Optimal management of inflammatory bowel disease (IBD) with concomitant
We performed a multicenter review of all inpatients with IBD and PCR diagnosed CDI. Outcomes included length of stay, 30- and 90-day readmission, colectomy during admission and within 3 months, intensive care unit (ICU) admission, CDI relapse and death for patients who received corticosteroid (CS) after CDI diagnosis versus those that did not. Propensity-adjusted regression analysis of outcomes based on CS usage was performed.
We identified 177 IBD patients with CDI, 112 ulcerative colitis and 65 Crohn’s disease. For IBD overall, CS after CDI diagnosis was associated with prolonged hospitalization (5.5 days: 95% confidence interval [CI], 1.5–9.6 days;
CS use among IBD inpatients with CDI diagnosed by PCR is associated with poorer outcomes and would seem to reinforce the importance of
Inflammatory bowel disease (IBD), mainly including CD and UC, is a condition caused by a dysregulated immune response to non-pathogenic gut microflora resulting in spontaneous and chronic inflammation of the bowel [
Given the similar presentations, IBD flare may be clinically indistinguishable from CDI. Treatment of IBD with CDI presents a clinical dilemma, as IBD therapies may need to continue or even be intensified to treat the underlying disease, but may result in worse outcomes in those with concurrent CDI [
Most prior investigations of IBD and CDI outcomes have diagnosed CDI by enzyme immunoassay (EIA) testing for toxin A/B [
For the management of inpatients with IBD exacerbation, CS remain a mainstay of acute therapy. To date, no studies have investigated whether CDI diagnosed by high sensitivity PCR with IBD carries the same risk for adverse outcomes as CDI diagnosed by EIA testing during hospitalization for IBD exacerbation. Our goal was to analyze the effect of CS use on the clinical outcomes in IBD inpatients with CDI diagnosed by PCR alone.
The study was approved by the Northwell Health System and Stony Brook Institutional Review Boards (IRB No. HS16-0306). The study population was defined as all patients 18 years of age or older hospitalized with a diagnosis of IBD and concomitant PCR-diagnosed CDI at 7 institutions across the Northwell Health system (2 tertiary care hospitals and 5 community hospitals) and Stony Brook University Hospital from 2011 to 2016 identified via Sunrise and Cerner PowerChart, the centralized clinical data registry for Northwell Health and Stony Brook University Hospital respectively. While a positive PCR alone may indicate colonization without infection, the study marks the period of time in which 1-step PCR testing without additional EIA toxin assay was the standard method of CDI diagnosis at all of the institutions studied, and the results reflect this method of diagnosis. During the study period laboratory protocol specified that only stools without any formation, Bristol Stool Scale 6 or 7, would undergo PCR testing which is a common method of excluding potential cases of
Patients admitted with IBD and PCR-diagnosed CDI were stratified into 2 groups: patients who received CS post-CDI diagnosis and patients who did not receive CS post-CDI diagnosis. CS use post-CDI diagnosis was defined as any dose of CS use in the inpatient setting after the diagnosis of CDI and given for at least 3 days. Pre-CDI diagnosis CS use and inpatient immunomodulator/biologic use were also evaluated for their effect on adverse outcomes. Pre-CDI diagnosis CS use was defined as any dose used in the outpatient or inpatient setting prior to the diagnosis of CDI. Pre-admission immunomodulator/biologic therapy was defined by patient reported active use of 6-mercaptopurine, azathioprine, methotrexate, infliximab, adalimumab, certolizumab, golimumab, vedolizumab or ustekinumab in their admission medications list. Inpatient immunomodulator/biologic therapy was defined by the use of 6-mercaptopurine, azathioprine, methotrexate, infliximab, adalimumab, certolizumab, golimumab, vedolizumab or ustekinumab documented as ordered in the hospital record. Demographic data such as age, gender and disease type, CD versus UC were collected. Given the absence of validated clinical or endoscopic disease severity indices for CD or UC from the medical record, surrogate demographic and clinical markers previously used in retrospective studies to assess colitis severity such as patient’s age, BMI, albumin, creatinine, white blood cell count and hypotension (defined as systolic blood pressure <100 mmHg) within 48 hours of admission were collected.
The outcomes assessed were: length of stay, 30- and 90-day readmission with IBD flare or CDI symptoms defined as having diarrhea, abdominal pain or blood in stool, colectomy within 3 months of admission, intensive care unit (ICU) admission during initial admission, colon perforation requiring colectomy during the same hospitalization, CDI relapse defined as re-hospitalization within 3 months of previous admission with CDI, and death. Patients who underwent colectomies were censored for readmission outcomes as patients could not be readmitted for symptoms of colitis post-colectomy. Outcomes were evaluated for the entire cohort and then stratified by disease UC and CD respectively.
