Background
Methods
Patients and case definition
Vaginal samples and API 20C identification
Molecular identification
Candida species | Primer name | Forward(5′-3′) | Reverse(5′-3′) | Amplified fragment size (bp) | References |
---|---|---|---|---|---|
C. albicans complexes | HWP1 | GCTACCACTTCAGAATCATCATC | GCACCTTCAGTCGTAGAGACG | C. albicans:839 and 941 C. africana:700 C. dubliniensis:569 | Shan,2014 |
C. glabrata complexes | GLA NIV BRA | CGGTTGGTGGGTGTTCTGC AGGGAGGAGTTTGTATCTTTCAAC GGGACGGTAAGTCTCCCG | ACCAGAGGGCGCAATGTG | C. glabrata:397 C. bracarensis: 223 C. nivariensis:293 | Li,2014 |
C. parapsilosis complexes | mCPF mCOF mCMF | TTTGCTTTGGTAGGCCTTCTA TAAGTCAACTGATTAACTAAT AACTGCAATCCTTTTCTTTCTA | AATATCTGCAATTCATATTACT | C. parapsilosis:171 C. orthopsilosis:109 C. metapsilosis:217 | Asadzadeh,2015 |
Rare yeast | NL1,NL4 | GCATATCAATAAGCGGAGGAAAAG-3’ | GGTCCGTGTTTCAAGACGG | 500–600 | Leaw,2006 |
Antifungal susceptibility testing
Statistical analysis
Results
Strain distribution and yeast identification
Candida identified by molecular methods (abbreviation) | Candida identified by API 20C (isolates) | Correct identification/total,% | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
CA (2866) | CG(489) | CP (85) | CT (57) | CK (27) | SC (24) | C. famata (13) | CL (4) | RH (4) | C. inconspicua (3) | C. humicola (2) | ||
C. albicans (CA) | 2707 | 24 | 0 | 7 | 4 | 1 | 1 | 0 | 3 | 0 | 1 | 2707/2748,98.51 |
C. africana | 48 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0/49,0 |
C. dubliniensis | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0/1,0 |
C. glabrata (CG) | 52 | 439 | 7 | 7 | 2 | 7 | 4 | 0 | 1 | 0 | 0 | 439/519,84.59 |
C. nivariensis | 0 | 7 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0/9,0 |
C. bracarensis | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0/2,0 |
C. parapsilosis (CP) | 7 | 4 | 61 | 2 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 61/76,80.26 |
C. orthopsilosis | 1 | 1 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0/6,0 |
C. metapsilosis | 3 | 5 | 8 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 0/20,0 |
C. tropicalis (CT) | 10 | 2 | 2 | 40 | 0 | 4 | 3 | 0 | 0 | 0 | 0 | 40/61,65.57 |
C. krusei (CK) | 28 | 2 | 1 | 0 | 18 | 1 | 0 | 1 | 0 | 3 | 0 | 18/54,33.33 |
