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Abstract

Background:

Clostridioides difficile infection (CDI) is a clinical challenge associated with poor outcomes in patients with inflammatory bowel disease (IBD).

Objectives:

To identify clinical risk factors for CDI and its recurrence among patients with IBD.

Design:

Case–control cohort study of IBD patients with and without episodes of CDI.

Methods:

A case–control study of 279 IBD patients with CDI. Medical history and IBD-related symptoms 3 months preceding a toxin-positive CDI were recorded and compared with age- and sex-matched IBD patients without CDI. Outcomes of CDI in IBD patients were recorded 2–6 months after CDI.

Results:

Based on clinical symptoms and fecal calprotectin levels, IBD is active before CDI. Recently diagnosed IBD seemed to increase the risk for CDI. Corticosteroid usage frequently preceded CDI episodes. Advanced therapies were not associated with CDI. Antibiotic intake was not registered before CDI in 30% of the episodes. Recurrent CDI (rCDI) occurred in 30% (84/279) of IBD-CDI patients and 67% (90/135) of those episodes were registered within 90 days from the preceding episode. Most (79%) rCDI patients had ulcerative colitis (UC). CDI could complicate underlying IBD by increasing the need for escalation in IBD-related medical therapy and leading to hospitalization but it did not seem to increase the risk of colectomy.

Conclusion:

The major risk factors associated with CDI in IBD patients were IBD activity before infection, UC and colonic Crohn’s disease, short duration of IBD, corticosteroid usage, and hospitalization. Patients with active IBD and a shorter disease duration may benefit from more frequent follow-ups in the early stages, as they appear to be at higher risk of developing CDI.

Keywords

gastrointestinal infections inflammatory bowel disease

Introduction

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal (GI) tract. The two major subtypes are Crohn’s disease (CD) and ulcerative colitis (UC). Unclassified IBD (IBD-U) is a subtype that exhibits characteristics of both UC and CD. The prevalence of IBD has increased worldwide in the past few decades, especially in industrialized countries.^1,2 Typical disease onset is in young adulthood; however, increasing incidence has also been observed in the elderly.³ A combination of hereditary predisposition, abnormal intestinal immunity, intestinal bacteria, and nutritional and environmental factors have all been estimated to influence the onset of IBD.⁴ IBD is characterized by relapses and remitting episodes with poorly characterized etiology and an unpredictable clinical course.

GI infections cause approximately 10% of disease flares in IBD patients.⁵ One common such infection is caused by Clostridioides difficile.⁶ Clostridioides difficile infection (CDI) has been noted to increase in incidence among IBD patients and complicate the course of underlying IBD.^7–10 CDI frequently leads to flare-ups of underlying IBD, causes treatment failure in IBD remission, increases the need for colectomy, and even raises mortality rates.^9,11–13 The risk of CDI among IBD patients is nearly five-fold compared to the general population, and its recurrence has been reported to be slightly higher than in non-IBD patients (30% vs 24%).^14,15 Patients with UC have reportedly been more susceptible to CDI than CD patients.^8,12

IBD appears to be an independent risk factor for CDI, even without antibiotics exposure or hospitalization.^7,16 Other IBD-related risk factors, such as pre-existing colonic inflammation and the use of immunosuppressants and biologicals, have been evaluated to predispose to CDI.^17–19

IBD patients with CDI pose a clinical challenge in getting correctly diagnosed due to presenting with symptoms similar to an IBD flare and CDI. These two conditions require distinctly different treatment approaches. For an IBD flare, treatment often involves escalating immunosuppression. However, in cases of active CDI, treatment focuses on reducing immunosuppression and administering antibiotics.

This study sought to characterize the risk factors for CDI in IBD patients in the era of the common use of biological and immunosuppressive medication and the effect of CDI on the course of IBD in a large case–control setting. We also examined whether active IBD predisposed individuals to CDI.

