Background
Materials and methods
Study selection
Inclusion and exclusion criteria
Inclusion criteria
Exclusion criteria
Quality assessment
Data extraction
Statistical analysis
Results
Literature search
Study characteristics
first author | publication time | country | study design | diagnostic criteria | clinical setting | biomarker | sample size | TP | FP | FN | TN | SEN (%) | SPE (%) | average age | test method |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Anand [23]a | 2015 | India | PS | culture+ | ICU | PCT | 118 | 68 | 6 | 4 | 40 | 94.4 | 87 | 49.3 | IF |
IL-6 | 118 | 46 | 5 | 26 | 41 | 63.9 | 89 | 49.3 | ECLI | ||||||
Anand [23] b | 2015 | India | PS | clinical,culture- | ICU | PCT | 136 | 83 | 13 | 7 | 33 | 92.2 | 72 | 52.1 | IF |
IL-6 | 136 | 42 | 12 | 48 | 34 | 47 | 73 | 52.1 | ECLI | ||||||
Bauer [26] | 2016 | America | PS | clinical | ICU | CD64 | 196 | 84 | 20 | 26 | 66 | 76.4 | 76.7 | FCM | |
PCT | 216 | 88 | 25 | 32 | 71 | 73.1 | 74.2 | IF | |||||||
Cardelli [27] | 2008 | Italy | PS | clinical,culture+ | ICU | CD64 | 112 | 50 | 5 | 2 | 55 | 96 | 91.7 | 63 | FCM |
PCT | 112 | 49 | 27 | 3 | 33 | 94 | 70 | 63 | IF | ||||||
Castelli [28] | 2004 | Italy | PS | clinical,culture+ | ICU | PCT | 49 | 21 | 2 | 13 | 13 | 61.7 | 86.7 | IF | |
Cheval [29] | 2000 | France | PS | clinical | ICU | PCT | 60 | 28 | 5 | 4 | 23 | 87.5 | 82.1 | 56.3 | IF |
Clec’h [25] a | 2006 | France | PS | clinical | SICU | PCT | 67 | 28 | 9 | 3 | 27 | 91.7 | 74.2 | 63 | IF |
Clec’h [25] b | 2006 | France | PS | clinical | MICU | PCT | 76 | 29 | 2 | 7 | 38 | 80.6 | 95 | 60.1 | IF |
Davis [30] | 2006 | America | RS | clinical,culture+ | ED | CD64 | 100 | 33 | 18 | 5 | 44 | 86.8 | 71 | FCM | |
Dimoula [31] | 2014 | Belgium | PS | clinical | ICU | CD64 | 468 | 92 | 47 | 11 | 318 | 89.3 | 87.1 | 58.7 | FCM |
Du [32] | 2003 | China | PS | clinical | ICU | PCT | 51 | 16 | 8 | 4 | 23 | 80 | 74.2 | 64.7 | IF |
IL-6 | 51 | 17 | 8 | 3 | 23 | 85 | 74 | 64.7 | EIA | ||||||
Feng [33] | 2012 | China | PS | clinical | ICU | PCT | 132 | 69 | 12 | 33 | 18 | 67.6 | 60 | ELISA | |
Gaini [34] | 2006 | Denmark | PS | clinical | GW | PCT | 93 | 56 | 9 | 18 | 10 | 75.7 | 52.6 | 63 | IF |
IL-6 | 93 | 60 | 4 | 14 | 15 | 81.1 | 78.9 | 63 | ECLI | ||||||
Gamez-Diaz [35] | 2011 | Colombia | PS | clinical | ED | CD64 | 610 | 266 | 73 | 138 | 133 | 65.8 | 65 | Leuko64 kit | |
Gerrits [36] | 2013 | Netherla-nds | PS | clinical | ICU | CD64 | 44 | 25 | 1 | 0 | 18 | 100 | 94.7 | 71.8 | Leuko64 kit |
