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1. Predicting β-lactam susceptibility from the genome of Streptococcus pneumoniae and other mitis group streptococci

Author

Helle Brander Eriksen, Kurt Fuursted, Anders Jensen, Christian Salgård Jensen, Xiaohui Nielsen, Jens Jørgen Christensen, Patricia Shewmaker, Ana Rita Rebelo, Frank Møller Aarestrup, Kristian Schønning, Hans-Christian Slotved, and the One Day in Denmark (ODiD) Consortium

Subjects
penicillin-binding proteins, penicillin, genotypic susceptibility, pneumococcus, Streptococcus, Microbiology, QR1-502
Abstract

IntroductionFor Streptococcus pneumoniae, β-lactam susceptibility can be predicted from the amino acid sequence of the penicillin-binding proteins PBP1a, PBP2b, and PBP2x. The combination of PBP-subtypes provides a PBP-profile, which correlates to a phenotypic minimal inhibitory concentration (MIC). The non-S. pneumoniae Mitis-group streptococci (MGS) have similar PBPs and exchange pbp-alleles with S. pneumoniae. We studied whether a simple BLAST analysis could be used to predict phenotypic susceptibility in Danish S. pneumoniae isolates and in internationally collected MGS.MethodIsolates with available WGS and phenotypic susceptibility data were included. For each isolate, the best matching PBP-profile was identified by BLAST analysis. The corresponding MICs for penicillin and ceftriaxone was retrieved. Category agreement (CA), minor-, major-, and very major discrepancy was calculated. Genotypic-phenotypic accuracy was examined with Deming regression.ResultsAmong 88 S. pneumoniae isolates, 55 isolates had a recognized PBP-profile, and CA was 100% for penicillin and 98.2% for ceftriaxone. In 33 S. pneumoniae isolates with a new PBP-profile, CA was 90.9% (penicillin) and 93.8% (ceftriaxone) using the nearest recognized PBP-profile. Applying the S. pneumoniae database to non-S. pneumoniae MGS revealed that none had a recognized PBP-profile. For Streptococcus pseudopneumoniae, CA was 100% for penicillin and ceftriaxone in 19 susceptible isolates. In 33 Streptococcus mitis isolates, CA was 75.8% (penicillin) and 86.2% (ceftriaxone) and in 25 Streptococcus oralis isolates CA was 8% (penicillin) and 100% (ceftriaxone).ConclusionUsing a simple BLAST analysis, genotypic susceptibility prediction was accurate in Danish S. pneumoniae isolates, particularly in isolates with recognized PBP-profiles. Susceptibility was poorly predicted in other MGS using the current database.

Published
2023
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2. Performance of an Antigen-Based Test for Asymptomatic and Symptomatic SARS-CoV-2 Testing at Two University Campuses - Wisconsin, September-October 2020

Author

Ian W, Pray, Laura, Ford, Devlin, Cole, Christine, Lee, John Paul, Bigouette, Glen R, Abedi, Dena, Bushman, Miranda J, Delahoy, Dustin, Currie, Blake, Cherney, Marie, Kirby, Geroncio, Fajardo, Motria, Caudill, Kimberly, Langolf, Juliana, Kahrs, Patrick, Kelly, Collin, Pitts, Ailam, Lim, Nicole, Aulik, Azaibi, Tamin, Jennifer L, Harcourt, Krista, Queen, Jing, Zhang, Brett, Whitaker, Hannah, Browne, Magdalena, Medrzycki, Patricia, Shewmaker, Jennifer, Folster, Bettina, Bankamp, Michael D, Bowen, Natalie J, Thornburg, Kimberly, Goffard, Brandi, Limbago, Allen, Bateman, Jacqueline E, Tate, Douglas, Gieryn, Hannah L, Kirking, Ryan, Westergaard, Marie, Killerby, and Phili, Wong

Subjects
Adult, Male, Emergency Use Authorization, medicine.medical_specialty, Health (social science), Adolescent, Universities, Epidemiology, Student Health Services, Health, Toxicology and Mutagenesis, Population, 01 natural sciences, Asymptomatic, Sensitivity and Specificity, 03 medical and health sciences, Young Adult, 0302 clinical medicine, COVID-19 Testing, Wisconsin, Health Information Management, Antigen, Internal medicine, medicine, Humans, 030212 general & internal medicine, 0101 mathematics, education, Antigens, Viral, Asymptomatic Diseases, education.field_of_study, Viral culture, business.industry, SARS-CoV-2, 010102 general mathematics, COVID-19, General Medicine, Middle Aged, Specimen collection, Nasal Swab, Female, medicine.symptom, business
Abstract

Antigen-based tests for SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), are inexpensive and can return results within 15 minutes (1). Antigen tests have received Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for use in asymptomatic and symptomatic persons within the first 5-12 days after symptom onset (2). These tests have been used at U.S. colleges and universities and other congregate settings (e.g., nursing homes and correctional and detention facilities), where serial testing of asymptomatic persons might facilitate early case identification (3-5). However, test performance data from symptomatic and asymptomatic persons are limited. This investigation evaluated performance of the Sofia SARS Antigen Fluorescent Immunoassay (FIA) (Quidel Corporation) compared with real-time reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 detection among asymptomatic and symptomatic persons at two universities in Wisconsin. During September 28-October 9, a total of 1,098 paired nasal swabs were tested using the Sofia SARS Antigen FIA and real-time RT-PCR. Virus culture was attempted on all antigen-positive or real-time RT-PCR-positive specimens. Among 871 (79%) paired swabs from asymptomatic participants, the antigen test sensitivity was 41.2%, specificity was 98.4%, and in this population the estimated positive predictive value (PPV) was 33.3%, and negative predictive value (NPV) was 98.8%. Antigen test performance was improved among 227 (21%) paired swabs from participants who reported one or more symptoms at specimen collection (sensitivity = 80.0%; specificity = 98.9%; PPV = 94.1%; NPV = 95.9%). Virus was isolated from 34 (46.6%) of 73 antigen-positive or real-time RT-PCR-positive nasal swab specimens, including two of 18 that were antigen-negative and real-time RT-PCR-positive (false-negatives). The advantages of antigen tests such as low cost and rapid turnaround might allow for rapid identification of infectious persons. However, these advantages need to be balanced against lower sensitivity and lower PPV, especially among asymptomatic persons. Confirmatory testing with an FDA-authorized nucleic acid amplification test (NAAT), such as RT-PCR, should be considered after negative antigen test results in symptomatic persons, and after positive antigen test results in asymptomatic persons (1).

Published
2020

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