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Tables
- TABLE 1
FilmArray BCID panel targets and prevalence of positive results by age group for the prospective clinical study arm
FilmArray BCID resulta No. (%) of patients Totalc Pediatricd Adulte Gram-positive bacteria Enterococcus 102 (7) 5 (3) 97 (7) Listeria monocytogenes 0 (0) 0 (0) 0 (0) Staphylococcus 780 (50) 74 (50) 706 (50) S. aureus 257 (16) 25 (17) 232 (16) Streptococcus 140 (9) 21 (14) 119 (8) S. agalactiae (GBS) 18 (1) 2 (1) 16 (1) S. pneumoniae 26 (2) 3 (2) 23 (2) S. pyogenes (GAS) 8 (1) 2 (1) 6 (<1) Gram-negative bacteria A. baumannii 16 (1) 1 (1) 15 (1) Enterobacteriaceae 307 (20) 27 (18) 280 (20) Enterobacter cloacaeb 24 (2) 4 (3) 20 (1) Escherichia coli 149 (10) 16 (11) 133 (9) Klebsiella oxytoca 6 (<1) 1 (1) 5 (<1) Klebsiella pneumoniae 74 (5) 5 (3) 69 (5) Proteus 22 (1) 0 (0) 22 (2) Serratia marcescens 22 (1) 1 (1) 21 (1) Haemophilus influenzae 8 (1) 3 (2) 5 (<1) Neisseria meningitidis 1 (<1) 0 (0) 1 (0) P. aeruginosa 52 (3) 4 (3) 48 (3) Yeast Candida albicans 20 (1) 1 (1) 19 (1) Candida glabrata 14 (1) 0 (0) 14 (1) Candida krusei 4 (<1) 1 (1) 3 (<1) Candida parapsilosis 8 (1) 0 (0) 8 (1) Candida tropicalis 3 (<1) 0 (0) 3 (<1) Antimicrobial resistance genes mecA 491 (31) 46 (31) 445 (31) vanA/B 36 (2) 0 (0) 36 (3) blaKPC 6 (<1) 0 (0) 6 (<1) - TABLE 2
OPOs not targeted by BCID and identified in the prospective clinical arm only
OPO No. of isolates OPO No. of isolates Abiotrophia or Granulicatella speciesa 7b Lactobacillus species 3 Achromobacter xylosoxidans 1 Micrococcus species 27 Acinetobacter species (not A. baumannii) 23c Moraxella catarrhalis 1 Actinomyces odontolyticus 2 Moraxella species 2 Actinomyces species 1 Mycobacterium fortuitum complex 1 Aerococcus species 3 Neisseria species 2 Aeromonas sobria 1 Paenibacillus species 1 Bacillus cereus 19 Pasteurella multocida 2 Bacillus species 14 Pasteurella species 1 Brevibacterium species 2 Pasteurella stomatis 1d Brevundimonas species 2 Propionibacterium species 1 Burkholderia cepacia complex 2 Pseudomonas species 5 Candida kefyr 1 Pseudomonas stutzeri 1d Capnocytophaga species 1 Raoultella ornithinolytica 4d Chryseobacterium meningosepticum 1 Raoultella planticola 1d Chryseobacterium indologenes 1 Rhizobium radiobacter 1 Chryseomonas luteola 1 Rhodococcus species 1 Corynebacterium jeikeium 1 Rothia (Stomatococcus) mucilaginosa 4 Corynebacterium species/diphtheroids 48 Sphingomonas mucosissima 1 Cryptococcus neoformans 2 Staphylococcus pettenkoferi 16e Flavobacterium species 1 Stenotrophomonas maltophilia 10 Fusarium species 1 Weeksella virosa 1 Kocuria kristinae 1 ↵a Formerly nutritionally deficient streptococci.
↵b One of seven Abiotrophia spp. was identified by 16S rRNA gene sequencing during discrepancy investigations. It had been misidentified phenotypically as a Streptococcus species.
↵c Of 23 isolates, 17 were Acinetobacter spp. not A. baumannii and 10 were phenotypically A. baumannii. The latter were revealed to be A. pittii, A. nosocomialis, A. bereziniae, and A. radioresistens by 16S rRNA gene sequencing.
↵d Other organisms identified during the resolution of discrepancies between BCID and the phenotypic comparator assays included one Pasteurella stomatis isolate (phenotypic ID, E. coli), one Pseudomonas stutzeri isolate (phenotypic ID, P. aeruginosa), one Raoultella planticola isolate (phenotypic ID, K. pneumoniae), and four R. ornithinolytica isolates (phenotypic ID, K. oxytoca).
↵e Although all Staphylococcus spp. are intended to be detected by the panel, these species do not react with either of the Staphylococcus sp. target assays. Several less common Staphylococcus spp. are not detected or are detected with lower sensitivity (18).
