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| Model Number |
RFIT-ASY-0118 |
| Medical Device Problem Code |
False Negative Result (1225)
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| Health Effect - Clinical Code |
No Clinical Signs, Symptoms or Conditions (4582)
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| Date of Event |
12/20/2025
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Type of Reportable Event
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Serious Injury
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Additional Manufacturer Narrative
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Investigation: idarraga et al.Published a study, "filmarray in cerebrospinal fluid: the challenge of false negatives in pediatric herpetic encephalitis" which describes a potential false negative hsv-1 and a potential false negative hhv-6 on the filmarray meningitis/encephalitis (me) panel during patient testing.The patient was a previously healthy 20-month-old male, with complete immunization schedule, no relevant perinatal or past medical history, and no family history of epilepsy or febrile seizures.He presented with a 48-hour history of fever reaching 39°c, followed by his first episode of complex febrile seizure characterized by generalized hypertonia, ocular deviation, and a duration of approximately 3 minutes, with a prolonged postictal state of 30 minutes.He subsequently developed focal status epilepticus involving the right upper limb, refractory to management with midazolam, phenytoin, and phenobarbital, which prompted referral to a tertiary care center.On admission, weight was 10.7 kg and height 83 cm.Initial studies revealed mild leukocytosis and elevated c-reactive protein, with normal serum electrolytes.Blood, urine, and csf cultures were negative.Csf gram stain was also negative.Brain ct demonstrated bilateral frontoparietal hypodensities, while mri showed lesions consistent with multifocal ischemia or an inflammatory or infectious process suggestive of encephalitis.Lumbar puncture was performed and empirical therapy with ceftriaxone, vancomycin, and acyclovir was initiated.Both the biofire pneumonia panel and endotracheal secretion culture was positive for methicillin resistant staphylococcus aureus (mrsa), and clindamycin was added.However, within the first 48 hours, the patient developed hyperreflexia, generalized rigidity, dysautonomia (persistent tachycardia and labile blood pressure), spontaneous myoclonus, and progressive decline in consciousness with central respiratory failure, requiring orotracheal intubation and transfer to the pediatric intensive care unit (picu).Initial csf analysis revealed no pleocytosis or biochemical alterations.Furthermore, the me panel was negative for all targets.Consequently, acyclovir was discontinued.In the setting of neurological deterioration, autoimmune encephalitis was suspected.Complement analysis showed low c3 with normal c4.Immunological tests, including anti-nmda receptor, anti-mog, and anti-aqp4 antibodies, were all negative.Cervical spine mri revealed findings consistent with acute disseminated encephalomyelitis (adem).Immunomodulatory treatment was started with intravenous immunoglobulin (2 gm/kg over 2 days) followed by five sessions of plasmapheresis.Partial improvement of hypertonia was observed, but axial rigidity and altered alertness persisted, with grade i papilledema confirmed by ophthalmology.Given the need for prolonged video-eeg monitoring and specialized management, the patient was referred to a quaternary care center.On day 7 of illness, repeat lumbar puncture revealed pleocytosis (94 cells/mm³), elevated protein, and hypoglycorrhachia.The new sample was tested on the me panel, which was positive for hsv-1 and hhv-6.Brain mri demonstrated supratentorial white matter abnormalities, intra-axial hemorrhagic lesions, and punctate bilateral hemorrhages, consistent with viral meningoencephalitis and adem.High-dose intravenous acyclovir (20 mg/kg every 8 hours) was restarted and completed for 21 days.Additional therapy included methylprednisolone pulses (30 mg/kg/day for 5 days) and intravenous immunoglobulin (1 gm/kg) following plasmapheresis.During hospitalization, the patient required multiple anticonvulsants (phenobarbital, levetiracetam, and lacosamide).He developed spastic quadriparesis confirmed by neuroimaging with extensive demyelination and required tracheostomy and gastrostomy for long-term support.At discharge, he was afebrile, with decreased frequency of seizures and no epileptiform activity on video-eeg.A multidisciplinary follow-up was arranged with neurology, infectious diseases, genetics (whole-exome sequencing), and rehabilitation, given the high risk of postencephalitic epilepsy and persistent motor neurological sequelae.The patient developed severe neurological sequelae, including spastic quadriparesis, epilepsy, and functional dependence.The publication stated that acyclovir was discontinued for this patient due to the negative me panel result.The publication further stated that a single negative initial pcr can lead to diagnostic delays and devastating neurological outcomes in pediatric herpetic encephalitis.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 adverse neurological outcome.The initial negative hsv result occurred early in the disease course, a context in which low csf viral burden and false-negative pcr results are well recognized.Hsv encephalitis was prematurely excluded from the differential diagnosis, leading to inappropriate discontinuation of acyclovir despite persistent and progressive encephalitic features.Subsequent repeat testing confirmed hsv infection, consistent with known biological limitations of early csf molecular testing rather than assay failure.Overall, the evidence supports that the poor outcome in this patient resulted from diagnostic and management error, specifically delayed sustained antiviral therapy, and not from a malfunction or unexpected performance of the me panel.Conclusion: biofire¿s investigation into this event is ongoing, and further information has been requested from the author.The full investigation and associated conclusions will be provided in the supplemental report.No remedial action, corrective action, preventive action, or fsca has been deemed necessary at this time.Publication: doi:10.5005/jp-journals-10081-1503.