Gibot [37] | 2012 | France | PS | clinical | ICU | CD64 | 300 | 130 | 7 | 24 | 139 | 84.4 | 95.2 | 61.5 | FCM |
PCT | 300 | 128 | 30 | 26 | 124 | 83.1 | 84.9 | 61.5 | ECLI | ||||||
Gros [38] | 2012 | France | PS | clinical, culture+ | MICU | CD64 | 293 | 93 | 16 | 55 | 129 | 62.8 | 89 | 59.5 | Leuko64 kit |
Gupta [24] a | 2018 | India | PS | culture+ | PCT | 242 | 193 | 5 | 3 | 41 | 98.5 | 89.1 | ECLI | ||
Gupta [24] b | 2018 | India | PS | clinical,culture- | PCT | 109 | 55 | 10 | 8 | 36 | 87.3 | 78.3 | ECLI | ||
Harbarth [39] | 2001 | Switzerla-nd | PS | clinical | ICU | PCT | 78 | 58 | 4 | 2 | 14 | 97 | 78 | ECLI | |
IL-6 | 78 | 40 | 5 | 20 | 13 | 67 | 72 | ECLI | |||||||
Hausfater [40] | 2002 | France | PS | clinical | ED | PCT | 195 | 42 | 15 | 26 | 112 | 61.8 | 88.2 | 47 | IFA |
Hsu [41] | 2011 | China | PS | clinical, culture+ | RICU | CD64 | 66 | 49 | 1 | 6 | 10 | 89 | 90.9 | 68.3 | FCM |
PCT | 66 | 31 | 0 | 24 | 11 | 56.4 | 100 | 68.3 | IF | ||||||
Ivancević [16] | 2008 | Serbia | PS | clinical,culture+ | ED | PCT | 98 | 42 | 15 | 16 | 25 | 72.4 | 62.5 | 54.7 | IF |
Jämsä [42] | 2015 | Finland | PS | clinical | ICU | CD64 | 42 | 27 | 1 | 0 | 14 | 100 | 93 | 64.4 | FCM |
Jekarl [43] | 2012 | Korea | PS | clinical | ED | PCT | 177 | 58 | 13 | 20 | 86 | 74.4 | 86.7 | 51.5 | ECLI |
IL-6 | 177 | 51 | 17 | 27 | 82 | 65.4 | 82.9 | 51.5 | ECLI | ||||||
Kofoed [44] | 2007 | Denmark | PS | clinical,culture+ | ED/GW | PCT | 151 | 77 | 23 | 19 | 32 | 80.2 | 58.2 | ECLI | |
Latour-Pérez [45] | 2010 | Spain | PS | clinical | ICU | PCT | 114 | 53 | 5 | 19 | 37 | 73.6 | 88.1 | IF | |
Lewis [46] | 2015 | UK | RS | clinical, culture+ | ICU | CD64 | 153 | 43 | 12 | 40 | 58 | 51.8 | 82.6 | FCM | |
Mat-Nor [47] | 2016 | Malaysia | PS | clinical | ICU | PCT | 239 | 93 | 20 | 71 | 55 | 57 | 73 | 47 | IF |
IL-6 | 239 | 82 | 26 | 82 | 49 | 50 | 65 | 47 | EI | ||||||
Meynaar [48] | 2011 | Netherlands | PS | clinical,culture+ | ICU | PCT | 76 | 31 | 9 | 1 | 35 | 97 | 80 | IF | |
IL-6 | 76 | 29 | 26 | 3 | 18 | 91 | 41 | ECLI | |||||||
Mokart [18] | 2005 | France | PS | clinical | ICU | PCT | 50 | 13 | 10 | 3 | 24 | 81 | 72 | ECLI | |
IL-6 | 50 | 14 | 14 | 2 | 20 | 87.5 | 58.8 | EIA | |||||||
Muller [49] | 2000 | Switzerla-nd | PS | clinical | MICU | PCT | 101 | 53 | 3 | 6 | 39 | 89.8 | 92.9 | IFA | |
IL-6 | 101 | 38 | 9 | 21 | 33 | 64.4 | 78.6 | EIA | |||||||
