FILMARRAY ME PANEL
Report
- Report Number
- 3002773840-2026-00002
- Event Type
- Death
- Date Received
- January 16, 2026
- Date of Event
- April 13, 2024
- Report Date
- March 26, 2026
- Manufacturer
- BIOFIRE DIAGNOSTICS, LLC
- Product Code
- PLO
- UDI-DI
- 00815381020123
- PMA / PMN Number
- K160462
- Adverse Event
- Yes
- Report Source
- Manufacturer report
- Reporter Location
- MY
- Reporter Occupation
- OTHER HEALTH CARE PROFESSIONAL
- Health Professional
- Yes
Narratives
LEONG ET AL. PUBLISHED A STUDY "A LETHAL CASE OF CRYPTOCOCCAL MENINGITIS IN AN APPARENTLY IMMUNOCOMPETENT PATIENT: A CASE REPORT HIGHLIGHTING DIAGNOSTIC PITFALLS AND THERAPEUTIC CHALLENGES," WHICH DESCRIBES A POTENTIAL FALSE NEGATIVE CRYPTOCOCCUS NEOFORMANS/GATTII RESULT ON THE FILMARRAY MENINGITIS/ENCEPHALITIS (ME) PANEL DURING PATIENT TESTING. A 41-YEAR-OLD MALE WITH NO PRIOR MEDICAL ILLNESS PRESENTED TO A PRIVATE HOSPITAL IN MALACCA, MALAYSIA, ON APRIL 13, 2024. HE HAD A ONE-WEEK HISTORY OF FEVER, HEADACHE, PHOTOPHOBIA, AND ALTERED MENTAL STATUS. HE DENIED ANY INTRAVENOUS DRUG USE OR ANY RECENT HISTORY OF TRAVELING. ON EXAMINATION, HE WAS INITIALLY CONFUSED, WITH OCCASIONAL INCOHERENT SPEECH. THE INITIAL GLASGOW COMA SCALE (GCS) SCORE ON PRESENTATION WAS E4V4M6. HOWEVER, HE DID NOT EXHIBIT ANY SIGNS OF MENINGISM, AND THERE WAS NO CLINICAL EVIDENCE SUGGESTIVE OF OPPORTUNISTIC INFECTION UPON EXAMINATION. BILATERAL PUPILS WERE EQUAL AND RESPONSIVE TO LIGHT STIMULI. HIS BLOOD PRESSURE ON ARRIVAL WAS 131/90 MM HG, PULSE RATE WAS 70 BEATS PER MINUTE, OXYGEN SATURATION ON ROOM AIR WAS 98% VIA PULSE OXIMETRY, AND HE WAS AFEBRILE. THE REMAINDER OF THE NEUROLOGICAL EXAMINATION WAS UNREMARKABLE, AND FUNDOSCOPIC EXAMINATION OF BOTH EYES WAS NORMAL. INITIAL BLOOD INVESTIGATIONS REVEALED LEUKOCYTOSIS, WITH A WHITE CELL COUNT OF 17.6 × 10¿/L AND ELEVATED SERUM C-REACTIVE PROTEIN (CRP) OF 202 MG/L. OTHER BIOCHEMICAL PARAMETERS WERE UNREMARKABLE, WITH NORMAL RENAL AND LIVER FUNCTION TESTS. THE PATIENT ALSO TESTED NEGATIVE FOR HEPATITIS B, HEPATITIS C, AND HUMAN IMMUNODEFICIENCY VIRUS (HIV). MAGNETIC RESONANCE IMAGING AND ANGIOGRAPHY (MRI/MRA) OF THE BRAIN (T2-WEIGHTED) DEMONSTRATED EVIDENCE OF SULCAL AND LEPTOMENINGEAL ENHANCEMENT ON POST-IV GADOLINIUM CONTRAST ENHANCEMENT, SUGGESTIVE OF MENINGITIS. THE PATIENT WAS SUBSEQUENTLY ADMITTED FOR FURTHER EVALUATION AND WAS EMPIRICALLY TREATED FOR MENINGITIS WITH INTRAVENOUS CEFTRIAXONE 2 G EVERY 12 HOURS AND INTRAVENOUS ACYCLOVIR 500 MG EVERY EIGHT HOURS. A DIAGNOSTIC LUMBAR PUNCTURE WAS PERFORMED ON APRIL 13, 2024, DEMONSTRATING A HIGH OPENING PRESSURE OF 33 CM H2O. THE MACROSCOPIC APPEARANCE