- Email: [email protected]
Ten-year review of Clostridium difficile infection in acute care hospitals in the USA, 2005–2014
Accepted Manuscript A 10-year Review of Clostridium difficile Infection in Acute Care Hospitals in the United States: A Nationwide Analysis 2005-2014 Ruihong Luo, MD, PhD, Tamar Barlam, MD, MSc PII:
S0195-6701(17)30542-X
DOI:
10.1016/j.jhin.2017.10.002
Reference:
YJHIN 5247
To appear in:
Journal of Hospital Infection
Received Date: 7 August 2017 Accepted Date: 2 October 2017
Please cite this article as: Luo R, Barlam T, A 10-year Review of Clostridium difficile Infection in Acute Care Hospitals in the United States: A Nationwide Analysis 2005-2014, Journal of Hospital Infection (2017), doi: 10.1016/j.jhin.2017.10.002. 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
A 10-year Review of Clostridium difficile Infection in Acute Care Hospitals in the United States:
2
A Nationwide Analysis 2005-2014
3
Ruihong Luo, MD, PhD, Tamar Barlam, MD, MSc
4 5
Affiliations: Section of Infectious Diseases, Boston University School of Medicine, Boston, Massachusetts, USA.
7
Short title: C. difficile infection in acute care hospitals
8
Word count: Main text: 1610; Abstract: 74
9
References: 10
SC
6
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1
Correspondence: Tamar Barlam, Boston Medical Center, 771 Albany Street, Dowling 3 North, Boston, MA 02118
12
USA.Telephone: 1-617-414-5190. Email: [email protected]. Fax: 617-414-5190
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14
15
Abstract Clostridium difficile infection (CDI) is a major health concern for acute care hospitals because of the increase in the number and severity of cases. We used the Nationwide Inpatient
17
Sample database to do a 10-year review on the trends in incidence, mortality and hospital
18
charges for CDI patients in acute care hospitals during 2005-2014. We found an increased CDI
19
incidence and hospital charges, but a decreased mortality during the 10 year study period.
20
Introduction
SC
Clostridium difficile infection (CDI) has increased substantially since the year 2000.
M AN U
21
RI PT
16
Many strategies have proven successful in reducing CDI incidence, particularly antibiotic
23
stewardship, infection control and environmental management interventions [1]. Published data
24
suggests a levelling-off or decline in CDI incidence in hospitalized patients after 2009 [2], but
25
the number of cases remains high.
TE D
22
We sought to assess the change in incidence, mortality and hospital charges for CDI
27
patients in acute care hospitals for the years 2005 to 2014, and to investigate the risk factors
28
associated with hospital-onset CDI (HOCDI) and CDI-related mortality.
29
Methods
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We performed a retrospective cohort study using data from the Healthcare Cost and
31
Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) from 2005 to 2014. NIS is an all-
32
payer inpatient care database representing 20% of non-federal acute-care hospitals in the United
33
States, including community, general, and academic centers but not long-term care facilities.
34
Each discharge is weighted to allow for estimates projected to a national level. Each individual
ACCEPTED MANUSCRIPT
hospitalization is deidentified and maintained in the NIS as a unique entry with one primary
36
discharge diagnosis and up to 24 secondary diagnoses [3]. This study was approved by the
37
Institutional Review Board of Boston University Medical Campus.
38
RI PT
35
The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9CM) code was used to identify patients aged ≥ 18 years with a discharge diagnosis of CDI
40
(008.45). HOCDI was defined as a patient with a secondary diagnosis of CDI and a length of
41
hospital stay (LOS) ≥ 2 days. Non-hospital onset CDI (Non-HOCDI) was defined as a patient
42
with a primary diagnosis of CDI or those with a secondary diagnosis of CDI but LOS < 2 days.
43
We randomly selected 4% of HOCDI patients for our analysis. We selected a control group of
44
patients without CDI by performing 1:1 matching with cases of HOCDI by age, sex and calendar
45
year of hospitalization.
