Table 1.
Survey of available methodologies for fungal diagnostics, including commercially available kits, with indication of assay and manufacturer, biomarker, principle, scope, sensitivity and specificity, approval information, limit of detection (LoD), time, clinical sample and reference work.
| Assay (manufacturer) | Biomarker—principle | Scope | Goal | Sensitivity/specificity (%) | Approval | LoD* | Time | Clinical specimens | References |
|---|---|---|---|---|---|---|---|---|---|
| ePlex BCID-FP (GenMark DX) | DNA—r.f.u. | 19 Candida spp. | I | u.d./u.d. | u.d. | — | 1.5 h | Blood culture | Maubon et al. 2018 |
| Yeast Traffic Light PNA FISH™ (AdvanDX) | DNA—r.f.u. | 5 Candida spp. | I | –/– | FDA | — | 1.5 h | Blood culture (+) | Ibáñez-Martínez, Ruiz-Gaitán and Pemán-García 2017 |
| FilmArray® BCID Panel (Biomerieux) | DNA—r.f.u. | 5 Candida spp. | I + R | 100/99.8–100 | IVD/CE | — | 1 h | Blood culture | Southern et al. 2015; McCoy et al. 2016; Salimnia et al. 2016 |
| T2 Candida Panel (T2 Biosystems) | DNA—r.f.u. (MR) | 5 Candida spp. | I | 91.1/99.4 | FDA | 1 cfu/mL | 4.5 h | Blood | Mylonakis et al. 2015; Pappas et al. 2016; Pfaller, Wolk and Lowery 2016; Zervou et al. 2017 |
| IRIDICA BAC BSI (Abbott Diagnostics) | DNA—PCR + MS | Pan-microbial | I | 81/84 | IVD/CE/FDA | 8 cfu/mL | 6 h | Blood, tissue, OSF, BAL, ETA | Metzgar et al. 2016; Stevenson et al. 2016 |
| UMD Universal (Molzym) | DNA—ITS-based qPCR + seq | Pan-fungal + pan-bacterial | I | –/– | IVD/CE | 10 cfu/mL | 24 h | Body fluids, tissue, swabs | Kühn et al. 2011; Borde et al. 2015 |
| SeptiTestTM (Molzym) | DNA—qPCR + seq | Pan-fungal + pan-bacterial | I | 48/86 | IVD/CE | — | 7–8 h | Blood | Stevenson et al. 2016 |
| Light Cycler SeptiFast Test MGRADE® (Roche) | DNA—LC multiplex PCR | 5 Candida spp. | RI | 65/86 | IVD/CE | 30 cfu/mL | 6 h | Blood | Stevenson et al. 2016 |
| Prove-it®Sepsis (MobiDiag) | DNA—PCR + hyb | Pan-yeast (incl. 8 Candida spp.) | I + R | 95/99 | IVD/CE | — | 3.5a h | Blood | Aittakorpi et al. 2012 |
| MagiplexTM Sepsis Real-time Test (Seegene) | DNA—multiplex qPCR | Sepsis panel (incl. 5 Candida spp.) | D + I | –/– | IVD/CE | — | 3a h | Blood | Denina et al. 2016 |
| RenDx Fungiplex (Renshaw Diagnostics) | DNA–28S rRNA PCR-SERS | Pan-Aspergillus + pan-Candida | D + I | 80 (Candida)/87.5 | IVD/CE | 20 g/r | 6 h | Blood | White et al. 2014 |
| MycoReal Candida (Ingenetix) | DNA—ITS2 PCR LC-hyb | 7 Candida spp. | I | –/– | RUO | — | 2a h | n.s. | Mutschlechner et al. 2016 |
| RealLine (Bioron) | DNA—multiplex STI Kits | C. albicans + Gardnerella vaginalis | D + I | –/100 | IVD/CE | — | 2 h | Saliva, urine, SEC | Bioron 2016 |
| AllplexTM STI/BV Panel Assays-Candidiasis Assay (Seegene) | DNA—multiplex qPCR | STI panel (incl. 7 Candida spp.) | D + I | –/– | IVD/CE | — | 2.5a h | Genital swab, urine, LBCS | Seegene 2019 |
| FungiXpert (Era Biology) | DNA—multiplex qPCR | C. albicans/Aspergillus | D + I | –/– | IVD/CE | — | 2a h | BAL, fluids | Era Biology 2018 |
| AmpliSens® Candida albicans-FEP (AmpliSens®) | DNA—qPCR | C. albicans | I | –/– | IVD/CE | 1000– 2000 cfu/mL | — | Urogentital swabs and urine samples | AmpliSens®2018 |
| Fungiplex® Aspergillus Azole-R IVD Real-Time PCR Kit (Bruker Daltonics) | DNA—multiplex qPCR | Mutation in Cyp51A (TR34 and TR46) | DI | 100/(LoD = 50 ge) 100 | IVD | 50 ge | <2 h | Serum, plasma and BAL | Bruker 2018a |
| Fungiplex® Universal RuO Real-Time PCR Kit (Bruker Daltoics) | DNA—multiplex qPCR | All fungal DNA plus internal control | BI | 98/98 | RUO | 50 input copies | <2 h | n.s. | Bruker 2018b |
| Fungiplex® Candida auris Real-Time PCR Kit (Bruker Daltonics) | DNA—qPCR | C. auris plus internal control | DI | 97.3/99.8 | RUO | 10 input copies | <2 h | n.s. | Bruker 2018c |