Saccharomyces cerevisiae (SC) | 2 | 1 | 1 | 0 | 1 | 7 | 0 | 0 | 0 | 0 | 0 | 7/12,58.33 |
C. lusitaniae (CL) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1/1,100 |
C. fabianii | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0/3,0 |
Trichosporon asahii () | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0/1,0 |
Rhodotorula (RH) | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0/3,0 |
C. guilliermondii | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0/2,0 |
Kodamaea ohmeri | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0/2,0 |
Issatchenkia terricola | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0/2,0 |
Torulaspora pretoriensis | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0/1,0 |
Kazachstania bovina | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0/1,0 |
Kluyveromyces marianus | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0/1,0 |
Total | 2866 | 489 | 85 | 57 | 27 | 24 | 13 | 4 | 4 | 3 | 2 | 3273/3574,91.58 |
Antifungal susceptibility
Antifungal agents | ||||||||
---|---|---|---|---|---|---|---|---|
Candida species(n) | BUC | CLO | FLC | ITC | MIC | TEC | VRC | |
C. albicans, n = 1272 | Range | 0.015–32 | 0.015–32 | 0.06–128 | 0.015–32 | 0.015–32 | 0.015–32 | 0.015–8 |
GM | 0.11 | 0.05 | 0.79 | 0.09 | 0.30 | 0.15 | 0.07 | |
MIC90 | 1 | 0.25 | 4 | 1 | 4 | 2 | 0.5 | |
R | 7.7% | 10.2% | 6.2% | |||||
C. africana, n = 49 | Range | 0.015–2. | 0.015–4 | 0.125–1 | 0.015–1 | 0.015-0.5 | 0.03–16 | 0.03–0.5 |
GM | 0.04 | 0.04 | 0.25 | 0.04 | 0.04 | 0.07 | 0.04 | |
MIC90 | 0.06 | 0.06 | 0.5 | 0.06 | 0.125 | 0.5 | 0.06 | |
C. dubliniensis n = 1 | Range | 0.015 | 0.015 | 4 | 0.125 | 0.03 | 0.015 | 0.015 |
C. glabrata, n = 267 | Range | 0.015–16 | 0.015–16 | 0.125–128 | 0.015–32 | 0.015–32 | 0.015–32 | 0.015–32 |
GM | 0.21 | 0.20 | 1.48 | 0.38 | 0.25 | 0.16 | 0.09 | |
MIC90 | 1 | 1 | 8 | 4 | 2 | 1 | 0.25 | |
R | 3.4% | 29.1% | – | |||||
C. nivariensis, n = 9 | Range | 0.03–1 | 0.03–0.5 | 0.125–32 | 0.03–0.5 | 0.03–16 | 0.03–1 | 0.03–4 |
MIC50 | 0.03 | 0.06 | 2 | 0.5 | 0.03 | 0.03 | 0.06 | |
MIC90 | 0.125 | 0.125 | 4 | 0.5 | 2 | 1 | 0.5 | |
C. bracarensis, n = 2 | Range | 0.03–1 | 0.03–0.5 | 0.25–2 | 0.125–2 | 0.03–4 | 0.03–1 | 0.03–0.125 |
