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(b)(6) reported a potential false positive c.Neoformans/gattii result on the filmarray me panel after testing a patient csf sample.The patient was a (b)(6) year-old, male patient with symptoms of head trauma.On (b)(6) 2020, a csf sample was collected via spinal tap, tested on the filmarray me panel, and the result was positive for c.Neoformans/gattii.Using the same sample for all testing, a repeat filmarray me panel was performed on (b)(6) 2020, and was negative for all assays.Cryptococcal antigen tests of the csf and serum were negative on unknown dates, and a cytospin gram stain resulted in "no organisms seen." fungal culture was negative at 48 hours on (b)(6) 2020.According to the customer, the filmarray me panel positive c.Neoformans/gattii result was reported to the physician (date unknown) and there was inappropriate treatment.It is unknown when or what treatment was initiated, and as of (b)(6) 2020, the patient was still in the hospital.When asked if the patient was harmed due to the filmarray me panel result, the customer responded "possibly." biofire has made multiple attempts to receive clarification about this statement and further detail about this event, but has been unable to obtain more information.The customer reported that filmarray me panel pouches are prepared in the same area where other samples are processed, and that decontamination procedures are performed before each pouch preparation.The customer also noted that the csf sample was not diluted or centrifuged prior to testing, and that pouches are prepared according to the filmarray me panel quick guide (https://www.Online-ifu.Com/iti0012).Quality control (qc) records for pouch lot# 164419 (kit lot# 1307219) were reviewed.This pouch lot passed qc criteria and was found within specification.No run malfunction occurred and the filmarray instruments (serial# (b)(4) [initial run] & (b)(4) [repeat run]) were working within design specifications.Conclusion: based on the information provided, the investigation concluded that the most likely causes for the discrepant c.Neoformans/gattii result are 1) sensitivity/specificity differences between the filmarray me panel and comparator methods when testing a sample with low organism levels, or 2) contamination.Sensitivity/specificity differences between the filmarray me panel and comparator methods when testing a sample with low organism levels.The filmarray me panel is a highly-sensitive molecular test that can detect the presence of target nucleic acid independent of organism viability.Molecular-based methods are widely recognized as being more sensitive than culture and other phenotypic methods for identifying pathogens in clinical samples.Thus, it is possible that the discordant results between the filmarray me panel, the comparator antigen test, and culture is due to comparator sensitivity/specificity differences.In addition, analysis of the initial filmarray me panel run file suggests that the cryptococcus assay is likely present in the sample at low levels.Pcr methods can be affected by the level of target nucleic acid, and samples with lower levels of genetic material may product variable detections.Discrepancies between filmarray me panel runs can be observed upon repeat testing of samples with low organism levels.According to table 9 of the filmarray me panel instruction booklet, in the prospective clinical study, the c.Neoformans/gattii assay compared to pcr with bi-directional sequencing showed an overall ppa of 100% (1/1) and an overall npa of 99.7% (95% ci 99.3-99.9%).C.Neoformans/gattii was detected in 2/4 fp specimens using a commercially available antigen test.One fp 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.In this study, 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 (table 14, https://www.Online-ifu.Com/iti0035).The limit of detection (lod) for the c.Neoformans/gattii assay is 100 cfu/ml (table 17, https://www.Online-ifu.Com/iti0035).Contamination.The customer stated that pouches are prepared in the same area that other samples are processed, and that they follow recommended decontamination procedures before preparing each filmarray me panel pouch.While pouch loading instructions and recommended cleaning steps are sufficient to eliminate contamination the vast majority of the time, it is possible that some organism/nucleic acid/amplicon could be introduced during any part of the testing process.The contamination prevention and decontamination technical note [flm1-prt-0230] recommends that a biosafety cabinet used to perform viral, bacterial, or fungal culture should not be used for specimen preparation or filmarray reagent setup.It is possible that some organism/nucleic acid/amplicon could have been introduced into the pouch from the laboratory environment, equipment used for test setup, or personnel handling the samples/pouches.Caution should be exercised during sample collection, handling, and testing to reduce the potential occurrence of erroneous results.The filmarray me panel is indicated as an aid in the diagnosis of specific agents of meningitis and/or encephalitis and results are meant to be used in conjunction with other clinical, epidemiological, and laboratory data.Results from the filmarray me panel are not intended to be used as the sole basis for diagnosis, treatment, or other patient management decisions.Positive results do not rule out co-infection with organisms not included in the filmarray me panel.The agent detected may not be the definite cause of the disease.
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(b)(6) reported a discrepant cryptococcus neoformans/gattii (c.Neoformans/gattii) result on the filmarray meningitis/encephalitis (me) panel after testing a cerebrospinal fluid (csf) sample from a (b)(6) year-old, male patient.Due to the filmarray me panel result, the patient received inappropriate treatment for an unknown period of time.When asked if the patient was harmed, the customer responded "possibly." attempts to receive clarification of this statement and further event details have been unsuccessful.Upon investigation, no malfunction occurred and the filmarray me panel system was performing within specification.The investigation concluded that the most likely causes for the discrepant result are sensitivity/specificity differences between the filmarray me panel and comparator methods when testing a sample with low levels of organism, or contamination.
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