OF THE CSF SAMPLE WAS CLEAR AND COLORLESS. FURTHER ANALYSIS REVEALED HYPOGLYCORRHACHIA, WITH CSF GLUCOSE OF 2.3 MMOL/L, RANDOM BLOOD GLUCOSE OF 6.9 MMOL/L, A CSF-TO-SERUM GLUCOSE RATIO OF 0.33, AND ELEVATED CSF PROTEIN OF 1.4 G/L, WITH LYMPHOCYTIC PLEOCYTOSIS. THE INITIAL CSF CELL COUNT WAS 335 CELLS/L (NEUTROPHILS 5%, LYMPHOCYTES 95%), AND NO ORGANISMS WERE SEEN ON THE CSF GRAM STAIN. INDIAN INK STAINING WAS NEGATIVE AND BACTERIAL CULTURE WAS NEGATIVE. THE ME PANEL WAS ALSO NEGATIVE FOR ALL TARGETS. THIS IS THE ONLY TIME ME PANEL WAS PERFORMED FOR THIS PATIENT. DESPITE THE HIGH OPENING PRESSURE AND CSF PROFILE SUGGESTIVE OF FUNGAL MENINGITIS OR TUBERCULOUS MENINGITIS (TBM), CRYPTOCOCCAL ANTIGEN TESTING WAS INADVERTENTLY OMITTED FROM THE INITIAL CSF WORKUP, AS THE FOCUS REMAINED ON BACTERIAL AND VIRAL PATHOGENS AS WELL AS TBM. ON APRIL 15, 2024, THE PATIENT WAS TRANSFERRED TO THE HIGH DEPENDENCY WARD IN MALACCA GENERAL HOSPITAL DUE TO FINANCIAL CONSTRAINTS. A REPEAT LUMBAR PUNCTURE WAS PERFORMED DUE TO NEUROLOGICAL DETERIORATION. CSF ANALYSIS FROM APRIL 17, 2024 REVEALED FINDINGS SIMILAR TO THE PREVIOUS SAMPLE. GRAM STAIN WAS NEGATIVE, BACTERIAL AND FUNGAL CULTURE WERE NEGATIVE, INDIA INK MICROSCOPY WAS NEGATIVE, AND CRYPTOCOCCUS ANTIGEN (IMMY CRAG LATERAL FLOW ASSAY) WAS ALSO NEGATIVE. THE ME PANEL WAS NOT PERFORMED ON THE SECOND LUMBAR PUNCTURE. ON APRIL 18, 2024, THE PATIENT¿S CONDITION FURTHER DETERIORATED, AND HE WAS INTUBATED FOR AIRWAY PROTECTION, REQUIRING VASOPRESSOR SUPPORT. REPEAT CT OF THE BRAIN SHOWED WORSENING CEREBRAL EDEMA AND COMMUNICATING HYDROCEPHALUS. THE CASE WAS REFERRED TO THE NEUROSURGICAL TEAM FOR EMERGENCY SURGICAL CSF DIVERSION, AND THE PATIENT SUBSEQUENTLY UNDERWENT PERCUTANEOUS PLACEMENT OF A LUMBAR DRAIN. ON APRIL 23, 2024, THE CSF CRAG (IMMY LATERAL FLOW ASSAY) OBTAINED FROM THE LUMBAR DRAIN TESTED POSITIVE. INDIAN INK MICROSCOPY WAS ALSO POSITIVE, DEMONSTRATING A FEW ENCAPSULATED YEASTS. NO CRYPTOCOCCAL ANTIGENEMIA WAS DETECTED, AND BOTH BLOOD AND CSF CULTURES DID NOT YIELD ANY CRYPTOCOCCUS. THE BIOFIRE ME PANEL WAS NOT PERFORMED ON THIS SAMPLE. URGENT REFERRAL TO THE INFECTIOUS DISEASE (ID) TEAM WAS MADE, AND THE DIAGNOSIS OF CRYPTOCOCCAL MENINGITIS WAS ESTABLISHED AFTER 10 DAYS OF HOSPITAL ADMISSION. THE PATIENT WAS PROMPTLY INITIATED ON COMBINATION ANTIFUNGAL THERAPY WITH PARENTERAL AMPHOTERICIN B DEOXYCHOLATE 60 MG EVERY 24 HOURS (0.7 MG/KG/DAY) AND ORAL FLUCYTOSINE 2 G EVERY SIX HOURS (25 MG/KG/DOSE). LIPOSOMAL OR LIPID-BASED AMPHOTERICIN B FORMULATIONS WERE NOT AVAILABLE, AND THUS THE CONVENTIONAL DEOXYCHOLATE FORMULATION WAS USED. HOWEVER, THE CLINICAL