M AN U
The variables of demographics (age, sex and ethnicity), source of admission (from
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46
SC
39
community, other acute care hospitals or long-term care facilities), discharge outcome (death or
48
survival), length of hospital stay (LOS), and total hospital charges were extracted from the NIS
49
dataset to provide subject characteristics. The hospital charges refer to the charges that the
50
hospital levied to the patients. All dollar amounts in this report were adjusted to inflation based
51
on the year 2014. The LOS refers to the total number of continuous days a patient was
52
hospitalized. We examined Charlson comorbidity index (CCI) score by identifying comorbid
53
conditions using their corresponding ICD-9-CM codes.
AC C
EP
47
54
CDI incidence was defined as the number of hospitalizations with a CDI discharge
55
diagnostic code for each year of the study among all hospital admissions. The outcomes of
56
interest were the trends for CDI incidence, mortality and hospital charges for each year of the
ACCEPTED MANUSCRIPT
study period and overall, assessed by Poisson regression. The comparison between HOCDI and
58
the control group was analyzed using Pearson X2 test for categorical variables and student’s t test
59
for continuous variables. Adjusting for demographics, source of admission, LOS and CCI in the
60
HOCDI and control groups, the risk factors associated with the diagnosis of HOCDI were
61
evaluated by logistic regression. Based the discharge outcomes, hospitalizations with CDI were
62
divided into a survival group and a death group. Risk factors for CDI-related mortality were
63
evaluated by logistic regression after adjusting for demographics, source of admission, CCI and
64
source of CDI (HOCDI and Non-HOCDI). A p-value < 0.05 was considered statistically
65
significant. All analyses were performed using Statistical Program for Social Sciences (SPSS)
66
version 22.0 (IBM, NY).
67
Results
SC
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There were 3,337,910 CDI-related hospitalizations identified out of a total of
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68
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57
318,703,355 hospitalizations (1.05%). The 10-year incidence of non-HOCDI and HOCDI was
70
0.42% and 0.63%, respectively. During the study period, the general CDI incidence increased at
71
an average annual rate of 3.3% (95% CI 2.7% - 3.8%) (P<0.001), while the average annual
72
incidence of HOCDI and non-HOCDI increased 1.4% (0.9% - 1.8%) and 2.0% (1.6% - 2.4%),
73
respectively (P<0.001) (Figure 1).
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There were 133,278 hospitalizations in each of the HOCDI and the control groups. The
75
average age of the patients was 69.1±16.8 years; 42.1% were male. The HOCDI group had
76
longer LOS (median 7 vs. 3 days, p<0.001), higher CCI (scores ≥ 3, 32.9% vs. 20%, p<0.001)
77
and were more often admitted from long-term care facilities (LTCFs) than from the community
78
(6.5% vs. 3.0%, p<0.001) compared with the control group. In a multivariate analysis, after
ACCEPTED MANUSCRIPT
79
adjusting for demographics, LOS and CCI, patients transferred from LTCFs had twice the risk of
80
HOCDI than those admitted from the community (OR=2.02, 95% CI 1.83-2.23). The overall rate of mortality of the hospitalizations with CDI was 8.5%, and significantly
82
decreased over the study period, from 9.7% in 2005 to 6.8% in 2014 (P<0.001) (Figure 2). After
83
adjusting for demographics, LOS and CCI, the patients admitted from LTCFs were at 30%
84
increased risk for mortality (OR=1.33, 95% CI 1.31-1.35) compared with those admitted from
85
the community, and the patients with HOCDI had a threefold increased risk of death during
86
hospitalization compared with those with non-HOCDI (OR=3.02, 95% CI 2.97-3.07).
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81
The sum of charges for CDI related hospitalizations increased from $20.1 billion in 2005
88
to $31.4 billion in 2014, with an average increasing rate of 2.0% (95% CI 1.2% - 2.8%, p<0.001)
89
annually. The median charge per CDI hospitalization increased from $41,974 in 2005 to $46,663
90
in 2009 (P<0.001), and then started to decrease from $45,725 in 2010 to $41,875 in 2014
91
(P<0.001).
92
Discussion
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We found the incidence of both HOCDI and non-HOCDI increased in patients
94
hospitalized at acute care hospitals during 2005-2014, with a greater increase in non-HOCDI.
95
CDI has been recognized in community and nursing home settings [4]. Although there are few
96
published studies examining the impact of non-HOCDI on the occurrence of HOCDI in acute
97
care hospitals, the incidence of community-onset CDI in a hospital is used for risk adjustment of
98
HOCDI metrics reported to the U.S. Centers for Disease Control and Prevention [5].
