Antibiotic-resistant Pseudomonas aeruginosa infection in patients with bronchiectasis: prevalence, risk factors and prognostic implications

Figures & data

Figure 1 Flow chart of the selected population.

Abbreviation: PA, Pseudomonas aeruginosa.

Table 1 Demographic and clinical characteristics of bronchiectasis patients with and without PA-resistant in sputum

Items	Parameters	All patients (N=147)	PA-R (n=88)	PA-S (n=59)	P-value
Anthropometry	Age, years	59.7±18.2	61.7±17.3	56.7±19.1	0.10
	Female	82 (55.8)	46 (52.3)	36 (61.0)	0.30
	BMI (kg/m^2)	18.1±3.2	17.4±2.4	19.1±3.9	0.001
	Nonsmokers	107 (72.8)	61 (69.3)	46 (78.0)	0.25
Disease-related parameters	No of acute exacerbations within 1 year >2	95 (64.6)	69 (78.4)	26 (44.1)	<0.001
	No of hospital admissions within 1 year >1	88 (59.9)	65 (73.8)	23 (39.0)	<0.001
	Modified Reiff HRCT score	11.4±4.7	12.8±5.0	9.4±3.4	<0.001
	mMRC dyspnea score	2.3±1.3	2.8±1.2	1.5±1.2	<0.001
Lung function	FVC pred %	65.3±19.4	63.5±20.4	68.0±17.6	0.16
	FEV1 pred %	53.6±21.1	51.4±22.7	56.9±18.1	0.12
Comorbidity	CHD	18 (12.2)	12 (13.6)	6 (10.2)	0.53
	Hypertension	30 (20.4)	20 (22.7)	10 (16.9)	0.39
	Stroke	3 (2.0)	3 (3.4)	0 (0)	0.15
	Pulmonary hypertension	52 (35.4)	43 (48.9)	9 (15.3)	<0.001
	DM	9 (6.1)	6 (6.8)	3 (5.1)	0.67
Prior treatment	Systemic corticosteroids (prior 3 months)	81 (55.1)	59 (67.0)	22 (37.3)	<0.001
	Antibiotics (prior 3 months)	126 (85.7)	84 (95.5)	42 (71.2)	<0.001
	Antibiotics (prior 1 month)	95 (64.6)	64 (72.7)	31 (52.5)	0.01
Current medications	ICS	71 (48.3)	42 (47.7)	29 (49.1)	0.87
	LABA	68 (46.3)	40 (45.5)	28 (47.5)	0.81
	LAMA	52 (35.4)	33 (37.5)	19 (32.2)	0.51
	Chronic macrolide treatment	45 (30.6)	28 (31.8)	17 (28.8)	0.70
Etiology	Post-infectious	44 (29.9)	25 (28.4)	19 (32.2)	0.62
	Immunodeficiency	3 (2.0)	3 (3.4)	0 (0)	0.15
	Miscellaneous known causes	54 (36.7)	31 (35.2)	23 (39)	0.64
	Idiopathic	46 (31.3)	29 (33.0)	17 (28.8)	0.60

Note: The significance of bold values P<0.05.

Abbreviations: BMI, body mass index; CHD, chronic heart disease; DM, diabetes mellitus; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; HRCT, high-resolution computed tomography; ICS, inhaled corticosteroid; LABA, long-acting beta-agonist; LAMA, long-acting muscarinic antagonist; mMRC, modified Medical Research Council; PA, Pseudomonas aeruginosa; PA-R, PA-resistant; PA-S, PA-sensitive.

Table 2 Factors associated with the presence of PA-resistant in patients with bronchiectasis in a logistic regression model

Factors	B	Exp (B)	95% CI Exp (B)	P-value
Antibiotics (prior 1 month)	1.82	6.18	2.22–17.19	<0.001
No of acute exacerbations within 1 year >2	1.03	2.81	1.02–7.77	0.046
mMRC dyspnea scores	0.66	1.93	1.34–2.78	<0.001
Modified HRCT scores	0.14	1.15	1.04–1.28	<0.001
Antibiotics (prior 3 months)	1.28	3.60	0.90–14.44	0.07

Notes: Variables were adjusted for age, BMI, comorbid conditions, mMRC dyspnea score, acute exacerbations or hospitalizations in the past years, FEV₁% of predicted, HRCT scores and prior treatment. The significance of bold values P<0.05.

Abbreviations: B, B coefficient; BMI, body mass index; Exp (B), exponentiation of the B coefficient; FEV₁, forced expiratory volume in 1 second; mMRC, modified Medical Research Council; HRCT, high-resolution computed tomography; PA, Pseudomonas aeruginosa.

