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A customer in (b)(6) notified biomérieux of obtaining discrepant meropenem results for three (3) separate patient isolates in association with the etest® meropenem test strip (ref.513800, lot 1007278480).The patient isolates were also testing via vitek® 2 ast-n233 test kit and pcr.The summary of results is listed below.Patient 3: strain id - klebsiella pneumoniae; vitek® ast-n233 result - mic>8, resistant; etest® result - mic=4, intermediate.Pcr result - carbapenemase kpc type detected, resistant t.There is no indication or report from the laboratory that the discrepant result led to any adverse event related to any patient's state of health.Biomérieux will initiate an internal investigation.
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This report was initially submitted following notification from a customer in germany regarding discrepant meropenem results for three (3) separate patient isolates in association with the etest® meropenem test strip (ref.513800, lot 1007278480).The patient isolates were also tested via vitek® 2 ast-n233 test kit and pcr.The summary of results is listed below.Patient (b)(4): strain id - klebsiella pneumoniae.Vitek® ast-n233 result - mic>8, resistant.Etest® result - mic=4, intermediate.Pcr result - carbapenemase kpc type detected, resistant.A biomérieux internal investigation was performed on atcc® quality control strains and on the strains submitted to check the performance of the etest® mp32 on the impacted lot number.The results are detailed below: 1.Retained samples analysis biomérieux retains samples of every lot number released to the market.The retained samples for the two impacted lot numbers that you reported were investigated.For etest® mp32, the lot number 1007278480, expiry date 31-mar-2022 was tested in parallel with a reference lot number 1007735480, expiry date 12-nov-2022.Conformance to our specifications was verified with the following atcc quality control strains that were also tested to release etest mp32 strips: atcc® 25285¿ bacteroides fragilis atcc® 49619¿ streptococcus pneumoniae atcc® 49766¿ haemophilus influenzae atcc® 27853¿ pseudomonas aeruginosa atcc® 25922¿ escherichia coli the etest® mp32 performance of the impacted lot and the reference lot number comply with the specifications.2.Analysis of provided strains the identification of the three provided strains were confirmed internally with vitek® 2 gn cards.Strain 3 was correctly identified as klebsiella pneumoniae.Two types of colonies were observed during the culture of strain 3.The grey colonies were named s3g and the white colonies s3b.Each colony was isolated, identified and antibiotic susceptibility was tested using vitek® 2 ast-n233/xn05 card.The ast results were different between the two colonies.Then, each of them was tested independently.2.1 breakpoints used eucast clinical 2020 breakpoints: meropenem for enterobacterales: s < or = 2 mg/l - r > 8 mg/l 2.2 strains characterization strain 3 b (s3b) and strain 3 g (s3g)) were tested by pcr to confirm that they were enterobacteriae producing carbapenemases: s3g /s3b were oxa-48 like strains.The agar dilution (ad) was tested since it was the method used for the etest® mp32 strips development.The following results were obtained: for meropenem : -s3b mic = 0.5 mg/ l (s) -s3g mic = 0.5 mg/l (s) the broth microdilution (bmd) was also tested since it was the method used for imipenem drug development in ast-n223 cards used by the customer.The following results were obtained: for meropenem : -s3b mic = 0.5 mg/l (s) -s3g mic = 1 mg/ l (s) 2.3 results with the etest method the two strains were tested on the impacted etest® mp32 lot number 1007278480 and in parallel with a reference lot etest® mp32 lot number 1007735480, expiry date 12-nov-2022 the results were the following: for meropenem: -s3b mp mic = 8 mg/l (i) on the impacted lot and 16 mg/l (r ) on the reference lot -s3g mp mic = 1 mg/l (s) on the impacted lot and 2 mg/l (s) on the reference lot note: presence of microcolonies in the inhibition zone for s3b and s3g.Strain s3 *********** the strain presents a polymorphism (presence of grey and white colonies).The two colonies (s3b and s3g) gave susceptible results by the reference methods (ad and bmd).For the strain s3b, the etest ® mp32 mic was within essential agreement compared to the reference mic (ad) leading to category errors for meropenem.For the strain s3g, the etest® mp32 mic was within essential agreement compared to the reference mic (ad) on the impacted lot, but were essential agreement errors on the reference lot without any category error.Microcolonies were observed in the inhibition zone of the two strains and in larger proportion for s3b.This highlighted a heterogeneous expression of the resistance in the s3 strain.For this reason, s3 should be considered as an atypical strain and the most resistant results should be considered.3.Complaint trend analysis no other complaint was registered on the etest® mp32 lot number 1007278480.No loss of performances were found during the investigation.One investigation is in progress on 2 patients strains on etest ® mp32.4.Conclusion a polymorphism was observed on the s3 strain.The two types of colonies were tested.The s3g strain was susceptible with etest ® mp32 whereas the s3b strain was intermediate and resistant.The strain was confirmed to be heterogeneous which may explain the variability of etest® results between both colonies.The trend analysis of the complaints does not show any deviation on the reference product etest® mp32 reference 513800.As a conclusion, the performance of this lot etest® meropenem was within specifications and the investigation did not identify any product performance issue.Complaints trend analysis for this reference will continue to be monitored.It is also important to highlight that etest® products should always be stored according to the temperature specified on the packaging, until the given expiry date.Products can always be stored lower than the maximum temperature specified.That is why, it is recommended to store etest® meropenem (mp32), reference 513800 at -20°c instead 2-8°c.
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