EF_SASCode_Tbl2:3

SAS code for analysis of data from chart review and for analysis of mortality risk factor

EF_Data_ChartReview_Tbl2and3

Data for Tables 2 and

EF_DataDictionary_ChartReview_Tbl2and3

Data dictionary for CR

Results of polymerase chain reaction for <i>vanR/vanS</i> and antimicrobial susceptibility for 77 sterile-site <i>Enterococcus faecium</i> isolates stratified by VRE and VVE.

<p>Results of polymerase chain reaction for <i>vanR/vanS</i> and antimicrobial susceptibility for 77 sterile-site <i>Enterococcus faecium</i> isolates stratified by VRE and VVE.</p

EF_TotalData_Tbl1

Shows data on all E. faecium sterile site isolates including susceptibility results and PCR result

PFGE_Table4

Pulsed-field gel electrophoresis of E. faecium blood isolates of patients with breakthrough bacteremia with VSE, VVE or VRE (see Table 4 in manuscript)

Risk factors and outcome of patients with bacteremia caused by vancomycin-resistant (VRE), -variable (VVE), and -sensitive <i>Enterococcus faecium</i> (VSE), TIBDN hospitals, 2012–2016.

<p>Risk factors and outcome of patients with bacteremia caused by vancomycin-resistant (VRE), -variable (VVE), and -sensitive <i>Enterococcus faecium</i> (VSE), TIBDN hospitals, 2012–2016.</p

Univariable and multivariable logistic regression analyses to assess 30-day mortality among patients with <i>E</i>. <i>faecium</i> bacteremia.

<p>Univariable and multivariable logistic regression analyses to assess 30-day mortality among patients with <i>E</i>. <i>faecium</i> bacteremia.</p

Low 2012–13 Influenza Vaccine Effectiveness Associated with Mutation in the Egg-Adapted H3N2 Vaccine Strain Not Antigenic Drift in Circulating Viruses

<div><p>Background</p><p>Influenza vaccine effectiveness (VE) is generally interpreted in the context of vaccine match/mismatch to circulating strains with evolutionary drift in the latter invoked to explain reduced protection. During the 2012–13 season, however, detailed genotypic and phenotypic characterization shows that low VE was instead related to mutations in the egg-adapted H3N2 vaccine strain rather than antigenic drift in circulating viruses.</p><p>Methods/Findings</p><p>Component-specific VE against medically-attended, PCR-confirmed influenza was estimated in Canada by test-negative case-control design. Influenza A viruses were characterized genotypically by amino acid (AA) sequencing of established haemagglutinin (HA) antigenic sites and phenotypically through haemagglutination inhibition (HI) assay. H3N2 viruses were characterized in relation to the WHO-recommended, cell-passaged vaccine prototype (A/Victoria/361/2011) as well as the egg-adapted strain as per actually used in vaccine production. Among the total of 1501 participants, influenza virus was detected in 652 (43%). Nearly two-thirds of viruses typed/subtyped were A(H3N2) (394/626; 63%); the remainder were A(H1N1)pdm09 (79/626; 13%), B/Yamagata (98/626; 16%) or B/Victoria (54/626; 9%). Suboptimal VE of 50% (95%CI: 33–63%) overall was driven by predominant H3N2 activity for which VE was 41% (95%CI: 17–59%). All H3N2 field isolates were HI-characterized as well-matched to the WHO-recommended A/Victoria/361/2011 prototype whereas all but one were antigenically distinct from the egg-adapted strain as per actually used in vaccine production. The egg-adapted strain was itself antigenically distinct from the WHO-recommended prototype, and bore three AA mutations at antigenic sites B [H156Q, G186V] and D [S219Y]. Conversely, circulating viruses were identical to the WHO-recommended prototype at these positions with other genetic variation that did not affect antigenicity. VE was 59% (95%CI:16–80%) against A(H1N1)pdm09, 67% (95%CI: 30–85%) against B/Yamagata (vaccine-lineage) and 75% (95%CI: 29–91%) against B/Victoria (non-vaccine-lineage) viruses.</p><p>Conclusions</p><p>These findings underscore the need to monitor vaccine viruses as well as circulating strains to explain vaccine performance. Evolutionary drift in circulating viruses cannot be regulated, but influential mutations introduced as part of egg-based vaccine production may be amenable to improvements.</p></div

Three-dimensional model of antigenic-site differences between circulating H3N2 viruses and the 2012–13 egg-adapted A/Victoria/361/2011 IVR-165 high growth reassortant vaccine strain.

<p>One HA1 monomer is shown with five previously defined antigenic site residues of A–E colored in light green, dark green, light blue, dark blue and purple, respectively, mapped onto a related crystal structure (A/X-31(H3N2), PDB, 1HGG) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092153#pone.0092153-Sauter1" target="_blank">[27]</a> using PyMOL <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0092153#pone.0092153-The1" target="_blank">[28]</a>. The most prevalent antigenic site amino acid differences between circulating clade 3C viruses in Canada relative to the egg-adapted A/Victoria/361/2011 IVR-165 vaccine reassortant strain are shown in red and labelled with coloured font representing their antigenic sites, viewed from the front (A) or side (B). Three amino acid differences (Q156H, V186G and Y219S) are owing to mutation in the egg-adapted IVR-165 vaccine strain rather than circulating viruses which instead share identity with the MDCK-passaged WHO reference prototype at these positions. RBS indicates approximate location of the receptor-binding site.</p