Table 3 Demographic and clinical characteristics of bronchiectasis patients according to survival status at the end of the study

Items	Parameters	Survivors (n=111)	Nonsurvivors (n=36)	P-value
Anthropometry	Age, years	56.3±17.0	72.4±11.8	<0.001
	Female	66 (59.5)	16 (44.4)	0.12
	BMI (kg/m^2)	18.6±3.3	16.5±1.9	<0.001
	Nonsmokers	82 (73.9)	25 (69.4)	0.60
Disease-related parameters	No of acute exacerbations within 1 year >2	74 (66.7)	21 (58.3)	0.36
	No of hospital admissions within 1 year >1	68 (61.3)	20 (55.6)	0.54
	Modified Reiff HRCT score	10.9±4.6	13.0±4.6	0.019
	mMRC dyspnea score	2.2±1.3	2.8±1.2	0.019
Lung function	FVC pred %	68.2±20.2	56.2±13.1	0.001
	FEV1 pred %	55.9±21.8	46.4±17.2	0.018
Comorbid conditions	CHD	13 (11.7)	5 (13.8)	0.73
	Hypertension	20 (18.1)	10 (27.7)	0.21
	Stroke	2 (1.8)	1 (2.7)	0.72
	Pulmonary hypertension	34 (30.6)	18 (50.0)	0.035
	DM	7 (6.4)	2 (5.6)	0.87
Prior treatment	Systemic corticosteroids (prior 3 months)	54 (48.6)	27 (75.0)	0.006
	Antibiotics (prior 3 months)	93 (83.8)	33 (91.7)	0.24
	Antibiotics (prior 1 month)	68 (61.3)	27 (75.0)	0.13
Current medications	ICS	51 (45.9)	20 (55.6)	0.32
	LABA	48 (43.2)	20 (55.6)	0.20
	LAMA	38 (34.2)	14 (38.9)	0.61
	Chronic macrolide treatment	35 (31.5)	10 (27.8)	0.67
Etiology	Post-infectious	32 (28.8)	12 (33.3)	0.61
	Immunodeficiency	3 (2.7)	0 (0)	0.19
	Miscellaneous known causes	42 (37.8)	12 (33.3)	0.63
	Idiopathic	34 (30.6)	12 (33.3)	0.76
PA	Isolate of PA-R	64 (57.7)	24 (66.7)	0.34

Note: The significance of bold values P<0.05.

Abbreviations: BMI, body-mass index; CHD, chronic heart disease; DM, diabetes mellitus; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; HRCT, high-resolution computed tomography; ICS, inhaled corticosteroid; LABA, long-acting beta-agonist; LAMA, long-acting muscarinic antagonist; mMRC, modified Medical Research Council; PA, Pseudomonas aeruginosa; PA-R, PA-resistant.

Table 4 Variables associated with all-cause mortality in patients with bronchiectasis in a Cox proportional hazard regression model

Factors	B	Exp (B)	95% CI Exp (B)	P-value
Age	0.11	1.11	1.05–1.17	<0.001
BMI (kg/m^2)	−0.60	0.55	0.39–0.76	<0.001
HRCT scores	0.15	1.16	1.02–1.32	0.02
Isolates of PA-resistant	0.95	2.59	0.83–8.11	0.10

Notes: The significance of bold values P<0.05. Variables were adjusted for age, BMI, comorbid conditions, mMRC dyspnea score, FEV₁% of predicted, FVC% of predicted and HRCT scores.

Abbreviations: B, B coefficient; BMI, body mass index; Exp (B), exponentiation of the B coefficient; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; HRCT, high-resolution computed tomography; mMRC, modified Medical Research Council; PA, Pseudomonas aeruginosa.

Figure 2 The Kaplan–Meier survival curves for bronchiectasis patients with PA-R isolate (n=88; 24 deaths) and with PA-S isolate (n=59; 12 deaths).

Note: Patients with PA-R isolate were not associated with increased mortality compared to those with PA-S isolate (log-rank test, 0.66; P=0.42).
Abbreviations: PA, Pseudomonas aeruginosa; PA-R, PA-resistant; PA-S, PA-sensitive.

