The value of serum procalcitonin in differential diagnosis of invasive candidiasis: a meta analysis_West China Medical Journal

Authors：

DING Xiaojuan , WANG Dan , ZHANG Yaozhi ,  HE Jianqing

Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding?author：

HE Jianqing, Email: 18980602293@qq.com

Keywords：

Procalcitonin; invasive candidiasis; diagnosis; meta analysis

DOI：

10.7507/1002-0179.202011100

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Objective To explore the value of procalcitonin (PCT) in differential diagnosis of invasive candidiasis. Methods PubMed, Embase, Medline, Cochrane Library, China National Knowledge Infrastructure and Wanfang Data were searched for articles published from the dates of establishment of databases to January 2021. A prospective and retrospective cohort studies and a case-control studies of PCT in differential diagnosis of invasive candidiasis were collected. RevMan 5.3 software QUADAS-2 risk assessment tool was used to evaluate the quality of the literature. Meta-Disc 1.4 software was used to determine whether the original data had threshold effect and heterogeneity. Stata 14.0 software was used to analyze meta, judge publication bias and draw Deeks diagram. Results A total of 9 articles and 943 patients were included. There were 259 cases in candida group and 684 cases in control group. The study showed that the total sensitivity was 0.86 [95% confidence interval (CI) (0.80, 0.91)], specificity was 0.78 [95%CI (0.70, 0.84)], positive likelihood ratio was 3.92 [95%CI (2.77, 5.55)], negative likelihood ratio was 0.18 [95%CI (0.12, 0.27)], the area under receiver operator characteristic curve was 0.90 [95%CI (0.87, 0.92)], diagnostic odds ratio was 19.75 [95%CI (10.71, 36.43)]. The results of heterogeneity test showed that there was heterogeneity caused by non-threshold effect between studies. The results of subgroup analysis showed that the heterogeneity I² value of PCT<2 ng/mL subgroup decreased significantly, and the result was more stable, with sensitivity. The results show that sensitivity was 0.86 [95%CI (0.79, 0.91)], specificity was 0.72 [95%CI (0.63, 0.80)], the area under receiver operator characteristic curve was 0.87 [95%CI (0.83, 0.89)]. Conclusions Serum PCT in the differential diagnosis of invasive candidiasis has certain accuracy and negative predictive value. However, PCT is only an auxiliary test. The differential diagnosis of invasive candidiasis should be combined with clinical features and other diagnostic indexes.

Citation： DING Xiaojuan, WANG Dan, ZHANG Yaozhi, HE Jianqing. The value of serum procalcitonin in differential diagnosis of invasive candidiasis: a meta analysis. West China Medical Journal, 2022, 37(7): 1050-1058. doi: 10.7507/1002-0179.202011100 Copy