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Event or Problem Description
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Idarraga et al.Published a study, "filmarray in cerebrospinal fluid: the challenge of false negatives in pediatric herpetic encephalitis" which describes a potential false negative hsv-1 and a potential false negative hhv-6 on the filmarray meningitis/encephalitis (me) panel during testing of a csf sample from a 20-month-old male patient.The publication suggested that the biofire result led to premature discontinuation of acyclovir, which contributed to neurological sequelae, including spastic quadriparesis and functional dependence.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.
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Event or Problem Description
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(b)(6).Published a study, "(b)(6)" which describes a potential false negative hsv-1 and a potential false negative hhv-6 on the filmarray meningitis/encephalitis (me) panel during testing of a csf sample from a 20-month-old male patient.The publication suggested that the biofire result led to premature discontinuation of acyclovir, which contributed to neurological sequelae, including spastic quadriparesis and functional dependence.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.Update for supplemental report: upon following with the authors, they indicated the study sample was from over a year ago.The first filmarray result was from another client (fundación club noel), but the child had been experiencing symptoms for less than 24 hours, so the possibility of a false negative was very high.The patient did not require any further intervention and suffered no lasting effects from discontinuing the treatment.Biofire is still investigating this event in order to determine the root cause.The full investigation and associated conclusions will be provided in a future supplemental report.
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Additional Manufacturer Narrative
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Investigation: (b)(6) published a study, "(b)(6)" which describes a potential false negative hsv-1 and a potential false negative hhv-6 on the filmarray meningitis/encephalitis (me) panel during patient testing.The patient was a previously healthy 20-month-old male, with complete immunization schedule, no relevant perinatal or past medical history, and no family history of epilepsy or febrile seizures.He presented with a 48-hour history of fever reaching 39°c, followed by his first episode of complex febrile seizure characterized by generalized hypertonia, ocular deviation, and a duration of approximately 3 minutes, with a prolonged postictal state of 30 minutes.He subsequently developed focal status epilepticus involving the right upper limb, refractory to management with midazolam, phenytoin, and phenobarbital, which prompted referral to a tertiary care center.On admission, weight was 10.7 kg and height 83 cm.Initial studies revealed mild leukocytosis and elevated c-reactive protein, with normal serum electrolytes.Blood, urine, and csf cultures were negative.Csf gram stain was also negative.Brain ct demonstrated bilateral frontoparietal hypodensities, while mri showed lesions consistent with multifocal ischemia or an inflammatory or infectious process suggestive of encephalitis.Lumbar puncture was performed and empirical therapy with ceftriaxone, vancomycin, and acyclovir was initiated.Both the biofire pneumonia panel and endotracheal secretion culture was positive for methicillin resistant staphylococcus aureus (mrsa), and clindamycin was added.However, within the first 48 hours, the patient developed hyperreflexia, generalized rigidity, dysautonomia (persistent tachycardia and labile blood pressure), spontaneous myoclonus, and progressive decline in consciousness with central respiratory failure, requiring orotracheal intubation and transfer to the pediatric intensive care unit (picu).Initial csf analysis revealed no pleocytosis or biochemical alterations.Furthermore, the me panel was negative for all targets.Consequently, acyclovir was discontinued.In the setting of neurological deterioration, autoimmune encephalitis was suspected.Complement analysis showed low c3 with normal c4.Immunological tests, including anti-nmda receptor, anti-mog, and anti-aqp4 antibodies, were all negative.Cervical spine mri revealed findings consistent with acute disseminated encephalomyelitis (adem).Immunomodulatory