Point-of-care procalcitonin test to reduce antibiotic exposure in patients hospitalized with acute exacerbation of COPD

Figures & data

Figure 1 CONSORT diagram showing patient flow.

Abbreviations: PCT, procalcitonin; PPP, per-protocol population; ITT, intention-to-treat; CONSORT, Consolidated Standards of Reporting Trials.

Figure 2 PCT-guided antibiotic therapy – algorithm.

Abbreviation: PCT, procalcitonin.

Table 1 Baseline characteristics of the study population, overall and by randomization

Characteristics	All (N=120)	PCT group (n=62)	Control group (n=58)
Demographics
Age, years, median (IQR)	72 (63, 80)	72 (64, 80)	73 (61, 78)
Male sex, n (%)	47 (39)	21 (34)	26 (45)
Preexisting illnesses, n (%)
COPD	110 (92)	58 (94)	52 (91)
Hypertension	39 (33)	19 (31)	20 (34)
Coronary heart disease	22 (18)	9 (15)	13 (22)
Chronic heart failure	19 (16)	8 (13)	11 (19)
Osteoporosis	18 (15)	9 (15)	9 (16)
Cerebrovascular disease	12 (10)	7 (11)	5 (9)
Diabetes mellitus	12 (10)	9 (15)	3 (5)
Neoplastic disease	8 (7)	6 (10)	2 (3)
Renal dysfunction	4 (3)	2 (3)	2 (3)
Lung function, COPD history
FEV1, L, median (IQR)	1.0 (0.7, 1.2)	0.9 (0.7, 1.1)	1.0 (0.7, 1.2)
FEV1 % predicted, median (IQR)	40 (29, 53)	43 (32, 54)	35 (28, 51)
Exacerbation within last 12 months, n (%)	54 (45)	29 (47)	25 (43)
Exacerbations within last 12 months, n, median (IQR)	0 (0, 2)	1 (0, 1)	0 (0, 2)
Long-term oxygen therapy, n (%)	15 (12)	7 (11)	8 (14)
Smoking history
Active smoker, n (%)	51 (43)	26 (42)	25 (43)
Ex-smoker, n (%)	64 (53)	32 (52)	32 (55)
Never smoker, n (%)	3 (3)	2 (3)	1 (2)
Pack-years of smoking, years, median (IQR)	40 (25, 50)	40 (25, 50)	40 (25, 50)

Abbreviations: PCT, procalcitonin; IQR, interquartile range; FEV₁, forced expiratory volume in 1 second.

Table 2 Clinical characteristics and final diagnoses of the study population, overall and by randomization

Characteristics	All (N=120)	PCT group (n=62)	Control group (n=58)
Clinical history, n (%)
Coughing	101 (84)	50 (81)	51 (88)
Increased sputum	61 (51)	32 (52)	29 (50)
Purulent sputum	44 (37)	26 (42)	18 (31)
Dyspnea	113 (94)	57 (92)	56 (97)
Clinical findings
Confusion, n (%)	1 (1)	1 (2)	0 (0)
Respiratory rate, breaths/min, median (IQR)	22 (20, 24)	22 (20, 24)	22 (19, 24)
Systolic blood pressure, mmHg, median (IQR)	131 (121, 142)	130 (121, 143)	131 (121, 140)
Diastolic blood pressure, mmHg, median (IQR)	72 (62, 81)	72 (60, 82)	74 (65, 81)
Heart rate, beats/min, median (IQR)	90 (77, 102)	90 (77, 101)	92 (79, 107)
Body temperature, °C, median (IQR)	36.6 (36.4, 36.9)	36.6 (36.4, 36.8)	36.7 (36.4, 37.1)
SaO2, %, median (IQR)	94 (92, 95)	94 (93, 95)	94 (92, 96)
Laboratory findings
PCT, ng/mL, median (IQR)		0.06 (0.00, 0.25)
CRP, mg/L, median (IQR)	27 (1, 80)	42 (1, 112)	22 (1, 54)
Leukocyte count, cells/µL, median (IQR)	9.2 (4.4, 14.0)	9.7 (4.7, 15.0)	8.8 (3.8, 13.8)
Arterial blood gas
PaO2, kpa, median (IQR)	8.7 (7.6, 10.7)	8.7 (7.5, 10.2)	8.8 (7.7, 10.9)
PaCO2, kpa, median (IQR)	5.4 (4.9, 6.4)	5.2 (4.8, 6.3)	6.8 (5.0, 6.7)
pH, n, median (IQR)	7.42 (7.37, 7.45)	7.43 (7.39, 7.45)	7.41 (7.37, 7.44)
HCO3−, mmol/L, median (IQR)	26.2 (24.7, 27.9)	25.7 (24.3, 27.6)	26.6 (24.5, 29.4)
Lactate, mmol/L, median (IQR)	1.4 (1.0, 2.1)	1.5 (1.0, 2.2)	1.2 (0.9, 2.1)
Final diagnosis, n (%)
COPD exacerbation	116 (97)	60 (97)	56 (97)
CAP	30 (25)	19 (31)	11 (19)
Acute heart failure	8 (7)	6 (10)	2 (3)
Pulmonary embolism	2 (2)	1 (2)	1 (2)
Atrial fibrillation	3 (2)	1 (2)	2 (3)
Other	11 (9)	5 (8)	6 (10)

Note: CAP defined as infiltrate on X-ray and CRP ≥50 mg/L.