99 100
AC C
EP
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We found that patients who were transferred from LTCFs were at higher risk for HOCDI compared with those admitted from the community. Thus, we suspect that patients from LTCFs
ACCEPTED MANUSCRIPT
are exposed to CDI risks before admission to an acute care hospital. Hunter et al estimated that
102
there were approximately 113,000 cases of CDI with onset in nursing homes in the United States
103
in 2012, representing approximately one quarter of all U.S. CDI cases, and 73% of those cases
104
did not require hospitalization [6]. This shows that C. difficile exposure is common for patients at
105
LTCFs.
CDI is known to worsen patient outcomes and increase hospital charges [1]. We found
SC
106
RI PT
101
the in-hospital mortality of CDI significantly decreased from 2008 to 2014. With the high
108
awareness of CDI in hospitalized patients and the increased use of rapid and accurate diagnostic
109
tests like nucleic acid amplification [7], many patients are diagnosed sooner and outcomes are
110
optimized with the early implementation of appropriate treatment. We also found that the
111
charges per CDI-related hospitalization decreased since 2010. However, the annual total charges
112
for CDI-related hospitalizations still grew, likely due to the increasing incidence of CDI. Thus,
113
CDI prevention is imperative to decrease the cost of CDI-related hospitalizations in acute care
114
hospitals.
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107
Our study has several limitations. First and foremost, we cannot be certain that all CDI
116
cases occurred during the hospitalization. Subjects were identified from the database based on
117
discharge diagnoses of CDI. For patients with multiple readmissions, the discharge diagnosis of
118
CDI from a prior hospitalization may have resulted in a discharge diagnosis based on the same
119
occurrence of CDI. Because of the inability to identify unique patients in this database, we could
120
not rule out this possibility. Hence, we may have overestimated the CDI incidence in our study.
121
Second, all diagnoses were based on administrative claims data using ICD-9-CM codes. Coding
122
errors leading to missed or erroneous diagnoses are possible. Similarly, CDI subjects were
123
identified using administrative diagnostic codes not confirmed by laboratory data. Nevertheless,
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studies have shown good correlation between a C. difficile toxin assay and ICD-9-CM coding [8].
125
Third, given the lack of laboratory data in NIS and ICD-9-CM codes for the C.difficile ribotypes,
126
our study could not evaluate the impact of hypervirulent C.difficile ribotypes on CDI incidence
127
and the outcomes of infected patients. Fourth, the severity of comorbidities is associated with the
128
outcomes of hospitalized patients. We were unable to tell the severity of a disease because of the
129
limitation of claims data. Our study might have underestimated the burden of comorbidities and
130
therefore the impact on the outcomes of CDI patients.
SC
Despite these limitations, this 10-year review of CDI occurrence in acute care hospitals in
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the United States demonstrated decreased in-hospital mortality, but increased incidence and
133
hospital charges. Patients admitted from LTCFs have higher CDI risk and increase the burden of
134
CDI in acute care hospitals.
Antibiotic stewardship, in combination with strong infection control programmes, is
136
highly effective in reducing the incidence of CDI in hospitals [9]. Antibiotic stewardship is
137
increasingly recognized as an essential activity for every acute care facility. CDI prevention in
138
LTCFs is an equally high priority but implementing antibiotic stewardship programmes and
139
other measures have been more challenging. A recently published systematic review including
140
14 studies on antibiotic stewardship programs in nursing homes indicated that antibiotic
141
stewardship did not significantly change the CDI rates [10]. The LTCFs environments such as
142
residence in close, shared quarters, shared toilet facilities, and limited ability to isolated infected
143
residents are common.
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Continued efforts to improve antibiotic stewardship and infection control across healthcare settings, including long term care, is essential to curb the increasing incidence of CDI
146
and reduce the significant impact of CDI on patient outcomes and healthcare costs.
147
Acknowledgements
148
We would like to thank Dr. Janice Weinberg for her assistance with the statistical analysis in this study.
150
References
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1. Louh IK, Greendyke WG, Hermann EA, Hermann EA, Davidson KW, Falzon L, et al.