Methods

Study design

This was a retrospective, single-center cohort study performed in Finland with a high IBD prevalence of 1% of the population and equal access to high-quality health care.²⁰ The clinical data of 279 IBD patients diagnosed with a CDI episode were collected from electronic patient charts of Helsinki University Hospital (HUH). The medical records from 2008 to 2021 were reviewed, and data from these records were collected between October 2021 and March 2023. A subset of the study individuals was included in a previous study.²¹ The reporting of this study conforms to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.²²

Patients

All patients were diagnosed with IBD according to clinical evaluation and standard clinical, endoscopic, radiological, and histological diagnostic investigations. Patients diagnosed with IBD less than 1 month before CDI and patients under 18 years of age were excluded. The patients were treated according to international guidelines and local routines, which endorse CDI testing upon IBD flare-ups and other GI symptoms.

CDI episodes

The CDI episodes were diagnosed according to clinical routines and confirmed with the polymerase chain reaction method of a toxin gene in the clinical laboratory. Recurrent CDI (rCDI) was defined as a symptomatic CDI with a positive stool test following an eradication treatment of the previous CDI diagnosed at least 14 days before. The time interval between separate CDI infections was calculated as days between the two consecutive diagnostic tests.

Clinical data

In the patient characteristics, we included Montreal classifications of IBD, duration of IBD at the time of CDI diagnosis, and the morbidity of patients according to the Charlson Comorbidity Index (CCI).

Different clinical parameters (e.g., medical therapy, hospitalization, and disease activity) were collected 3 months before the toxin-positive CDI test. We also examined patient reports up to 6 months after CDI to monitor IBD activity and assess the need to intensify IBD-related therapy. In Table 2, immunosuppressants and biologicals were analyzed separately but also combined as pooled groups: immunosuppressants included azathioprine, mercaptopurine, methotrexate, calcineurin inhibitors, and tofacitinib while biologicals included infliximab, adalimumab, vedolizumab, and golimumab.

Hospitalization prior to CDI was analyzed as a risk factor for developing CDI. However, the reasons for hospitalization preceding CDI varied and were not recorded. During CDI, we examined whether it caused severe symptoms that led to hospitalization. IBD activity was defined by symptoms (abdominal pain, fever, diarrhea, and bloody stools) and fecal calprotectin (FC) levels as a surrogate marker of inflammation. Values considered normal for FC were <200 μg/g.^22–24 FC were recorded 3 months before the CDI, within the first month from the CDI diagnosis, and 2–6 months after the CDI was diagnosed.

We recorded the risk of undergoing surgery up to 1 year after CDI.

Finally, the need to intensify medical therapy for IBD 2–6 months after CDI was investigated. Therapy intensification included an increase in dosage, adding another IBD medication, a course of corticosteroids, or switching from immunosuppressants to biologicals.

Control series

A control group of 277 available age- and sex-matched IBD patients without a history of CDI were identified from the HUH IBD and infection registers (Table 1). For two patients, an age-matched control was not available in the register, and eight controls were included with loose age criteria (±1–10 years). The patient selection did not consider medication history. Case–control matched clinical data were collected according to the CDI episode landmark.

Table 1.

Characteristics of the patients.

Patient characteristics	IBD cases with CDI	IBD controls
Age
(Average ± SD) years	37.0 ± 16.2	37.0 ± 16.1
Sex
Males, n (%)	160 (57%)	160 (58%)
Females, n (%)	119 (43%)	117 (42%)
IBD subtypes
UC, n (%)	196 (70%)	162 (58%)
CD, n (%)	74 (27%)	112 (40%)
IBD-U, n (%)	9 (3%)	3 (2%)
CDI episodes
Total, n	415	NA
One episode, n (%)	195 (70%)	NA
>1 episodes, n (%)	84 (30%)	NA
IBD diagnosis
<2 years, n (%)	95 (34%)	33 (12%)
<5 years, n (%)	45 (16%)	60 (22%)
>5 years, n (%)	132 (47%)	180 (65%)
Missing data, n	7	4
Montreal classification
Colonic distribution (E2/E3, L2/L3), n (%)	238 (86%)	234 (84%)
CCI
Mild (0–2), n (%)	250 (90%)	257 (93%)
Moderate (3–4), n (%)	25 (9%)	18 (6%)
Severe (>5), n (%)	4 (1%)	2 (1%)

CCI, Charlson Comorbidity Index; CD, Crohn’s disease; CDI, Clostridioides difficile infection; IBD, inflammatory bowel disease; NA, not applicable; SD, standard deviation; UC, ulcerative colitis.

