Detection of Inflammatory Biomarkers Among Patients with Sepsis of Gram-Negative Bacteria: A Cross-Sectional Study

Figures & data

Figure 1 Double-disc synergy test 1. Positive test: Enhancement of zone of inhibition from amoxicillin–clavulanic acid towards ceftazidime disc and ceftriaxone disc (black arrow).

Figure 2 Double-disc synergy test 2. Positive test: Enhancement of zone inhibition from ceftazidime–avibactam towards ceftriaxone (black arrow).

Table 1 Socio-Demographic Characteristics Among Patients with Sepsis

Socio Demographic Characteristic		Blood Culture		Total	P-value
		Positive	Negative
		Frequency (%)
Age (years)	>30	11 (14.47)	27 (38.0)	38 (25.85)	0.001*
	30–50	29 (38.16)	28 (39.4)	57 (38.78)
	>50	36 (47.37)	16 (22.5)	52 (35.37)
	Mean ± SD	49.46±18.31	39.08 ±17.68
Sex	Male	45 (59.21)	36 (50.7)	81 (55.10)	0.3001
	Female	31 (40.79)	35 (49.3)	66 (44.90)
Occupation	Housewife	24 (31.58)	31 (43.7)	55 (37.41)	0.028*
	Worker	26 (34.21)	21 (29.6)	47 (31.97)
	Student	9.0 (11.84)	15 (21.1)	24 (16.33)
	Retired	14 (18.42)	3.0 (4.2)	17 (11.56)
	Employer	3.0 (3.95)	1.0 (1.4)	4 (2.72)
Hospitalization duration (weeks)	1	30 (39.47)	16 (22.5)	46 (31.29)	0.081
	2	20 (26.32)	22 (31.0)	42 (28.57)
	>2	26 (34.21)	33 (46.5)	59 (40.14)
Total		76 (51.70)	71 (48.29)	147 (100)

Notes: *Significant difference using Chi-square test, SD ± Standard deviation.

Table 2 Causes of Infection Among Patients with Sepsis

Type of Infection	Causes of Infection	N (%)	Total, N (%)	P-value
Skin and soft tissue infection	Burn	32 (36.8)	62 (42.18)	0.041*
	Postoperative wound	16 (43.2)
	Abscess	14 (60.9)
Respiratory tract infection	COVID-19	25 (28.7)	33 (22.45)
	Aspiration pneumonia	8 (21.6)
Device-related infection	Mechanical ventilation	18 (20.7)	32 (21.77)
	Endotracheal tube	5 (13.5)
	Catheters & C.V line	9 (39.1)
Bone and joint infection	Road traffic accident	9 (10.3)	14 (9.52)
	Falling from height	5 (13.5)
Chronic kidney disease	Dialysis	2 (2.3)	4 (2.72)
	Renal transplantation	2 (5.4)
Intra-abdominal infection	Colostomy	1 (1.1)	2 (1.36)
	Acute abdomen	1 (2.7)
Total			147 (100)

Notes: *Significant difference using Chi-square test.

Abbreviations: C.V line, central venous line; COVID-19, coronavirus disease-19.

Table 3 Isolated Gram-Negative Bacteria from Patients with Sepsis

Types of Gram-Negative Bacteria		Blood Culture Positive	Other Sources	Total	P-value
		N (%)
Enterobacteriaceae	Escherichia coli	25 (51.02)	15 (41.67)	40 (47.06)	0.412
	Klebsiella pneumonia	17 (34.69)	18 (50)	35 (41.18)
	Proteus mirabilis	3 (6.12)	1 (2.78)	4 (4.71)
	Raoultella ornithinolytica	1 (2.04)	2 (5.56)	3 (3.53)
	Enterobacter cloacae	2 (4.08)	0 (0.0)	2 (2.35)
	Salmonella	1 (2.04)	0 (0.0)	1 (1.18)
	Total	49 (30.24)	36 (22.22)	85 (100.0)
Non-fermenter	Pseudomonas aeruginosa	21 (60)	19 (45.24)	40 (51.95)	0.202
	Acinetobacter baumannii	12 (34.29)	21 (50.0)	33 (42.86)
	Burkholderia cepacia	0 (0.0)	2 (4.76)	2 (2.6)
	Alcaligenes faecalis	1(2.86)	0 (0.0)	1 (1.3)
	Stenotrophomonas maltophilia	1 (2.86)	0 (0.0)	1 (1.3)
	Total	35 (21.6)	42 (25.92)	77 (100.0)

Table 4 Number and Percentage of Phenotypic Tests for ESBL Detection

Gram-Negative Bacteria		Total	Screen Tests			Confirmatory Test (CD)	P-value
			Screen 1	Screen 2	Screen 3
		N (%)
Enterobacteriaceae	K. pneumonia	35(41.18)	32(46.38)	12(54.55)	31(47.69)	17(50)	0.436
	E. coli	40(47.06)	29(42.03)	8.0(36.36)	27(41.54)	14(41.18)
	Proteus mirabilis	4.0(4.71)	4.0(5.8)	2.0(9.09)	4.0(6.15)	1.0(2.94)
	Raoultella ornithinolytica	3.0(3.53)	3.0(4.35)	0.0(0.0)	3.0(4.62)	2.0(5.88)
	Salmonella	1.0(1.18)	0.0(0.0)	0.0(0.0)	0.0(0.0)	0.0(0.0)
	Enterobacter cloacae	2.0(2.35)	1.0(1.45)	0.0(0.0)	0.0(0.0)	0.0(0.0)
	Total	85(52.5)	69(42.6)	22(13.6)	65(40.1)	34(21)
Non-fermenter	P. aeruginosa	40(51.95)	29(51.79)	3.0(27.27)	25(52.08)	17(51.52)	0.751
	Acinetobacter baumannii	33(42.86)	24(42.86)	8.0(72.73)	21(43.75)	14(42.42)
	Stenotrophomonas maltophilia	1.0(1.3)	0.0(0.0)	0.0(0.0)	0.0(0.0)	0.0(0.0)
	Alcaligenes faecalis	1.0(1.3)	1.0(1.79)	0.0(0.0)	1.0(2.08)	0.0(0.0)
	Burkholderia cepacia	2.0(2.6)	2.0(3.57)	0.0(0.0)	1.0(2.08)	2.0(6.06)
	Total	77(47.5)	56(34.6)	11(6.8)	48(29.6)	33(20.4)