MIC50 | 0.03 | 0.03 | 0.25 | 0.125 | 0.03 | 0.03 | 0.03 | |
MIC90 | 1 | 0.5 | 2 | 2 | 4 | 1 | 0.125 | |
C. parapsilosis, n = 76 | Range | 0.03–4 | 0.015–1 | 0.125–4 | 0.03–4 | 0.03–4 | 0.015–32 | 0.015–2 |
GM | 0.18 | 0.04 | 0.47 | 0.07 | 0.54 | 0.03 | 0.04 | |
MIC90 | 1 | 0.06 | 1 | 0.25 | 2 | 0.03 | 0.06 | |
R | 0 | 3% | 1% | |||||
C. metapsilosis, n = 20 | Range | 0.03–1 | 0.03–0.25 | 0.25–4 | 0.03–1 | 0.03–8 | 0.015–0.05 | 0.015–0.06 |
GM | 0.16 | 0.04 | 0.79 | 0.08 | 0.48 | 0.04 | 0.03 | |
MIC90 | 1 | 0.06 | 2 | 1 | 4 | 0.25 | 0.06 | |
C. orthopsilosis, n = 6 | Range | 0.03–8 | 0.03–1 | 0.125–4 | 0.03–1 | 0.25–8 | 0.03–0.25 | 0.03–0.25 |
MIC50 | 0.5 | 0.06 | 1.0 | 0.25 | 1.0 | 0.03 | 0.06 | |
MIC90 | 8 | 1 | 4 | 1 | 8 | 0.25 | 0.25 | |
C. tropicalis, n = 61 | Range | 0.03–2 | 0.015–0.5 | 0.125–128 | 0.015–32 | 0.03–32 | 0.03–2 | 0.03–4 |
GM | 0.15 | 0.05 | 0.66 | 0.07 | 0.70 | 0.08 | 0.05 | |
MIC90 | 1 | 0.25 | 8 | 0.125 | 8 | 0.25 | 0.25 | |
R | 10.9% | 5.6% | 4.3% | |||||
C. krusei, n = 54 | Range | 0.06–16 | 0.015–0.5 | 0.25–64 | 0.015–4 | 0.03–16 | 0.03–4 | 0.03–1 |
GM | 0.85 | 0.08 | 15.69 | 0.27 | 0.72 | 0.14 | 0.21 | |
MIC90 | 4 | 0.5 | 64 | 1 | 8 | 1 | 0.5 | |
R | – | 12.5% | 0 | |||||
Saccharomyces cerevisiae, n = 12 | Range | 0.015–2 | 0.015–1 | 0.125–32 | 0.015–2 | 0.06–8 | 0.015–0.5 | 0.03–1 |
GM | 0.1 | 0.09 | 1.2 | 0.20 | 0.54 | 0.11 | 0.09 | |
MIC90 | 0.5 | 0.5 | 8 | 2 | 4 | 0.5 | 0.25 | |
C. guilliermondii, n = 2 | Range | 0.06–4 | 0.03–4 | 0.5–16 | 0.125–16 | 1–16 | 0.03–0.25 | 0.06–1 |
MIC50 | 0.06 | 0.03 | 0.5 | 0.125 | 1 | 0.03 | 0.06 | |
MIC90 | 4 | 4 | 16 | 16 | 16 | 0.25 | 1 | |
R | 0 | 50% | 0 | |||||
C. lusitaniae, n = 1 | Range | 0.03 | 0.03 | 0.125 | 0.03 | 0.03 | 0.03 | 0.03 |
C.Fabianii, n = 3 | Range | 0.03–0.25 | 0.03–0.06 | 0.5–1 | 0.03–0.25 | 0.125–1 | 0.03 | 0.03 |
MIC50 | 0.125 | 0.03 | 0.5 | 0.06 | 0.125 | 0.03 | 0.03 | |
MIC90 | 0.25 | 0.06 | 1 | 0.25 | 1 | 0.03 | 0.03 | |
Trichosporon asahii,n = 1 | Range | 0.03 | 0.03 | 0.25 | 0.03 | 0.06 | 0.03 | 0.03 |
Rhodotorula, n = 3 | Range | 0.03–0.5 | 0.03–1 | 4–128 | 0.03–8 | 0.25–8 | 0.03–0.5 | 0.03–1 |
MIC50 | 0.06 | 0.06 | 64 | 2 | 1 | 0.06 | 0.03 | |
MIC90 | 0.5 | 1 | 128 | 8 | 8 | 0.5 | 1 | |