Statistical analyses were performed using Intercooled Stata software, version 12.0 (StataCorp, College Station, TX, USA). Fisher exact test was used for comparisons of categorical variables.
We identified 177 patients with IBD and PCR diagnosed CDI (154 from the 7 Northwell Health institutions and 23 from Stony Brook University Hospital) from 2011 to 2016, 61% female and approximately two-thirds with UC (
During hospitalization 37 patients (21%) had endoscopic evaluation, of which 18 had colonoscopy and 19 had flexible sigmoidoscopy. Among the clinical parameters of disease severity analyzed, patients not receiving CS following CDI diagnosis were more likely to have a creatinine level greater than 1.3 mg/dL (
The median length of stay for all patients was 7 days (interquartile range, 4–11 days). On the unadjusted analysis, median length of stay for patients who received CS post-CDI diagnosis was 8 days compared to 6 days in patients who did not receive CS post-CDI diagnosis (
Median length of stay for UC patients who received CS post-CDI diagnosis was 8 days compared to 5 days in patients who did not receive CS post-CDI diagnosis (
Median length of stay for CD patients who received CS post-CDI diagnosis was 7.5 days compared to 5 days in patients who did not receive CS post-CDI diagnosis (
CS use post-CDI diagnosis was associated with prolonged hospitalization (5.5 days: 95% CI, 1.5–9.6 days;
CS use post-CDI diagnosis in UC patients was associated with prolonged hospitalization (6.2 days: 95% CI, 0.4–12.0 days;
We performed a sensitivity analyses accounting for dose ranges, and demonstrated no differences in the association of receiving CS following CDI diagnosis on length of stay, 30-day readmission, 90-day readmission and CDI relapse. Colectomy and ICU stay outcomes were too small for analysis.
In the present study, we have demonstrated that patients who received CS for presumed IBD exacerbation following a diagnosis of CDI by PCR had an increased length of hospital stay, higher rate of ICU admission and increased rate of colectomy by propensity-adjusted regression analysis. Pre-CDI diagnosis CS use alone was not associated with negative outcomes. The wide confidence intervals with patients at higher risk of colectomy and ICU admission are in keeping with the small number of outcomes in this cohort. When stratified by IBD type, CS post-CDI diagnosis was not associated with adverse outcomes in the CD group but was associated with an increased length of stay and ICU admission in UC patients. Propensityadjusted regression analysis was not performed for immunomodulator/biologic use for subgroups of UC and CD as the outcomes were too small for analysis.
Given the paucity of available data, there is significant variability in treatment practices for patients with IBD flares and CDI [
Ben-Horin et al. [
While we have shown an association between CS use and adverse outcomes, limitations of the retrospective study design prevent drawing any stronger conclusions of a direct cause and effect relationship. Our main limiting factor, common to other retrospective work analyzing IBD populations, was the lack of standard IBD clinical activity scores to allow for additional analysis of outcomes by disease severity. Also, with only 21% of our own patients having either colonoscopy or sigmoidoscopy, we were unable to analyze outcomes by endoscopic disease severity or phenotype. Though surrogate markers of disease severity used in other recent retrospective studies of IBD and
Gaps in the medical record, as well the small number of endoscopic procedures also prevented analysis by IBD clinical characteristics beyond the diagnosis of CD or UC. Additional bias would include the lack of a protocol directing the choice of antibiotic therapy prescribed, though the analysis found no gross difference in antibiotics used between those receiving and not receiving CS.
It is important to note that the decision to begin CS was made for almost all patients prior to or immediately following their CDI diagnosis, that is, patients receiving CS following CDI diagnosis were generally not given an opportunity to recover with a trial of antibiotic therapy alone, as recent expert opinion has recommended [
In conclusion, we have demonstrated that among hospitalized patients with UC and PCR diagnosed CDI, post-CDI diagnosis CS use was associated with an increased risk of colectomy, ICU admission and prolonged hospitalization. Our findings suggest that CS use among hospitalized UC patients with PCR diagnosed
The authors received no financial support for the research, authorship, and/or publication of this article.
No potential conflict of interest relevant to this article was reported.
Lim HW and Sultan K designed the study, collected, analyzed and interpreted the data. Lim HW, Schuster IP, and Sultan K performed the literature review and wrote the article. Rajapakse R, Monzur F, and Sultan K critically revised the manuscript. Khan S provided administrative and material support. Lim HW is the article guarantor. Approval of final manuscript: all authors.