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Clostridium difficile infection in acute care hospitals: Systematic review and best practices
153
for prevention. Infect Control Hosp Epidemiol 2017; 38 (4): 476-82
154
2. Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med 2015; 372: 825-34
156
3. HCUP NIS Database Documentation. Healthcare Cost and Utilization Project (HCUP).
157
March 2017. Agency for Healthcare Research and Quality, Rockville, MD. www.hcup-
158
us.ahrq.gov/db/nation/nis/nisdbdocumentation.jsp. Accessed on 8-1-2017
160 161
4. Centers for Disease Control and Prevention (CDC). Vital signs: preventing Clostridium difficile infections. MMWR Morb Mortality Wkly Rep 2012; 61: 157-62
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5. Dudeck MA, Weiner LM, Malpiedi PJ, Edwards JR, Peterson KD, Sievert DM. Risk adjustment for healthcare for healthcare facility-onset C. difficile and MRSA bacteremia
163
laboratory-identified event reporting in NHSN. https://www.cdc.gov/nhsn/pdfs/mrsa-
164
cdi/riskadjustment-mrsa-cdi.pdf. Access on 8-1-2017
165
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6. Hunter JC, Mu Y, Dumyati GK, Farley MM, Winston LG, Johnston HL, et al. Burden of
166
nursing home-onset Clostridium difficile infection in the United States: Estimates of
167
incidence and patient outcomes. Open Forum Infect Dis 2016; 3(1): ofv196. Doi:
168
10.1093/ofid/ofv196.
169
7. Bogaty C, Levesque S, Garenc C, Frenette C, Bolduc D, Galarneau LA, et al. Trends in the
170
use of laboratory tests for the diagnosis of Clostridium difficile infection and association
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with incidence rate in Quebec, Canada, 2010-2014. Am J Infect Control 2017 May 23.
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DOI:10.1016/j.ajic.2017.04.002
174 175
8. Dubberke ER, Reske KA, McDonald LC, Fraser VJ. ICD-9 codes and surveillance for Clostridium difficile-associated disease. Emerg Infect Dis. 2006; 12: 1576-1579 9. Baur D, Gladstone BP, Burkert F, Carrara E, Foschi F, Dobele S, et al. Effect of antibiotic
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stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria
177
and Clostridium difficile infection: a systematic review and meta-analysis. Lancet Infect Dis.
178
2017; 17 (9): 990-1001
10. Feldstein D, Sloane PD, Feltner C. Antibiotic stewardship programs in nursing homes: A
180
systematic review. J Am Med Dir Assoc 2017 Aug 7. DOI: 10.1016/j.jamda.2017.06.019
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Incidence (%) 1.4
0.91
0.95
0.96
1.01
0.67 0.6
0.6
0.61
0.58
0.59
0.61
0.6 0.4 0.31
2005
2006
0.38
0.41
0.4
0.42
2007
2008
2009
2010
0
0.47
0.66
0.49
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0.2
0.34
1.18
General CDI
1.04
0.8
1.16
2011
0.69
SC
1
1.01
1.15
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1.16
1.2
2012
0.71
HOCDI
Non-HOCDI
0.48
0.48
2013
2014 Year
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Figure 1 The trend of Clostridium difficile infection incidence during 2005-2014 *CDI: Clostridium difficile infection; HOCDI: Hospital onset CDI; Non-HOCDI: Non-hospital onset CDI
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Mortality 12 9.7% 9.2%
9.4%
9.8% 9.3% 8.6% 8.0%
8
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10
7.3%
7.3%
6.8%
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6
2
0 2005
2006
2007
2008
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2009
2010
2011
2012
2013
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Figure 2 In-hospital mortality of Clostridium difficile infection patients (2005-2014)
2014
Year
S0195-6701(17)30542-X
DOI:
10.1016/j.jhin.2017.10.002
Reference:
YJHIN 5247
To appear in:
Journal of Hospital Infection
Received Date: 7 August 2017 Accepted Date: 2 October 2017
Please cite this article as: Luo R, Barlam T, A 10-year Review of Clostridium difficile Infection in Acute Care Hospitals in the United States: A Nationwide Analysis 2005-2014, Journal of Hospital Infection (2017), doi: 10.1016/j.jhin.2017.10.002. 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
A 10-year Review of Clostridium difficile Infection in Acute Care Hospitals in the United States:
2
A Nationwide Analysis 2005-2014
3
Ruihong Luo, MD, PhD, Tamar Barlam, MD, MSc
4 5
Affiliations: Section of Infectious Diseases, Boston University School of Medicine, Boston, Massachusetts, USA.