Notes: Screen 1: Antibiotic profile, Screen 2: DDST1 (double-disc synergy test 1 by amoxicillin–clavulanic acid), Screen 3: DDST2 (double-disc synergy test2 by ceftazidime–avibactam), CD: combined disc test by (ceftazidime/ceftazidime–clavulanic acid).

Table 5 Sensitivity and Specificity of Inflammatory and Coagulation Biomarkers Among Patients with Sepsis

Inflammatory and Coagulation Markers		Blood Culture				Sensitivity%	Specificity%	AUC	Lower±Upper	P-value
		Negative		Positive
		Fr	%	Fr	%
PTX-3	Negative	65	91.5	59	77.63	91.5	22.4	0.571	0.478±0.664	0.02
	Positive	6	8.5	17	22.37
PCT	Negative	18	25.4	9	11.84	25.4	88.2	0.573	0.48±0.667	0.035
	Positive	53	74.6	67	88.16
ADM	Negative	8	11.3	12	15.79	11.3	84.2	0.476	0.383±0.57	0.424
	Positive	63	88.7	64	84.21
LBP	Negative	70	98.6	67	88.16	98.6	11.8	0.553	0.46±0.646	0.012
	Positive	1	1.4	9	11.84
IL-17A	Negative	70	98.6	75	98.68	98.6	01.3	0.5	0.406±0.594	0.861
	Positive	1	1.4	1	1.32
LDH	Negative	37	52.1	34	44.74	52.1	55.3	0.541	0.447±0.634	0.371
	Positive	34	47.9	42	55.26
CRP	Negative	6	8.5	1	1.3	0.08	0.99	0.304	0.131±0.477	0.042
	Positive	65	91.5	75	98.7
PT	Negative	57	80.3	49	64.47	80.3	35.5	0.581	0.489±0.674	0.033
	Positive	14	19.7	27	35.53
PTT	Negative	63	88.7	67	88.16	88.7	11.8	0.504	0.41±0.598	0.913
	Positive	8	11.3	9	11.84
INR	Negative	55	77.5	60	78.95	77.5	21.1	0.494	0.40±0.588	0.828
	Positive	16	22.5	16	21.05
WBC	Low	2	2.8	16	21.05	0.028	0.211	0.459	0.365±0.553	0.001*
	Normal	28	39.4	17	22.37	0.394	0224
	High	41	57.7	43	56.58	0.577	0.566
Total		71	100	76	100

Notes: *Significant difference using Chi-square test. The cut-off value of PCT: 194.350–276.252 pg/mL, PTX-3: 1111–2987ng/mL, ADM: 3.888–6.416 ng/L, IL_17A: 46.507–83.576 ng/L, LBP: 4.467–12.715 ng/mL, LDH: 135–225U/L, CRP: 0–5 mg/L.

Abbreviations: Fr, frequency; AUC, area under curve; PTX-3, pentraxin-3; PCT, procalcitonin; ADM, adrenomedullin; LBP, lipopolysaccharide binding protein; IL-17A, interleukin-17A; LDH, lactate dehydrogenase; CRP, C-creative protein; PT, prothrombin time; PTT, partial thromboplastin time; WBC, white blood cell; INR, international normalized ratio.

Table 6 Comparison of Mean Score of Different Biomarkers with Blood Culture Results Among Patients with Sepsis

Inflammatory and Coagulation Biomarkers	Blood Culture				Significant Test
	Positive		Negative		t-test	P-value
	Mean	S.D	Mean	SD
PTX-3	2722.8003	3499.83526	1822.1732	787.89482	2.118	0.036
PCT	1137.0573	622.74616	877.7539	739.97145	2.304	0.023
ADM	175.4357	200.36036	184.2598	183.78401	−0.278	0.782
LBP	0.2633	8.44317	−2.0932	4.06451	2.132	0.035
IL_17A	16.6605	28.55305	14.2690	20.23767	0.582	0.561
LDH	334.0658	327.73072	365.6338	563.56808	−0.418	0.676
CRP	358.4226	1805.86456	592.6276	2619.33682	−0.635	0.527
PT	15.9142	2.99991	14.9615	1.97646	2.257	0.026
PTT	31.4434	9.06557	32.1310	9.40893	−0.451	0.853
INR	1.5479	1.34983	1.5145	1.40893	0.147	0.884
WBC	11.7125	7.41576	14.3686	7.73359	−2.126	0.035

Abbreviations: SD, standard deviation; PTX-3, pentraxin-3; PCT, procalcitonin; ADM, adrenomedullin; LBP, lipopolysaccharide binding protein; IL-17A, interleukin-17A; LDH, lactate dehydrogenase; CRP, C-creative protein; PT, prothrombin time; PTT, partial thromboplastin time; WBC, white blood cell; INR, international normalized ratio.

Figure 3 ROC curve of biomarkers.