Kodamaea ohmeri, n = 2 | Range | 0.125–0.5 | 0.03 | 0.25–2 | 0.125–0.25 | 0.25–0.5 | 0.03 | 0.03 |
MIC50 | 0.125 | 0.03 | 0.25 | 0.125 | 0.25 | 0.03 | 0.03 | |
MIC90 | 0.5 | 0.03 | 2 | 0.25 | 0.5 | 0.03 | 0.03 | |
Issatchenkia terricola,n = 2 | Range | 1–4 | 0.06–0.125 | 32–64 | 0.25–0.5 | 0.5 | 0.25 | 0.25 |
MIC50 | 1 | 0.06 | 32 | 0.25 | 0.5 | 0.25 | 0.25 | |
MIC90 | 4 | 0.125 | 64 | 0.5 | 0.5 | 0.25 | 0.25 | |
Torulaspora pretoriensis,n = 1 | Range | 0.25 | 0.03 | 8 | 0.5 | 0.5 | 0.125 | 0.125 |
ATCC90028a | Range | 0.015–0.5 | 0.015–0.5 | 0.125–2 | 0.015–4 | 0.008–0.015 | 0.015–32 | 0.015–8 |
GM | 0.04 | 0.03 | 0.21 | 0.08 | 0.06 | 0.03 | 0.03 | |
MIC90 | 0.125 | 0.03 | 0.5 | 0.25 | 0.015 | 0.03 | 0.03 | |
Candida species(n) | Antifungal agents | |||||||
AmB | FLU | NYS | TEB | AFG | CFG | MFG | ||
C. albicans n = 1272 | Range | 0.015–32 | 0.03–128 | 0.03–32 | 0.03–256 | 0.008–0.5 | 0.008–0.5 | 0.008–0.5 |
GM | 0.22 | 0.70 | 1.60 | 45.11 | 0.015 | 0.1 | 0.03 | |
MIC90 | 0.5 | 4 | 8 | 256 | 0.03 | 0.25 | 0.25 | |
R | 3.3% | 0 | 0 | 0 | ||||
C. africana n = 49 | Range | 0.03–32 | 0.06–8 | 0.125–4 | 0.25–256 | 0.008–0.03 | 0.015–0.5 | 0.008–0.5 |
GM | 0.08 | 0.68 | 0.5 | 17.31 | 0.01 | 0.06 | 0.02 | |
MIC90 | 1 | 2 | 4 | 128 | 0.015 | 0.25 | 0.06 | |
C. dubliniensis n = 1 | Range | 0.06 | 0.06 | 0.25 | 16 | 0.008 | 0.015 | 0.008 |
C. glabrata n = 267 | Range | 0.03–2 | 0.06–16 | 0.03–32 | 0.25–256 | 0.008–0.5 | 0.008–0.5 | 0.008–0.5 |
GM | 0.29 | 0.18 | 3.39 | 26.62 | 0.03 | 0.11 | 0.05 | |
MIC90 | 1 | 1 | 8 | 256 | 0.06 | 0.25 | 0.25 | |
R | 0 | 0 | 0 | 0 | ||||
C. nivariensis n = 9 | Range | 0.06–2 | 0.125–4 | 0.5–4 | 1–256 | 0.015–0.06 | 0.08–0.5 | 0.015–0.5 |
MIC50 | 0.06 | 0.5 | 1 | 128 | 0.06 | 0.25 | 0.015 | |
MIC90 | 2 | 2 | 4 | 256 | 0.06 | 0.5 | 0.5 | |
C. bracarensis n = 2 | Range | 0.06–1 | 0.125–2 | 0.25–8 | 8–256 | 0.015–0.03 | 0.125–0.5 | 0.015–0.5 |
MIC50 | 0.06 | 0.125 | 0.25 | 8 | 0.015 | 0.125 | 0.015 | |
MIC90 | 1 | 2 | 8 | 256 | 0.03 | 0.5 | 0.5 | |
C. parapsilosis n = 76 | Range | 0.03–2 | 0.125–8 | 0.03–32 | 0.25–256 | 0.008–1 | 0.008–1 | 0.008–1 |
GM | 0.19 | 0.14 | 0.59 | 0.62 | 0.69 | 0.60 | 0.54 | |
MIC90 | 1 | 0.125 | 4 | 32 | 0.5 | 0.5 | 0.5 | |
R | 0 | 5.2% | 5.2% | 1.3% | ||||