| Fungitell (Associates of Cape Cod) | Antigen–1,3-β-d-glucan detection | Pan-fungal (except Mucormycetes) | D | depends on cohort/81.1–86.5 | IVD/CE/FDA | n/a | 1 h | Serum, CSF | Liss et al. 2016; Stevens et al. 2016 |
| Platelia Candida Ag Plus (BioRad) | Antigen—Candida mannan detection by ELISA | Candida spp. | D | 40–70%sd/70–98 % | IVD/CE | n/a | 4 h | Serum, plasma | Lunel et al. 2011 |
| Candida antigen Serion ELISA (Institut Virion\Serion GmbH) | Antigen—Candida mannan detection by ELISA | Candida spp. | D | 52/98 | IVD/CE | n/a | 4 h | Serum, plasma | Hartl et al. 2018 |
| Cryptococcal Antigen Lateral Flow Assay (IMMY) | Antigen—IC detection | Cr. neoformans/Cr. gattii | D | 98–100/97–100 | IVD/CE/FDA | n/a | 15 min | Serum, CSF | Vidal and Boulware 2015 |
| Cryptococcal Antigen Latex Agglutination Assay (IMMY) | Antigen—Latex agglutination | Cr. neoformans | D | 93–100/93–100 | IVD/CE | 0.5–25 ng/mL | 2 h | Serum, CSF | Binnicker et al. 2012 |
| Cryptococcal Antigen enzyme immunoassay (IMMY) | Antigen—ELISA | Cr. neoformans/Cr. gattii | D | 98r/97r | IVD/CE | n/a | 3 h | Serum, CSF | Binnicker et al. 2012 |
| Histoplasma Antigen EIA (IMMY) | Antigen—ELISA | Histoplasma capsulatum | D | 64/99 | IVD/CE | n/a | 4 h | Urine | LeMonte et al. 2007; Theel et al. 2013 |
| Cryptococcal Antigen Latex Agglutination System (Meridian Bioscience) | Antigen—Latex agglutination | Cr. neoformans | D | 100/100 | IVD/CE | n/a | 4.5 h | Serum, CSF | Jaye et al. 1998 |
| Premier® Cryptococcal Antigen (Meridian Bioscience) | Antigen—ELISA | Cr. neoformans | D | 100/97 | IVD/CE | n/a | 1.5 h | Serum, CSF | Gade et al. 1991 |
| IR Biotyper Kit (Bruker Daltonics) | Polysaccharides—r.f.u. | All microorganisms | ST | –/– | RUO | — | <3 h | Agar plate | Bruker 2018d; Bruker 2018e |
| MALDI Sepsityper Kit (Bruker Daltonics) | Protein—r.f.u. (MALDI-TOF MS) | Yeasts + bacteria | I | –/– | IVD/CE | 1 mL | 15–20 min | Blood culture (+) | Scohy et al. 2018 |
| AuxaColor™ 2 (Bio-Rad) | Enzymatic—color pH indicator | 33 most frequently isolated yeasts in medical mycology | I | –/– | FDA | — | 24–48 h | Blood culture (+) | Ibáñez-Martínez, Ruiz-Gaitán and Pemán-García 2017 |
| BactiCard® Candida (Remel, Lenexa, KS, USA) | Enzymatic—using NGL/PRO | Mainly C. albicans | I | 97.8/92.5 | IVD | — | 30 s | Agar plate | Cárdenes et al. 2004 |
| Candida albicans Test Kit (MUREX C. albicans 50) (Remel) | Enzymatic—using NGL/PRO | Mainly C. albicans | I | 100/100 | IVD | — | 0.5–1 h | Agar plate | Fenn et al. 1996 |
| O.B.I.S. C. albicans(Oxoid) | Enzymatic—using NGL/PRO | Mainly C. albicans | I | 100/100 | — | 3 to 5 colonies (each 1 mm) | 0.5–1 h | Agar plate |
r.f.u.—ready for use; MR—magnetic resonance; MS—mass spectrometry; seq—sequencing; LC—light cycler (Roche); hyb—hybridization; STI—sexually transmitted infection; IC—immunochromatographic; NGL—β-galactosaminidase; PRO—proline arylamidase; u.d.—under development; FDA—The Food and Drug Administration, USA; IVD—in vitro diagnostics; CE—European conformity; RUO—research use only; sd—highly species dependent; r—retrospective; *—for Candida; g/r—genomes/reaction; ge—genome equivalents; n/a—not available; a—excluding DNA extraction; (+)—positive; OSF—other sterile fluids; BAL—bronchoalveolar lavage; ETA—endotracheal aspirate; n.s.—not specified; SEC—scrapings of epithelial cells; LBCS—liquid-based cytology specimen; CSF—cerebrospinal fluid; I—identification; D—detection; RI—rapid identification; DI—direct identification (without culturing); BI—broad identification (without culturing); D + I—detection and identification; R—detection of resistance; ST = strains sub-typing. The authors to not claim to be complete, additional Candida detecting system might have been marketed with EC, IVD or FDA label.