Accepted Manuscript Risk Factors for Slowly Resolving Pneumonia in the Intensive Care Unit Meiling Li , MD, Jialin Liu , MD PhD, Ruoming Tan , MD, Zhaojun Liu , MD, Jianyong Yin , MD, Hongping Qu , MD PII:
S1684-1182(14)00235-7
DOI:
10.1016/j.jmii.2014.11.005
Reference:
JMII 571
To appear in:
Journal of Microbiology, Immunology and Infection
Received Date: 18 September 2013 Revised Date:
2 June 2014
Accepted Date: 6 November 2014
Please cite this article as: Li M, Liu J, Tan R, Liu Z, Yin J, Qu H, Risk Factors for Slowly Resolving Pneumonia in the Intensive Care Unit, Journal of Microbiology, Immunology and Infection (2014), doi: 10.1016/j.jmii.2014.11.005. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title page
1
Title: Risk Factors for Slowly Resolving Pneumonia in the Intensive Care Unit
3
Running title: a retrospective and cohort-based study among ICU in a
4
university-affiliated hospital in Shanghai
5
Meiling Li1†,MD; Jialin Liu2,MD, PhD; Ruoming Tan1,MD; Zhaojun Liu1,MD;
6
Jianyong Yin1, MD Hongping Qu1†*,MD;
7
1 Department of Critical Care Medicine and Respiratory intensive care unit, Ruijin
8
Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
9
2 Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong
M AN U
SC
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2
10
University School of Medicine, Shanghai, China
11
† Co-authers, these authors contributed equally to this work
13
TE D
12
Email address (Meiling Li): [email protected]
14 15
*
16
Name: Hongping Qu
17
Institution: Department of Critical Care Medicine and Respiratory intensive care unit
18
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
19
Address: 197 Rui-Jin Er Rd., Bld. 36, Shanghai 200025, China
20
E-mail: [email protected]
21
Tel: 86-021-64370045 Ext. 680901
22
Fax: 86-021-64674301
AC C
EP
Corresponding author
1
ACCEPTED MANUSCRIPT 23
Statement
24
All authors declare that they have no financial or other potential conflicts of interest
25
and never submitted the manuscript, in whole or in part, to other journals.
RI PT
26 27 28
SC
29
M AN U
30 31 32 33
37 38 39 40
EP
36
AC C
35
TE D
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41 42 43 44 2
ACCEPTED MANUSCRIPT
Abstract
45
Background: Slowly resolving pneumonia poses early identified challenges and
47
medical costs abandon for clinicians with few literatures among ICU.
48
Methods: This was a retrospective and cohort-based study among ICU in a
49
university-affiliated hospital in Shanghai. Medical records of pneumonia patients in
50
ICU between April 2008 and February 2011were reviewed retrospectively to evaluate
51
the risk factors for slowly resolving pneumonia.
52
Results: In all, 106 pneumonia patients among ICU were identified as
53
immune-competent bacteritic pneumonia. There were 62
54
showed slowly resolving pneumonia and their radiographic infiltrations were
55
completely resolved from five to eight weeks. The multivariate logistic regression
56
analysis demonstrated that initial treatment with an inappropriate antibiotic use,
57
multi-lobar infiltration and a high CURB-65 score were independent risk factors for
58
slowly resolving pneumonia, with OR values of 8.338 (95% CI 2.117-32.848), 11.184
59
(95% CI 2.526-49.514) and 2.329 (95% CI 1.172-4.626), respectively. The length of
60
the ICU stay in the slowly resolving pneumonia group was twice longer than in the
61
normally resolving pneumonia group (62.27±73.73 vs. 32.25±23, p=0.002). The
62
28-day and 60-day mortality rates in the slowly resolving pneumonia group were
63
17.74% and 25.81%, respectively. In addition, the 60-day mortality rate was
64
significantly higher in the SRP group than the NRP group (25.81% vs. 6.82%,
65
respectively; p=0.012).Moreover, slowly resolving pneumonia was an independent
66
risk factor for 60-day mortality (OR 5.687, 95% CI 1.334-24.240).
M AN U
SC
RI PT
46
AC C
EP
TE D
58.49% patients who
3
ACCEPTED MANUSCRIPT 67
Conclusions: Treatment with an inappropriate antibiotic, multi-lobar infiltration and a
68
high CURB-65 score were independent risk factors for slowly resolving pneumonia.