- TABLE 3
Performance summary of the BCID panel versus the comparator assays for bacteria in both clinical and seeded positive blood cultures combined
Organism Isolates detecteda: BCID/comparator No. of results: BCID/comparator Sensitivity or PPAb: TP/(TP + FN) (%) 95% CI Specificity or NPAb: TN/(TN + FP) (%) 95% CI Clinical arm Seeded arm TP +/+ FP +/− FN −/+ TN −/− Gram-positive bacteria Enterococcus 102/101 29/29 127 4 3 2,073 127/130 (97.7) 93.4–99.5 2,073/2,077 (99.8) 99.5–99.9 L. monocytogenes 0/0 36/36 36 0 0 2,171 36/36 (100) 90.3–100 2,171/2,171 (100) 99.8–100 Staphylococcus 780/797 2/1 770 12 28 1,397 770/798 (96.5) 95.0–97.7 1,397/1,409 (99.1) 98.5–99.6 S. aureus 257/257 0/0 253 4 4 1,946 253/257 (98.4) 96.1–99.6 1,946/1,950 (99.8) 99.5–99.9 Streptococcus 140/141 63/62 198 5 5 1,999 198/203 (97.5) 94.3–99.2 1,999/2,004 (99.8) 99.4–99.9 S. agalactiae (group B) 18/18 18/18 36 0 0 2,171 36/36 (100) 90.3–100 2,171/2,171 (100) 99.8–100 S. pneumoniae 26/25 12/12 36 2 1 2,168 36/37 (97.3) 85.8–99.9 2,168/2,170 (99.9) 99.7–100 S. pyogenes (group A) 8/7 31/31 38 1 0 2,168 38/38 (100) 90.7–100 2,168/2,169 (99.9) 99.7–100 Total 1,331/1,346 191/189 1,494 28 41 16,093 1,494/1,535 (97.3) 96.4–98.1 16,093/16,121 (99.8) 99.7–99.9 Gram-negative bacteria A. baumannii 16/14 40/37 51 5 0 2,151 51/51 (100) 93.0–100 2,151/2,156 (99.8) 99.5–99.9 Enterobacteriaceae 307/310 187/188 490 4 8 1,705 490/498 (98.4) 96.9–99.3 1,705/1,709 (99.8) 99.4–99.9 E. cloacae complex 24/22 17/17 38 3 1 2,165 38/39 (97.4) 86.5–99.9 2,165/2,168 (99.9) 99.6–100 E. coli 149/148 6/5 150 5 3 2,049 150/153 (98.0) 94.4–99.6 2,049/2,054 (99.8) 99.4–99.9 K. oxytoca 6/6 54/58 59 1 5 2,142 59/64 (92.2)c 82.7–97.4 2,142/2,143 (99.9) 99.7–100 K. pneumoniae 74/71 37/34 102 9 3 2,093 102/105 (97.1) 91.9–99.4 2,093/2,102 (99.6) 99.2–99.8 Proteus 22/22 17/17 39 0 0 2,168 39/39 (100) 91.0–100 2,168/2,168 (100) 99.8–100 S. marcescens 22/22 55/55 76 1 1 2,129 76/77 (98.7) 93.0–100 2,129/2,130 (99.9) 99.7–100 H. influenzae 8/8 35/35 43 0 0 2,164 43/43 (100) 91.8–100 2,164/2,164 (100) 99.8–100 N. meningitidis 1/1 35/35 36 0 0 2,171 36/36 (100) 90.3–100 2,171/2,171 (100) 99.8–100 P. aeruginosa 52/52 0/0 51 1 1 2,154 51/52 (98.1) 89.7–100 2,154/2,155 (99.9) 99.7–100 Total 681/676 483/481 1135 29 22 23,091 1,135/1,157 (98.1) 97.1–98.8 23,091/23,120 (99.9) 99.8–99.9 ↵a Culture or culture and 16S rRNA gene sequencing for A. baumannii.
↵b The data in these columns are based on the combined results from the clinical and seeded specimens. Sensitivity refers to performance with clinical specimens, while PPA refers to performance with seeded specimens. Despite the differences in names and usage, they were calculated identically. Likewise, specificity refers to performance with prospective samples, while NPA is used for seeded specimens. They were also calculated identically. These data were obtained in the initial analyses and have not been changed to reflect subsequent investigations of discordant results. Investigations of discordant results are described in Results and summarized in Table 5.
↵c K. oxytoca is the only organism that apparently failed to meet the prespecified criterion of a sensitivity of >95%. However, this was due to an unavoidable error in phenotypic identification. When this was resolved, the sensitivity for this organism exceeded 98.3%.
