Determinants of infection for antibiotic initiation at pediatric emergency admission: A prospective observational study

Table 1 Baseline characteristics of participants

Variables	No infection (n = 348)	Suspected infection (n = 209)	Probable infection (n = 114)	Confirmed infection (n = 131)	P value
Sex					0.177
Male	197 (24.56)	125 (15.59)	58 (7.23)	84 (10.47)
Female	151 (18.83)	84 (10.47)	56 (6.98)	47 (5.86)
Age					0.376
3 months-1 year	133 (16.58)	72 (8.98)	38 (4.74)	43 (5.36)
> 1 year-4 years	74 (9.23)	36 (4.49)	18 (2.24)	35 (4.36)
> 4 years-9 years	75 (9.35)	54 (6.73)	30 (3.74)	27 (3.37)
> 9 years-14 years	66 (8.23)	47 (5.86)	28 (3.49)	26 (3.24)
Fever					< 0.001
Absent	222 (27.68)	44 (5.49)	38 (5.74)	49 (6.12)
Present	126 (15.71)	165(20.57)	76 (9.48)	82 (10.22)
Cough					0.032
Absent	217 (27.06)	126 (15.71)	69 (8.60)	98 (12.22)
Present	131 (16.33)	83 (10.35)	45 (5.61)	33 (4.11)
Features of capillary leak					< 0.001
Absent	328 (40.90)	182 (22.69)	93 (11.60)	97 (12.09)
Present	20 (2.49)	27 (3.37)	21 (2.62)	34 (4.24)
Fast breathing/dyspnea					0.017
Absent	219 (27.31)	145 (18.08)	59 (7.36)	86 (10.72)
Present	129 (16.08)	64 (7.98)	55 (6.86)	45 (5.61)
Lower urinary tract symptoms					0.001
Absent	348 (43.39)	209 (26.06)	114 (14.21)	128 (15.96)
Present	0 (0)	0 (0)	0 (0)	3 (0.37)
Seizures					0.045
Absent	302 (37.66)	176 (21.94)	107 (13.30)	108 (13.47)
Present	46 (5.74)	33 (4.12)	7 (0.87)	23 (2.87)
Altered sensorium					0.018
Absent	308 (38.4)	169 (21.07)	98 (12.22)	103 (12.84)
Present	40 (4.99)	40 (4.99)	16 (2.00)	28 (3.49)
Earache/ear discharge					0.029
Absent	348 (43.39)	206 (25.69)	114 (14.21)	128 (15.96)
Present	0 (0)	3 (0.37)	0 (0)	3 (0.37)
Chest pain					0.002
Absent	339 (42.27)	204 (25.44)	104 (12.97)	130 (16.21)
Present	9 (1.12)	5 (0.62)	10 (1.25)	1 (0.12)
Oliguria					0.001
Absent	341 (42.52)	205 (25.56)	110 (13.71)	119 (14.84)
Present	7 (0.87)	4 (0.50)	4 (0.50)	12 (1.50)
Temperature					< 0.001
36 °C-38 °C	286 (35.66)	133 (16.58)	80 (9.98)	95 (11.85)
> 38 °C	42 (5.24)	60 (7.48)	32 (3.99)	31 (3.87)
< 36 °C	20 (2.49)	16 (2.00)	2 (0.25)	5 (0.62)
Pallor					< 0.001
Absent	308 (38.40)	161 (20.07)	90 (11.22)	83 (10.35)
Present	40 (4.99)	48 (5.99)	24 (2.99)	48 (5.99)
Air entry					< 0.001
Normal	323 (40.27)	186 (23.19)	84 (10.47)	117 (14.59)
Abnormal	25 (3.12)	23 (2.87)	30 (3.74)	14 (1.75)
Murmur					< 0.001
Absent	316 (39.40)	165 (20.57)	95 (11.85)	124 (15.46)
Present	32 (3.99)	44 (5.49)	19 (2.37)	7 (0.87)
Peripheries					0.025
Warm	334 (41.65)	187 (23.32)	107 (13.34)	123 (15.34)
Cold	14 (1.75)	22 (2.74)	7 (0.87)	8 (1.00)
Peripheral pulses					0.002
Normal	341 (42.52)	190 (23.69)	107 (13.34)	121 (15.09)
Abnormal	7 (0.87)	19 (2.37)	7 (0.87)	10 (1.25)
Organomegaly					< 0.001
Absent	302 (37.66)	159 (19.83)	81 (10.10)	89 (11.10)
Present	46 (5.74)	50 (6.23)	33 (4.11)	42 (5.24)
Abdominal tenderness					0.005
Absent	347 (43.27)	199 (24.81)	111 (13.84)	127 (15.84)
Present	1 (0.12)	10 (1.25)	3 (0.37)	4 (0.50)
GCS					0.001
Normal	258 (32.17)	124 (15.46)	75 (9.35)	77 (9.60)
Abnormal (< 15)	90 (11.22)	85 (10.60)	39 (4.86)	54 (6.73)
Pupillary abnormalities (size and reaction)					0.041
Normal	345 (43.02)	205 (25.56)	113 (14.09)	125 (15.59)
Abnormal	3 (0.37)	4 (0.50)	1 (0.12)	6 (0.75)
Meningeal signs					< 0.001
Absent	346 (43.14)	194 (24.19)	109 (13.59)	125 (15.59)
Present	2 (0.25)	15 (1.87)	5 (0.62)	6 (0.75)
Rash					0.008
Absent	339 (42.27)	192 (23.94)	107 (13.34)	119 (14.84)
Present	9 (1.12)	17 (2.12)	7 (0.87)	12 (1.50)
Cellulitis					0.004
Absent	345 (43.02)	197 (24.56)	108 (13.47)	123 (15.34)
Present	3 (0.37)	12 (1.50)	6 (0.75)	8 (1.00)
Antibiotics started in golden hour					< 0.001
No	348 (43.39)	0 (0)	29 (3.62)	37 (4.61)
Yes	0 (0)	209 (26.06)	85 (10.60)	94 (11.72)
Prior antibiotic use					< 0.001
Not received	311 (38.78)	142 (17.71)	69 (8.60)	84 (10.47)
Received	37 (4.61)	67(8.35)	45 (5.61)	47 (5.86)
Immunodeficiency status					< 0.001
No	339 (42.27)	175 (21.82)	100 (12.47)	109 (13.59)
Yes	9 (1.12)	34 (4.24)	14 (1.75)	22 (2.74)
Chronic illness					0.003
No	180 (22.44)	78 (9.73)	45 (5.61)	52 (6.48)
Yes	168 (20.95)	131 (16.33)	69 (8.60)	79 (9.85)