7
Short title: C. difficile infection in acute care hospitals
8
Word count: Main text: 1610; Abstract: 74
9
References: 10
SC
6
RI PT
1
Correspondence: Tamar Barlam, Boston Medical Center, 771 Albany Street, Dowling 3 North, Boston, MA 02118
12
USA.Telephone: 1-617-414-5190. Email: [email protected]. Fax: 617-414-5190
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13
ACCEPTED MANUSCRIPT
14
15
Abstract Clostridium difficile infection (CDI) is a major health concern for acute care hospitals because of the increase in the number and severity of cases. We used the Nationwide Inpatient
17
Sample database to do a 10-year review on the trends in incidence, mortality and hospital
18
charges for CDI patients in acute care hospitals during 2005-2014. We found an increased CDI
19
incidence and hospital charges, but a decreased mortality during the 10 year study period.
20
Introduction
SC
Clostridium difficile infection (CDI) has increased substantially since the year 2000.
M AN U
21
RI PT
16
Many strategies have proven successful in reducing CDI incidence, particularly antibiotic
23
stewardship, infection control and environmental management interventions [1]. Published data
24
suggests a levelling-off or decline in CDI incidence in hospitalized patients after 2009 [2], but
25
the number of cases remains high.
TE D
22
We sought to assess the change in incidence, mortality and hospital charges for CDI
27
patients in acute care hospitals for the years 2005 to 2014, and to investigate the risk factors
28
associated with hospital-onset CDI (HOCDI) and CDI-related mortality.
29
Methods
AC C
30
EP
26
We performed a retrospective cohort study using data from the Healthcare Cost and
31
Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) from 2005 to 2014. NIS is an all-
32
payer inpatient care database representing 20% of non-federal acute-care hospitals in the United
33
States, including community, general, and academic centers but not long-term care facilities.
34
Each discharge is weighted to allow for estimates projected to a national level. Each individual
ACCEPTED MANUSCRIPT
hospitalization is deidentified and maintained in the NIS as a unique entry with one primary
36
discharge diagnosis and up to 24 secondary diagnoses [3]. This study was approved by the
37
Institutional Review Board of Boston University Medical Campus.
38
RI PT
35
The International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9CM) code was used to identify patients aged ≥ 18 years with a discharge diagnosis of CDI
40
(008.45). HOCDI was defined as a patient with a secondary diagnosis of CDI and a length of
41
hospital stay (LOS) ≥ 2 days. Non-hospital onset CDI (Non-HOCDI) was defined as a patient
42
with a primary diagnosis of CDI or those with a secondary diagnosis of CDI but LOS < 2 days.
43
We randomly selected 4% of HOCDI patients for our analysis. We selected a control group of
44
patients without CDI by performing 1:1 matching with cases of HOCDI by age, sex and calendar
45
year of hospitalization.
M AN U
The variables of demographics (age, sex and ethnicity), source of admission (from
TE D
46
SC
39
community, other acute care hospitals or long-term care facilities), discharge outcome (death or
48
survival), length of hospital stay (LOS), and total hospital charges were extracted from the NIS
49
dataset to provide subject characteristics. The hospital charges refer to the charges that the
50
hospital levied to the patients. All dollar amounts in this report were adjusted to inflation based
51
on the year 2014. The LOS refers to the total number of continuous days a patient was
52
hospitalized. We examined Charlson comorbidity index (CCI) score by identifying comorbid
53
conditions using their corresponding ICD-9-CM codes.
AC C
EP
47
54
CDI incidence was defined as the number of hospitalizations with a CDI discharge
55
diagnostic code for each year of the study among all hospital admissions. The outcomes of
56
interest were the trends for CDI incidence, mortality and hospital charges for each year of the
ACCEPTED MANUSCRIPT
study period and overall, assessed by Poisson regression. The comparison between HOCDI and
58
the control group was analyzed using Pearson X2 test for categorical variables and student’s t test
59
for continuous variables. Adjusting for demographics, source of admission, LOS and CCI in the
60
HOCDI and control groups, the risk factors associated with the diagnosis of HOCDI were
61
evaluated by logistic regression. Based the discharge outcomes, hospitalizations with CDI were
62
divided into a survival group and a death group. Risk factors for CDI-related mortality were
63
evaluated by logistic regression after adjusting for demographics, source of admission, CCI and
64
source of CDI (HOCDI and Non-HOCDI). A p-value < 0.05 was considered statistically
65
significant. All analyses were performed using Statistical Program for Social Sciences (SPSS)
66
version 22.0 (IBM, NY).