Statistical analyses

The data were analyzed, and statistical tests were performed using the R software (version R-4.3.1, R Foundation for Statistical computing, Vienna, Austria) environment. All tests were two-sided, and p-values <0.05 were considered statistically significant. Fisher’s exact test determined the differences in binary variables.

Ethical statement

This was a register-based study approved by the local hospital committee, and according to Finnish legislation, further ethical approval or informed consent was not needed as the patients were not contacted.

Results

Patient characteristics

Altogether, 279 IBD patients with CDI episodes were identified between 2008 and 2021 from the HUH IBD and infection registry (“IBD-CDI cohort,” Table 1). The median age upon the first CDI was 37 years (range from 18 to 85, SD ±16.2), and 57% were men.

As expected, UC was the most common IBD subtype in both cohorts (70% vs 58%, IBD-CDI vs controls, respectively) with significant overrepresentation among the IBD-CDI patients (p = 0.001, Table 1). The morbidity between the IBD-CDI cohort and controls was similar according to the CCI (Table 1).

CDI and its recurrence among IBD patients

IBD-CDI cases were characterized according to CDI recurrence. Up to 415 CDI episodes in the 279 IBD-CDI cohort patients (range = 1–7, Figure 1(a)). Recurrence of CDI occurred in 84 of the IBD patients (30%). The median time interval between rCDI episodes was 53 days (range: 14–1759 days), with 25% and 67% of all recurrences occurring within 30 and 90 days from the diagnosis of the preceding infection, respectively (Figure 1(b)). We conducted a further analysis of patients who experienced an rCDI episode within 90 days (rCDI⁹⁰) and identified 67 such cases. Interestingly, we observed a bimodal profile in the time-to-recurrence histogram with modes occurring at 3 and 8 weeks within the 90-day rCDI window (Figure 1(b)).

Figure 1.

Distribution of CDI episodes. (a) Histogram showing the distribution of CDI episode burden per IBD-CDI patient. (b) Histogram showing the distribution of time intervals between recurrent CDI episodes. Logarithmic scale on the X-axis. The line indicates the median interval (53 days) and the dashed line indicates the 90-day cutoff.

Of the patients with rCDI⁹⁰, most had UC (n = 53, 79%), with rCDI⁹⁰ occurring more often in UC patients than CD patients (p = 0.023). By contrast, when no time limit was applied, the trend remained similar but did not reach statistical significance (UC vs CD, p = 0.075), suggesting that UC may predispose IBD patients to earlier recurrence of CDI. Moreover, 98% (60/61) of the IBD patients with rCDI⁹⁰ had UC and colonic CD according to the Montreal classification (Table 1); however, the difference was not statistically significant compared to patients with no rCDI⁹⁰ (p = 0.2).

Clinical IBD features and medication associated with CDI

Corticosteroids and aminosalicylates were the most commonly used IBD-related medications in the IBD-CDI cohort, whereas in the control group, aminosalicylates and thiopurines were the most frequently used (Table 2). In the IBD-CDI cohort, corticosteroid usage preceded 267 CDI episodes (64%), while in the control group, corticosteroid intake was detected only in 87 cases (21%) (Fisher’s exact, p < 0.001). By contrast, thiopurines were more frequent in the control group (n = 207, 50%) than in the IBD-CDI cohort (n = 170, 41%, Fisher’s exact, p = 0.0097). Besides corticosteroid intake, antibiotics and proton pump inhibitors (PPIs) were more common in the IBD-CDI cohort (Table 2). In the pooled analysis of immunosuppressants and biologicals, the immunosuppressants were frequently used in the control group (56% vs 47%, respectively, p = 0.008), whereas there was no significant difference between the cohorts in the use of biologicals nor both drug groups being used simultaneously (Table 2).

