National Trends (2007-2013) of Clostridium difficile Infection in Patients with Septic Shock: Impact on Outcome
BACKGROUND: Clostridium difficile is the most common infectious cause of healthcare-associated diarrhea and is associated with worse outcomes and higher cost. Patients with septic shock (SS) are at increased risk of acquiring C. difficile infections (CDIs) during hospitalization, but little data are available on CDI complicating SS.
OBJECTIVE: Prevalence of CDI in SS between 2007-2013 and impact of CDI on outcomes in SS.
DESIGN: We used the National Inpatient Sample to identify hospitalizations (2007-2013) of adults with SS and CDI and the Nationwide Readmissions Database 2013 to calculate 30-day readmissions.
MAIN MEASUREMENTS: Outcomes were prevalence of CDI in SS, effect on mortality, length of stay (LOS), and 30-day readmission.
RESULTS: There were 2,031,739 hospitalizations with SS (2007-2013). CDI was present in 8.2% of SS. The in-hospital mortality of SS with and without CDI were comparable (37.1% vs 37.0%; P = 0.48). Median LOS was longer for SS with CDI (13 days vs 9 days; P < 0.001). LOS >75th percentile (>17 days) was 36.9% in SS with CDI vs 22.7% without CDI (P < 0.001). Similarly, LOS > 90th percentile (> 29 days) was 17.5% vs 9.1%, P < 0.001. Odds of LOS >75% and >90% in SS were greater with CDI (odds ratio [OR] 2.11; 95% confidence interval [CI], 2.06-2.15; P < 0.001 and OR 2.25; 95% CI, 2.22-2.28; P < 0.001, respectively). Hospital readmission of SS with CDI was increased, adjusted OR 1.26 (95% CI, 1.22-1.31; P < 0.001).
CONCLUSIONS: CDI complicating SS is common and is associated with increased hospital LOS and 30-day hospital readmission. This represents a population in which a focus on prevention and treatment may improve clinical outcomes.
© 2017 Society of Hospital Medicine
Outcomes
Our primary outcome of interest was the total and yearly prevalence of CDI in patients with SS from 2007 to 2013. The secondary outcomes were mortality, LOS, and 30-day readmissions in patients with SS with and without CDI.
Statistical Analysis
Weighted data from NIS were used for all analyses. Demographics, hospital characteristics, and outcomes of all patients with SS were obtained. The prevalence of CDI was calculated for each calendar year. The temporal trends of outcomes (LOS and in-hospital mortality) of patients were plotted for patients with SS with and without CDI. A χ2 test of trend for proportions was used with the Cochran-Armitage test to calculate statistical significance of changes in prevalence. To test for statistical significance of the temporal trends of LOS, a univariate linear regression was used, with calendar year as a covariate. Independent samples t test, a Mann-Whitney U test, and a χ2 test were used to determine statistical significance of parameters between the group with CDI and the group without CDI.
Prolonged LOS was defined either as a LOS > 75th or > 90th percentile of LOS among all patients with SS. To identify if CDI was associated with a prolonged LOS after adjusting for patient and hospital characteristics, a multivariate logistic regression analysis was used. Variables included in the regression model were age, gender, race, Charlson-Deyo Comorbidity Index, hospital characteristics (hospital region, hospital-bed size, urban versus rural location, and teaching status), calendar year, and use of mechanical ventilation. Data on cases were available for all the above covariates except hospital characteristics, such as teaching status, location, and bed size (these were missing for 0.7% of hospitals).
Stata 13.1.0 (Stata Corp, College Station, TX) and SPSS 23.0 (SPSS Inc., Chicago, IL) were used to perform statistical analyses. A P value of <0.05 was considered statistically significant.
RESULTS
Demographics
A total of 2,031,739 hospitalizations of adults with SS were identified between 2007 and 2013. CDI was present in 166,432 (8.2%) of these patients. Demographic data are displayed in Table 1. CDI was more commonly observed in elderly patients (> 65 years) with SS; 9.3% among the elderly versus 6.6% among individuals < 65 years; P < 0.001. The prevalence of CDI was greater in urban than in rural hospitals (8.4% vs 5.4%; P < 0.001) and greater in teaching than in nonteaching hospitals (8.7% vs 7.7%; P < 0.001). The prevalence of CDI in SS remained stable between 2007 and 2013 (Table 2).
Mortality
In the overall study cohort, the in-hospital mortality for SS was 37%. The in-hospital mortality rate of patients with SS complicated by a CDI was comparable to the mortality rate of patients without a CDI (37.1% vs 37.0%; P = 0.48). The mortality of patients with SS, with or without CDI, progressively decreased from 2007 to 2013 (P value for trend < 0.001 for each group; Figure 1).
Length of Stay
The median LOS for all patients with SS was 9 days. Patients with CDI had a longer median LOS than did those without CDI (13 vs 9 days; P < 0.001). Between 2007 and 2013, the median LOS of CDI group decreased from 14 to 12 days (P < 0.001) while that of non-CDI group decreased from 9 to 8 days (P < 0.001; Figure 2). We also examined LOS among subgroups who were discharged alive and those who died during hospitalization. For patients who were discharged alive, the LOS with and without CDI was 15 days versus 10 days, respectively (P < 0.001). For patients who died during hospitalization, LOS with and without CDI was 10 days versus 6 days, respectively (P < 0.001).
The 75th percentile of LOS of the total SS cohort was 17 days. An LOS > 17 days was observed in 36.9% of SS patients with CDI versus 22.7% without CDI (P < 0.001). After adjusting for patient and provider level variables, the odds of a LOS > 17 days were significantly greater for SS patients with CDI (odds ratio [OR] 2.11; 95% confidence interval [CI], 2.06-2.15; P < 0.001).
The 90th percentile of LOS of the total SS cohort was 29 days. An LOS > 29 days was observed in 17.5% of SS patients with a CDI versus 9.1% without a CDI (P < 0.001). After adjustment for patient and provider level variables, the odds of a LOS > 29 days were significantly greater for SS patients with a CDI (OR 2.25; 95% CI, 2.22-2.28; P < 0.001).
Hospital Readmission
In 2013, patients with SS and CDI had a higher rate of 30-day readmission as compared to patients with SS without CDI (9.8% vs 7.4% respectively; P < 0.001). The multivariate adjusted OR for 30-day readmission for patients with SS and a CDI was 1.26 (95% CI, 1.22-1.31; P < 0.001).
