← Product Code [LON](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON) · K040845 # VITEK 2 ESBL TEST (K040845) _bioMerieux, Inc. · LON · Jun 8, 2004 · Microbiology · SESE_ **Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON/K040845 ## Device Facts - **Applicant:** bioMerieux, Inc. - **Product Code:** [LON](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON.md) - **Decision Date:** Jun 8, 2004 - **Decision:** SESE - **Submission Type:** Traditional - **Regulation:** 21 CFR 866.1645 - **Device Class:** Class 2 - **Review Panel:** Microbiology ## Intended Use The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 System for the automated quantitative or qualitative susceptibility testing of isolated colonies for most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus agalactiae, and S. pneumoniae. The VITEK®2 ESBL Test is intended for use with the VITEK®2 Antimicrobial Susceptibility Test System (AST) as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. ## Device Story VITEK®2 ESBL Test is an automated laboratory aid for detecting ESBLs in specific gram-negative bacilli. Input: isolated bacterial colonies. Process: organism activity monitored in seven test card wells (control, plus cefepime, cefotaxime, and ceftazidime, each with/without clavulanic acid). Algorithm evaluates growth patterns; compares activity in antimicrobial wells with/without clavulanic acid. Output: positive/negative ESBL result. Used in clinical microbiology laboratories; operated by laboratory technicians. Results assist clinicians in determining antimicrobial susceptibility; positive results indicate resistance to penicillins, cephalosporins, and aztreonam. Benefits: rapid identification of ESBL-producing organisms to guide appropriate antibiotic therapy. ## Clinical Evidence Performance evaluated using fresh and stock clinical isolates and stock challenge strains. Compared against the NCCLS ESBL Disk Diffusion Confirmatory Test. Results demonstrated 97.7% overall Category Agreement. Reproducibility and Quality Control testing yielded acceptable results. ## Technological Characteristics Automated short-term incubation antimicrobial susceptibility device. Uses miniaturized doubling dilution technique for MIC determination. Card contains specific antimicrobial concentrations (Cefepime, Cefotaxime, Ceftazidime, and combinations with Clavulanic Acid). System performs automated filling, sealing, and incubation/reading. Operates via the VITEK 2 System platform. ## Regulatory Identification A fully automated short-term incubation cycle antimicrobial susceptibility system is a device that incorporates concentrations of antimicrobial agents into a system for the purpose of determining in vitro susceptibility of bacterial pathogens isolated from clinical specimens. Test results obtained from short-term (less than 16 hours) incubation are used to determine the antimicrobial agent of choice to treat bacterial diseases. ## Special Controls *Classification.* Class II (special controls). The special control for this device is FDA's guidance document entitled “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA.” ## Predicate Devices - VITEK ESBL Test (N50510/S081) ## Submission Summary (Full Text) > This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com. > > Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/). {0} 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY DEVICE ONLY TEMPLATE A. 510(k) Number: k040845 B. Purpose of Submission: Addition of ESBL Test to the VITEK®2 Antimicrobial Susceptibility Test System C. Analyte The following antimicrobial concentrations will be included in the VITEK®2 ESBL Test. Cefepime Cefepime/Clavulanic Acid Cefotaxime Cefotaxime/Clavulanic Acid Ceftazidime Ceftazidime/Clavulanic Acid D. Type of Test: Quantitative growth based detection algorithm using predetermined growth thresholds E. Applicant: bioMerieux, Inc. F. Proprietary and Established Names: VITEK®2 ESBL Test G. Regulatory Information: 1. Regulation section: 866.1645 Short-Term Antimicrobial Susceptibility Test System 2. Classification: II 3. Product Code: LON System, Test, Automated, Antimicrobial Susceptibility, Short Incubation 4. Panel: 83 Microbiology H. Intended Use: 1. Intended use(s): The VITEK®2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK®2 System for the automated quantitative or qualitative susceptibility testing of isolated colonies for most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus agalactiae, and S. pneumoniae. {1} Page 2 of 5 The VITEK®2 ESBL Test is intended for use with the VITEK®2 Antimicrobial Susceptibility Test System (AST) as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. 2. **Indication(s) for use:** This will include the testing of VITEK®2 ESBL Test as a confirmatory test to detect the presence of extended-spectrum beta-lactamase (ESBLs) in *Escherichia coli*, *Klebsiella pneumoniae*, and *Klebsiella oxytoca*. 3. **Special condition for use statement(s):** For ESBL positive strains, the test interpretation should be reported as resistant for all penicillins, cephalosporins and aztreonam. A negative ESBL Test result does not rule out the presence of an ESBL masked by an AMPC beta-lactamase Prescription use only 4. **Special instrument Requirements:** Not applicable I. **Device Description:** The ESBL analysis for the VITEK 2 system is based on monitoring organism activity (growth) in seven different wells on the test card. One well is a control containing only growth media. The other six are cefepime, cefotaxime, and ceftazidime, each with and without clavulanic acid. Organism activity is monitored in the control well to determine whether sufficient activity is present to complete the analysis and to determine the length of incubation. No ESBL result is reported unless the organism reaches predetermined growth thresholds. Once the organism reaches the exponential phase, incubation is extended a set amount of time to evaluate the activity in the antimicrobial wells with and without clavulanic acid. J. **Substantial Equivalence Information:** 