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The U.S. Food & Drug Administration (FDA) regulates the marketing of manufacturers’ in vitro diagnostic tests (IVDs), including assays for the detection of SARS-CoV-2. The U.S. government’s Clinical Laboratory Improvement Amendments (CLIA) of 1988 regulates the studies that a clinical diagnostic laboratory needs to perform for an IVD before placing it into use. Until recently, the FDA has authorized the marketing of SARS-CoV-2 IVDs exclusively through the Emergency Use Authorization (EUA) pathway. The regulatory landscape continues to evolve, and IVDs will eventually be required to pass through conventional non-EUA FDA review pathways once the emergency declaration is terminated, in order to continue to be marketed as an IVD in the United States. When FDA regulatory status of an IVD changes or is anticipated to change, the laboratory should review manufacturer information and previously performed internal verification studies to determine what, if any, additional studies are needed before implementing the non-EUA version of the IVD in accordance with CLIA regulations. Herein, the College of American Pathologists’ Microbiology Committee provides guidance for how to approach regulatory considerations when an IVD is converted from EUA to non-EUA status.

We used an in vitro technique to investigate blood volumes required to detect bacteremia and fungemia with low concentrations of an organism. At 1 to 10 CFU/ml, Escherichia coli , Staphylococcus epidermidis , Staphylococcus aureus , Listeria monocytogenes , Candida albicans , and Candida parapsilosis isolates were detected in volumes as low as 0.5 ml. Detection of Streptococcus agalactiae and detection of bacteremia at

This study compared the performance of the Carba NP assay, published by the Clinical and Laboratory Standards Institute, and the Rosco Rapid Carb Screen kit. Carba NP had superior sensitivity, but both assays required an increased inoculum to detect carbapenemase production in isolates with bla NDM , bla IMP , and bla OXA-48 .

Assays that expedite the reporting of organism identification and antibiotic susceptibility status in positive blood cultures can fast track interventions that improve clinical outcomes. We evaluated the Verigene Gram-positive blood culture nucleic acid test (BC-GP) in two pediatric hospitals. Positive BacT/Alert Pediatric FAN blood cultures with Gram-positive organisms were tested using the BC-GP in tandem with routine laboratory procedures. To test organisms underrepresented in the clinical blood culture evaluation, blood culture bottles were spiked with diluted organism suspensions at concentrations of 10 to 100 CFU per milliliter. A total of 249 Gram-positive bacterial isolates were recovered from 242 blood cultures. The BC-GP detected Staphylococcus aureus , methicillin-susceptible S. aureus , and methicillin-resistant S. aureus with sensitivities of 100%, 99%, and 100% and specificities of 100%, 100%, and 99.5%, respectively. The BC-GP detected Staphylococcus epidermidis , methicillin-susceptible S. epidermidis , and methicillin-resistant S. epidermidis with sensitivities of 95%, 80%, and 96%, respectively, and 100% specificity. The BC-GP correctly identified 14/15 cases of Enterococcus faecalis and Enterococcus faecium bacteremia and 9 cases of Streptococcus pneumoniae . It misidentified 5/15 clinical blood cultures with Streptococcus mitis / Streptococcus oralis and 1/3 blood cultures spiked with Streptococcus anginosus group as S. pneumoniae . The BC-GP detected a case of Streptococcus pyogenes bacteremia but failed to detect 2/3 clinical blood cultures with Streptococcus agalactiae . BC-GP's rapid accurate detection of Staphylococcus spp., E. faecium , and E. faecalis and its ability to ascertain mecA , vanA , and vanB status may expedite clinical decisions pertaining to optimal antibiotic use. False-positive S. pneumoniae results may warrant reporting of only “ Streptococcus spp.” when this organism is reported by the BC-GP.

We evaluated the investigational use only (IUO) version of the rapid Verigene Gram-negative blood culture test (BC-GN), a microarray that detects 9 genus/species targets ( Acinetobacter spp., Citrobacter spp., Enterobacter spp., Escherichia coli / Shigella spp., Klebsiella oxytoca , Klebsiella pneumoniae , Proteus spp., Pseudomonas aeruginosa , and Serratia marcescens ) and 6 antimicrobial resistance determinants ( bla CTX-M , bla KPC , bla NDM , bla VIM , bla IMP , and bla OXA ) directly from positive blood cultures. BC-GN was performed on positive BacT/Alert Pediatric FAN and Bactec Peds Plus blood cultures with Gram-negative organisms at two tertiary pediatric centers. Vitek MS (bioMérieux, Durham, NC) was used to assign gold standard organism identification. The Check MDR CT-102 microarray (Check Points B.V., Wageningen, Netherlands) was used as an alternative method for detecting resistance determinants. In total, 104 organisms were isolated from 97 clinical blood cultures. BC-GN correctly detected 26/26 cultures with Acinetobacter spp., P. aeruginosa , and S. marcescens , 5/6 with Citrobacter spp., 13/14 with Enterobacter spp., 23/24 with E. coli , 2/3 with K. oxytoca , 16/17 with K. pneumoniae , and 0/1 with Proteus spp. BC-GN appropriately reported negative BC-GN results in 8/13 blood cultures that grew organisms that were not represented on the microarray but failed to detect targets in 3/5 cultures that grew multiple Gram-negative organisms. BC-GN detected 5/5 and 1/1 clinical blood cultures with bla CTX-M and bla VIM . All 6 results were corroborated by Check MDR CT-102 microarray testing. The Verigene BC-GN test has the potential to expedite therapeutic decision making in pediatric patients with Gram-negative bacteremia. Sensitivity was satisfactory but may be suboptimal in mixed Gram-negative blood cultures.