1.	Ascioglu S, Rex JH, de Pauw B, et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis, 2002, 34(1): 7-14.
2.	Bassetti M, Garnacho-Montero J, Calandra T, et al. Intensive care medicine research agenda on invasive fungal infection in critically ill patients. Intensive Care Med, 2017, 43(9): 1225-1238.
3.	Puig‐Asensio M, Padilla B, Garnacho‐Montero J, et al. Epidemiology and predictive factors for early and late mortality in Candida bloodstream infections: a population-based surveillance in Spain. Clin Microbiol Infect, 2014, 20(4): O245-O254.
4.	Kett DH, Azoulay E, Echeverria PM, et al. Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study. Crit Care Med, 2011, 39(4): 665-670.
5.	Hoenigl M, Zollner-Schwetz I, Sill H, et al. Epidemiology of invasive fungal infections and rationale for antifungal therapy in patients with haematological malignancies. Mycoses, 2011, 54(5): 454-459.
6.	Bassetti M, Mikulska M, Viscoli C. Bench-to-bedside review: therapeutic management of invasive candidiasis in the intensive care unit. Crit Care, 2010, 14(6): 244.
7.	Dandona P, Nix D, Wilson MF, et al. Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrinol Metab, 1994, 79(6): 1605-1608.
8.	Bassetti M, Russo A, Righi E, et al. Role of procalcitonin in bacteremic patients and its potential use in predicting infection etiology. Expert Rev Anti Infect Ther, 2019, 17(2): 99-105.
9.	Lam SW, Bauer SR, Fowler R, et al. Systematic review and meta-analysis of procalcitonin-guidance versus usual care for antimicrobial management in critically ill patients: focus on subgroups based on antibiotic initiation, cessation, or mixed strategies. Crit Care Med, 2018, 46(5): 684-690.
10.	Wirz Y, Meier MA, Bouadma L, et al. Effect of procalcitonin-guided antibiotic treatment on clinical outcomes in intensive care unit patients with infection and sepsis patients: a patient-level meta-analysis of randomized trials. Crit Care, 2018, 22(1): 191.
11.	Raineri SM, Cortegiani A, Vitale F, et al. Procalcitonin for the diagnosis of invasive candidiasis: what is the evidence?. J Intensive Care, 2017, 5: 58.
12.	Dou YH, Du JK, Liu HL, et al. The role of procalcitonin in the identification of invasive fungal infection-a systemic review and meta-analysis. Diagn Microbiol Infect Dis, 2013, 76(4): 464-469.
13.	Whiting PF, Rutjes AW, Westwood ME, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med, 2011, 155(8): 529-536.
14.	Fagan TJ. Letter: nomogram for Bayes theorem. N Engl J Med, 1975, 293(5): 257.
15.	Hellmich M, Lehmacher W. A ruler for interpreting diagnostic test results. Methods Inf Med, 2005, 44(1): 124-126.
16.	Goldberg KM, Iglewicz B. Bivariate extensions of the boxplot. Technometrics, 1992, 34(3): 307-320.
17.	Distefano G, Curreri R, Betta P, et al. Procalcitonin serum levels in perinatal bacterial and fungal infection of preterm infants. Acta Paediatr, 2004, 93(2): 216-219.
18.	Charles PE, Dalle F, Aho S, et al. Serum procalcitonin measurement contribution to the early diagnosis of candidemia in critically ill patients. Intensive Care Med, 2006, 32(10): 1577-1583.
19.	Charles PE, Castro C, Ruiz-Santana S, et al. Serum procalcitonin levels in critically ill patients colonized with Candida spp: new clues for the early recognition of invasive candidiasis?. Intensive Care Med, 2009, 35(12): 2146-2150.
20.	Martini A, Gottin L, Menestrina N, et al. Procalcitonin levels in surgical patients at risk of candidemia. J Infect, 2010, 60(6): 425-430.
21.	Montagna MT, Coretti C, Rella A, et al. The role of procalcitonin in neonatal intensive care unit patients with candidemia. Folia Microbiol (Praha), 2013, 58(1): 27-31.
22.	Cortegiani A, Russotto V, Montalto F, et al. Procalcitonin as a marker of Candida species detection by blood culture and polymerase chain reaction in septic patients. BMC Anesthesiol, 2014, 14: 9.
23.	Miglietta F, Faneschi ML, Lobreglio G, et al. Procalcitonin, C-reactive protein and serum lactate dehydrogenase in the diagnosis of bacterial sepsis, SIRS and systemic candidiasis. Infez Med, 2015, 23(3): 230-237.
24.	Giacobbe DR, Mikulska M, Tumbarello M, et al. Combined use of serum (1, 3)-β-D-glucan and procalcitonin for the early differential diagnosis between candidaemia and bacteraemia in intensive care units. Crit Care, 2017, 21(1): 176.
25.	Pieralli F, Corbo L, Torrigiani A, et al. Usefulness of procalcitonin in differentiating Candida and bacterial blood stream infections in critically ill septic patients outside the intensive care unit. Intern Emerg Med, 2017, 12(5): 629-635.
26.	Garey KW, Rege M, Pai MP, et al. Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis, 2006, 43(1): 25-31.
27.	奚晶晶, 王紅, 楊鈞. 降鈣素原在膿毒癥患者中的動態變化及中藥干預的影響. 中國中西醫結合急救雜志, 2007, 14(6): 327-329.
28.	曾文美, 毛璞, 黃勇波, 等. 膿毒癥預后影響因素分析及預后價值評估. 中國中西醫結合急救雜志, 2015, 22(2): 118-123.
29.	林詩杰, 劉升明. 肺炎合并膿毒癥患者檢測血清降鈣素原、超敏 C 反應蛋白的臨床意義. 實用醫學雜志, 2011, 27(24): 4440-4442.
30.	周振軍, 孫新林, 文平, 等. 探討降鈣素原在顱腦手術術后顱內感染的診斷價值. 中華神經醫學雜志, 2013, 12(6): 621-624.
31.	Nijsten MW, Olinga P, The TH, et al. Procalcitonin behaves as a fast responding acute phase protein in vivo and in vitro. Crit Care Med, 2000, 28(2): 458-461.
32.	Tavares E, Maldonado R, Ojeda ML, et al. Circulating inflammatory mediators during start of fever in differential diagnosis of gram-negative and gram-positive infections in leukopenic rats. Clin Diagn Lab Immunol, 2005, 12(9): 1085-1093.
33.	Linscheid P, Seboek D, Schaer DJ, et al. Expression and secretion of procalcitonin and calcitonin gene-related peptide by adherent monocytes and by macrophage-activated adipocytes. Crit Care Med, 2004, 32(8): 1715-1721.
34.	Mengoli C, Cruciani M, Barnes RA, et al. Use of PCR for diagnosis of invasive aspergillosis: systematic review and meta-analysis. Lancet Infect Dis, 2009, 9(2): 89-96.
35.	Whiteley R. Screening and likelihood ratio infographic. Br J Sports Med, 2016, 50(14): 837-838.