Muzlovic [17] | 2016 | Slovenia | PS | clinical,culture+ | ICU | CD64 | 32 | 25 | 1 | 0 | 6 | 100 | 85.7 | 61.8 | Leuko64 kit |
PCT | 32 | 21 | 0 | 4 | 7 | 81.8 | 100 | 61.8 | IF | ||||||
Papadimitriou [50] | 2015 | Greece | PS | clinical,culture+ | ICU | CD64 | 66 | 24 | 3 | 5 | 34 | 83 | 92 | FCM | |
Righi [51] | 2014 | Italy | PS | clinical,culture+ | ICU | CD64 | 93 | 55 | 1 | 6 | 31 | 90.1 | 96.9 | 58.7 | FCM |
Ruokonen [52] | 2002 | Switzerla-nd | PS | clinical,culture+ | ICU | PCT | 208 | 110 | 24 | 52 | 22 | 67.9 | 47.8 | IF | |
Selberg [53] | 2000 | Germany | PS | clinical,culture+ | ICU | PCT | 33 | 19 | 5 | 3 | 6 | 86 | 54 | 47.9 | IF |
IL-6 | 33 | 19 | 5 | 3 | 6 | 86.4 | 54.5 | 47.9 | EIA | ||||||
Shokouhi [22] a | 2017 | Iran | PS | culture+ | PCT | 192 | 76 | 18 | 16 | 82 | 82.6 | 82 | 43.9 | ELISA | |
Shokouhi [22] b | 2017 | Iran | PS | culture+ | PCT | 184 | 58 | 30 | 26 | 70 | 69.1 | 70 | 73.1 | ELISA | |
Spoto [54] | 2018 | Italy | PS | clinical, culture+ | ICU/GW | PCT | 159 | 60 | 1 | 49 | 49 | 55 | 98 | 70.5 | IF |
Suprin [55] | 2000 | France | PS | clinical. culture+ | ICU | PCT | 95 | 49 | 6 | 26 | 14 | 65.3 | 70 | 57 | IF |
Talebi-Taher [20] | 2014 | Iran | PS | clinical | ED | PCT | 100 | 44 | 14 | 6 | 36 | 88.8 | 71.1 | 76.3 | IF |
Tan [56] | 2016 | Malaysia | PS | clinical,culture+ | ED | CD64 | 51 | 34 | 1 | 8 | 8 | 80.9 | 88.9 | 53.7 | FCM |
Tromp [57] | 2002 | Netherla-nds | PS | culture+ | ED | PCT | 342 | 49 | 120 | 6 | 167 | 89.1 | 58.2 | IF | |
IL-6 | 342 | 34 | 79 | 21 | 208 | 61.8 | 72.5 | EI | |||||||
Tsalik [58] | 2012 | America | PS | clinical,culture+ | ED | PCT | 336 | 168 | 33 | 79 | 56 | 68 | 62.9 | ECLI | |
IL-6 | 336 | 144 | 29 | 103 | 60 | 58.3 | 67.4 | ECLI | |||||||
Wang [59] | 2013 | China | RS | culture+ | ICU | PCT | 586 | 100 | 162 | 20 | 304 | 83.3 | 65.2 | IF | |
Zhang [21] | 2017 | China | PS | clinical | ICU | PCT | 70 | 36 | 6 | 14 | 14 | 72 | 70 | 92.6 | ECLI |
Huang [60] | 2012 | China | PS | clinical | ICU | PCT | 72 | 40 | 3 | 9 | 20 | 82.3 | 84.9 | 66.2 | ELISA |
Lu [19] | 2016 | China | PS | clinical | ICU | CD64 | 420 | 111 | 35 | 19 | 255 | 85.1 | 87.8 | FCM | |
Shao [61] | 2014 | China | PS | clinical | ICU/RD | CD64 | 87 | 63 | 4 | 6 | 14 | 91.3 | 77.8 | 54 | FCM |
Tang [62] | 2017 | China | PS | clinical | ICU | PCT | 221 | 74 | 24 | 15 | 108 | 83.2 | 82.1 | 51.6 | ECLI |
clinical | ICU | IL-6 | 221 | 67 | 77 | 22 | 55 | 75.3 | 41.2 | 51.6 | ECLI | ||||