We thank Kay Chen, BS of Stony Brook University Hospital for assistance with data collection.
Demographic and Clinical Characteristics of the Study Population
Characteristic | All patients (n=177) | Received CS post-CDI diagnosis (n=64) | Did not receive CS post-CDI diagnosis (n=113) | |
---|---|---|---|---|
Age (yr) | 46 (28–67) | 38 (23–62) | 53 (32–71) | 0.003 |
Female sex | 108 (61.02) | 38 (59.38) | 70 (61.95) | 0.736 |
BMI (kg/m2) | 24 (20–28) | 24 (20–28) | 24 (20–28) | 0.797 |
UC | 112 (63.28) | 44 (68.75) | 68 (60.18) | 0.330 |
CD | 65 (36.72) | 20 (31.25) | 45 (39.82) | 0.330 |
Race | 0.969 | |||
White | 95 (53.67) | 35 (54.69) | 60 (53.10) | |
African American | 12 (6.78) | 4 (6.25) | 8 (7.08) | |
Asian | 11 (6.21) | 4 (6.25) | 7 (6.19) | |
Other/multiracial | 59 (33.33) | 21 (32.81) | 38 (33.63) | |
Proton pump inhibitor/H2 blocker on prior month | 43 (24.29) | 14 (21.88) | 29 (25.66) | 0.572 |
Immunomodulator/biologic used in prior month | 68 (38.42) | 24 (37.50) | 44 (38.94) | 0.850 |
Inpatient immunomodulator/biologic use | 72 (40.68) | 33 (51.56) | 39 (34.51) | 0.027 |
Pre-admit CS use | 32 (18.08) | 20 (31.25) | 12 (10.62) | 0.001 |
Pre-CDI diagnosis CS use | 76 (42.94) | 53 (82.81) | 23 (20.35) | 0.000 |
Time to CDI diagnosis (day) | 1 (1–2) | 2 (1–3) | 1 (1–2) | 0.987 |
Values are presented as median (interquartile range) or number (%).
Significant
CS, corticosteroid; CDI,
Clinical Parameters Indicating Severity at Presentation of the Study Population
Parameter | All patients (n=177) | Received CS post-CDI diagnosis (n=64) | Did not receive CS post-CDI diagnosis (n=113) | |
---|---|---|---|---|
Leukocytosis >15×103 cells/μL | 61 (34.46) | 34 (53.13) | 27 (23.89) | 0.563 |
Hypoalbuminemia <2.5 g/dL | 31 (17.51) | 10 (15.63) | 21 (18.58) | 0.614 |
Elevated creatinine >1.3 mg/dL | 35 (19.77) | 7 (10.94) | 28 (24.78) | 0.026 |
Systolic blood pressure <100 mmHg | 73 (41.24) | 24 (37.50) | 49 (43.36) | 0.651 |
Values are presented as number (%).
Significant
CS, corticosteroid; CDI,
Unadjusted Outcomes Analysis for All Patients
Outcome | All patients (n=177) | Received CS post-CDI diagnosis (n=64) | Did not receive CS post-CDI diagnosis (n=113) | |
---|---|---|---|---|
Length of stay in days | 7 (4–11) | 8 (5–16) | 6 (3–9) | 0.001 |
30-Day readmission | 16 (9.04) | 4 (6.25) | 12 (10.62) | 0.407 |
90-Day readmission | 28 (15.82) | 7 (10.94) | 21 (18.58) | 0.252 |
Colectomy within 3 months of admission | 14 (7.91) | 8 (12.50) | 6 (5.31) | 0.089 |
ICU admission | 14 (7.91) | 9 (14.06) | 5 (4.42) | 0.007 |
Colon perforation | 3 (1.69) | 3 (4.69) | 0 | 0.020 |
CDI relapse | 26 (14.69) | 7 (10.94) | 19 (16.81) | 0.289 |
Death | 5 (2.82) | 2 (3.13) | 3 (2.65) | 0.856 |
Values are presented as median (interquartile range) or number (%).