67
Results
SC
M AN U
There were 3,337,910 CDI-related hospitalizations identified out of a total of
TE D
68
RI PT
57
318,703,355 hospitalizations (1.05%). The 10-year incidence of non-HOCDI and HOCDI was
70
0.42% and 0.63%, respectively. During the study period, the general CDI incidence increased at
71
an average annual rate of 3.3% (95% CI 2.7% - 3.8%) (P<0.001), while the average annual
72
incidence of HOCDI and non-HOCDI increased 1.4% (0.9% - 1.8%) and 2.0% (1.6% - 2.4%),
73
respectively (P<0.001) (Figure 1).
AC C
74
EP
69
There were 133,278 hospitalizations in each of the HOCDI and the control groups. The
75
average age of the patients was 69.1±16.8 years; 42.1% were male. The HOCDI group had
76
longer LOS (median 7 vs. 3 days, p<0.001), higher CCI (scores ≥ 3, 32.9% vs. 20%, p<0.001)
77
and were more often admitted from long-term care facilities (LTCFs) than from the community
78
(6.5% vs. 3.0%, p<0.001) compared with the control group. In a multivariate analysis, after
ACCEPTED MANUSCRIPT
79
adjusting for demographics, LOS and CCI, patients transferred from LTCFs had twice the risk of
80
HOCDI than those admitted from the community (OR=2.02, 95% CI 1.83-2.23). The overall rate of mortality of the hospitalizations with CDI was 8.5%, and significantly
82
decreased over the study period, from 9.7% in 2005 to 6.8% in 2014 (P<0.001) (Figure 2). After
83
adjusting for demographics, LOS and CCI, the patients admitted from LTCFs were at 30%
84
increased risk for mortality (OR=1.33, 95% CI 1.31-1.35) compared with those admitted from
85
the community, and the patients with HOCDI had a threefold increased risk of death during
86
hospitalization compared with those with non-HOCDI (OR=3.02, 95% CI 2.97-3.07).
M AN U
SC
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81
The sum of charges for CDI related hospitalizations increased from $20.1 billion in 2005
88
to $31.4 billion in 2014, with an average increasing rate of 2.0% (95% CI 1.2% - 2.8%, p<0.001)
89
annually. The median charge per CDI hospitalization increased from $41,974 in 2005 to $46,663
90
in 2009 (P<0.001), and then started to decrease from $45,725 in 2010 to $41,875 in 2014
91
(P<0.001).
92
Discussion
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87
We found the incidence of both HOCDI and non-HOCDI increased in patients
94
hospitalized at acute care hospitals during 2005-2014, with a greater increase in non-HOCDI.
95
CDI has been recognized in community and nursing home settings [4]. Although there are few
96
published studies examining the impact of non-HOCDI on the occurrence of HOCDI in acute
97
care hospitals, the incidence of community-onset CDI in a hospital is used for risk adjustment of
98
HOCDI metrics reported to the U.S. Centers for Disease Control and Prevention [5].
99 100
AC C
EP
93
We found that patients who were transferred from LTCFs were at higher risk for HOCDI compared with those admitted from the community. Thus, we suspect that patients from LTCFs
ACCEPTED MANUSCRIPT
are exposed to CDI risks before admission to an acute care hospital. Hunter et al estimated that
102
there were approximately 113,000 cases of CDI with onset in nursing homes in the United States
103
in 2012, representing approximately one quarter of all U.S. CDI cases, and 73% of those cases
104
did not require hospitalization [6]. This shows that C. difficile exposure is common for patients at
105
LTCFs.