COURSE WAS FURTHER COMPLICATED BY HYPERNATREMIA AND ACUTE KIDNEY INJURY. IN SPITE OF THE ANTIFUNGAL TREATMENT REGIMEN AND CSF DIVERSION, THE PATIENT EVENTUALLY SUCCUMBED TO HIS ILLNESS DUE TO MULTIORGAN FAILURE. THE PATIENT DIED ON AN UNKNOWN DATE. THE PUBLICATION NOTED THAT THE BIOFIRE ME PANEL CRYPTOCOCCUS ASSAY IS KNOWN TO HAVE POOR PREDICTIVE VALUE IN PATIENTS WITH LOW DISEASE BURDEN. THE PUBLICATION ALSO NOTED THAT IN THIS CASE, THE INITIAL OMISSION OF CRAG TESTING AND THE OVEREMPHASIS ON BACTERIAL MENINGITIS OR TBM COMBINED WITH NEGATIVE ME PANEL RESULTS MAY HAVE DIRECTLY CONTRIBUTED TO THE DELAY IN DIAGNOSIS. THE PUBLICATION FINALLY STATED THAT THE DIAGNOSTIC DIFFICULTIES ENCOUNTERED WITH THIS PATIENT EVENTUALLY LEAD TO THE DELAYED DIAGNOSIS AND MORTALITY. BIOFIRE MEDICAL AFFAIRS HAS ASSESSED THIS EVENT BASED ON INFORMATION AVAILABLE IN THE PUBLICATION. ¿¿THIS ASSESSMENT FOUND THAT THE ME PANEL RESULTS DID NOT CONTRIBUTE TO THE PATIENT'S DEATH. THE ME PANEL WAS CONSISTENT WITH OTHER DIAGNOSTIC METHODS AND THE PATIENT'S OUTCOME REFLECTS DELAYED RECOGNITION OF A LOW-BURDEN INFECTION. THE PATIENT¿S INITIAL CSF FINDINGS WERE CONSISTENT WITH FUNGAL OR TB MENINGITIS, HOWEVER FUNGAL ETIOLOGIES WERE NOT INCLUDED IN THE EARLY DIFFERENTIAL, AND EMPIRIC ANTIFUNGAL THERAPY WAS NOT INITIATED. THE BIOFIRE ME PANEL PERFORMED ON DAY 0 WAS NEGATIVE, BUT SUBSEQUENT TESTING DEMONSTRATED THAT THE FUNGAL BURDEN WAS EXTREMELY LOW, WITH FUNGAL CULTURE, INDIA INK, AND CRYPTOCOCCAL ANTIGEN REMAINING NEGATIVE THROUGH DAY 4 AND ONLY BECOMING POSITIVE BY DAY 10. THE ME PANEL WAS ONLY PERFORMED ON DAY 0 AND WAS NOT INCLUDED IN SUBSEQUENT TESTING. THIS PATTERN IS CONSISTENT WITH WELL-RECOGNIZED DIAGNOSTIC CHALLENGES OF CRYPTOCOCCAL MENINGITIS IN IMMUNOCOMPETENT HOSTS AND INDICATES ORGANISM LEVELS NEAR/BELOW THE LIMITS OF DETECTION OF BOTH MOLECULAR AND STANDARD-OF-CARE ASSAYS EARLY IN THE DISEASE COURSE. THE DELAYED DIAGNOSIS AND TREATMENT, RATHER THAN RELIANCE ON THE BIOFIRE ME PANEL, BEST EXPLAIN THE POOR OUTCOME. ADDITIONALLY, THE PATIENT¿S MULTISYSTEM ORGAN FAILURE¿AN ATYPICAL MANIFESTATION IN IMMUNOCOMPETENT CRYPTOCOCCAL MENINGITIS¿SUGGESTS OTHER CONTRIBUTING FACTORS, SUCH AS TREATMENT-RELATED TOXICITY AND ACUTE KIDNEY INJURY. OVERALL, THE EVIDENCE SUPPORTS THAT THE BIOFIRE ME PANEL DID NOT CONTRIBUTE TO THE PATIENT¿S DEATH, AND THE OUTCOME REFLECTS DELAYED RECOGNITION OF A LOW-BURDEN INFECTION RATHER THAN DIAGNOSTIC FAILURE THE AUTHORS WERE UNABLE TO PROVIDE RUN FILES OR LOT INFORMATION UPON REQUEST, THUS NO RUN FILE ANALYSIS OR QC RECORD REVIEW COULD BE PERFORMED FOR THIS INVESTIGATION. CONCLUSION: THE