- TABLE 4
Performance summary of the FilmArray BCID panel versus culture for Candida spp. in positive blood cultures
Organism Isolates detected: BCID/comparator No. of results: BCID/comparator Sensitivity or PPAa: TP/(TP + FN) (%) 95% CI Specificity or NPAa: TN/(TN + FP) (%) 95% CI Clinical arm Seeded arm TP +/+ FP +/− FN −/+ TN −/− Candida albicans 20/16 48/48 64 4 0 2,139 64/64 (100) 94.4–100 2,139/2,143 (99.8) 99.5–99.9 Candida glabrata 14/12 37/37 49 2 0 2,156 49/49 (100) 92.7–100 2,156/2,158 (99.9) 99.7–100 Candida krusei 4/4 33/33 37 0 0 2,170 37/37 (100) 90.5–100 2,170/2,170 (100) 99.8–100 Candida parapsilosis 9/7 52/54 59 2 2 2,144 59/61 (96.7) 88.7–99.6 2,144/2,146 (99.9) 99.7–100 Candida tropicalis 3/3 36/36 39 0 0 2,168 39/39 (100) 91.0–100 2,168/2,168 (100) 99.8–100 All yeast isolates 49/42 207/208 248 8 2 10,777 248/250 (99.2) 97.1–99.9 10,777/10,785 (99.9) 99.9–100 ↵a Sensitivity and specificity refer to performance with the prospective specimens only. PPA and NPA refer to performance with the seeded specimens. These are unresolved data and do not reflect the further investigations discussed in Results.
- TABLE 5
Summary of outcomes of discordant organism result investigations
Result and analyte No. of results No. of investigationsa Comparator result confirmed FilmArray result confirmed Both results incorrectb Inconclusive BCID FP results Enterococcus 4 1 3 Staphylococcus 12 11 1 S. aureus 4 0 1 3 Streptococcus 5 1 1 3 S. pneumoniae 2 1 1 S. pyogenes 1 1 A. baumannii 5 5 Enterobacteriaceae 4 1 3 E. cloacae complex 3 1 2 E. coli 5 1 2 2 K. pneumoniae 9 4 3 2 K. oxytoca 1 1 S. marcescens 1 1 P. aeruginosa 1 1 C. albicans 4 4 C. glabrata 2 2 C. parapsilosis 2 2 Total 65 12 18 5 30 % of total FP results 18 28 8 46 BCID FN results Enterococcus 3 3 Staphylococcus 28 20 1 7 S. aureus 4 1 2 1 Streptococcus 5 3 2 S. pneumoniae 1 1 Enterobacteriaceae 8 4 3 1 E. cloacae complex 1 1 E. coli 3 3 K. pneumoniae 3 1 1 1 K. oxytoca 5 1 4 S. marcescens 1 1 P. aeruginosa 1 1 C. parapsilosis 2 2 Total 65 34 18 1 12 % of total FN results 52 28 2 18 ↵a The method used was investigation of possible sample mix-ups, reculturing from frozen aliquots of the blood culture bottle fluid, sequencing directly from the bottle if isolated organisms were expected, or sequencing from resubcultured isolated organisms if more than one isolate per bottle was present. For bacterial resolution, 16S rRNA gene sequences were analyzed and for yeast, ITS1 was analyzed. See Materials and Methods for further information. Three apparent blood culture bottle mix-ups and one apparent bottle selection error were resolved in favor of BCID.
↵b See Results for further information regarding the indicated organism.
- TABLE 6
Comparison of FilmArray BCID resistance gene results to the prespecified comparator assay (PCR/sequencing directly from blood culture bottle)
Antimicrobial resistance gene(s) Isolates detected: BCID/comparator No. of results: BCID/comparator Sensitivity or PPAa: TP/(TP + FN) (%) 95% CI Specificity or NPAa: TN/(TN + FP) (%) 95% CI Clinical arm Seeded arm TP +/+ FP +/− FN −/+ TN −/− mecA in association with: All Staphylococcus isolates detectedb 491/494 2/2 488 5 8 281 488/496 (98.4) 96.8–99.3 281/286 (98.3) 96.0–99.4 Staphylococcus and S. aureus isolates detected 137/139 0/0 137 0 2 118 137/139 (98.6) 94.9–99.8 118/118 (100) 96.9–100 vanA/B in association with Enterococcus isolates detected 36/36 28/28 64 0 0 67 64/64 (100)c 94.4–100 67/67 (100) 94.6–100 blaKPC in association with Enterobacteriaceae and/or A. baumannii and/or P. aeruginosa isolates detected 6/6d 33/33 39 0 0 558 39/39 (100)e 91.0–100 558/558 (100) 99.3–100 ↵a Sensitivity and specificity refer to performance with the prospective specimens only. PPA and NPA refer to performance with the seeded specimens. These are unresolved data.
↵b Either Staphylococcus or S. aureus isolates detected or both.
↵c Of the 64 Enterococcus isolates, 11 (17.2%) carried the vanB gene as determined by bidirectional sequence analysis.
↵d All six isolates were identified as K. pneumoniae.
↵e These isolates included 30 of K. pneumoniae, 2 of E. cloacae, and 1 of E. coli.
