Comparison of the Panther Fusion and BD MAX GBS Assays for Detection of Group B Streptococcus in Prenatal Screening Specimens

3 Running title: Panther Fusion GBS vs BD MAX GBS assay 4 5 Gregory J. Berry, Fan Zhang, Ryhana Manji, Stefan Juretschko 6 7 1. Infectious Disease Diagnostics, Northwell Health Laboratories, Little Neck, NY 8 2. Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School 9 of Medicine at Hofstra/Northwell 10 11 Corresponding author: 12 Gregory J. Berry, Ph.D., D(ABMM), Infectious Disease Diagnostics, Northwell Health 13 Laboratories, 59-25 Little Neck Parkway, Little Neck, New York 11362 14 Phone: 516.224.8506, FAX: 718.224.6585; email: gberry1@northwell.edu 15 16 [This accepted manuscript was published on 28 August 2019 with a standard copyright line (“© 2019 17 American Society for Microbiology. All Rights Reserved.”). The authors elected to pay for open access for 18 the article after publication, necessitating replacement of the original copyright line, and this change was 19 made on 18 September 2019.] 20 JCM Accepted Manuscript Posted Online 28 August 2019 J. Clin. Microbiol. doi:10.1128/JCM.01034-19 Copyright © 2019 Berry et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.


INTRODUCTION
GBS is the leading cause of infection in newborns in the United States (1) with 0.22 early-onset 39 GBS disease (EOD) cases per 1,000 live births in 2016 (2). GBS can be vertically transmitted 40 from a colonized mother to her newborn during labor and delivery (intrapartum) and can result in 41 septicemia, meningitis or, more rarely, pneumonia in newborns, with EOD symptoms appearing 42 within 7 days of birth and late onset cases appearing as late as 3 months post-delivery (3). 43 It is estimated that 10%-30% of pregnant women in the United States are colonized by GBS (4). 44 The current American College of Obstetricians and Gynecologists (ACOG) guidelines for the 45 prevention of EOD recommend universal antepartum screening of pregnant women for GBS 46 colonization at 36 0/7-37 6/7 weeks of gestation. GBS screening is followed by intrapartum 47 antibiotic prophylaxis for GBS-positive women unless a prelabor cesarean birth is performed in 48 the setting of intact membranes (1). Although this strategy has led to a dramatic decrease in the 49 incidence of EOD since its initial inception in the 1990s (5), culture is a slow process (requires 50 up to 3 days) with suboptimal sensitivity compared to molecular assays (6,7). Nucleic acid 51 amplification tests (NAATs) for the detection of GBS have the potential to remedy the 52 limitations of GBS culture by offering higher sensitivity and rapid time to results (8). Hence, 53 many laboratories have implemented FDA-approved NAATs for routine GBS screening of 54 pregnant women (9). This study compares the clinical performance and workflow characteristics

61
The analytical sensitivity (limit of detection, or LoD) of each NAAT assay was evaluated using 62 quantified strains of Streptococcus agalactiae serotypes III and V. Serial dilutions were made to 63 represent 10, 30, 100, 300, and 1000 colony forming units (CFU) per mL and tested in replicates 64 of ten. Separate LoD panels were made for each serotype. All GBS serotype panels were 65 prepared at the same time, aliquoted into individual tubes for each of ten replicates at each 66 concentration, stored frozen, and thawed on day of testing.

107
A total of 510 vaginal-rectal specimens collected prepartum were tested simultaneously in both 108 assays for the presence of GBS after broth enrichment. The BD MAX GBS assay, which was the  (Table 3).

131
Northwell Health Laboratories processes more than 1,300 specimens per month on average for 132 GBS testing, necessitating consideration of workflow efficiency in any platform decision. Both Demand for more sensitive testing with faster turnaround times is constantly increasing, while at 155 the same time, many laboratories are experiencing increasing testing volume and workforce 156 shortages. Due to these demands, testing platforms that allow laboratories to partially (or fully) 157 automate testing and deliver these results are becoming necessary. In this study, we evaluated the 158 performance two such platforms, the BD MAX and the Panther Fusion for the detection of GBS 159 in prenatal screening specimens. 160 Overall, the Panther Fusion had a slightly lower LOD than the BD MAX and both assays showed negative. Repeat results were identical to initial results for both assays (Panther Fusion +/ BD 168 MAX -). Culture results for this same specimen were negative. While culture was negative, it is 169 quite possible that this specimen was still GBS positive, especially considering that culture has 170 been shown to be less sensitive than various molecular methods for the detection of GBS (6, 7).

171
It is also possible that the Panther Fusion detected GBS in this specimen due to the assay's lower 172 LOD for GBS when compared to the BD MAX, as shown in Table 1. Differences in the Lim 173 broth inoculum used in the assays (15 μL of the enriched specimen in the BD MAX GBS assay 9 vs. 1 mL of specimen for the Panther Fusion GBS assay) could also potentially contribute to the 175 analytical differences seen between the two assays.