MOST LIKELY CAUSE OF THE POTENTIAL FALSE NEGATIVE RESULT WAS DUE LOW-LEVEL ORGANISM/NUCLEIC ACID WITHIN THE SAMPLE WHICH WAS NEAR/BELOW THE LIMIT OF DETECTION (LOD) FOR THE BIOFIRE ME PANEL. THE BIOFIRE ME PANEL WAS CONSISTENT WITH OTHER DIAGNOSTIC METHODS PERFORMED ON THE SAME SAMPLE. FOR THE CSF SAMPLE COLLECTED ON APRIL 13, 2024, INDIA INK STAIN WAS NEGATIVE, AND NO CRYPTOCOCCUS ANTIGEN (CRAG) TEST WAS COMPLETED. THE SAMPLE COLLECTED ON APRIL 23, 2024 FROM A LUMBAR DRAIN RESULTED WITH A POSITIVE CRAG TEST AND INDIA INK STAIN. ME PANEL WAS NOT PERFORMED ON THIS SAMPLE. THE SAMPLES COLLECTED ON APRIL 13 AND APRIL 23 CANNOT BE DIRECTLY COMPARED DUE TO DISEASE PROGRESSION BETWEEN COLLECTION TIMES. THE ME PANEL WAS CONSISTENT WITH COMPARATORS FOR THE ONLY SAMPLE ON WHICH IT WAS PERFORMED. IT IS THEREFORE LIKELY THAT THE CRYPTOCOCCUS TARGET WAS PRESENT NEAR/BELOW THE DETECTABLE LIMIT OF THE BIOFIRE ME PANEL. THIS IS CONSISTENT WITH SIMILARLY NEGATIVE COMPARATORS ON THE FIRST TWO COLLECTED SAMPLES. FALSE NEGATIVE RESULTS MAY OCCUR WHEN THE CONCENTRATION OF ORGANISM IN THE SPECIMEN IS NEAR/BELOW THE DEVICE LIMIT OF DETECTION (LOD), AND THE REPRODUCIBILITY OF RESULTS WITH PCR IS DEPENDENT ON THE LEVELS OF NUCLEIC ACID AVAILABLE FOR AMPLIFICATION. THE ME PANEL DETECTS NUCLEIC ACID WITHIN CSF SAMPLES, WHILE CRYPTOCOCCAL ANTIGEN TESTS DETECTS THE CRYPTOCOCCUS ANTIGEN (CRAG) IN CSF. THE MOST SENSITIVE TEST FOR PRIMARY CRYPTOCOCCAL MENINGITIS (CM) IS THE DETECTION OF CRAG IN CSF OR BLOOD. CRAG IS SHED IN LARGE AMOUNTS IN THE CSF AND BLOOD AND CAN BE DETECTED EVEN PRIOR TO THE ONSET OF CLINICAL SYMPTOMS. PCR-BASED DIAGNOSIS OF CRYPTOCOCCAL MENINGITIS HAS NOT BEEN WIDELY DEVELOPED GIVEN THE HIGH SENSITIVITY, WIDE AVAILABILITY, AND LOW COST OF CRAG TESTING. THERE HAVE BEEN REPORTS OF NEGATIVE RESULTS BY THE BIOFIRE ME PANEL IN PATIENTS WITH NEWLY DIAGNOSED CRYPTOCOCCAL MENINGITIS AND POSITIVE CRAG AND/OR CULTURE. ADDITIONALLY, DISCORDANT CRAG AND BIOFIRE 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. FOR THIS PATIENT, CRAG TESTING WAS INADVERTENTLY OMITTED ON THE FIRST COLLECTED CSF SAMPLE. BIOMÉRIEUX RECOMMENDS THAT PATIENTS WITH A SUSPICION OF CRYPTOCOCCAL MENINGITIS AND A NEGATIVE CRYPTOCOCCAL PCR RESULT, SUCH AS BY THE BIOFIRE ME PANEL, BE TESTED FOR CRAG. FOR ADDITIONAL INFORMATION, PLEASE SEE THE CRYPTOCOCCUS DETECTION BY THE BIOFIRE® FILMARRAY® MENINGITIS/ENCEPHALITIS (ME) PANEL TECHNICAL NOTE: HTTPS://WWW.BIOMERIEUX.COM/CONTENT/DAM/BIOMERIEUX-COM/SERVICE-SUPPORT/SUPPORT-DOCUMENTS/TECHNICAL-NOTES/MENINGITISENCEPHALITIS-TECH-NOTES/FLM1-PRT-0278-CRYPTO-DETECTION-BY-THE-ME-PANEL-TECH-NOTE.PDF. A