69
Key words
71
Pneumonia; resolution; antibiotic therapy; radiographic infiltrations; critically ill; risk
72
factors
RI PT
70
SC
73 74
M AN U
75 76 77
81 82 83 84 85
EP
80
AC C
79
TE D
78
86 87 88
4
ACCEPTED MANUSCRIPT
Introduction
90
The unapparent resolution of pulmonary infiltrates includes both non-resolving
91
and slowly resolving pneumonia (SRP) poses diagnostic and treatment challenges for
92
clinicians as a common consultation problem.1,2 Non-resolving pneumonia often
93
represents a noninfectious process that mimics an infectious process.3,4 Slowly
94
resolving pneumonia is usually associated with host- or treatment-related factors.5,6
95
Advances in the procedures used to diagnose pneumonia have led to a declining
96
incidence of non-resolving pneumonia, while the incidence of slowly resolving
97
pneumonia is definitely rising with multiple supporting methods.7,8 Kirtland and
98
Winterbauer first proposed a definition of slowly resolving pneumonia that referred to
99
immune-competent patients who exhibited improved clinical symptoms with
100
antibiotic therapy and chest radiographs with less than 50% clearing by 2 weeks or
101
less than complete clearing at 4 weeks.9,10 To date, the literature concerning slowly
102
resolving pneumonia was too limited to evaluate or treat slowly resolving pneumonia.
103
Although the precise incidence of slowly resolving pneumonia is not well established,
104
early studies reported that 25-67% of the pulmonary infiltration of pneumonia patients
105
showed delayed resolution along with high mortality,11 prolonged hospital stays and
106
high treatment costs.8 Some studies on critically ill patients found that as many as
107
47% of pneumonia cases showed delayed resolution.12 Due to its high incidence and
108
poor outcome, the recognition and resolution of slowly resolving pneumonia in the
109
ICU deserve more attention from clinicians.
110
AC C
EP
TE D
M AN U
SC
RI PT
89
The objective of this study was to investigate the incidence, length of ICU stay, 5
ACCEPTED MANUSCRIPT 111
outcome and risk factors associated with slowly resolving pneumonia in critically ill
112
patients to promote the identification of high-risk patients.
113
Materials and Methods
115
RI PT
114
Ethical Statements
We did no harm to participants and just evaluated radiographic resolution and
117
clinical features of participants. We promised to hold all the information of
118
participants as a confidential manner. The study protocol and consent procedure with
119
waiver of written consent was approved by the Shanghai Jiao Tong University School
120
of Medicine affiliated Ruijin Hospital Ethics Committee.
M AN U
SC
116
121
Study Population
TE D
122
The study group was sampled from patients who were admitted to the intensive
124
care unit in a 1,300-bed university-affiliated hospital with a diagnosis of pneumoniaa
125
between April 2008 and February 2011. The inclusion criteria included pneumonia
126
patients who reached clinical stabilityb due to treatment in ICU with a complete
127
resolution or resolution of infiltrate differentiated from chronic changes. The
128
exclusion criteria included patients with immunodepressionc, interstitial pneumonia,
129
pulmonary tumor, pulmonary tuberculosis, H1N1 and other respiratory tract virus
130
legionnaires pneumonia, mycoplasma pneumonia, chlamydia pneumonia and acute
131
respiratory distress syndrome.
132
a
AC C
EP
123
Pneumonia was defined as a new or progressive infiltrate as seen on a chest 6
ACCEPTED MANUSCRIPT 133
radiograph or CT scan along with a high clinical suspicious of pneumonia, defined
134
with at least one of the following: fever (>38
135
leukocytosis (>12000 WBC/mm3), altered mental status with no other recognized
136
cause (for adults older than 70 years),and at least two of the following: (a) new onset
137
of purulent sputum, or change in character of sputum, or increased respiratory
138
secretions, or increased suctioning requirements,(b) new onset or worsening cough, or
139
dyspnea, or increased ventilation demand.
