IN PATIENTS WITH NEWLY DIAGNOSED CRYPTOCOCCAL MENINGITIS AND POSITIVE CRAG AND/OR CULTURE. ADDITIONALLY, DISCORDANT CRAG AND FILMARRAY ME PANEL RESULTS HAVE BEEN OBSERVED IN PERSONS EITHER ON ANTIFUNGAL TREATMENT AT THE TIME OF TESTING OR WITH A PAST HISTORY OF TREATED DISEASE IN WHICH THE CRAG REMAINS POSITIVE. THE FILMARRAY ME PANEL DETECTS NUCLEIC ACID WITHIN THE CSF SAMPLE, WHILE CRAG TEST DETECTS THE CRYPTOCOCCUS ANTIGEN IN THE CSF SAMPLE. PCR-BASED DIAGNOSIS OF CRYPTOCOCCAL MENINGITIS HAS NOT BEEN WIDELY DEVELOPED GIVEN THE HIGH SENSITIVITY, WIDE AVAILABILITY, AND LOW COST OF CRAG TESTING. A NEGATIVE FILMARRAY ME PANEL RESULT DOES NOT EXCLUDE THE POSSIBILITY OF CNS INFECTION AND SHOULD NOT BE USED AS THE SOLE BASIS FOR DIAGNOSIS, TREATMENT, OR OTHER MANAGEMENT DECISIONS. CLINICAL PERFORMANCE: ACCORDING TO TABLE 9. FILMARRAY ME PROSPECTIVE CLINICAL PERFORMANCE SUMMARY OF THE FILMARRAY ME PANEL INSTRUCTION BOOKLET (WWW.ONLINE-IFU.COM/ITI0035), THE PERFORMANCE CLAIM FOR THE C. NEOFORMANS/GATTII ASSAY COMPARED TO PCR WITH BI-DIRECTIONAL SEQUENCING SHOWED AN OVERALL POSITIVE PERCENT AGREEMENT (PPA) OF 100% (1/1) AND AN OVERALL NEGATIVE PERCENT AGREEMENT (NPA) OF 99.7% (95% CI 99.3-99.9%) C. NEOFORMANS/GATTII WAS DETECTED IN 2/4 FALSE POSITIVE SPECIMENS USING A COMMERCIALLY AVAILABLE ANTIGEN TEST. ONE FALSE POSITIVE SPECIMEN WAS POSITIVE BY STANDARD CULTURE. TO SUPPLEMENT THE RESULTS OF THE PROSPECTIVE CLINICAL STUDY, AN EVALUATION OF 235 PRESELECTED ARCHIVED SPECIMENS (OF WHICH 25 WERE NEGATIVE) WAS PERFORMED. ACCORDING TO TABLE 14. FILMARRAY ME PANEL ARCHIVED SPECIMEN PERFORMANCE DATA SUMMARY OF THE FILMARRAY ME PANEL INSTRUCTION BOOKLET, THE C. NEOFORMANS/GATTII ASSAY COMPARED TO A CONFIRMATORY MOLECULAR TEST (E.G., PCR WITH BI-DIRECTIONAL SEQUENCING) SHOWED A PPA OF 100% (95% CI 83.2-100%) AND AN NPA OF 100% (95% CI 97.8-100%). ONE SPECIMEN WAS SEQUENCED AND IDENTIFIED AS C. GATTII AND 18 WERE C. NEOFORMANS.
SUMMARY: (B)(6) CANADA) REPORTED A POTENTIAL FALSE NEGATIVE CRYPTOCOCCUS NEOFORMANS/GATTII RESULT ON THE FILMARRAY MENINGITIS/ENCEPHALITIS (ME) PANEL AFTER TESTING A PATIENT'S CEREBROSPINAL FLUID (CSF) SAMPLE. DUE TO THE FILMARRAY ME PANEL RESULT, THE PATIENT'S DIAGNOSIS AND TREATMENT WAS DELAYED. THE CUSTOMER REPORTED THAT THE PATIENT PASSED AWAY AND THEIR DEATH APPEARED TO BE MULTIFACTORIAL, BUT THE DIAGNOSTIC DELAY POSSIBLY CONTRIBUTED TO THE UNFAVORABLE OUTCOME FOR THE PATIENT. 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.
SUMMARY: (B)(6) HÔPITAL (QUEBEC, CANADA) REPORTED A POTENTIAL FALSE NEGATIVE CRYPTOCOCCUS NEOFORMANS/GATTII RESULT ON THE FILMARRAY MENINGITIS/ENCEPHALITIS (ME) PANEL AFTER TESTING A PATIENT'S CEREBROSPINAL FLUID (CSF) SAMPLE. DUE TO THE FILMARRAY ME PANEL RESULT, THE PATIENT'S DIAGNOSIS AND TREATMENT WAS DELAYED. THE CUSTOMER REPORTED THAT THE PATIENT PASSED AWAY AND THEIR DEATH APPEARED TO BE MULTIFACTORIAL, BUT THE DIAGNOSTIC DELAY POSSIBLY CONTRIBUTED TO THE UNFAVORABLE OUTCOME FOR THE PATIENT. UPON INVESTIGATION, NO MALFUNCTION OCCURRED AND THE FILMARRAY ME PANEL WAS WORKING WITHIN SPECIFICATION. THE INVESTIGATION CONCLUDED THAT THE MOST LIKELY CAUSE FOR THE DISCREPANT C. NEOFORMANS/GATTII RESULT WAS SENSITIVITY/SPECIFICITY DIFFERENCES BETWEEN THE FILMARRAY ME PANEL AND TRADITIONAL LABORATORY METHODS.
Devices
| Seq | Brand | Generic | Product Code | Manufacturer | Model | Lot | UDI-DI |
|---|---|---|---|---|---|---|---|
| 1482609 | FILMARRAY® MENINGITIS/ENCEPHALITIS (ME) PANEL | FILMARRAY® MENINGITIS/ENCEPHALITIS (ME) PANEL | PLO | BIOFIRE DIAGNOSTICS, LLC | RFIT-ASY-0118 | 1625324 | 00815381020123 |
Patients
| Seq | Age | Sex | Outcome | Treatment |
|---|---|---|---|---|
| 1 | 71 YR | Male | Death |