Performance of Procalcitonin to Distinguish Fungal from Bacterial Infections in Patients with Systemic Lupus Erythematosus

Figures & data

Table 1 Baseline Characteristics of Gram-Positive Bacterial, Gram-Negative Bacterial and Fungal Infection Groups

Variable^†	Bacterial Group (n=43)		Fungal Group (n=26)	P-value*
	Gram-Positive Bacterial (n=22)	Gram-Negative Bacterial (n=21)
Female, n (%)	20 (90.9%)	16 (76.2%)	24 (92.31%)	0.305
Age (year), mean (SD)	43.32 (16.81)	44.38 (14.72)	47.73 (14.50)	0.307
Diabetes mellitus, n (%)	2 (9.1%)	6 (28.6%)	6 (23.08%)	0.766
Disease activity and organ involvement
SLEDAI score, mean (SD)	11.32 (6.31)	9.55 (5.58)	7.54 (4.71)	0.037
Disease course (year), median (IQR)	6.50 (0.7–16.8)	4.00 (0.30–13.0)	4.00 (0.4–9.5)	0.406
Lupus nephritis, n (%)	15 (68.2%)	11 (52.4%)	17 (65.38%)	0.683
Interstitial lung disease, n (%)	1 (4.6%)	3 (14.3%)	4 (15.38%)	0.444
Infection time course (day), median (IQR)	6.50 (3.3–10.0)	14.0 (6.0–15.0)	10.0 (5.3–15.0)	0.559
Laboratory results
ESR (mm/h), median (IQR)	37 (17–61)	53 (28–70)	44 (16–80)	0.906
Albumin (g/L), mean (SD)	24.2 (6.5)	27.1 (5.9)	28.2 (7.3)	0.121
Creatinine (μmol/L), median (IQR)	86 (59–182)	82 (54–175)	69 (55–106)	0.165
Urea nitrogen (mmol/L), median (IQR)	10.5 (7.0–16.6)	9.0 (6.6–23.8)	7.2 (5.6–15.1)	0.133
WBC (*10^9/L), mean (SD)	7.99 (4.02)	8.80 (5.20)	7.93 (3.60)	0.666
Platelet count (*10^9/L), median (IQR)	104 (56 −178)	105 (41–147)	134 (69–204)	0.139
Lactate (mmol/L), mean (SD)	2.09 (1.44)	2.63 (2.03)	2.09 (0.89)	0.488
CRP (mg/L), median (IQR)	38 (9–117)	49 (6–115)	23 (5–56)	0.122
Procalcitonin (ng/mL), median (IQR)	1.43 (0.14–8.26)	0.57 (0.20–2.57)	0.22 (0.09–0.44)	0.016
qSOFA score, n (%)				0.581
score = 0	16 (72.7%)	13 (61.9%)	17 (65.4%)
score = 1	5 (22.7%)	5 (23.8%)	8 (30.8%)
score = 2	1 (4.6%)	3 (14.3%)	1 (3.9%)
SOFA score, mean (SD)	4.94 (2.15)	4.87 (2.67)	5.32 (2.31)	0.451
Sepsis, n (%)	17 (77.3%)	15 (71.4%)	21 (80.8%)	0.545
Mortality, n (%)	9 (40.9%)	7 (33.3%)	6 (23.1%)	0.222

Notes: *P-values were calculated to compare the differences between the bacterial and fungal groups. Comparison of continuous variables using student-t test and Mann–Whitney nonparametric test. Categorical variables were compared using chi-squared test or Fisher exact test. ^†Data are presented as median (interquartile range) or mean (standard deviation).

Abbreviations: SLEDAI, systemic lupus erythematosus disease activity index; ESR, erythrocyte sedimentation rate; WBC, white blood cell; CRP, C-reactive protein; SOFA, sequential organ failure assessment; qSOFA, quick sequential organ failure assessment.

Figure 1 Study population flow diagram.

Abbreviations: SLE, Systemic Lupus Erythematosus; PCT, procalcitonin.

Figure 2 PCT concentrations in patients with different groups.

Notes: (A) The box-plots and Scatter-plots represent serum concentrations of PCT (procalcitonin) in the fungal, bacterial, gram-positive bacterial, and gram-negative bacterial infection patients. *The p-value was calculated using Mann–Whitney nonparametric test to verify differences in PCT between the fungal and other groups. (B) The box-plots and Scatter-plots represent serum concentrations of PCT in the respiratory, abdominal/urinary, skin/soft-tissue and other groups. ^#The p-value was calculated by Kruskal–Wallis nonparametric test.

Table 2 Results of the ROC Analysis for Predicting Fungal Infection

Variable	AUROC (95% CI)	P-value	Adjusted AUROC (95% CI)*	Cut-Off^†	Spec.	Sens.	PPV	NPV	LR+	LR-
PCT	0.674 (0.545–0.803)	0.016	0.731 (0.602–0.859)	0.49	0.581	0.769	0.526	0.807	1.838	0.397
CRP	0.612 (0.476–0.748)	0.122	0.716 (0.580–0.852)	109	0.279	0.923	0.436	0.857	1.280	0.276
ESR	0.509 (0.363–0.654)	0.906	0.583 (0.438–0.729)	15	0.884	0.269	0.583	0.667	2.315	0.827
WBC	0.514 (0.373–0.655)	0.843	0.581 (0.440–0.722)	7.03	0.605	0.500	0.433	0.667	1.265	0.827
PCT+CRP	0.646 (0.514–0.777)	0.044	/	/	0.372	0.923	0.471	0.889	1.470	0.207
PCT+ESR	0.688 (0.559–0.817)	0.009	/	/	0.884	0.462	0.706	0.731	3.969	0.609
PCT+WBC	0.677 (0.548–0.846)	0.014	/	/	0.512	0.846	0.552	0.846	1.733	0.301

Notes: *Adjusted AUROC was adjusted for infection site and SLEDAI score based on 1000 bootstrap calculation, p values of Variable between AUROC and Adjusted AUROC were all less than 0.001. ^†Evaluated at Youden’s index maximum.

Abbreviations: PCT, procalcitonin; CRP, C-reactive protein; WBC, white blood cell; ESR, erythrocyte sedimentation rate; AUROC, area under the receiver operating characteristic curves; Sens., sensitivity; Spec., specificity; PPV, positive predictive value; NPV, negative predictive value; LR+, positive likelihood ratio; LR-, negative likelihood ratio.

Figure 3 ROC curve and AUROC of fungal infection by PCT and other biomarkers.

Notes: ROC curve shows the sensitivity and specificity for various cutoff values on the PCT, CRP, WBC, ESR and the combination of PCT and ESR. The discriminative ability of the biomarker for the diagnose of fungal infection was expressed as a AUROC. *The AUROC of PCT showed differences compared to CRP, WBC, or ESR (p < 0.001). ^#The AUROC of PCT+ESR showed no significant differences, as compared to PCT alone (p = 0.693).

Abbreviations: ROC curve, receiver operator characteristic curve; AUROC, area under the receiver operating characteristic curve; PCT, procalcitonin; CRP, C-reactive protein; WBC, white blood cell; ESR, erythrocyte sedimentation rate.