140
b
141
a respiratory rate ≤24 breaths/min, systolic blood pressure ≥90 mmHg, arterial oxygen
142
saturation ≥90% or PaO2 ≥ 60mmHg in room air, the ability to maintain oral intake
143
and a normal mental status.10
144
c
145
neutrophils/L for 110 days); the receipt of an allogeneic stem cell transplant; the
146
prolonged use of corticosteroids (a mean minimum dose of 0.3 mg of prednisone
147
equivalent/kg/day for 13 weeks); treatment with another recognized T cell suppressant
148
such as cyclosporine, TNF-a blockers, specific monoclonal antibodies, or nucleoside
149
analogs during the past 90 days; or inherited severe immunodeficiency (such as
150
chronic granulomatous disease or severe combined immunodeficiency). 13
152
RI PT
SC
, a heart rate ≤100 beats/min,
M AN U
Clinical stability was defined as a temperature ≤37.8
EP
TE D
Immunodepression was defined as a recent history of neutropenia (
S1684-1182(14)00235-7
DOI:
10.1016/j.jmii.2014.11.005
Reference:
JMII 571
To appear in:
Journal of Microbiology, Immunology and Infection
Received Date: 18 September 2013 Revised Date:
2 June 2014
Accepted Date: 6 November 2014
Please cite this article as: Li M, Liu J, Tan R, Liu Z, Yin J, Qu H, Risk Factors for Slowly Resolving Pneumonia in the Intensive Care Unit, Journal of Microbiology, Immunology and Infection (2014), doi: 10.1016/j.jmii.2014.11.005. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title page
1
Title: Risk Factors for Slowly Resolving Pneumonia in the Intensive Care Unit
3
Running title: a retrospective and cohort-based study among ICU in a
4
university-affiliated hospital in Shanghai
5
Meiling Li1†,MD; Jialin Liu2,MD, PhD; Ruoming Tan1,MD; Zhaojun Liu1,MD;
6
Jianyong Yin1, MD Hongping Qu1†*,MD;
7
1 Department of Critical Care Medicine and Respiratory intensive care unit, Ruijin
8
Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
9
2 Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong
M AN U
SC
RI PT
2
10
University School of Medicine, Shanghai, China
11
† Co-authers, these authors contributed equally to this work
13
TE D
12
Email address (Meiling Li): [email protected]
14 15
*
16
Name: Hongping Qu
17
Institution: Department of Critical Care Medicine and Respiratory intensive care unit
18
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
19
Address: 197 Rui-Jin Er Rd., Bld. 36, Shanghai 200025, China
20
E-mail: [email protected]
21
Tel: 86-021-64370045 Ext. 680901
22
Fax: 86-021-64674301
AC C
EP
Corresponding author
1
ACCEPTED MANUSCRIPT 23
Statement
24
All authors declare that they have no financial or other potential conflicts of interest
25
and never submitted the manuscript, in whole or in part, to other journals.
RI PT
26 27 28
SC
29
M AN U
30 31 32 33
37 38 39 40
EP
36
AC C
35
TE D
34
41 42 43 44 2
ACCEPTED MANUSCRIPT
Abstract
45
Background: Slowly resolving pneumonia poses early identified challenges and
47
medical costs abandon for clinicians with few literatures among ICU.
48
Methods: This was a retrospective and cohort-based study among ICU in a
49
university-affiliated hospital in Shanghai. Medical records of pneumonia patients in
50
ICU between April 2008 and February 2011were reviewed retrospectively to evaluate
51
the risk factors for slowly resolving pneumonia.
52
Results: In all, 106 pneumonia patients among ICU were identified as
53
immune-competent bacteritic pneumonia. There were 62
54
showed slowly resolving pneumonia and their radiographic infiltrations were
55
completely resolved from five to eight weeks. The multivariate logistic regression
56
analysis demonstrated that initial treatment with an inappropriate antibiotic use,
57
multi-lobar infiltration and a high CURB-65 score were independent risk factors for
58
slowly resolving pneumonia, with OR values of 8.338 (95% CI 2.117-32.848), 11.184
59
(95% CI 2.526-49.514) and 2.329 (95% CI 1.172-4.626), respectively. The length of
60
the ICU stay in the slowly resolving pneumonia group was twice longer than in the
61
normally resolving pneumonia group (62.27±73.73 vs. 32.25±23, p=0.002). The
62
28-day and 60-day mortality rates in the slowly resolving pneumonia group were
63
17.74% and 25.81%, respectively. In addition, the 60-day mortality rate was
64
significantly higher in the SRP group than the NRP group (25.81% vs. 6.82%,
65
respectively; p=0.012).Moreover, slowly resolving pneumonia was an independent
66
risk factor for 60-day mortality (OR 5.687, 95% CI 1.334-24.240).
M AN U
SC
RI PT
46
AC C
EP
TE D
58.49% patients who
3
ACCEPTED MANUSCRIPT 67
Conclusions: Treatment with an inappropriate antibiotic, multi-lobar infiltration and a
68
high CURB-65 score were independent risk factors for slowly resolving pneumonia.
