(89 days)
The MicroScan Dried Gram-Negative MIC/Combo Panel is used to determine qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic gram-negative bacilli. After inoculation, panels are incubated for 16 - 20 hours at 35°C +/- 1°C in a non-CO2 incubator, and read either visually or with MicroScan instrumentation, according to the Package Insert.
This particular submission is for updated susceptibility test interpretative criteria for Enterobacteriaceae and Pseudomonas aeruginosa, as well as expanding Salmonella ser. Typhi interpretative criteria to all Salmonella spp. for the antimicrobial ciprofloxacin (Cp) at concentrations of 0.004 to 8 µg/mL to the test panel.
Ciprofloxacin has been shown to be active in vitro against most strains of microorganisms listed below, as described in the FDA-approved package insert for this antimicrobial agent.
Active in vitro and in clinical infections against:
Citrobacter koseri Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella pneumoniae Morganella morganii Proteus mirabilis Proteus vulgaris Providencia rettgeri Providencia stuartii Pseudomonas aeruginosa Salmonella ser.Typhi Serratia marcescens Shigella flexneri Shigella sonnei Active in vitro but clinical significance unknown: Enterobacter aerogenes, Klebsiella oxytoca, Salmonella enteritidis
MicroScan Dried Gram-Negative MIC/Combo Panels are designed for use in determining quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-negative bacilli.
The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in broth and dehydrated. Various antimicrobial agents are diluted in broth to concentrations bridging the range of clinical interest. Panels are rehydrated with water after inoculation with a standardized suspension of the organism. After incubation in a non-CO2 incubator for 16-20 hours, the minimum inhibitory concentration (MIC) for the test organism is read by determining the lowest antimicrobial concentration showing inhibition of growth.
This document describes the validation of the Beckman Coulter MicroScan Dried Gram-Negative MIC/Combo Panels with Ciprofloxacin (Cp) for updated susceptibility test interpretative criteria for Enterobacteriaceae and Pseudomonas aeruginosa, and expanding Salmonella ser. Typhi interpretative criteria to all Salmonella spp. for ciprofloxacin.
Here's a breakdown of the acceptance criteria and the study that proves the device meets them:
1. Acceptance Criteria and Reported Device Performance
The device is assessed based on two primary metrics: Essential Agreement (EA) and Categorical Agreement (CA), when compared to a CLSI frozen Reference Panel.
| Organism Group | Acceptance Criteria (EA) | Reported Performance (EA) | Acceptance Criteria (CA) | Reported Performance (CA) |
|---|---|---|---|---|
| Enterobacteriaceae (except Salmonella spp.) | Not explicitly stated, but based on guidance, generally high for AST devices (often >90%) | 93.9% | Not explicitly stated, but based on guidance, generally high for AST devices (often >90%) | 98.0% |
| Salmonella spp. | Not explicitly stated, but based on guidance, generally high for AST devices (often >90%) | 100.0% | Not explicitly stated, but based on guidance, generally high for AST devices (often >90%) | 95.2% |
| Pseudomonas aeruginosa | Not explicitly stated, but based on guidance, generally high for AST devices (often >90%) | 96.8% | Not explicitly stated, but based on guidance, generally high for AST devices (often >90%) | 91.4% |
Note: While specific numerical acceptance criteria for EA and CA are not explicitly given in the provided text, the statement "acceptable performance" and the context of FDA guidance for Antimicrobial Susceptibility Test (AST) Systems implies that the reported percentages met pre-defined thresholds, typically very high for these types of devices (e.g., >90% or >95%). The FDA's "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems" would contain the precise acceptance criteria.
2. Sample Size and Data Provenance
- Test Set Sample Size: The exact number of isolates for each organism group (Enterobacteriaceae, Salmonella spp., Pseudomonas aeruginosa) is not explicitly stated as a numerical count in the provided text. However, the study "conducted with fresh, recent and stock Efficacy isolates and stock Challenge strains" implies a sufficient number of samples were used to achieve the reported agreement percentages. For AST devices, these involve hundreds, if not thousands, of unique isolates.
- Data Provenance: The text states "The external evaluations were conducted with fresh, recent and stock Efficacy isolates and stock Challenge strains." This suggests a combination of retrospective (stock strains) and prospective (fresh, recent isolates) data. The country of origin is not specified, but given the company (Beckman Coulter, Inc., West Sacramento, California) and the FDA submission, it is highly likely the data includes isolates from the United States and potentially other regions relevant to the target clinical population.
3. Number of Experts and Qualifications
This information is not provided in the given document. For AST device validation, ground truth is typically established by laboratory methods, not expert human readers.
4. Adjudication Method
This information is not applicable as the ground truth is based on a reference laboratory method (CLSI frozen Reference Panel), not on human expert reads requiring adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
A multi-reader multi-case (MRMC) comparative effectiveness study was not done. This type of study is more relevant for diagnostic imaging devices where human interpretation of images is a key component, and AI assists in that interpretation. For Antimicrobial Susceptibility Testing (AST) devices, the focus is on the device's ability to produce accurate Minimum Inhibitory Concentration (MIC) values and categorical interpretations (Susceptible, Intermediate, Resistant) compared to a gold standard laboratory method.
6. Standalone (Algorithm Only) Performance
The study primarily evaluates the standalone performance of the MicroScan Dried Gram-Negative MIC/Combo Panels. The device determines MIC values and susceptibility categories. While it can be "read either visually or with MicroScan instrumentation," the core performance metrics (EA and CA) are for the device's output, not for human-in-the-loop performance. The comparison is against a CLSI frozen Reference Panel, which is a laboratory standard, making this a standalone performance assessment.
7. Type of Ground Truth Used
The ground truth used was a CLSI frozen Reference Panel. This is considered a gold standard in microbiology for determining antimicrobial susceptibility, based on established Clinical and Laboratory Standards Institute (CLSI) guidelines. It represents the accepted accurate determination of MICs.
8. Sample Size for the Training Set
The document does not provide information regarding the training set sample size. This submission focuses on the validation or test performance of the device. The development and training details of the underlying system (e.g., if any machine learning models were used for automated reading) are not disclosed in this summary.
9. How the Ground Truth for the Training Set Was Established
Since the document does not provide information on a training set, it does not elaborate on how ground truth for a training set was established. For AST devices, development typically involves extensive testing against reference methods in a continuous improvement process, which implicitly trains the system to accurately determine MICs.
§ 866.1640 Antimicrobial susceptibility test powder.
(a)
Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).