1. Ascioglu S, Rex JH, de Pauw B, et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis, 2002, 34(1): 7-14.
2. Bassetti M, Garnacho-Montero J, Calandra T, et al. Intensive care medicine research agenda on invasive fungal infection in critically ill patients. Intensive Care Med, 2017, 43(9): 1225-1238.
3. Puig‐Asensio M, Padilla B, Garnacho‐Montero J, et al. Epidemiology and predictive factors for early and late mortality in Candida bloodstream infections: a population-based surveillance in Spain. Clin Microbiol Infect, 2014, 20(4): O245-O254.
4. Kett DH, Azoulay E, Echeverria PM, et al. Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study. Crit Care Med, 2011, 39(4): 665-670.
5. Hoenigl M, Zollner-Schwetz I, Sill H, et al. Epidemiology of invasive fungal infections and rationale for antifungal therapy in patients with haematological malignancies. Mycoses, 2011, 54(5): 454-459.
6. Bassetti M, Mikulska M, Viscoli C. Bench-to-bedside review: therapeutic management of invasive candidiasis in the intensive care unit. Crit Care, 2010, 14(6): 244.
7. Dandona P, Nix D, Wilson MF, et al. Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrinol Metab, 1994, 79(6): 1605-1608.
8. Bassetti M, Russo A, Righi E, et al. Role of procalcitonin in bacteremic patients and its potential use in predicting infection etiology. Expert Rev Anti Infect Ther, 2019, 17(2): 99-105.
9. Lam SW, Bauer SR, Fowler R, et al. Systematic review and meta-analysis of procalcitonin-guidance versus usual care for antimicrobial management in critically ill patients: focus on subgroups based on antibiotic initiation, cessation, or mixed strategies. Crit Care Med, 2018, 46(5): 684-690.
10. Wirz Y, Meier MA, Bouadma L, et al. Effect of procalcitonin-guided antibiotic treatment on clinical outcomes in intensive care unit patients with infection and sepsis patients: a patient-level meta-analysis of randomized trials. Crit Care, 2018, 22(1): 191.
11. Raineri SM, Cortegiani A, Vitale F, et al. Procalcitonin for the diagnosis of invasive candidiasis: what is the evidence?. J Intensive Care, 2017, 5: 58.
12. Dou YH, Du JK, Liu HL, et al. The role of procalcitonin in the identification of invasive fungal infection-a systemic review and meta-analysis. Diagn Microbiol Infect Dis, 2013, 76(4): 464-469.
13. Whiting PF, Rutjes AW, Westwood ME, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med, 2011, 155(8): 529-536.
14. Fagan TJ. Letter: nomogram for Bayes theorem. N Engl J Med, 1975, 293(5): 257.
15. Hellmich M, Lehmacher W. A ruler for interpreting diagnostic test results. Methods Inf Med, 2005, 44(1): 124-126.
16. Goldberg KM, Iglewicz B. Bivariate extensions of the boxplot. Technometrics, 1992, 34(3): 307-320.
17. Distefano G, Curreri R, Betta P, et al. Procalcitonin serum levels in perinatal bacterial and fungal infection of preterm infants. Acta Paediatr, 2004, 93(2): 216-219.
18. Charles PE, Dalle F, Aho S, et al. Serum procalcitonin measurement contribution to the early diagnosis of candidemia in critically ill patients. Intensive Care Med, 2006, 32(10): 1577-1583.
