Bacterial and Viral Infection in Patients Hospitalized for Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Implication for Antimicrobial Management and Clinical Outcome

Figures & data

Figure 1. Flowchart of the study. COPD, chronic obstructive pulmonary disease; NAAT, nucleic acid amplification test.

Table 1. List of respiratory pathogens detected by each of the two commercial molecular multiplex kits used in this study.

	Seegene test	Fast-track test
Viruses	Influenza A virus	Influenza A virus (FLU A)
	Influenza A-H1N1pdm09	Influenza A-H1N1pdm09 virus
	Influenza B virus	Influenza B virus
	Influenza A-H1 virus	–
	Influenza A-H3 virus	–
	Respiratory syncytial virus A	Respiratory syncytial virus A
	Respiratory syncytial virus B	Respiratory syncytial virus B
	Coronavirus NL63	Coronavirus NL63
	Coronavirus 229E	Coronavirus 229E
	Coronavirus OC43	Coronavirus OC43
	–	Coronavirus HKU-1
	Parainfluenza virus type 1	Parainfluenza virus type 1
	Parainfluenza virus type 2	Parainfluenza virus type 2
	Parainfluenza virus type 3	Parainfluenza virus type 3
	Parainfluenza virus type 4	Parainfluenza virus type 4
	Adenovirus	Adenovirus
	Enterovirus	Enterovirus
	Rhinovirus	Rhinovirus
	Human metapneumovirus	Human metapneumovirus A
	–	Human metapneumovirus B
	Bocavirus	Bocavirus
	–	Parechovirus
Bacteria	Mycoplasma pneumoniae	Mycoplasma pneumoniae
	Chlamydia pneumoniae	Chlamydia pneumoniae
	Legionella pneumophila	–

Table 2. Demographics together with clinical and biological characteristics at hospital admission of the 84 patients exhibiting an exacerbation of COPD included into the study.

Patients’ characteristics	All patients
Age in years, mean (SD)	67.8 (10)
Male sex, no. (%)	78 (92.9)
Smoking history in packets/year, mean (SD)	52.3 (64)
Number of previous exacerbations in the last 12 months, mean (SD)	2.5 (1.7)
BMI in kg/m^2, mean (SD)	25.7 (4.9)
GOLD severity classification
Stage 4, no. (% )	30 (35.7)
Stage 3, no. (%)	47 (56)
Stage 2, no. (% )	7 (8.3)
PaO2 in kPa, mean (SD)^a	14 (1.4)
PaCO2, in kPa, mean (SD)^a	5.9 (1.9)
pH, mean (SD)	7.3 (0.06)
WBC in cells/mm^3*10^3, mean (SD)	12.4 (6)
CRP in mg/l, mean (SD)	58 (56)

^a These values were recorded while the patients were under oxygen supplementation.

BMI, body mass index; CRP, C-reactive protein; PaCO₂, partial pressure of carbon dioxide in arterial blood; PaO₂, partial pressure of oxygen in arterial blood; SD, standard deviation; WBC, white cell blood count.

Table 3. List of pathogens recovered from the sputum samples of the patients of the study.

Pathogen	Number
Conventional bacteriological cultures (n = 74)^a	15
– Acinetobacter baumannii	2
– Escherichia coli	1
– Klebsiella pneumoniae	2
– Haemophilus influenzae	3
– Haemophilus parainfluenzae	1
– Pseudomonas aeruginosa	3
– Staphylococcus aureus	1
– Streptococcus pneumoniae	2
Molecular testing (n = 84)
Bacteria	1
– Chlamydia pneumoniae	1
Viruses	63
– Influenza virus A/H1N1	7
– Influenza virus A/H3N2	5
– Influenza virus B	1
– Rhinovirus	33
– Respiratory syncytial virus B	1
– Parainfluenza virus type 1	2
– Parainfluenza virus type 3	1
– Human coronavirus 229E	2
– Human coronavirus OC43	2
– Human coronavirus NL63	2
– Human coronavirus HKU-1^b	2
– Human bocavirus	4
– Adenovirus	1

^a The result was considered positive for a threshold of 10⁷ UFC/ml. Ten sputum samples could not be tested by conventional culture.

^b The HKU-1 type of human coronavirus was available only in the Fast-track panel.

Table 4. Description of the 15 pathogen associations recorded in the 74 patients tested for bacterial and viral agents in sputum specimen.

