Lab Matters Summer 2024 | Page 29

INFECTIOUS DISEASES

By Shannon Mahoney , senior specialist , Advanced Molecular Detection

Nearly five years later , the NGS Quality Initiative has developed over 100 published products , addressing all 12 quality system essentials established by the Clinical Laboratory Systems Institute ( CLSI ). The tools published as part of the NGS Quality Initiative are designed to be customizable to fit the needs of individual laboratories .

Carbapenem-resistant Acinetobacter baumannii ( CRAB ) are classified as an urgent public health threat by the US Centers for Disease Control and Prevention ( CDC ) due to frequently being resistant to nearly all antibiotics used for treatment . CDC estimated in 2019 there were 8,500 infections among hospitalized patients , which were associated with an estimated 700 deaths . Patients can be asymptomatically colonized , meaning the organisms may be present on or in the body without causing symptoms , and they can persist in the environment , potentially causing large and difficult to control outbreaks in healthcare facilities .

Some CRAB may contain genes that enable the production of carbapenemase enzymes , which destroy carbapenem antibiotics . Patients infected or colonized with CRAB are important to identify quickly in healthcare facilities to limit transmission to other patients and to control outbreaks . Public health laboratories , as part of the CDC Antimicrobial Resistance Laboratory Network ( AR Lab Network ) are tasked with identifying isolates of CRAB and determining which , if any , contain carbapenemase genes

The Orange County Public Health Laboratory ( OCPHL ), a member of the

AR Lab Network , had received over 300 CRAB isolates by 2022 from local laboratories in its jurisdiction for detection of carbapenemase genes . While commonly used commercial assays to detect certain carbapenemases such as OXA-48 like genes , these are less commonly found in Acinetobacter species . In June 2023 , to more rapidly identify the genes more commonly associated with Acinetobacter species ( i . e ., OXA-23 , OXA-24 / 40 like , OXA-58 like , and OXA-235 like ), OCPHL turned to validating a next generation sequencing ( NGS ) approach . Detecting these genes through NGS technology meant they could reduce the turnaround time for reporting results and get those results into the hands of the infection prevention / infection control professionals . Getting the results back quickly allows more rapid implementation of actions to limit the risk of transmission and prevent potential outbreaks . To perform this validation quickly OCPHL utilized the tools published by the NGS Quality Initiative .

Launched in 2019 through a partnership between APHL and CDC , the NGS Quality Initiative ’ s goal was to develop tools and resources to aid public health laboratories in the development of a comprehensive quality management system ( QMS ) for their NGS and bioinformatics work .

To help validate their CRAB NGS assay , the team at OCPHL utilized the NGS Quality Initiative ’ s Validation Plan as a resource to improve their own validation template , supplying them with a standardized format for conducting this and future NGS validations . From the Validation Plan , OCPHL was able to target their internal validation plan templates to be better configured to specific NGS components , permitting them to recategorize and modify a range of internal documentation aimed at validations .

“ Before we decided to use the Validation Plan , our previous validations had started to become hurdles , as the requirements for them continuously differed from our already-changing internal template ,” said Julia Wolfe , supervising microbiologist at OCPHL . Wolfe went on to cite how the utilization of the Validation Plan guided OCPHL to generate a standardized template that included necessary metrics geared toward NGS testing , such as the adoption of metrics like limits of detection and applicable genome regions .

Ultimately , applications like OCPHL ’ s are just one of a myriad of ways the NGS Quality Initiative can help serve public health laboratories and their sequencing operations . g