T2Resistance - Detection of Resistance Related Genes

T2Resistance 510(k) Study Protocol - Detection and Identification of Several Classes of Resistance Genes in Both Gram-positive and Gram-negative Pathogens

The purpose of this study is to evaluate the safety and effectiveness of the T2Resistance Panel by validating clinical performance in three study arms:

1. Prospective arm: positive percent agreement (PPA) and negative percent agreement (NPA) against genetic determinants of resistance detected in whole blood clinical samples or isolates collected from positive blood cultures prospectively collected clinical samples of whole blood.
2. Contrived arm: positive percent agreement (PPA) and negative percent agreement (NPA) against samples with known status, via spiking healthy whole blood samples with bacterial strains harboring the resistance gene targets on the T2Resistance Panel.
3. Healthy donor arm: negative percent agreement (NPA) with presumed negativity of healthy donor whole blood samples.

The data from all arms of the study will be used to support the Premarket Notification for the T2Resistance Panel to the U.S. Food and Drug Administration.

Primary Endpoints

The primary endpoints of this study with the T2Resistance Panel are estimated sensitivity, specificity, and safety.

The purpose of this study is to evaluate the safety and effectiveness of the T2Resistance Panel by validating clinical performance in three study arms:

1. Prospective arm: positive percent agreement (PPA) and negative percent agreement (NPA) against genetic determinants of resistance detected in whole blood clinical samples or isolates collected from positive blood cultures prospectively collected clinical samples of whole blood.
2. Contrived arm: positive percent agreement (PPA) and negative percent agreement (NPA) against samples with known status, via spiking healthy whole blood samples with bacterial strains harboring the resistance gene targets on the T2Resistance Panel.
3. Healthy donor arm: negative percent agreement (NPA) with presumed negativity of healthy donor whole blood samples.

The data from all arms of the study will be used to support the Premarket Notification for the T2Resistance Panel to the U.S. Food and Drug Administration.

Primary Endpoints

The primary endpoints of this study with the T2Resistance Panel are estimated sensitivity, specificity, and safety.

Sensitivity

The estimated sensitivity of the T2Resistance Panel will be derived from two metrics:

1. Prospective arm: positive concordance between a positive result on the T2Resistance Panel and a positive sequencing result from a whole blood sample or isolate from positive blood culture
2. Contrived arm: positive concordance between a positive result on the T2Resistance Panel and a sample spiked with a bacterial isolates sequence confirmed to be harboring a known resistance gene on the T2Resistance Panel.

The Contrived arm of the study will consist of ≥ 350 whole blood samples spiked with titer levels ranging from < 1 CFU/mL to 100 CFU/mL. These samples will be provided to selected test sites for testing. Sensitivity values will be calculated separately for each channel and study arm, e.g., Prospective and Contrived study arms for blaKPC, blaCTX-M, blaNDM / blaVIM / blaIMP, blaOXA-48 Group, vanA / vanB, mecA / mecC and AmpC (blaCMY / blaDHA) channels.

Specificity

The estimated specificity of the T2Resistance Panel will be derived from three metrics:

1. Prospective arm: negative concordance between a negative ("Target not Detected") result on the T2Resistance Panel and a negative sequencing result from whole blood sample or isolate from positive blood culture
2. Healthy donor arm: negative concordance between a negative ("Target not Detected") result on the T2Resistance Panel and a presumed negativity of healthy donor whole blood sample
3. Contrived arm: negative concordance between a negative ("Target not Detected") result in a given channel of the T2Resistance Panel and the presence of a spiked bacteria known to not harbor the given resistance gene on the T2Resistance Panel

Specificity values will be calculated separately for each channel and study arm, e.g., Prospective, Healthy donor, and Contrived study arms for blaKPC, blaCTX-M, blaNDM / blaVIM / blaIMP, blaOXA-48 Group, vanA / vanB, mecA / mecC and AmpC (blaCMY / blaDHA) channels.

Safety

There are no expected adverse events that are directly related to the T2Resistance Panel and the T2Dx Instrument as a result of participating in this study. Since the device does not come in contact with the patients and the test results are not used in clinical practice as part of standard of care, the only adverse events associated with study participation is the collection of blood samples for T2Resistance Panel testing.

Inclusion Criteria:

Prospective Arm:

• Obtain informed consent according to institutional requirements, as needed.
• Patient has had a diagnostic blood culture ordered per routine standard of care.
• Patient is 18 years of age or older.

Exclusion Criteria:

Prospective Arm

• Patient has other co-morbid condition(s) that, in the opinion of the Investigator, could limit the patient's ability to participate in the study or impact the scientific integrity of the study.
• Patient has had previous specimens tested for the T2Resistance Panel with valid results.