Abbreviations: PCT, procalcitonin; IQR, interquartile range; SaO₂, arterial oxygen saturation; CRP, C-reactive protein; PaO₂, arterial blood oxygen tension; PaCO₂, arterial blood carbon dioxide tension; CAP, community-acquired pneumonia; HCO₃−, hydrogen carbonate.

Table 3 Antibiotic exposure, antibiotic prescription rate, and length of hospital stay by randomization

	PCT group	Control group	Relative risk (95% CI)	P-value
All patients (intention-to-treat)	n=62	n=58
Antibiotic exposure, d, mean (median [IQR])	6.1 (3.5 [0, 10])	9.0 (8.5 [1, 11])		0.017
Antibiotic prescription rate, day 1, n (%)	36 (58)	43 (74)	0.8 (0.6–1.0)	0.08
Antibiotic prescription rate, day 5, n (%)	26 (42)	39 (67)	0.6 (0.4–0.9)	0.006
Length of stay, d, mean (median [IQR])	4.5 (4 [2, 6])	5.1 (3 [1, 7])		0.6
CAP (intention-to-treat)	n=19	n=11
Antibiotic exposure, d, mean (median [IQR])	9.7 (7 [4, 11])	14.0 (10 [7, 16])		0.146
Antibiotic prescription rate, day 1, n (%)	18 (95)	11 (100)	0.9 (0.9–1.1)	1.0
Antibiotic prescription rate, day 5, n (%)	14 (74)	11 (100)	0.7 (0.6–1.0)	0.129
Length of stay, d, mean (median [IQR])	5 (5 [3, 6])	7.2 (5 [4, 12])		0.436
All patients (per-protocol population)	n=38	n=46
Antibiotic exposure, d, mean (median [IQR])	2.7 (0 [0, 4])	9.5 (10 [5, 12])		<0.0001
Antibiotic prescription rate, day 1, n (%)	15 (39)	36 (78)	0.5 (0.3–0.8)	0.0004
Antibiotic prescription rate, day 5, n (%)	8 (21)	34 (74)	0.3 (0.2–0.5)	<0.0001
Length of stay, d, mean (median [IQR])	4 (4 [2, 6])	5.1 (3 [1, 7])		0.9
CAP (per-protocol population)	n=11	n=10
Antibiotic exposure, d, mean (median [IQR])	5.6 (5 [2, 9])	11.5 (10 [7, 14])		0.014
Antibiotic prescription rate, day 1, n (%)	10 (91)	10 (100)	0.9 (0.8–1.1)	1.0
Antibiotic prescription rate, day 5, n (%)	6 (55)	10 (100)	0.5 (0.3–0.9)	0.035
Length of stay, d, mean (median [IQR])	5 (5 [4, 6])	6 (4.5 [4, 9])		0.956

Note: CAP defined as infiltrate on X-ray and CRP ≥50 mg/L.

Abbreviations: PCT, procalcitonin; d, day; IQR, interquartile range; CAP, community acquired pneumonia; CI, confidence interval; CRP, C-reactive protein.

Figure 3 Antibiotic exposure in patients receiving antibiotic therapy, intention-to-treat.

Note: Red bars indicate primary endpoints of study.

Abbreviations: PCT, procalcitonin; d, days.

Figure 4 Antibiotic exposure in patients receiving antibiotic therapy, per-protocol population.

Note: Red bars indicate primary endpoints of study.
Abbreviations: PCT, procalcitonin; d, days.

Table 4 Rates of combined adverse outcomes and mortality by randomization group

	PCT group	Control group	Relative risk (95% CI)	P-value
All patients (intention-to-treat)	n=62	n=58
Composite adverse events, n (%)	22 (35)	15 (26)	1.4 (0.8–2.4)	0.32
Death, n (%)	1 (2)	2 (3)	0.5 (0.0–5.0)	0.61
ICU admission, n (%)	0 (0)	1 (2)	0.0	0.48
Readmission overall, n (%)	21 (34)	13 (22)	1.5 (0.8–2.7)	0.22
Readmission with AECOPD or CAP, n (%)	12 (19)	12 (21)	0.9 (0.5–1.9)	1.00
All patients (per-protocol population)	n=38	n=46
Composite adverse events, n (%)	14 (37)	14 (30)	1.2 (0.7–2.2)	0.64
Death, n (%)	1 (3)	1 (2)	1.2 (0.1–18.7)	1.00
ICU admission, n (%)	0 (0)	0 (0)	n/a	n/a
Readmission overall, n (%)	13 (34)	13 (28)	1.2 (0.6–2.3)	0.64
Readmission with COPD or CAP, n (%)	8 (21)	11 (24)	0.9 (0.4–2.0)	0.80

Notes: CAP defined as infiltrate on X-ray and CRP ≥50 mg/L. Composite adverse events defined as readmission, ICU admission, or death, all within 28 days after inclusion.

Abbreviations: PCT, procalcitonin; ICU, intensive care unit; CAP, community-acquired pneumonia; CI, confidence interval; AECOPD, acute exacerbation of COPD; n/a, not applicable.