NEGATIVE BIOFIRE 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. IT IS IMPORTANT THAT BIOFIRE RESULTS BE USED IN CONJUNCTION WITH OTHER CLINICAL, EPIDEMIOLOGICAL, OR LABORATORY INFORMATION. CLINICAL PERFORMANCE CAN BE FOUND IN TABLES 9 AND 14 OF THE FILMARRAY ME PANEL INSTRUCTION BOOKLET (HTTPS://WWW.BIOFIREDX.QARAD.EIFU.ONLINE/ITI/ALL?KEYCODE=ITI0035); WHILE THE LIMIT OF DETECTION (LOD) VALUES FOR THE ANALYTES ON THE FILMARRAY ME PANEL CAN BE FOUND IN TABLE 17. 2025 LEONG ET AL. CUREUS 17(12): E98447. DOI 10.7759/CUREUS.98447
LEONG ET AL. PUBLISHED A STUDY "A LETHAL CASE OF CRYPTOCOCCAL MENINGITIS IN AN APPARENTLY IMMUNOCOMPETENT PATIENT: A CASE REPORT HIGHLIGHTING DIAGNOSTIC PITFALLS AND THERAPEUTIC CHALLENGES," WHICH DESCRIBES A POTENTIAL FALSE NEGATIVE CRYPTOCOCCUS NEOFORMANS/GATTII RESULT ON THE FILMARRAY MENINGITIS/ENCEPHALITIS (ME) PANEL DURING PATIENT TESTING. A 41-YEAR-OLD MALE WITH NO PRIOR MEDICAL ILLNESS PRESENTED TO A PRIVATE HOSPITAL IN MALACCA, MALAYSIA, ON APRIL 13, 2024. HE HAD A ONE-WEEK HISTORY OF FEVER, HEADACHE, PHOTOPHOBIA, AND ALTERED MENTAL STATUS. HE DENIED ANY INTRAVENOUS DRUG USE OR ANY RECENT HISTORY OF TRAVELING. ON EXAMINATION, HE WAS INITIALLY CONFUSED, WITH OCCASIONAL INCOHERENT SPEECH. THE INITIAL GLASGOW COMA SCALE (GCS) SCORE ON PRESENTATION WAS E4V4M6. HOWEVER, HE DID NOT EXHIBIT ANY SIGNS OF MENINGISM, AND THERE WAS NO CLINICAL EVIDENCE SUGGESTIVE OF OPPORTUNISTIC INFECTION UPON EXAMINATION. BILATERAL PUPILS WERE EQUAL AND RESPONSIVE TO LIGHT STIMULI. HIS BLOOD PRESSURE ON ARRIVAL WAS 131/90 MM HG, PULSE RATE WAS 70 BEATS PER MINUTE, OXYGEN SATURATION ON ROOM AIR WAS 98% VIA PULSE OXIMETRY, AND HE WAS AFEBRILE. THE REMAINDER OF THE NEUROLOGICAL EXAMINATION WAS UNREMARKABLE, AND FUNDOSCOPIC EXAMINATION OF BOTH EYES WAS NORMAL. INITIAL BLOOD INVESTIGATIONS REVEALED LEUKOCYTOSIS, WITH A WHITE CELL COUNT OF 17.6 × 10¿/L AND ELEVATED SERUM C-REACTIVE PROTEIN (CRP) OF 202 MG/L. OTHER BIOCHEMICAL PARAMETERS WERE UNREMARKABLE, WITH NORMAL RENAL AND LIVER FUNCTION TESTS. THE PATIENT ALSO TESTED NEGATIVE FOR HEPATITIS B, HEPATITIS C, AND HUMAN IMMUNODEFICIENCY VIRUS (HIV). MAGNETIC RESONANCE IMAGING AND ANGIOGRAPHY (MRI/MRA) OF THE BRAIN (T2-WEIGHTED) DEMONSTRATED EVIDENCE OF SULCAL AND LEPTOMENINGEAL ENHANCEMENT ON POST-IV GADOLINIUM CONTRAST ENHANCEMENT, SUGGESTIVE OF MENINGITIS. THE PATIENT WAS SUBSEQUENTLY ADMITTED FOR FURTHER EVALUATION AND WAS EMPIRICALLY TREATED FOR MENINGITIS WITH INTRAVENOUS CEFTRIAXONE 2 G EVERY 12 HOURS AND INTRAVENOUS ACYCLOVIR 500 MG EVERY EIGHT HOURS. A DIAGNOSTIC LUMBAR PUNCTURE WAS PERFORMED ON APRIL 13, 2024, DEMONSTRATING A