Wang [63] | 2017 | China | PS | clinical | MD | CD64 | 44 | 23 | 1 | 6 | 14 | 79.5 | 93.3 | 47.1 | FCM |
Xing [64] | 2008 | China | PS | clinical | ED/GW/ICU | PCT | 149 | 84 | 6 | 8 | 51 | 91.3 | 89.5 | 67.3 | IF |
Xu [65] | 2009 | China | PS | clinical | ICU/HD | CD64 | 68 | 57 | 1 | 1 | 9 | 98.3 | 90 | FCM | |
Zhang [66] | 2012 | China | PS | clinical | CD64 | 55 | 30 | 5 | 5 | 15 | 85.7 | 75 | 50.6 | FCM | |
Zhao [67] | 2017 | China | PS | clinical | ICU | PCT | 104 | 67 | 5 | 11 | 21 | 85.9 | 81.8 | 57.9 | IF |
Zhao [68] | 2016 | China | RS | clinical | ED | PCT | 393 | 255 | 10 | 52 | 76 | 83.2 | 88.1 | 42 | ECLI |
IL-6 | 393 | 249 | 14 | 58 | 72 | 81.1 | 83.7 | 42 | EIA | ||||||
Zhao [69] | 2014 | China | PS | clinical | ED | PCT | 652 | 340 | 40 | 112 | 160 | 75.2 | 80 | 72 | ELISA |
IL-6 | 652 | 366 | 78 | 86 | 122 | 81 | 61 | 72 | EIA |
Quality assessment
Heterogeneity test
Pooled effect size result
Publication bias analysis
Heterogeneity analysis
Meta-regression
Sensitivity analysis
Subgroup analysis
category | studies | SEN (95% CI) | SPE (95%CI) | DOR (95% CI) | AUC (95% CI) | SEN-I2 (%) | SPE-I2 (%) |
---|---|---|---|---|---|---|---|
overall | 19 | 0.89 [0.82, 0.93] | 0.88 [0.84,0.92] | 59 [30, 115] | 0.94 [0.91,0.96] | 90.39 | 76.03 |
subgroup analysis based on sample size | |||||||
size≥100 | 8 | 0.82 [0.71,0.89] | 0.87 [0.81,0.91] | 29 [13,64] | 0.91 [0.88,0.93] | 91.53 | 78.72 |
size< 100 | 11 | 0.92 [0.86,0.96] | 0.90 [0.84,0.94] | 105 [44,252] | 0.95 [0.93,0.97] | 62.09 | 13.49 |
subgroup analysis based on country | |||||||
China | 6 | 0.89 [0.84, 0.93] | 0.86 [0.80,0.91] | 53 [30, 92] | 0.92 [0.89, 0.94] | 49.79 | 0.00 |
non-China | 13 | 0.88 [0.79, 0.94] | 0.89 [0.84,0.93] | 64 [24, 168] | 0.94 [0.92, 0.96] | 92.42 | 83.07 |
subgroup analysis based on patient scource | |||||||
ICU | 13 | 0.89 [0.80, 0.94] | 0.90 [0.86,0.93] | 73 [29, 183] | 0.94 [0.92, 0.96] | 93.18 | 78.96 |
non-ICU | 4 | – | – | – | – | – | – |
subgroup analysis based on assay method | |||||||
FMC | 16 | 0.87 [0.82, 0.91] | 0.88 [0.83,0.91] | 50 [27, 96] | 0.94 [0.91, 0.96] | 86.71 | 71.13 |
Leuko64 kit | 3 | – | – | – | – | – | – |
subgroup analysis based on mean age | |||||||
age ≥ 65 y | 2 | – | – | – | – | – | – |
age < 65 y | 11 | 0.89 [0.81, 0.94] | 0.90 [0.86,0.93] | 77 [37, 164] | 0.94 [0.91, 0.96] | 90.02 | 61.12 |
category | studies | SEN (95% CI) | SPE (95%CI) | DOR (95% CI) | AUC (95% CI) | SEN-I2 (%) | SPE-I2 (%) |