69
Key words
71
Pneumonia; resolution; antibiotic therapy; radiographic infiltrations; critically ill; risk
72
factors
RI PT
70
SC
73 74
M AN U
75 76 77
81 82 83 84 85
EP
80
AC C
79
TE D
78
86 87 88
4
ACCEPTED MANUSCRIPT
Introduction
90
The unapparent resolution of pulmonary infiltrates includes both non-resolving
91
and slowly resolving pneumonia (SRP) poses diagnostic and treatment challenges for
92
clinicians as a common consultation problem.1,2 Non-resolving pneumonia often
93
represents a noninfectious process that mimics an infectious process.3,4 Slowly
94
resolving pneumonia is usually associated with host- or treatment-related factors.5,6
95
Advances in the procedures used to diagnose pneumonia have led to a declining
96
incidence of non-resolving pneumonia, while the incidence of slowly resolving
97
pneumonia is definitely rising with multiple supporting methods.7,8 Kirtland and
98
Winterbauer first proposed a definition of slowly resolving pneumonia that referred to
99
immune-competent patients who exhibited improved clinical symptoms with
100
antibiotic therapy and chest radiographs with less than 50% clearing by 2 weeks or
101
less than complete clearing at 4 weeks.9,10 To date, the literature concerning slowly
102
resolving pneumonia was too limited to evaluate or treat slowly resolving pneumonia.
103
Although the precise incidence of slowly resolving pneumonia is not well established,
104
early studies reported that 25-67% of the pulmonary infiltration of pneumonia patients
105
showed delayed resolution along with high mortality,11 prolonged hospital stays and
106
high treatment costs.8 Some studies on critically ill patients found that as many as
107
47% of pneumonia cases showed delayed resolution.12 Due to its high incidence and
108
poor outcome, the recognition and resolution of slowly resolving pneumonia in the
109
ICU deserve more attention from clinicians.
110
AC C
EP
TE D
M AN U
SC
RI PT
89
The objective of this study was to investigate the incidence, length of ICU stay, 5
ACCEPTED MANUSCRIPT 111
outcome and risk factors associated with slowly resolving pneumonia in critically ill
112
patients to promote the identification of high-risk patients.
113
Materials and Methods
115
RI PT
114
Ethical Statements
We did no harm to participants and just evaluated radiographic resolution and
117
clinical features of participants. We promised to hold all the information of
118
participants as a confidential manner. The study protocol and consent procedure with
119
waiver of written consent was approved by the Shanghai Jiao Tong University School
120
of Medicine affiliated Ruijin Hospital Ethics Committee.
M AN U
SC
116
121
Study Population
TE D
122
The study group was sampled from patients who were admitted to the intensive
124
care unit in a 1,300-bed university-affiliated hospital with a diagnosis of pneumoniaa
125
between April 2008 and February 2011. The inclusion criteria included pneumonia
126
patients who reached clinical stabilityb due to treatment in ICU with a complete
127
resolution or resolution of infiltrate differentiated from chronic changes. The
128
exclusion criteria included patients with immunodepressionc, interstitial pneumonia,
129
pulmonary tumor, pulmonary tuberculosis, H1N1 and other respiratory tract virus
130
legionnaires pneumonia, mycoplasma pneumonia, chlamydia pneumonia and acute
131
respiratory distress syndrome.
132
a
AC C
EP
123
Pneumonia was defined as a new or progressive infiltrate as seen on a chest 6
ACCEPTED MANUSCRIPT 133
radiograph or CT scan along with a high clinical suspicious of pneumonia, defined
134
with at least one of the following: fever (>38
135
leukocytosis (>12000 WBC/mm3), altered mental status with no other recognized
136
cause (for adults older than 70 years),and at least two of the following: (a) new onset
137
of purulent sputum, or change in character of sputum, or increased respiratory
138
secretions, or increased suctioning requirements,(b) new onset or worsening cough, or
139
dyspnea, or increased ventilation demand.
140
b
141
a respiratory rate ≤24 breaths/min, systolic blood pressure ≥90 mmHg, arterial oxygen
142
saturation ≥90% or PaO2 ≥ 60mmHg in room air, the ability to maintain oral intake
143
and a normal mental status.10
144
c
145
neutrophils/L for 110 days); the receipt of an allogeneic stem cell transplant; the
146
prolonged use of corticosteroids (a mean minimum dose of 0.3 mg of prednisone
147
equivalent/kg/day for 13 weeks); treatment with another recognized T cell suppressant
148
such as cyclosporine, TNF-a blockers, specific monoclonal antibodies, or nucleoside
149
analogs during the past 90 days; or inherited severe immunodeficiency (such as
150
chronic granulomatous disease or severe combined immunodeficiency). 13
152
RI PT
SC
, a heart rate ≤100 beats/min,
M AN U
Clinical stability was defined as a temperature ≤37.8
EP
TE D
Immunodepression was defined as a recent history of neutropenia (