treatment was started with intravenous immunoglobulin (2 gm/kg over 2 days) followed by five sessions of plasmapheresis.Partial improvement of hypertonia was observed, but axial rigidity and altered alertness persisted, with grade i papilledema confirmed by ophthalmology.Given the need for prolonged video-eeg monitoring and specialized management, the patient was referred to a quaternary care center.On day 7 of illness, repeat lumbar puncture revealed pleocytosis (94 cells/mm³), elevated protein, and hypoglycorrhachia.The new sample was tested on the me panel, which was positive for hsv-1 and hhv-6.Brain mri demonstrated supratentorial white matter abnormalities, intra-axial hemorrhagic lesions, and punctate bilateral hemorrhages, consistent with viral meningoencephalitis and adem.High-dose intravenous acyclovir (20 mg/kg every 8 hours) was restarted and completed for 21 days.Additional therapy included methylprednisolone pulses (30 mg/kg/day for 5 days) and intravenous immunoglobulin (1 gm/kg) following plasmapheresis.During hospitalization, the patient required multiple anticonvulsants (phenobarbital, levetiracetam, and lacosamide).He developed spastic quadriparesis confirmed by neuroimaging with extensive demyelination and required tracheostomy and gastrostomy for long-term support.At discharge, he was afebrile, with decreased frequency of seizures and no epileptiform activity on video-eeg.A multidisciplinary follow-up was arranged with neurology, infectious diseases, genetics (whole-exome sequencing), and rehabilitation, given the high risk of postencephalitic epilepsy and persistent motor neurological sequelae.The patient developed severe neurological sequelae, including spastic quadriparesis, epilepsy, and functional dependence.The publication stated that acyclovir was discontinued for this patient due to the negative me panel result.The publication further stated that a single negative initial pcr can lead to diagnostic delays and devastating neurological outcomes in pediatric herpetic encephalitis.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 adverse neurological outcome.The initial negative hsv result occurred early in the disease course, a context in which low csf viral burden and false-negative pcr results are well recognized.Hsv encephalitis was prematurely excluded from the differential diagnosis, leading to inappropriate discontinuation of acyclovir despite persistent and progressive encephalitic features.Subsequent repeat testing confirmed hsv infection, consistent with known biological limitations of early csf molecular testing rather than assay failure.Overall, the evidence supports that the poor outcome in this patient resulted from diagnostic and management error, specifically delayed sustained antiviral therapy, and not from a malfunction or unexpected performance of the me panel.Update for supplemental report: upon following with the authors, they indicated the study sample was from over a year ago.The first filmarray result was from another client (fundación club noel), but the child had been experiencing symptoms for less than 24 hours, so the possibility of a false negative was very high.The patient did not require any further intervention and suffered no lasting effects from discontinuing the treatment.Conclusion: biofire¿s investigation into this event is ongoing.The full investigation and associated conclusions will be provided in a future supplemental report.Publication: doi:10.5005/jp-journals-10081-1503.
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Event or Problem Description
|
|
Idarraga et al.Published a study, "filmarray in cerebrospinal fluid: the challenge of false negatives in pediatric herpetic encephalitis" which describes a potential false negative hsv-1 and a potential false negative hhv-6 on the filmarray meningitis/encephalitis (me) panel during testing of a csf sample from a 20-month-old male patient.The publication suggested that the biofire result led to premature discontinuation of acyclovir, which contributed to neurological sequelae, including spastic quadriparesis and functional dependence.Follow-up communication with the authors indicated the patient did not require any further intervention and suffered no lasting effects from discontinuing the treatment.Based on information provided, the investigation concluded that the most likely cause for the potential false negative result was the hsv-1 and hhv-6 targets being present at levels near/below biofire limit of detection (lod) in the clinical sample.