Data are presented as n (%). GCS: Glasgow Coma Scale.

Table 2 Mean/median of quantitative variables of the study population

Variables	No infection	Suspected infection	Probable infection	Confirmed infection	Total
Age (year) (n = 802)	4.51 ± 4.25	5.14 ± 4.36	5.21 ± 4.22	4.77 ± 4.19	4.81 ± 4.27
Procalcitonin (ng/mL) (n = 262)	0.20 (0.06-0.70)	0.39 (0.14-4.15)	1.00 (0.24-5.66)	1.97 (0.34-7.69)	0.52 (0.14-3.80)
ESR (mm/hour) (n = 121)	36.93 ± 36.58	47.87 ± 43.02	72.23 ± 43.25	73.72 ± 47.85	56.81 ± 44.94
CRP (mg/dL) (n = 394)	19.5 (4.3-84.0)	87.5 (21.9-314.0)	113.9 (18.0-341.0)	140.6 (19.6-400.6)	61.7 (10.2-238.5)
ANC (per µL) (n = 802)	6275 (3775-9940)	6695 (4320-12300)	7800 (4895-12775)	9185 (4765-14065)	6515 (3987-11077)
TLC (per mm3) (n = 802)	11900 (8770-16480)	12400 (7810-17870)	14305 (8610-19440)	14210 (8090-20050)	12400 (8407-17862)
Albumin (g/dL) (n = 657)	3.99 ± 0.65	3.55 ± 0.76	3.35 ± 0.80	3.10 ± 0.91	3.62 ± 0.83
Platelets (per µL) (n = 800)	330000 (221000-440000)	260000 (121000-410000)	300000 (183000-399000)	248000 (139500-410500)	300000 (173250-429250)
Lactate (mmol/L) (n = 518)	1.61 (1.09-2.36)	1.66 (1.20-2.39)	1.56 (1.17-2.20)	1.53 (1.19-2.10)	1.60 (1.15-2.35)
Temp (°C) (n = 802)	36.97 ± 0.85	37.36 ± 1.19	37.47 ± 1.01	37.25 ± 1.08	36.08 ± 1.02

Data are presented as mean ± SD or median (25^th-75^th percentiles). ESR: Erythrocyte sedimentation rate; CRP: C-reactive protein; ANC: Absolute neutrophil count; TLC: Total leukocyte count.