---|---|---|---|---|---|---|---|
overall | 43 | 0.82[0.78, 0.85] | 0.78[0.74,0.82] | 16[11, 23] | 0.87[0.83,0.89] | 87.23 | 83.99 |
subgroup analysis based on sample size | |||||||
size≥100 | 27 | 0.82[0.77,0.86] | 0.78[0.73,0.83] | 16[11,25] | 0.87[0.84,0.90] | 90.42 | 88.98 |
size< 100 | 16 | 0.81[0.74,0.86] | 0.78[0.71,0.83] | 15[9.25] | 0.86[0.83,0.89] | 74.74 | 52.18 |
subgroup analysis based on country | |||||||
China | 11 | 0.79[0.74, 0.84] | 0.79[0.73,0.85] | 15[8, 26] | 0.86[0.83, 0.89] | 78.26 | 83.92 |
non-China | 33 | 0.83[0.77, 0.87] | 0.77[0.72,0.82] | 16[11, 25] | 0.87[0.84, 0.89] | 89.29 | 84.48 |
subgroup analysis based on patient scource | |||||||
ICU | 27 | 0.82[0.77, 0.86] | 0.78[0.72,0.82] | 16[10, 24] | 0.86[0.83, 0.89] | 86.20 | 76.10 |
non-ICU | 10 | 0.77[0.72, 0.82] | 0.74[0.64,0.81] | 9[6, 15] | 0.82[0.78, 0.85] | 74.39 | 90.16 |
subgroup analysis based on mean age | |||||||
age ≥ 65 y | 8 | 0.79[0.72, 0.8] | 0.84[0.75,0.90] | 20[12, 34] | 0.88[0.85, 0.91] | 86.45 | 74.39 |
age < 65 y | 20 | 0.80[0.73, 0.86] | 0.81[0.76,0.85] | 17[10, 29] | 0.87[0.84, 0.90] | 84.01 | 73.73 |
category | studies | SEN (95% CI) | SPE (95%CI) | DOR (95% CI) | AUC (95% CI) | SEN-I2 (%) | SPE-I2 (%) |
---|---|---|---|---|---|---|---|
overall | 16 | 0.72[0.65, 0.78] | 0.70[0.62,0.76] | 6[4, 9] | 0.77[0.73,0.80] | 89.27 | 85.07 |
subgroup analysis based on sample size | |||||||
size≥100 | 10 | 0.66[0.58,0.3] | 0.73[0.64,0.80] | 5[3,8] | 0.75[0.71,0.78] | 92.34 | 88.99 |
size< 100 | 6 | 0.83[0.73,0.83] | 0.64[0.51,0.75] | 8[5,14] | 0.81[0.77,0.84] | 52.42 | 62.91 |
subgroup analysis based on country | |||||||
China | 4 | – | – | – | – | – | – |
non-China | 12 | 0.69[0.59, 0.77] | 0.70[0.63,0.77] | 5[3, 8] | 0.75[0.71, 0.79] | 80.86 | 74.47 |
subgroup analysis based on patient scource | |||||||
ICU | 10 | 0.71[0.60, 0.80] | 0.74[0.66,0.81] | 8[4, 14] | 0.80[0.76, 0.83] | 91.94 | 80.76 |
non-ICU | 6 | 0.73[0.64, 0.80] | 0.66[0.54,0.75] | 5[3, 8] | 0.74[0.70, 0.78] | 84.28 | 84.97 |
subgroup analysis based on assay method | |||||||
EIA | 8 | 0.75[0.64, 0.83] | 0.70[0.63,0.76] | 7[4, 12] | 0.77[0.73, 0.81] | 91.31 | 67.89 |
ECLI | 8 | 0.69[0.59, 0.77] | 0.69[0.56,0.80] | 5[3, 9] | 0.75[0.71, 0.78] | 83.28 | 90.73 |
subgroup analysis based on mean age | |||||||
age ≥ 65 y | 1 | – | – | – | – | – | – |
age < 65 y | 9 | 0.71[0.61, 0.79] | 0.74[0.63, 0.82] | 7[4, 13] | 0.78 [0.75,0.82] | 90.46 | 90.59 |