HIGH OPENING PRESSURE OF 33 CM H2O. THE MACROSCOPIC APPEARANCE OF THE CSF SAMPLE WAS CLEAR AND COLORLESS. FURTHER ANALYSIS REVEALED HYPOGLYCORRHACHIA, WITH CSF GLUCOSE OF 2.3 MMOL/L, RANDOM BLOOD GLUCOSE OF 6.9 MMOL/L, A CSF-TO-SERUM GLUCOSE RATIO OF 0.33, AND ELEVATED CSF PROTEIN OF 1.4 G/L, WITH LYMPHOCYTIC PLEOCYTOSIS. THE INITIAL CSF CELL COUNT WAS 335 CELLS/L (NEUTROPHILS 5%, LYMPHOCYTES 95%), AND NO ORGANISMS WERE SEEN ON THE CSF GRAM STAIN. INDIAN INK STAINING WAS NEGATIVE AND BACTERIAL CULTURE WAS NEGATIVE. THE ME PANEL WAS ALSO NEGATIVE FOR ALL TARGETS. THIS IS THE ONLY TIME ME PANEL WAS PERFORMED FOR THIS PATIENT. DESPITE THE HIGH OPENING PRESSURE AND CSF PROFILE SUGGESTIVE OF FUNGAL MENINGITIS OR TUBERCULOUS MENINGITIS (TBM), CRYPTOCOCCAL ANTIGEN TESTING WAS INADVERTENTLY OMITTED FROM THE INITIAL CSF WORKUP, AS THE FOCUS REMAINED ON BACTERIAL AND VIRAL PATHOGENS AS WELL AS TBM. ON APRIL 15, 2024, THE PATIENT WAS TRANSFERRED TO THE HIGH DEPENDENCY WARD IN MALACCA GENERAL HOSPITAL DUE TO FINANCIAL CONSTRAINTS. A REPEAT LUMBAR PUNCTURE WAS PERFORMED DUE TO NEUROLOGICAL DETERIORATION. CSF ANALYSIS FROM APRIL 17, 2024 REVEALED FINDINGS SIMILAR TO THE PREVIOUS SAMPLE. GRAM STAIN WAS NEGATIVE, BACTERIAL AND FUNGAL CULTURE WERE NEGATIVE, INDIA INK MICROSCOPY WAS NEGATIVE, AND CRYPTOCOCCUS ANTIGEN (IMMY CRAG LATERAL FLOW ASSAY) WAS ALSO NEGATIVE. THE ME PANEL WAS NOT PERFORMED ON THE SECOND LUMBAR PUNCTURE. ON APRIL 18, 2024, THE PATIENT¿S CONDITION FURTHER DETERIORATED, AND HE WAS INTUBATED FOR AIRWAY PROTECTION, REQUIRING VASOPRESSOR SUPPORT. REPEAT CT OF THE BRAIN SHOWED WORSENING CEREBRAL EDEMA AND COMMUNICATING HYDROCEPHALUS. THE CASE WAS REFERRED TO THE NEUROSURGICAL TEAM FOR EMERGENCY SURGICAL CSF DIVERSION, AND THE PATIENT SUBSEQUENTLY UNDERWENT PERCUTANEOUS PLACEMENT OF A LUMBAR DRAIN. ON APRIL 23, 2024, THE CSF CRAG (IMMY LATERAL FLOW ASSAY) OBTAINED FROM THE LUMBAR DRAIN TESTED POSITIVE. INDIAN INK MICROSCOPY WAS ALSO POSITIVE, DEMONSTRATING A FEW ENCAPSULATED YEASTS. NO CRYPTOCOCCAL ANTIGENEMIA WAS DETECTED, AND BOTH BLOOD AND CSF CULTURES DID NOT YIELD ANY CRYPTOCOCCUS. THE BIOFIRE ME PANEL WAS NOT PERFORMED ON THIS SAMPLE. URGENT REFERRAL TO THE INFECTIOUS DISEASE (ID) TEAM WAS MADE, AND THE DIAGNOSIS OF CRYPTOCOCCAL MENINGITIS WAS ESTABLISHED AFTER 10 DAYS OF HOSPITAL ADMISSION. THE PATIENT WAS PROMPTLY INITIATED ON COMBINATION ANTIFUNGAL THERAPY WITH PARENTERAL AMPHOTERICIN B DEOXYCHOLATE 60 MG EVERY 24 HOURS (0.7 MG/KG/DAY) AND ORAL FLUCYTOSINE 2 G EVERY SIX HOURS (25 MG/KG/DOSE). LIPOSOMAL OR LIPID-BASED AMPHOTERICIN B FORMULATIONS WERE NOT AVAILABLE, AND THUS THE CONVENTIONAL