19. Charles PE, Castro C, Ruiz-Santana S, et al. Serum procalcitonin levels in critically ill patients colonized with Candida spp: new clues for the early recognition of invasive candidiasis?. Intensive Care Med, 2009, 35(12): 2146-2150.
20. Martini A, Gottin L, Menestrina N, et al. Procalcitonin levels in surgical patients at risk of candidemia. J Infect, 2010, 60(6): 425-430.
21. Montagna MT, Coretti C, Rella A, et al. The role of procalcitonin in neonatal intensive care unit patients with candidemia. Folia Microbiol (Praha), 2013, 58(1): 27-31.
22. Cortegiani A, Russotto V, Montalto F, et al. Procalcitonin as a marker of Candida species detection by blood culture and polymerase chain reaction in septic patients. BMC Anesthesiol, 2014, 14: 9.
23. Miglietta F, Faneschi ML, Lobreglio G, et al. Procalcitonin, C-reactive protein and serum lactate dehydrogenase in the diagnosis of bacterial sepsis, SIRS and systemic candidiasis. Infez Med, 2015, 23(3): 230-237.
24. Giacobbe DR, Mikulska M, Tumbarello M, et al. Combined use of serum (1, 3)-β-D-glucan and procalcitonin for the early differential diagnosis between candidaemia and bacteraemia in intensive care units. Crit Care, 2017, 21(1): 176.
25. Pieralli F, Corbo L, Torrigiani A, et al. Usefulness of procalcitonin in differentiating Candida and bacterial blood stream infections in critically ill septic patients outside the intensive care unit. Intern Emerg Med, 2017, 12(5): 629-635.
26. Garey KW, Rege M, Pai MP, et al. Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis, 2006, 43(1): 25-31.
27. 奚晶晶, 王紅, 楊鈞. 降鈣素原在膿毒癥患者中的動態變化及中藥干預的影響. 中國中西醫結合急救雜志, 2007, 14(6): 327-329.
28. 曾文美, 毛璞, 黃勇波, 等. 膿毒癥預后影響因素分析及預后價值評估. 中國中西醫結合急救雜志, 2015, 22(2): 118-123.
29. 林詩杰, 劉升明. 肺炎合并膿毒癥患者檢測血清降鈣素原、超敏 C 反應蛋白的臨床意義. 實用醫學雜志, 2011, 27(24): 4440-4442.
30. 周振軍, 孫新林, 文平, 等. 探討降鈣素原在顱腦手術術后顱內感染的診斷價值. 中華神經醫學雜志, 2013, 12(6): 621-624.
31. Nijsten MW, Olinga P, The TH, et al. Procalcitonin behaves as a fast responding acute phase protein in vivo and in vitro. Crit Care Med, 2000, 28(2): 458-461.
32. Tavares E, Maldonado R, Ojeda ML, et al. Circulating inflammatory mediators during start of fever in differential diagnosis of gram-negative and gram-positive infections in leukopenic rats. Clin Diagn Lab Immunol, 2005, 12(9): 1085-1093.
33. Linscheid P, Seboek D, Schaer DJ, et al. Expression and secretion of procalcitonin and calcitonin gene-related peptide by adherent monocytes and by macrophage-activated adipocytes. Crit Care Med, 2004, 32(8): 1715-1721.
34. Mengoli C, Cruciani M, Barnes RA, et al. Use of PCR for diagnosis of invasive aspergillosis: systematic review and meta-analysis. Lancet Infect Dis, 2009, 9(2): 89-96.
35. Whiteley R. Screening and likelihood ratio infographic. Br J Sports Med, 2016, 50(14): 837-838.

West China Medical Journal

The value of serum procalcitonin in differential diagnosis of invasive candidiasis: a meta analysis

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