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Additional Manufacturer Narrative
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Investigation:
idarraga et al.Published a study, "filmarray in cerebrospinal fluid: the challenge of false negatives in pediatric herpetic encephalitis" which describes a potential false negative hsv-1 and a potential false negative hhv-6 on the filmarray meningitis/encephalitis (me) panel during patient testing.The patient was a previously healthy 20-month-old male, with complete immunization schedule, no relevant perinatal or past medical history, and no family history of epilepsy or febrile seizures.He presented with a 48-hour history of fever reaching 39°c, followed by his first episode of complex febrile seizure characterized by generalized hypertonia, ocular deviation, and a duration of approximately 3 minutes, with a prolonged postictal state of 30 minutes.He subsequently developed focal status epilepticus involving the right upper limb, refractory to management with midazolam, phenytoin, and phenobarbital, which prompted referral to a tertiary care center.On admission, weight was 10.7 kg and height 83 cm.Initial studies revealed mild leukocytosis and elevated c-reactive protein, with normal serum electrolytes.Blood, urine, and csf cultures were negative.Csf gram stain was also negative.Brain ct demonstrated bilateral frontoparietal hypodensities, while mri showed lesions consistent with multifocal ischemia or an inflammatory or infectious process suggestive of encephalitis.Lumbar puncture was performed and empirical therapy with ceftriaxone, vancomycin, and acyclovir was initiated.Both the biofire pneumonia panel and endotracheal secretion culture was positive for methicillin resistant staphylococcus aureus (mrsa), and clindamycin was added.However, within the first 48 hours, the patient developed hyperreflexia, generalized rigidity, dysautonomia (persistent tachycardia and labile blood pressure), spontaneous myoclonus, and progressive decline in consciousness with central respiratory failure, requiring orotracheal intubation and transfer to the pediatric intensive care unit (picu).Initial csf analysis revealed no pleocytosis or biochemical alterations.Furthermore, the me panel was negative for all targets.Consequently, acyclovir was discontinued.In the setting of neurological deterioration, autoimmune encephalitis was suspected.Complement analysis showed low c3 with normal c4.Immunological tests, including anti-nmda receptor, anti-mog, and anti-aqp4 antibodies, were all negative.Cervical spine mri revealed findings consistent with acute disseminated encephalomyelitis (adem).Immunomodulatory treatment was started with intravenous immunoglobulin (2 gm/kg over 2 days) followed by five sessions of plasmapheresis.Partial improvement of hypertonia was observed, but axial rigidity and altered alertness persisted, with grade i papilledema confirmed by ophthalmology.Given the need for prolonged video-eeg monitoring and specialized management, the patient was referred to a quaternary care center.On day 7 of illness, repeat lumbar puncture revealed pleocytosis (94 cells/mm³), elevated protein, and hypoglycorrhachia.The new sample was tested on the me panel, which was positive for hsv-1 and hhv-6.Brain mri demonstrated supratentorial white matter abnormalities, intra-axial hemorrhagic lesions, and punctate bilateral hemorrhages, consistent with viral meningoencephalitis and adem.High-dose intravenous acyclovir (20 mg/kg every 8 hours) was restarted and completed for 21 days.Additional therapy included methylprednisolone pulses (30 mg/kg/day for 5 days) and intravenous immunoglobulin (1 gm/kg) following plasmapheresis.During hospitalization, the patient required multiple anticonvulsants (phenobarbital, levetiracetam, and lacosamide).He developed spastic quadriparesis confirmed by neuroimaging with extensive demyelination and required tracheostomy and gastrostomy for long-term support.At discharge, he was afebrile, with decreased frequency of seizures and no epileptiform activity on video-eeg.A multidisciplinary follow-up was arranged with neurology, infectious diseases, genetics (whole-exome sequencing), and rehabilitation, given the high risk of postencephalitic epilepsy and persistent motor neurological sequelae.The patient developed severe neurological sequelae, including spastic quadriparesis, epilepsy, and functional dependence.The publication stated that acyclovir was discontinued for this patient due to the negative me panel result.The publication further stated that a single negative initial pcr can lead to diagnostic delays and devastating neurological outcomes in pediatric herpetic encephalitis.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 adverse neurological outcome.The initial negative hsv result occurred early in the disease course, a context in which low csf viral burden and false-negative pcr results are well recognized.Hsv encephalitis was prematurely excluded from the differential diagnosis, leading to inappropriate discontinuation of acyclovir despite persistent and progressive encephalitic features.Subsequent repeat testing confirmed hsv infection, consistent with known biological limitations of early csf molecular testing rather than assay failure.Overall, the evidence supports that the poor outcome in this patient resulted from diagnostic and management error, specifically delayed sustained antiviral therapy, and not from a malfunction or unexpected performance of the me panel.Update for supplemental report:
follow-up communication with the authors indicated the study sample was from over a year ago.The first filmarray result was from another client (fundación club noel), but the child had been experiencing symptoms for less than 24 hours, so the possibility of a false negative was very high.The patient did not require any further intervention and suffered no lasting effects from discontinuing the treatment.Conclusion:
the medical affairs assessment is consistent with the publication's conclusion that the multiplex meningitis/encephalitis (me) panel did not contribute to the patient¿s adverse neurological outcome.The investigation concluded that the most likely cause for the potential false negative result was the hsv-1 and hhv-6 targets being present at levels near/below biofire limit of detection (lod) in the clinical sample.The initial negative hsv result occurred early in the disease course, a context in which low csf viral burden and false-negative pcr results are well recognized.Hsv encephalitis was prematurely excluded from the differential diagnosis, leading to inappropriate discontinuation of acyclovir despite persistent and progressive encephalitic features.Subsequent repeat testing confirmed hsv infection, consistent with known biological limitations of early csf molecular testing rather than assay failure.Overall, the evidence supports that the poor outcome in this patient resulted from diagnostic and management decisions made by the healthcare professional based on all available information and not from a malfunction or unexpected performance of the me panel.Publication: doi:10.5005/jp-journals-10081-1503.
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