Table 2.

Medications before CDI episodes.

Medical therapy	All CDI episodes		p-Value	First CDI episode		p-Value
Medical therapy	IBD-CDI, n (%)n_tot = 415	Controls, n (%)n_tot = 412		IBD-CDI, n (%)n_tot = 279	Controls, n (%)n_tot = 277	p-Value
Systemic corticosteroids	267 (64%)	87 (21%)	<0.001	170 (61%)	61 (22%)	<0.001
Aminosalicylates	278 (67%)	239 (58%)	0.0078	178 (64%)	158 (57%)	0.119
Thiopurines	170 (41%)	207 (50%)	0.0097	111 (40%)	131 (47%)	0.087
Anti-TNF	81 (20%)	86 (21%)	0.665	52 (19%)	61 (22%)	0.344
Calcineurin inhibitors	20 (5%)	0 (0%)	<0.001	13 (5%)	0 (0%)
Vedolizumab	10 (2%)	12 (3%)	0.673	4 (1%)	6 (2%)
Tofacitinib	0 (0%)	1 (0.2%)		0 (0%)	1 (0.3%)
Antibiotics	289 (70%)	66 (16%)	<0.001	179 (64%)	45 (16%)	<0.001
Proton pump inhibitors	149 (36%)	61 (15%)	<0.001	87 (31%)	38 (14%)	<0.001
Immunosuppressants	195 (47%)	232 (56%)	0.091	131 (47%)	150 (54%)	0.008
Biologics	87 (21%)	97 (24%)	0.219	55 (20%)	66 (24%)	0.405
Immunosuppressants or biologics	276 (67%)	275 (67%)	1.00	177 (63%)	182 (66%)	0.72
Immunosuppressants and biologics	53 (13%)	40 (10%)	0.19	34 (12%)	29 (10%)	0.51

Medical therapy was recorded 3 months before any CDI episode (under the “All CDI episodes” column) and before the first CDI episode (under the “First CDI episode” column) according to the IBD-CDI cohort and controls. Numbers indicate episodes, and the numbers in parenthesis indicate percentages from all episodes among the patients. p-Values indicate Fisher’s exact tests between the IBD-CDI and control cohorts. Immunosuppressants included azathioprine, mercaptopurine, methotrexate, calcineurin inhibitors, and tofacitinib. Biologicals included infliximab, adalimumab, vedolizumab, and golimumab.

CDI, Clostridioides difficile infection; IBD, inflammatory bowel disease.

In the IBD-CDI cohort, any CDI episode was preceded by hospitalization 3 months before infection in 32% (132/415) of the cases. In detail, 30% (84/279) of the IBD-CDI patients were hospitalized before their primary CDI. By contrast, only 5% (15/277) of the control patients were hospitalized within 3 months from the landmark (p < 0.001).

Next, we examined whether the duration of IBD (time from IBD diagnosis to CDI) had an impact on the susceptibility to CDI. A shorter disease duration (<2 years) before the first CDI episode was observed in 95 IBD patients (34%), compared to only 33 patients (12%) in the control group (p < 0.001). Moreover, IBD-related symptoms prior to the first CDI episode were observed in 66% of IBD patients with a disease duration of less than 2 years (63/95), compared to 43% of patients with an IBD diagnosis of over 5 years (56/128; p = 0.001).