DEOXYCHOLATE FORMULATION WAS USED. HOWEVER, THE CLINICAL COURSE WAS FURTHER COMPLICATED BY HYPERNATREMIA AND ACUTE KIDNEY INJURY. IN SPITE OF THE ANTIFUNGAL TREATMENT REGIMEN AND CSF DIVERSION, THE PATIENT EVENTUALLY SUCCUMBED TO HIS ILLNESS DUE TO MULTIORGAN FAILURE. THE PATIENT DIED ON AN UNKNOWN DATE. THE PUBLICATION NOTED THAT THE BIOFIRE ME PANEL CRYPTOCOCCUS ASSAY IS KNOWN TO HAVE POOR PREDICTIVE VALUE IN PATIENTS WITH LOW DISEASE BURDEN. THE PUBLICATION ALSO NOTED THAT IN THIS CASE, THE INITIAL OMISSION OF CRAG TESTING AND THE OVEREMPHASIS ON BACTERIAL MENINGITIS OR TBM COMBINED WITH NEGATIVE ME PANEL RESULTS MAY HAVE DIRECTLY CONTRIBUTED TO THE DELAY IN DIAGNOSIS. THE PUBLICATION FINALLY STATED THAT THE DIAGNOSTIC DIFFICULTIES ENCOUNTERED WITH THIS PATIENT EVENTUALLY LEAD TO THE DELAYED DIAGNOSIS AND MORTALITY. BIOFIRE MEDICAL AFFAIRS HAS ASSESSED THIS EVENT BASED ON INFORMATION AVAILABLE IN THE PUBLICATION. ¿¿THIS ASSESSMENT FOUND THAT THE ME PANEL RESULTS DID NOT CONTRIBUTE TO THE PATIENT'S DEATH. THE ME PANEL WAS CONSISTENT WITH OTHER DIAGNOSTIC METHODS AND THE PATIENT'S OUTCOME REFLECTS DELAYED RECOGNITION OF A LOW-BURDEN INFECTION. THE PATIENT¿S INITIAL CSF FINDINGS WERE CONSISTENT WITH FUNGAL OR TB MENINGITIS, HOWEVER FUNGAL ETIOLOGIES WERE NOT INCLUDED IN THE EARLY DIFFERENTIAL, AND EMPIRIC ANTIFUNGAL THERAPY WAS NOT INITIATED. THE BIOFIRE ME PANEL PERFORMED ON DAY 0 WAS NEGATIVE, BUT SUBSEQUENT TESTING DEMONSTRATED THAT THE FUNGAL BURDEN WAS EXTREMELY LOW, WITH FUNGAL CULTURE, INDIA INK, AND CRYPTOCOCCAL ANTIGEN REMAINING NEGATIVE THROUGH DAY 4 AND ONLY BECOMING POSITIVE BY DAY 10. THE ME PANEL WAS ONLY PERFORMED ON DAY 0 AND WAS NOT INCLUDED IN SUBSEQUENT TESTING. THIS PATTERN IS CONSISTENT WITH WELL-RECOGNIZED DIAGNOSTIC CHALLENGES OF CRYPTOCOCCAL MENINGITIS IN IMMUNOCOMPETENT HOSTS AND INDICATES ORGANISM LEVELS BELOW THE LIMITS OF DETECTION OF BOTH MOLECULAR AND STANDARD-OF-CARE ASSAYS EARLY IN THE DISEASE COURSE. THE DELAYED DIAGNOSIS AND TREATMENT, RATHER THAN RELIANCE ON THE BIOFIRE ME PANEL, BEST EXPLAIN THE POOR OUTCOME. ADDITIONALLY, THE PATIENT¿S MULTISYSTEM ORGAN FAILURE¿AN ATYPICAL MANIFESTATION IN IMMUNOCOMPETENT CRYPTOCOCCAL MENINGITIS¿SUGGESTS OTHER CONTRIBUTING FACTORS, SUCH AS TREATMENT-RELATED TOXICITY AND ACUTE KIDNEY INJURY. OVERALL, THE EVIDENCE SUPPORTS THAT THE BIOFIRE ME PANEL DID NOT CONTRIBUTE TO THE PATIENT¿S DEATH, AND THE OUTCOME REFLECTS DELAYED RECOGNITION OF A LOW-BURDEN INFECTION RATHER THAN DIAGNOSTIC FAILURE CONCLUSION: 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. 2025 LEONG ET AL. CUREUS 17(12): E98447. DOI 10.7759/CUREUS.98447.
