MAUDE Adverse Event Report: BIOMÉRIEUX, SA ETEST® AMOXI/CLAV 2/1 XL 256 WW S30

Catalog Number 412241

Device Problem Incorrect, Inadequate or Imprecise Result or Readings (1535)

Patient Problem No Clinical Signs, Symptoms or Conditions (4582)

Event Type  malfunction  

Event Description

An internal complaint was initiated following a review of a 2021 scientific publication entitled, "false amoxicillin/clavulanic acid susceptibility in bacteroides fragilis using gradient strip tests," by rentenaar, r.J.Et al.In this study the authors tested 27 clinical isolates (bacteroides fragilis) that were obtained from 2010 to 2020.The article specified that they tested one isolate per patient.This is a retrospective study and the isolates had to be thawed before testing.The isolates were tested for antibiotic susceptibility using etest® amoxicillin/clavulanic acid (reference #: 412241, batch #: unknown) and all results were susceptible.Seven (7) isolates obtained false susceptible results, or very major errors (vme).In addition, one isolate obtained a minor error or mie (minor discrepancy).Biomérieux is not aware of any adverse event related any patient's state of health.A biomérieux internal investigation has been initiated.Note: reference 412241 is not registered in the united states.The u.S.Similar device is product reference 412240.

Manufacturer Narrative

An internal complaint was initiated following a review of a scientific publication from netherlands entitled, "false amoxicillin/clavulanic acid susceptibility in bacteroides fragilis using gradient strip tests" by rob j.Rentenaar, bianca bovo-heijmans, joanna diggle, ad c.Fluit, mandy wooton.The study highlights some false susceptibility results obtained with bacteroides fragilis (anaerobic bacteria) and etest® amoxicillin/clavulanic acid (b)(6) (xl 256) strip, when compared to the agar dilution (ad) reference method using european committee on antimicrobial susceptibility testing (eucast) methodology and breakpoints.Etest amoxicillin/clavulanic acid (b)(6) (xl 256) strip, reference (b)(4), was developed according to clinical & laboratory standards institute (clsi) method.It is important to note that the clsi and the eucast provide two different guidelines for this ss-lactam/ss-lactamase inhibitor combination.Indeed, the clsi proposes an amoxicillin/clavulanic acid ratio of (b)(4) while the eucast proposes a fixed concentration of 2 g/ml for the clavulanic acid with increasing amoxicillin concentrations.Based on these elements, we performed a performance assessment of etest xl 256 which is described below.Historical data review: the gap between clsi and eucast ad methods were suspected to impact the reference values of the minimum inhibitory concentrations (mic) of amoxicillin/clavulanic combination.Etest xl 256 being developed compared to clsi ad, the research & development (r&d) team compared the performance of the etest xl 256 strip with the ad methodology of clsi and with eucast.An internal panel of (b)(4) was tested.Among those (b)(4) strains, (b)(4) strains (bacteroides dorei (b)(6), bacteroides fragilis (b)(6), bacteroides ovatus (b)(6), bacteroides pyogenes (b)(6), bacteroides thetaiotaomicron (b)(6), bacteroides uniformis (b)(6) and bacteroides vulgatus (b)(6) were tested with etest xl 256 and the two ad methods.Comparing directly the ad mics, the following results were obtained : - (b)(6) isolates obtained same mics between clsi and eucast methodology - the other 17 isolates gave higher mics with eucast methodology compared to clsi: * (b)(6) isolates obtained 1 doubling dilution higher with the eucast.* (b)(6) isolates obtained 2 doubling dilutions higher with the eucast.* (b)(6) isolates obtained 3 doubling dilutions higher with the eucast.* (b)(6) isolate obtained 4 doubling dilutions higher with the eucast.So it appears that the ad with the eucast methodology gives higher mics than the ad with the clsi methodology.The lower concentration of clavulanic acid used by the eucast methodology decreases the amoxicillin action which may explain the higher mic obtained with the eucast methodology.Clsi breakpoints [s = 4/2 g/ml, i = 8/4 g/ml, r = 16/8 g/ml].Eucast breakpoints [s = 4/2 g/ml, and r > 8/2 g/ml]).Etest xl 256 mics were compared to both ad reference mics giving the following results on the (b)(4)tested : according to the clsi - reading after 24 hours : ea = 89.3% / ca = 92.9% / me = 7.1% / me = 0% / vme = 0%.- reading after 48 hours : ea = 85.7% / ca = 100% / me = 0% / me = 0% / vme = 0%.According to the eucast - reading after 24 hours : ea = 60.7% / ca = 67.9% / me = 17.9% / me = 0% / vme = 44.4%.- reading after 48 hours : ea = 57.1% / ca = 71.1% / me = 17.9% / me = 0% / vme = 33.3%.The high rate of vme of etest xl 256, when compared to eucast ad methodology, described in the article was reproduced with this r&d study.This fact is due to the comparison with eucast methodology.The etest xl 256 is nevertheless correctly adjusted compared to the clsi ad methodology.Based on these elements, biomérieux has developed a new strip called etest acc (2018), reference (b)(4) with gradient strip aligned with the eucast methodology such as the use of a fixed clavulanic acid concentration.Complaint analysis: biomérieux reviewed scientific publications from 2015 to ongoing 2022, searching for etest amoxicillin/clavulanic acid.Two publications were found outside the related article.Among those 2 articles, only 1 was related to anaerobes.This article was reviewed and classified as ¿no impact¿ by biomérieux medical affairs meaning that there were no evidence in the article that the etest xl 256 strip was outside its expected level of performance.The complaint analysis did not reveal this issue as a system quality issue.Conclusion: the gap of performance reported in the article for etest amoxicillin/clavulanic acid (xl 256) was already known within biomérieux.Indeed the false susceptible etest xl 256 results reported in the study are due to the comparison to the eucast reference method whereas the etest xl 256 is developed compared to clsi.Internal data have already demonstrated that reference mics were higher with the eucast method compared to clsi.Following these data, biomérieux has developed a new strip called etest acc, reference (b)(4), with gradient strip aligned with the eucast methodology such as the use of a fixed clavulanic acid concentration.No trend is observed in the scientific articles search related to etest xl 256 with anaerobes strains and no trend is observed during the complaint trend analysis for etest xl 256.Then, at this point, there is no evidence that the etest xl 256 is outside its expected level of performance.As the investigation did not identify any product performance issue, neither corrective nor preventive actions will be implemented.