IBD activity upon CDI

IBD activity was assessed by comparing symptoms recorded 3 months before and 2–6 months post-infection. IBD symptoms were recorded 3 months before CDI in 50% of episodes (203/405) in the IBD-CDI cohort, whereas in the control group, symptoms were recorded in only 36% (149/412) cases before landmark (p < 0.001). Post-infection IBD symptoms were recorded in 73% (89/122) of patients in the IBD-CDI cohort compared to 27% (82/308) in the control group, showing a significant difference (p < 0.001). However, data on disease activity were missing for most patients in the IBD-CDI cohort (293 CDI episodes). Table 3 shows the distribution of symptoms among IBD patients during CDI, according to the IBD subtype. Higher defecation frequency was shown among UC patients (p = 0.396).

Table 3.

GI symptoms of inflammatory bowel disease patients during CDI.

Symptoms at CDI diagnosis	Crohn’s disease	Ulcerative colitis
Stools/day
10 or less, n (%)	29 (30%)	133 (38%)
>10, n (%)	14 (14%)	89 (26%)
Abdominal pain	32 (33%)	80 (27%)
Bloody stools	19 (20%)	143 (48%)

CDI, Clostridioides difficile infection; GI, gastrointestinal.

FC levels were assessed at three different time points: before, during, and after CDI. FC data was available as follows: before infection (cases = 175/415, controls = 109/412), during infection (cases = 253/415, controls = 115/412), and after infection (cases = 255/415, controls = 167/412). The FC levels were higher in the IBD-CDI patients at all the measured time points (Figure 2). In detail, the FC levels were highest preceding and during CDI and significantly lower following the infection (Figure S1(A)). Interestingly, during CDI, the FC levels of IBD-CDI patients who experienced rCDI⁹⁰ were higher than those who did not experience relapse (Figure S1(B)). Elevated FC levels were seen in 93% (37/40) of the IBD patients with rCDI⁹⁰, whereas 72% (91/126) of the non-rCDI⁹⁰ patients had FC levels over 200 μg/g (Figure S1(B), Fisher’s exact p = 0.009).

Figure 2.

Box and dot plot of FC levels 3 months before, within 1 month of, and 2–6 months after CDI in the IBD-CDI cohort. FC levels for controls were recorded according to the infection episode landmark. p Values for comparisons are shown above the plots.

Thus, the presence of symptoms and elevation in IBD activity markers are associated with CDI in patients with IBD.

Treatment and outcomes of CDI

Treatment of CDI

In the IBD-CDI cohort, 27% (112/415) of CDI episodes resulted in hospitalization, and 73% (303/415) of CDI episodes were treated as outpatients. Metronidazole was the most commonly used antibiotic in our study, followed by vancomycin: 274 (66%) CDI episodes were treated with metronidazole and 129 (31%) episodes with vancomycin. Fecal transplantation was performed after 18 (4%) CDI episodes. Fidaxomicin, rifaximin, and bezlotoxumab were used rarely (6 (1%), 2 (0.4%), and 1 (0.2%), respectively).

GI surgery after CDI

Seven patients underwent surgery urgently related to CDI; two of these patients had originally been scheduled for surgery due to dysplasia findings on colonoscopy, but the procedure was expedited due to severe colitis. One of the patients had ileitis and an abscess; thus, ileocecal resection was performed. One patient had sigmoid perforation during CDI leading to sigmoid resection and colostomy. The remaining three patients developed fulminant colitis after CDI and underwent colectomy and ileostomy. During the 1-year follow-up, three additional patients underwent a colectomy.

In the 1-year follow-up, the number of procedures was the same in both the controls and the IBD-CDI cohort, with no statistically significant difference between them.

Medical therapy intensification

In the IBD-CDI cohort, therapy intensification was needed after 225 CDI episodes. After the primary CDI episode, the need for intensification occurred after 155 cases. In comparison, only 91 control patients experienced therapy intensification within the follow-up period (p < 0.001).