1. **Predicate device name(s):** VITEK ESBL Test 2. **Predicate K number(s):** N50510/S081 3. **Comparison with predicate:** | Similarities | | | | --- | --- | --- | | Item | Device | Predicate | | Intended Use | Same | Same | | Test organism | Colonies of Gram-Negative bacilli | Same | | | <16 hours | <16 hours | {2} Page 3 of 5 | Differences | | | | --- | --- | --- | | Item | Device | Predicate | | Instrument | VITEK®2 System | VITEK® System | | Test Card | VITEK®2 card | VITEK® card | | Antibiotic | Contains additional antimicrobial, cefepime | Contains only cefotaxime and ceftazidime | ## K. Standard/Guidance Document Referenced (if applicable): Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA”; NCCLS M7 (M100-S14) “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard”. ## L. Test Principle: The detection of an ESBL is based on the inhibition of activity in the presence of clavulanic acid. The VITEK® 2 analysis looks for growth patterns that exhibit activity in the well containing the antimicrobial without clavulanic acid and limited activity in the corresponding antimicrobial well containing clavulanic acid. Each of the three pairs of wells is evaluated independently. If any one of the three pairs demonstrates the expected growth pattern (difference in activity with and without clavulanic acid) a positive test result is reported. ## M. Performance Characteristics (if/when applicable): ### 1. Analytical performance: a. Precision/Reproducibility: Ten gram-negative organisms were tested at three sites with >95% reproducibility. These same organisms were tested at one site nine times to determine the within site reproducibility of >95% also. This testing was performed using both the manual dilution of the inoculum and also the automatic dilution method. b. Linearity/assay reportable range: Not applicable c. Traceability (controls, calibrators, or method): | ORGANISM | Test Results | VITEK®2 AUTO-DIL | Reference AUTO-DIL | VITEK®2 MAN-DIL | Reference MAN-DIL | | --- | --- | --- | --- | --- | --- | | E. coli ATCC 25922 Expected Result: Neg | Negative | 78 | 15 | 74 | 15 | | | Positive | | | | | | | | | | | | | | | | | | | | K. pneumoniae ATCC 700603 Expected Result: Pos | Negative | 3 | 1 | 3 | 1 | | | Positive | 77 | 14 | 73 | 14 | | | | | | | | | | | | | | | {3} Page 4 of 5 Quality Control was performed during the studies using both the auto-dilution and the manual method of diluting the organisms. The false negative QC results were due to an incorrect QC organism that was used for QC testing. Inoculum density control was monitored using the DensiChek instrument. This was standardized weekly with all results recorded and in the expected range. Verification was performed during internal testing. d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: A clinical study was conducted at three sites using the VITEK®2 ESBL test and the NCCLS reference agar dilution method prepared as recommended in NCCLS M7 approved standard. Inoculum was prepared with direct colony suspension. Two methods of inoculation (manual and automated) were evaluated. Clinical testing was performed using the automated method of inoculation and the challenge set was tested using both the manual and the automated method. Greater than 99% of the isolates grew in the VITEK®2 ESBL test in less than 16 hours. The following table provides the results from the automated testing. | | Total | Number Neg | Number Pos | CA | % CA | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | | Clinical | 318 | 162 | 156 | 312 | 98.1 | 3 | 3 | | Challenge | 29 | 0 | 29 | 27 | 93.1 | 0 | 2 | | Combined | 347 | 162 | 185 | 339 | 97.7 | 3 | 5 | CA-Category Agreement maj-major discrepancies vmj-very major discrepancies CA is when the interpretation of the reference method agrees exactly with the interpretation of the VITEK®2 results. The 5 vmj errors were due to K. pneumoniae with a vmj error rate of 4.4% (5/113) for this report group. All clinical vmj errors were from one site. Two of the clinical vmj errors were very resistant as reflected in their antibiograms and were further characterized as an ESBL producer with AmpC. It was observed in these vmj errors that AmpC masked the detection of ESBL producers. {4} Page 5 of 5 Three of the 5 vmj errors would be recommended to be resistant by the Expert System as if it was an ESBL producer. This expert system interpretation included comments to the user further describing this phenomenon and providing reporting option to the user. Furthermore, a limitation statement will also be added to the package insert "A negative ESBL Test result does not rule out the presence of an ESBL masked by an AMPC beta-lactamase" alerting the user to this possibility. Manual Dilution: The challenge set of organisms was also tested at one site using the manual method of inoculation with the following performance that demonstrated that there was no difference between the two inoculation methods. | | Total | Number Neg | Number Pos | CA | %CA | maj | vmj | | --- | --- | --- | --- | --- | --- | --- | --- | | Challenge | 29 | 0 | 29 | 28 | 96.6 | 0 | 1 | b. Matrix comparison: Not applicable 3. Clinical studies: a. Clinical sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a and b are not applicable): Not Applicable 4. Clinical cut-off: Not applicable 5. Expected values: Negative – Strain does not produce ESBLs. Positive – Strain produces ESBLs. Test interpretation should be reported as resistant for all penicillins, cephalosporins, and aztreonam. The interpretative criteria and QC are the same as recommended in NCCLS. The expected results will be included in the package insert. N. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. --- **Source:** [https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON/K040845](https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/LON/K040845) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. If you're preparing [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/), [get in touch](https://innolitics.com/contact). **Cite:** Innolitics at https://innolitics.com