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A customer in the united states notified biomérieux of discrepant ceftazidime results for pseudomonas stutzeri in association with ceftazidime tz 256 us s30 (ref.412292, lot 1007980190, exp date 3/30/2022).The customer stated they had a vitek® 2 / etest® discrepancy for pseudo.Stutzeri for ceftazidime.The customer stated that vitek 2 reported ceftazidime as susceptible, but ceftazidime etest® reported as resistant.Summary: patient strain pseudomonas stutzeri from a wound sample.Vitek 2 result: ceftazidime mic=1, s.Etest result: ceftazidime mic=256, r.There is no evidence of off-label use by the customer.There is no indication or report from the customer that this event led to any adverse event related to any patient's state of health.
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An internal investigation was performed following notification from a customer in australia that they obtained discrepant results for a patient pseudomonas stutzeri strain, using vitek 2 ast-gn73 and etest® ceftazidime (tz 256).Susceptible results were obtained on vitek 2 [minimum inhibitory concentration (mic) value = 1 g/ml] whereas resistant results were obtained with etest (mic value = 256 g/ml).Investigation retained sample analysis: retained samples for the impacted lot number (1007980190) were tested in parallel with one internal lot number used as a reference lot (reference 412292, lot 1007837740, expiry date on 21 jan 2022).Tests were performed using the quality control (qc) strains pseudomonas aeruginosa atcc® 27853¿, escherichia coli atcc® 25922¿, staphylococcus aureus atcc® 29213¿ and haemophilus influenzae atcc® 49247¿ according to the qc protocol used for the release of each lot number.The qc results obtained for the four strains tested are within the expected range for the investigated etest lot and the reference etest lot tested.Moreover, no paradoxical effect of the ellipse was observed during these tests.Results : - pseudomonas aeruginosa atcc 27853 : mic values between 1 and 1.5 g/ml (expected range : 1 ¿ 4 g/ml).- escherichia coli atcc 25922 : mic values at 0.19 g/ml (expected range : 0.064 ¿ 0.5 g/ml).- staphylococcus aureus atcc 29213 : mic values between 8 and 12 g/ml (expected range : 4 ¿ 16 g/ml) - haemophilus influenzae atcc 49247 : mic values between 0.38 and 0.5 g/ml (expected range : 0.125 ¿ 1 g/ml).Complaint analysis: as of the date of this investigation, no other complaints were registered on this lot number for this type of issue.Customer sample analysis: tests were performed with the returned pseudomonas stutzeri patient strain.Two types of colonies were observed, grey diffuse colonies (called a) and distinct white colonies (called b).The two isolated colonies a and b were identified as pseudomonas stutzeri with vitek 2 gn id cards and vitek ms, which confirms that the strain presents a polymorphism (described in the scientific literature).Step 1 ¿ etest and reference method testing: clsi 2022 breakpoints were used to categorize the mic values obtained with the returned strain: [s = 8 - 16 i - r = 32].The first round of tests was then performed from a mix of colony a and b called "mass".The strain was tested with the agar dilution (ad) methodology (method used for the development of etest® tz 256) and a range of 0.03 g/ml to 32 g/ml.The following result was obtained : - mic ad = 1 g/ml (susceptible).The impacted etest® tz 256 lot (lot number 1007980190 reference 412292) and the etest® tz 256 lot number 1008611010 (reference 412292) used as a reference lot were also tested and the following result was obtained: - mic etest® tz 256 = 256 g/ml (resistant) on both lots tested.The strain presents a growth in the inhibition zone that raise the suspicion of a hetero-resistant strain but the paradoxal ellipse observed by the customer was not reproduced.This observation coupled to the discordant results between etest and the ad method lead to further testing on this strain and its polymorphism.Step 2 ¿ complementary testing on colonies a and b: colonies a and b and the mass were tested with: - etest tz 256.- ceftazidime disk diffusion method.- vitek 2 ast-gn73 cards.- broth microdilution.The following results were obtained: - etest: 0.5 g/ml (susceptible) for colony a and =256 g/ml (resistant) for colony b and mass.- disk diffusion: 27.85 mm (intermediate) for colony a, 0 mm (resistant) for colony b and mass.- vitek 2 ast-gn73: = 1 mg/l (susceptible) for colony a, colony b and mass.- bmd: = 256 g/ml for colony a, colony b and mass etest and disk diffusion results are homogeneous : microcolonies are observed in the inhibition zone of colony b and then of mass.Vitek 2 growth curves analysis shows growth at the higher concentrations that is not observed at the lowest ones and which can explain the susceptible mics.The bmd confirms this phenomenon and the fact that at the higher ceftazidime concentrations, a, b and the mass are resistant.These tests allowed to conclude to the presence of an induced resistance to ceftazidime (to the high concentrations) for this strain.It seems less expressed in colony a compared to colony b but on the mass (mixture of both) this difference is not perceptible.Step 3 ¿ confirmation of ad mic: the strain was tested again with the ad methodology by using a range extended up to 128 g/ml with the mass sample.We observed no growth at 1 g/ml, slighter one from 2 to 16 g/ml and clear growth after 32 g/ml.The mic obtained was then determined as = 256 g/ml.The etest results = 256 g/ml (resistant) the customer obtained with the pseudomonas stutzeri strain are then reproduced during this investigation but the paradoxical ellipse observed was not reproduced.The etest tz mic values are in agreement compared to the reference mic ad without any category error.The strain presents an induced resistance to ceftazidime (to the high concentrations) that explain the resistant results obtained on etest and can explain the gaps with vitek 2 results which algorithm cannot detect such uncommon behavior.Conclusion: the results of the quality control tests obtained during our investigation on the impacted etest® ceftazidime lot complied with specifications for the four strains tested.The customer's etest results = 256 g/ml (resistant) were reproduced.No paradoxical effect of the ellipse was observed during the internal testing.Nevertheless a growth was detected in the inhibition zone.This strain presents an induced resistance to ceftazidime (to the high concentrations) that could explain the differences observed between the methods tested.The etest method allows the detection of this mechanism and the etest tz mic values remain within essential agreement compared to the reference mic ad method without any category error.As no product performance issue was observed during the investigation, neither corrective nor preventive action will be implemented.
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