C. metapsilosis n = 20 | Range | 0.015–0.5 | 0.125–4 | 0.06–4 | 0.25–256 | 0.015–0.5 | 0.008–0.5 | 0.015–1 |
GM | 0.10 | 0.177 | 0.46 | 2.17 | 0.17 | 0.17 | 0.39 | |
MIC90 | 0.5 | 1 | 4 | 256 | 0.25 | 0.25 | 0.5 | |
C. orthopsilosis n = 6 | Range | 0.06–0.25 | 0.125–2 | 0.06–8 | 0.25–128 | 0.008–1 | 0.015–1 | 0.008–0.5 |
MIC50 | 0.125 | 1 | 0.5 | 64 | 0.008 | 0.03 | 0.25 | |
MIC90 | 0.25 | 2 | 8 | 128 | 1 | 1 | 0.5 | |
C. tropicalis n = 61 | Range | 0.03–1 | 0.125–32 | 0.03–8 | 0.25–256 | 0.015–0.125 | 0.008–0.5 | 0.008–0.5 |
GM | 0.19 | 0.23 | 0.54 | 60.02 | 0.03 | 0.24 | 0.04 | |
MIC90 | 0.5 | 1 | 4 | 256 | 0.06 | 0.5 | 0.5 | |
R | 1.8% | 0 | 0 | 0 | ||||
C. krusei n = 54 | Range | 0.03–1 | 0.125–32 | 0.03–4 | 16–256 | 0.015–0.5 | 0.008–1 | 0.008–0.5 |
GM | 0.43 | 4.2 | 0.32 | 75.66 | 0.08 | 0.08 | 0.15 | |
MIC90 | 1 | 16 | 1 | 256 | 0.125 | 0.5 | 0.25 | |
R | 2.9% | 0 | 1.85% | 0 | ||||
Saccharomyces cerevisiae n = 12 | Range | 0.03–4 | 0.06–8 | 0.125–32 | 0.25–256 | 0.015–0.5 | 0.008–0.5 | 0.015–0.5 |
GM | 0.18 | 0.21 | 0.78 | 53.20 | 0.14 | 0.10 | 0.18 | |
MIC90 | 1 | 1 | 8 | 256 | 0.5 | 0.25 | 0.25 | |
C. guilliermondii n = 2 | Range | 0.06–0.5 | 0.125–0.25 | 0.25–0.5 | 64–128 | 0.015–0.25 | 0.25–0.5 | 0.015–0.25 |
MIC50 | 0.06 | 0.125 | 0.25 | 64 | 0.015 | 0.25 | 0.015 | |
MIC90 | 0.5 | 0.25 | 0.5 | 128 | 0.25 | 0.5 | 0.25 | |
R | 0 | 0 | 0 | 0 | ||||
C. lusitaniae n = 1 | Range | 0.125 | 0.125 | 0.25 | 0.25 | 0.03 | 0.25 | 0.015 |
C. fabianii n = 3 | Range | 0.06–0.25 | 0.125 | 0.25 | 128 | 0.015–0.03 | 0.015–0.25 | 0.015–0.06 |
MIC50 | 0.06 | 0.125 | 0.25 | 128 | 0.015 | 0.015 | 0.03 | |
MIC90 | 0.25 | 0.125 | 0.25 | 128 | 0.03 | 0.25 | 0.06 | |
Trichosporon asahii n = 1 | Range | 0.125 | 1 | 0.25 | 128 | 0.015 | 0.5 | 0.015 |
Rhodotorula n = 3 | Range | 0.03–0.5 | 0.125 | 0.06–0.125 | 8–256 | 0.06–0.5 | 0.25–0.5 | 0.25–0.5 |
MIC50 | 0.03 | 0.125 | 0.06 | 8 | 0.06 | 0.25 | 0.25 | |
MIC90 | 0.5 | 0.125 | 0.125 | 256 | 0.5 | 0.5 | 0.5 | |
Kodamaea ohmeri n = 2 | Range | 0.125–1 | 0.125 | 0.5 | 128 | 0.015 | 0.125–0.25 | 0.015–0.03 |
MIC50 | 0.125 | 0.125 | 0.5 | 128 | 0.015 | 0.125 | 0.015 | |
MIC90 | 1 | 0.125 | 0.5 | 128 | 0.015 | 0.25 | 0.03 | |
Issatchenkia terricola n = 2 | Range | 0.125–0.5 | 8 | 0.5 | 128–256 | 0.06 | 0.06 | 0.008 |