• Brand Name: ETEST® AMOXI/CLAV 2/1 XL 256 WW S30
• Type of Device: ETEST® AMOXI/CLAV 2/1 XL 256 WW S30
• Manufacturer (Section D): BIOMÉRIEUX, SA; 3 route de port michaud; la balme 38390 ; FR 38390
• Manufacturer (Section G): BIOMÉRIEUX, SA; 3 route de port michaud; la balme 38390 ; FR 38390
• Manufacturer Contact: jeff scanlan ; 595 anglum road; hazelwood, MO 63042
• MDR Report Key: 11729207
• MDR Text Key: 280587711
• Report Number: 9615754-2021-00131
• Device Sequence Number: 1
• Product Code: JWY
• Combination Product (y/n): N
• Reporter Country Code: NL
• PMA/PMN Number: K950328
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: Foreign,Study,Literature,Health Professional,User Facility
• Reporter Occupation: Other Health Care Professional
• Type of Report: Initial,Followup
• Report Date: 05/04/2022

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 04/26/2021
• Is this an Adverse Event Report?: No
• Is this a Product Problem Report?: Yes
• Device Operator: Health Professional
• Device Catalogue Number: 412241
• Was Device Available for Evaluation?: No
• Is the Reporter a Health Professional?: Yes
• Date Manufacturer Received: 04/21/2022
• Was Device Evaluated by Manufacturer?: Device Not Returned to Manufacturer
• Is This a Reprocessed and Reused Single-Use Device?: No
• Type of Device Usage: A
• Patient Sequence Number: 1