Pathogen association	Number of cases
Bacterium-bacterium	1
– Klebsiella pneumoniae + Pseudomonas aeruginosa	1
Bacterium–virus(es)	7
– Haemophilus parainfluenzae + influenza virus A/H1N1	1
– Acinetobacter baumannii + influenza virus A/H1N1	1
– Acinetobacter baumannii + respiratory syncytial virus type B	1
– Klebsiella pneumonia + rhinovirus	1
– Haemophilus influenzae + rhinovirus	1
– Escherichia coli + rhinovirus	1
– Streptococcus pneumoniae + rhinovirus + parainfluenza virus type 1	1
Virus–virus	7
– Bocavirus + rhinovirus	4
– Adenovirus + rhinovirus	1
– Influenza virus A/H3N2 + rhinovirus	1
– Parainfluenza virus type 3 + human coronavirus HKU-1	1

Table 5. Baseline characteristics and follow-up of the 74 patients for whom a sputum specimen was available for conventional bacterial culture and molecular techniques, according to the category of pathogen(s) recovered from the sputum of COPD patients.

Variable	Group 1: Bacterial pathogen (n = 15)	Group 2: Viral pathogen (n = 38)	Group 3: No pathogen (n = 21)	p Value
Age in years, mean ± SD	67.6 ± 9	69.3 ± 8.5	65.3 ± 40.4	NS
Male sex, nb (%)	15 (100)	34 (89.5)	21 (100)	NS
Smoking history in packets/year, mean ± SD	72.2 ± 76.6	59 ± 70.7	41.9 ± 41.7	NS
Number of previous exacerbations in the last 12 months, mean ± SD	2.8 ± 1.7	2.7 ± 2	2.2 ± 1	NS
BMI in kg/m^2, mean ± SD	28.1 ± 4.7	25.7 ± 4.6	23.8 ± 5	NS
GOLD severity classification				0.05
– Stage 2, no. (%)	2 (13.3)	0 (0)	3 (14.3)
– Stage 3, no. (%)	6 (40)	19 (52.8)	14 (66.7)
– Stage 4, no. (% )	7 (46.7)	17 (47.2)	4 (19)
PaO2 in kPa , mean ± SD	16.6 ± 1.8	11.5 ± 0.6	17.9 ± 2.0	NS
PaCO2, in kPa , mean ± SD	5.8 ± 1.8	5.6 ± 1.9	6.02 ± 1.9	NS
pH, mean ± SD	7.38 ± 0.07	7.37 ± 0.06	7.34 ± 0.07	NS
WBC in cells/mm^3*10^3, mean ± SD	14.5 ± 8.3	12.4 ± 5.3	11.3 ± 6.4	NS
CRP in mg/l, mean ± SD	104.3 ± 70.8	40.3 ± 40.2	60.3 ± 57.7	0.001
Duration of treatment by levofloxacin				NS
– 2 days, nb (%)	4 (26.7)	21 (55.3)	9 (42.9)
– 7 days, nb (%)	11 (73.3)	17 (44.7)	12 (57.1)
Follow-up at 6 months
– Recurrence of exacerbation, n (%)	10 (66.7)	2 (5.3)	2 (9.5)	0.0001
– Death, nb (%)	3 (20)	1 (2.8)	1 (4.8)	NS
Follow-up at 12 months
– Recurrence of exacerbation nb (%)	12 (80)	4 (10.5)	3 (14.3)	0.0001
– Death, nb (%)	3 (21.4)	1 (2.8)	2 (9.5)	NS

Values are reported as mean ± SD or as frequency (%).

NS, not significant; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; BMI, body mass index; CRP, C-reactive protein; PaO₂, partial pressure of oxygen in arterial blood; PaCO₂, partial pressure of carbon dioxide in arterial blood; WBC, white cell blood count.

Table 6. Multivariate analysis conducted for studying the relationship between the occurrence of a new episode of exacerbation of COPD (recurrence) within 6 or 12 months and different explicative parameters in the 74 patients for whom univariate results are shown in Table 5.

Variable	Recurrence at 6 months			Recurrence at 12 months
	OR [CI 95%]	p Value		OR [CI 95%]	p Value
Number of previous episodes of exacerbation	1.27 [0.81–2.01]	0.31		1.27 [0.83–1.96]	0.13
CRP (< 36 mg/l vs > 36 mg/l)	1.40 [0.23–8.42]	0.71		4.54 [0.90–22.96]	0.07
GOLD score (4 vs 2 + 3)	0.20 [0.03–1.30]	0.09		0.51 [0.11–2.40]	0.39
Pathogen category (group 1 vs groups 2 + 3)	37.72 [5.93–239-93]	<0.0001		22.97 [4.76–120.75]	<0.0001