Table S1 MIC interpretive standards of the disk diffusion methodologies for PA according to the CLSI

Antibiotic	MIC interpretive standard (µg/mL)
	S	I	R
Gentamicin	≤4	8	≥16
Tobramycin	≤4	8	≥16
Amikacin	≤16	32	≥64
Ceftazidime	≤8	16	≥32
Cefepime	≤8	16	≥32
Ticarcillin–clavulanate	≤64/2	–	≥128/2
Piperacillin–tazobactam	≤64/4	–	≥128/4
Aztreonam	≤8	16	≥32
Meropenem	≤4	8	≥16
Imipenem	≤4	8	≥16
Ciprofloxacin	≤1	2	≥4
Levofloxacin	≤2	4	≥8
Colistin sulfate	≤2	4	≥8

Abbreviations: CLSI, Clinical and Laboratory Standards Institute; I, intermediate; MIC, minimal inhibitory concentration; PA, Pseudomonas aeruginosa; R, resistant; S, sensitive.

Table S2 Antibiotic resistance profile of 147 Pseudomonas aeruginosa isolates

Antibiotic	Number of susceptible strains (%)
Ciprofloxacin	114 (77.6)
Piperacillin–tazobactam	121 (82.3)
Ceftazidime	121 (82.3)
Imipenem	95 (64.6)
Gentamicin	131 (89.1)
Amikacin	141 (95.9)

Table S3 Baseline and clinical characteristics of bronchiectasis patients with PA-R in non-MDR and MDR groups in sputum

Items	Parameters	Non-MDR (n=54)	MDR (n=34)	P-value
Anthropometry	Age, years	62.7 (13.7)	60.2 (22.1)	0.52
	Female	31 (57.4)	15 (44.1)	0.22
	BMI (kg/m^2)	17.4 (2.9)	17.6 (1.2)	0.74
	Nonsmokers	40 (74.1)	21 (61.8)	0.22
Disease-related parameters	No of acute exacerbations within 1 year >2	39 (72.2)	30 (88.2)	0.08
	No of hospital admissions within 1 year >1	36 (66.7)	29 (85.3)	0.05
	Modified Reiff HRCT score	12.3 (5.1)	13.6 (4.8)	0.25
	mMRC dyspnea score	2.5 (1.3)	3.3 (0.5)	0.003
Lung function	FVC pred %	69.4 (21.0)	54.1 (15.5)	<0.001
	FEV1 pred %	58.6 (23.6)	40.0 (15.6)	<0.001
Comorbid conditions	CHD	9 (16.7)	3 (8.8)	0.30
	Hypertension	12 (22.2)	8 (23.5)	0.89
	Stroke	0 (0)	3 (8.8)	0.16
	Pulmonary hypertension	20 (37.0)	23 (67.6)	0.01
	DM	6 (11.1)	3 (8.8)	0.73
Prior treatment	Systemic corticosteroids (prior 3 months)	33 (61.1)	26 (76.5)	0.14
	Antibiotics (prior 3 months)	51 (94.4)	33 (97.1)	0.57
	Antibiotics (prior 1 month)	36 (66.7)	28 (82.4)	0.11
Current medications	ICS	26 (48.1)	16 (47.1)	0.92
	LABA	24 (44.4)	16 (47.1)	0.81
	LAMA	19 (35.2)	14 (41.2)	0.57
	Chronic macrolide treatment	13 (24.1)	15 (44.1)	0.18
Etiology	Post-infectious	15 (27.7)	10 (29.4)	0.87
	Immunodeficiency	1 (1.9)	2 (5.9)	0.31
	Miscellaneous known causes	18 (33.3)	13 (38.2)	0.64
	Idiopathic	20 (37.0)	10 (29.4)	0.46

Abbreviations: BMI, body-mass index; CHD, chronic heart disease; DM, diabetes mellitus; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; HRCT, high-resolution computed tomography; ICS, inhaled corticosteroid; LABA, long-acting beta-agonist; LAMA, long-acting muscarinic antagonist; MDR, multidrug resistant; mMRC, modified Medical Research Council; PA, Pseudomonas aeruginosa; PA-R, PA-resistant.

Table S4 Factors associated with the presence of MDR-PA in patients with bronchiectasis in a logistic regression model

Factors	B	Exp (B)	95% CI Exp (B)	P-value
Antibiotics (prior 1 month)	1.45	4.28	1.43–12.79	0.009
No of acute exacerbations within 1 year >2	1.35	3.86	1.07–13.92	0.04
mMRC dyspnea scores	0.86	2.37	1.26–4.47	0.007
Lower FEV1 pred %	0.04	1.04	1.01–1.06	0.003

Notes: The significance of bold values P<0.05. Variables were adjusted for age, BMI, comorbid conditions, mMRC dyspnea, acute exacerbations or hospitalizations in the past years, FEV₁% of predicted, FVC% of predicted.

Abbreviations: B, B coefficient; BMI, body mass index; Exp (B), exponentiation of the B coefficient; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; MDR, multidrug resistant; mMRC, modified Medical Research Council; PA, Pseudomonas aeruginosa.