LEONG ET AL. PUBLISHED A STUDY "A LETHAL CASE OF CRYPTOCOCCAL MENINGITIS IN AN APPARENTLY IMMUNOCOMPETENT PATIENT: A CASE REPORT HIGHLIGHTING DIAGNOSTIC PITFALLS AND THERAPEUTIC CHALLENGES," WHICH DESCRIBES A POTENTIAL FALSE NEGATIVE CRYPTOCOCCUS NEOFORMANS/GATTII RESULT ON THE FILMARRAY MENINGITIS/ENCEPHALITIS (ME) PANEL DURING PATIENT TESTING. THE PUBLICATION SUGGESTED THAT THE BIOFIRE RESULT MAY HAVE DIRECTLY CONTRIBUTED TO A DELAY IN DIAGNOSIS. THE PUBLICATION FURTHER CLAIMED THAT THE DIAGNOSTIC DIFFICULTIES ENCOUNTERED WITH THIS PATIENT EVENTUALLY LEAD TO THE DELAYED DIAGNOSIS AND MORTALITY. THE AUTHORS WERE UNABLE TO PROVIDE ANY ADDITIONAL INFORMATION REGARDING PATIENT IMPACT. THE INVESTIGATION CONCLUDED THAT THE MOST LIKELY CAUSE OF THE POTENTIAL FALSE NEGATIVE RESULT WAS LOW-LEVEL ORGANISM/NUCLEIC ACID WITHIN THE SAMPLE WHICH WAS NEAR/BELOW THE LIMIT OF DETECTION (LOD) FOR THE BIOFIRE ME PANEL.
LEONG ET AL. PUBLISHED A STUDY "A LETHAL CASE OF CRYPTOCOCCAL MENINGITIS IN AN APPARENTLY IMMUNOCOMPETENT PATIENT: A CASE REPORT HIGHLIGHTING DIAGNOSTIC PITFALLS AND THERAPEUTIC CHALLENGES," WHICH DESCRIBES A POTENTIAL FALSE NEGATIVE CRYPTOCOCCUS NEOFORMANS/GATTII RESULT ON THE FILMARRAY MENINGITIS/ENCEPHALITIS (ME) PANEL DURING PATIENT TESTING. THE PUBLICATION SUGGESTED THAT THE BIOFIRE RESULT MAY HAVE DIRECTLY CONTRIBUTED TO A DELAY IN DIAGNOSIS. THE PUBLICATION FURTHER CLAIMED THAT THE DIAGNOSTIC DIFFICULTIES ENCOUNTERED WITH THIS PATIENT EVENTUALLY LEAD TO THE DELAYED DIAGNOSIS AND MORTALITY. BIOFIRE HAS REQUESTED FURTHER INFORMATION FROM THE AUTHOR 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.
Devices
| Seq | Brand | Generic | Product Code | Manufacturer | Model | Lot | UDI-DI |
|---|---|---|---|---|---|---|---|
| 153607 | FILMARRAY ME PANEL | FILMARRAY ME PANEL | PLO | BIOFIRE DIAGNOSTICS, LLC | RFIT-ASY-0118 | 00815381020123 |
Patients
| Seq | Age | Sex | Outcome | Treatment |
|---|---|---|---|---|
| 1 | 41 YR | Male | Death |