Table 3 Diagnostic characteristics of different variables associated with a bacterial infection

Variable	Cutoff	AUC (95%CI)	Sensitivity	Specificity	PPV	NPV	LR+	LR-	Accuracy
CRP (mg/dL)	60	0.71 (0.63-0.79)	68.49	68.34	53.19	80.51	2.16	0.46	68.39
TLC (per mm3)	14170	0.55 (0.49-0.62)	51.15	66.95	36.81	78.45	1.55	0.73	62.63
ANC (per µL)	8800	0.59 (0.53-0.65)	47.33	72.99	39.74	78.64	1.75	0.72	65.97
ESR (mm/hour)	42	0.73 (0.59-0.88)	80.00	74.07	74.07	80.00	3.09	0.27	76.92
Procalcitonin (ng/mL)	0.72	0.74 (0.65-0.83)	70.37	75.31	65.52	79.22	2.85	0.39	73.33
Albumin (g/dL)	3.70	0.80 (0.75-0.85)	78.41	70.09	85.54	58.99	2.62	0.31	75.85
Lactate (mmol/L)	1.75	0.50 (0.43-0.57)	43.89	65.51	76.38	31.49	1.27	0.86	50.00

AUC: Area under the curve; ESR: Erythrocyte sedimentation rate; TLC: Total leukocyte count; CRP: C-reactive protein; ANC: Absolute neutrophil count; PPV: Positive predictive value; NPV: Negative predictive value; CI: Confidence interval; LR: Likelihood ratio.

Table 4 Binomial logistic regression for the predictors of bacterial infection

Variables	Univariate analysis		Multivariable analysis
	Crude odds ratio (95%CI)	P value	Adjusted odds ratio (95%CI)	P value
Color
Normal	1		1
Abnormal	4.074 (2.195-7.561)	< 0.001	2.362 (0.814-6.849)	0.114
Initial physiological changes
Stable	1		1
Non-threatening	1.576 (0.578-4.297)	0.374	1.478 (0.386-5.655)	0.568
Life-threatening	3.965 (1.489-10.556)	0.006	1.402 (0.333-5.896)	0.645
Fever
Absent	1		1
Present	2.382 (1.332-4.258)	0.003	2.388 (1.020-5.595)	0.045
Features of capillary leak
Absent	1		1
Present	5.210 (2.297-11.816)	< 0.001	5.929 (1.740-20.208)	0.004
Altered sensorium
Absent	1	0.001	1	0.007
Present	4.094 (1.825-9.183)		4.569 (1.501-13.907)
Oliguria
Absent	1	0.026	1	0.764
Present	4.808 (1.205-19.190)		1.350 (0.191-9.565)
Pallor
Absent	1	< 0.001	1	0.085
Present	4.386 (2.278-8.444)		2.453 (0.883-6.814)
Organomegaly
Absent	1	0.002	1	0.432
Present	2.704 (1.432-5.107)		0.672 (0.249-1.812)
Rash
Absent	1	0.022	1	0.304
Present	3.769 (1.214-11.702)		2.778 (0.395-19.522)
Cellulitis
Absent	1	0.013	1	0.1
Present	14.636 (1.764-121.417)		11.557 (0.623-214.319)
Immunodeficiency
No	1	0.002	1	0.151
Yes	4.803 (1.742-13.242)		2.641 (0.701-9.946)
Prior antibiotic use
No	1	< 0.001	1	0.006
Yes	5.512 (2.567-11.837)		4.312 (1.515-12.268)
CRP	1.004 (1.002-1.005)	< 0.001	1.003 (1.001-1.005)	0.001
ANC	1.000 (1.000-1.000)	0.021	1.000 (1.000-1.000)	0.237

CRP: C-reactive protein; ANC: Absolute neutrophil count; CI: Confidence interval.

Table 5 Predictors of childhood bacterial infection: Final model fitted by backward elimination method

Variables	Odds ratio (95%CI)	P value
Features of hypoperfusion
Normal	1	0.0007
Abnormal	3.833 (1.759-8.348)
Fever
Absent	1	0.0109
Present	2.815 (1.269-6.244)
Features of capillary leak
Absent	1	0.0003
Present	6.330 (2.322-17.259)
Altered sensorium
Absent	1	0.002
Present	5.184 (1.830-14.690)
Cellulitis
Absent	1	0.048
Present	13.409 (1.023-175.736)
Prior antibiotic use
No	1	0.0052
Yes	3.976 (1.511-10.464)
CRP	1.003 (1.001-1.005)	0.0004

CRP: C-reactive protein.

Table 6 Scoring system for initiation of antibiotics in golden hour in pediatric emergency medicine

Parameter	Assigned score
Severe acute malnutrition	2
Immunodeficient state	2
Fever (temp ≥ 38 °C)	2
Features of hypoperfusion	3
Altered sensorium	3
Prior antibiotic use in last 2 weeks	3
Features of capillary leak	5
Total score	20