CDI is known to worsen patient outcomes and increase hospital charges [1]. We found
SC
106
RI PT
101
the in-hospital mortality of CDI significantly decreased from 2008 to 2014. With the high
108
awareness of CDI in hospitalized patients and the increased use of rapid and accurate diagnostic
109
tests like nucleic acid amplification [7], many patients are diagnosed sooner and outcomes are
110
optimized with the early implementation of appropriate treatment. We also found that the
111
charges per CDI-related hospitalization decreased since 2010. However, the annual total charges
112
for CDI-related hospitalizations still grew, likely due to the increasing incidence of CDI. Thus,
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CDI prevention is imperative to decrease the cost of CDI-related hospitalizations in acute care
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hospitals.
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Our study has several limitations. First and foremost, we cannot be certain that all CDI
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cases occurred during the hospitalization. Subjects were identified from the database based on
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discharge diagnoses of CDI. For patients with multiple readmissions, the discharge diagnosis of
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CDI from a prior hospitalization may have resulted in a discharge diagnosis based on the same
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occurrence of CDI. Because of the inability to identify unique patients in this database, we could
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not rule out this possibility. Hence, we may have overestimated the CDI incidence in our study.
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Second, all diagnoses were based on administrative claims data using ICD-9-CM codes. Coding
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errors leading to missed or erroneous diagnoses are possible. Similarly, CDI subjects were
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identified using administrative diagnostic codes not confirmed by laboratory data. Nevertheless,
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studies have shown good correlation between a C. difficile toxin assay and ICD-9-CM coding [8].
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Third, given the lack of laboratory data in NIS and ICD-9-CM codes for the C.difficile ribotypes,
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our study could not evaluate the impact of hypervirulent C.difficile ribotypes on CDI incidence
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and the outcomes of infected patients. Fourth, the severity of comorbidities is associated with the
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outcomes of hospitalized patients. We were unable to tell the severity of a disease because of the
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limitation of claims data. Our study might have underestimated the burden of comorbidities and
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therefore the impact on the outcomes of CDI patients.
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Despite these limitations, this 10-year review of CDI occurrence in acute care hospitals in
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the United States demonstrated decreased in-hospital mortality, but increased incidence and
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hospital charges. Patients admitted from LTCFs have higher CDI risk and increase the burden of
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CDI in acute care hospitals.
Antibiotic stewardship, in combination with strong infection control programmes, is
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highly effective in reducing the incidence of CDI in hospitals [9]. Antibiotic stewardship is
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increasingly recognized as an essential activity for every acute care facility. CDI prevention in
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LTCFs is an equally high priority but implementing antibiotic stewardship programmes and
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other measures have been more challenging. A recently published systematic review including
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14 studies on antibiotic stewardship programs in nursing homes indicated that antibiotic
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stewardship did not significantly change the CDI rates [10]. The LTCFs environments such as
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residence in close, shared quarters, shared toilet facilities, and limited ability to isolated infected
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residents are common.
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Continued efforts to improve antibiotic stewardship and infection control across healthcare settings, including long term care, is essential to curb the increasing incidence of CDI
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and reduce the significant impact of CDI on patient outcomes and healthcare costs.
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Acknowledgements
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We would like to thank Dr. Janice Weinberg for her assistance with the statistical analysis in this study.
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References
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1. Louh IK, Greendyke WG, Hermann EA, Hermann EA, Davidson KW, Falzon L, et al.
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Incidence (%) 1.4
0.91
0.95
0.96
1.01
0.67 0.6
0.6
0.61
0.58
0.59
0.61
0.6 0.4 0.31
2005
2006
0.38
0.41
0.4
0.42
2007
2008
2009
2010
0
0.47
0.66
0.49
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0.2
0.34
1.18
General CDI
1.04
0.8
1.16
2011
0.69
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1
1.01
1.15
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1.16
1.2
2012
0.71
HOCDI
Non-HOCDI
0.48
0.48
2013
2014 Year
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Figure 1 The trend of Clostridium difficile infection incidence during 2005-2014 *CDI: Clostridium difficile infection; HOCDI: Hospital onset CDI; Non-HOCDI: Non-hospital onset CDI
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Mortality 12 9.7% 9.2%
9.4%
9.8% 9.3% 8.6% 8.0%
8
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7.3%
7.3%
6.8%
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2
0 2005
2006
2007
2008
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2009
2010
2011
2012
2013
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Figure 2 In-hospital mortality of Clostridium difficile infection patients (2005-2014)
2014
Year