MIC50 | 0.125 | 8 | 0.5 | 128 | 0.06 | 0.06 | 0.008 | |
MIC90 | 0.5 | 8 | 0.5 | 256 | 0.06 | 0.06 | 0.008 | |
Torulaspora pretoriensis n = 1 | Range | 0.125 | 0.125 | 0.25 | 16 | 0.015 | 0.125 | 0.015 |
ATCC90028a | Range | 0.03–2 | 0.125–8 | 0.25–16 | 1–256 | 0.008–0.015 | 0.015–0.5 | 0.008–0.015 |
GM | 0.22 | 0.64 | 1.31 | 88.22 | 0.01 | 0.09 | 0.01 | |
MIC90 | 1 | 2 | 8 | 256 | 0.015 | 0.5 | 0.015 |
AmB | FLU | NYS | TEB | AFG | CFG | MFG | BUC | CLO | FLC | ITC | MIC | TEC | VRC | ||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
C. albicans | |||||||||||||||
VVC | Range | 0.15–32 | 0.030–128 | 0.03–32 | 0.03–256 | 0.008–0.5 | 0.008–0.5 | 0.008–0.5 | 0.015–32 | 0.015–32 | 0.06–128 | 0.015–32 | 0.015–32 | 0.015–32 | 0.015–8 |
GM | 0.21 | 0.65 | 1.55 | 39.23 | 0.02 | 0.1 | 0.03 | 0.11 | 0.05 | 0.74 | 0.09 | 0.27 | 0.12 | 0.06 | |
MIC90 | 0.5 | 4 | 8 | 256 | 0.03 | 0.25 | 0.25 | 1 | 0.25 | 4 | 1 | 4 | 2 | 0.5 | |
RVVC | Range | 0.015–32 | 0.06–128 | 0.03–32 | 0.25–256 | 0.008–0.25 | 0.008–0.5 | 0.008–0.5 | 0.015–8 | 0.015–16 | 0.06–64 | 0.015–32 | 0.015–32 | 0.015–32 | 0.015–8 |
GM | 0.25 | 0.94 | 1.82 | 74.50 | 0.01 | 0.1 | 0.03 | 0.13 | 0.05 | 1.03 | 0.10 | 0.46 | 0.33 | 0.09 | |
MIC90 | 0.6 | 4 | 8 | 256 | 0.015 | 0.25 | 0.06 | 1 | 0.5 | 4 | 0.5 | 8 | 8 | 0.5 | |
P | 0.813 | 0.435 | 0.770 | 0 | 0.242 | 0.7 | 0.566 | 0.736 | 0.341 | 0.14 | 0.041 | 0.053 | 0 | 0.34 | |
C. glabrata | |||||||||||||||
VVC | Range | 0.03–2 | 0.06–16 | 0.03–32 | 0.25–256 | 0.015–0.5 | 0.008–0.5 | 0.008–0.5 | 0.015–16 | 0.015–16 | 0.125–128 | 0.015–32 | 0.015–16 | 0.015–32 | 0.015–32 |
GM | 0.33 | 0.18 | 3.88 | 40.63 | 0.03 | 0.06 | 0.05 | 0.24 | 0.23 | 1.68 | 0.42 | 0.25 | 0.15 | 0.09 | |
MIC90 | 1 | 1 | 8 | 256 | 0.06 | 0.25 | 0.25 | 1 | 1 | 8 | 4 | 2 | 1 | 0.25 | |
RVVC | Range | 0.03–2 | 0.06–2 | 0.03–16 | 0.25–256 | 0.008–0.06 | 0.008–0.5 | 0.008–0.5 | 0.015–8 | 0.03–4 | 0.125–128 | 0.03–32 | 0.03–32 | 0.015–32 | 0.015–32 |
GM | 0.20 | 0.17 | 2.31 | 8.86 | 0.02 | 0.06 | 0.04 | 0.16 | 0.134 | 1.03 | 0.29 | 0.27 | 0.17 | 0.11 | |
MIC90 | 0.5 | 1 | 8 | 256 | 0.03 | 0.25 | 0.25 | 1 | 1 | 16 | 2 | 4 | 2 | 0.5 | |
P | 0.017 | 0.366 | 0.035 | 0.015 | 0.058 | 0.68 | 0.78 | 0.87 | 0.25 | 0.1 | 1 | 0.043 | 0.683 | 0.293 |