Significant
CS, corticosteroid; CDI,
Unadjusted Outcome Analysis for UC Patients
Outcome | All UC patients (n=112) | Received CS post-CDI diagnosis (n=44) | Did not receive CS post-CDI diagnosis (n=68) | |
---|---|---|---|---|
Length of stay in days | 8 (4–12) | 8 (5–18) | 7 (4–10) | 0.048 |
30-Day readmission | 8 (7.14) | 3 (6.82) | 5 (7.35) | 0.919 |
90-Day readmission | 15 (13.39) | 5 (11.36) | 10 (14.71) | 0.252 |
Colectomy within 3 months of admission | 7 (6.25) | 6 (13.64) | 1 (1.47) | 0.009 |
ICU admission | 11 (9.82) | 7 (15.91) | 4 (5.88) | 0.007 |
Colon perforation | 3 (2.68) | 3 (6.82) | 0 | 0.028 |
CDI relapse | 18 (16.07) | 5 (11.36) | 13 (19.12) | 0.290 |
Death | 5 (4.46) | 2 (4.55) | 3 (4.41) | 0.960 |
Values are presented as median (interquartile range) or number (%).
Significant
CS, corticosteroid; CDI,
Unadjusted Outcome Analysis for CD patients
Outcome | All CD patients (n=65) | Received CS post-CDI diagnosis (n=20) | Did not receive CS post-CDI diagnosis (n=45) | |
---|---|---|---|---|
Length of stay in days | 10 (6–17) | 7.5 (5–14) | 5 (3–8) | 0.015 |
30-day readmission | 8 (12.31) | 1 (5.00) | 7 (15.56) | 0.234 |
90-day readmission | 13 (20.00) | 2 (10.00) | 11 (24.44) | 0.180 |
Colectomy within 3 months of admission | 7 (10.77) | 2 (10.00) | 5 (11.11) | 0.916 |
ICU admission | 3 (4.62) | 2 (10.00) | 1 (2.22) | 0.161 |
Colon perforation | 0 | 0 | 0 | NA |
CDI relapse | 8 (12.31) | 2 (10.00) | 6 (13.33) | 0.728 |
Death | 0 | 0 | 0 | NA |
Values are presented as median (interquartile range) or number (%).
Significant
CS, corticosteroid; CDI,
Outcomes: Propensity-Adjusted Regression Analysis
Outcome | Received CS pre-CDI diagnosis |
Received CS post-CDI diagnosis |
Inpatient Immunomodulator/biologic use |
|||
---|---|---|---|---|---|---|
OR (95% CI) | OR (95% CI) | OR (95% CI) | ||||
Length of stay (day) | 1.0 (–3.07 to 5.10) | 0.624 | 5.5 (1.45 to 9.56) | 0.008 |
0.3 (–2.92 to 3.61) | 0.835 |
30-Day readmission | 3.2 (0.89 to 11.77) | 0.074 | 0.2 (0.03 to 0.98) | 0.047 |
2.3 (0.70 to 7.52) | 0.169 |
90-Days readmission | 3.3 (1.16 to 9.17) | 0.025 |
0.3 (0.09 to 0.94) | 0.040 |
1.4 (0.56 to 3.39) | 0.478 |
Colectomy within 3 months of admission | 1.9 (0.32 to 10.84) | 0.483 | 5.5 (1.07 to 28.24) | 0.042 |
0.6 (0.15 to 2.08) | 0.381 |
ICU admission | 0.9 (0.15 to 5.15) | 0.894 | 7.8 (1.45 to 41.57) | 0.017 |
0.2 (0.04 to 0.96) | 0.054 |
CDI relapse | 1.4 (0.46 to 4.04) | 0.568 | 0.5 (0.16 to 1.74) | 0.297 | 0.8 (0.30 to 1.95) | 0.577 |
Significant
CS, corticosteroid; CDI,
Outcomes: Propensity-Adjusted Regression Analysis of CS Use Post-CDI Diagnosis Based on Types of IBD
Outcome | Received CS post-CDI diagnosis |
|||
---|---|---|---|---|
UC |
CD |
|||
OR (95% CI) | OR (95% CI) | |||
Length of stay (day) | 6.2 (0.41 to 12.01) | 0.036 |
1.6 (–3.88 to 7.16) | 0.553 |
30-Day readmission | 0.4 (0.05 to 2.92) | 0.356 | NA | |
90-Days readmission | 0.4 (0.09 to 1.91) | 0.264 | 0.2 (0.02 to 1.18) | 0.072 |
Colectomy within 3 months of admission | 10.8 (0.79 to 148.42) | 0.074 | 3.54 (0.12 to 80.52) | 0.427 |
ICU admission | 7.4 (1.14 to 48.67) | 0.036 |
NA | |
CDI relapse | 0.2 (0.01 to 3.28) | 0.273 | 0.9 (0.21 to 3.68) | 0.857 |
Significant
CS, corticosteroid; CDI,