Discussion

Increased incidence and recurrent episodes of CDI among patients with IBD is a clinical challenge that complicates the course of underlying IBD with poorly identified risk factors.^7,8 Based on previous studies, active colonic inflammation in IBD patients could predispose to CDI.^18,23 In our study, higher disease activity of IBD was frequently seen in IBD-CDI patients 3 months before infection. This finding is also reflected in the higher FC levels and the use of corticosteroids 3 months before CDI compared to control patients. Moreover, elevated FC levels were associated with rCDI⁹⁰.

UC patients have been noted to be more susceptible to CDI than CD patients.⁸ Our study also supports the association indicating that patients with UC appear to be at a higher risk of developing CDI and experiencing recurrent infections. This phenomenon could be explained by underlying IBD manifesting in the colon where C. difficile bacteria colonize.²⁴ This theory is also supported by the distribution of the Montreal classification among the patients studied, as most of the UC patients had extensive colitis (E3) and CD patients had colonic disease. Thus, active IBD and colonic inflammation are seemingly critical in the susceptibility of C. difficile colonization.

Young age and a short duration of IBD have been associated with more frequent IBD flares.^25,26 In our study, half of the IBD-CDI patients had been diagnosed with IBD less than 5 years before the CDI, and almost one-third of those had symptomatic IBD, supporting the previous findings that shorter disease duration and active IBD increase the risk of CDI. The onset of IBD could lead to dysbiosis, which could further predispose one to the colonization and activation of CDI.^27,28 We speculate that dysbiosis might stabilize with a longer disease duration of IBD, thus decreasing the probability of CDI activation.

Excluding corticosteroids, other IBD-related medications did not seem to increase the susceptibility for CDI in our study. Corticosteroids, antibiotics, and PPIs were frequently used prior to CDI in our data. In the general population, the risk of antibiotic-associated CDI is 7-fold to 10-fold higher during the therapy and the following 3 months compared with individuals with no exposure.²⁹ In our study, a moderately large proportion (30%) of CDI episodes and no prior antibiotic usage were detected, thus indicating another explanatory factor for CDI development in IBD patients. Moreover, thiopurine use was more common among control patients, thus not indicating a significant association for CDI, as previous studies have found.¹⁹ Biologic therapy did not differ between the cohorts in our study and thus did not appear to increase the risk of CDI.

Based on experience, biologicals have been relatively safe regarding infections. The more frequent use of thiopurines in the control group may indicate a more stable disease among patients using thiopurines.

CDI in IBD patients leads to IBD flare-ups, delays in IBD remission, or the need to intensify IBD therapy and increase the need for colectomy.^30,31 Some studies have reported the risk for emergency GI surgery to increase even six-fold in IBD patients with concomitant CDI compared to control patients.³² In our study, 27% of CDI episodes led to hospitalization, 21% of the IBD patients remained symptomatic after 2–6 months of CDI treatment, and about 50% of the IBD patients had their medications intensified. During the post-infectious follow-up time, FC levels remained elevated compared to control patients. Thus, our research supports that CDI tends to complicate underlying IBD, increasing the need for escalation of IBD-related medical therapy and leading to hospitalization. However, CDI seemed not to increase the risk of colectomy compared to controls, while seven IBD-CDI patients in our cohort underwent emergency GI surgery following CDI. After a 1-year follow-up, there were no differences between the rates of colectomies among the cohorts.

A significantly larger proportion of IBD patients in the IBD-CDI cohort had been hospitalized before CDI, supporting the idea that hospitalization increases the risk of CDI in the general population.³³ However, the relationship between hospitalization and CDI in IBD patients is less established, as hospitalization often coincides with IBD flares that may require corticosteroid treatment.³⁴ Consequently, these IBD patients appear to be at risk for nosocomial CDI.

CDI symptoms range from mild diarrhea to severe pseudomembranous colitis.³⁵ Antibiotics are the mainstay to treat CDI, and previous guidelines have recommended metronidazole as the first-line antibiotic in mild to moderate CDI.³⁶ Recently, vancomycin and fidaxomicin were recommended in updated guidelines as first-line antibiotics for CDI in IBD patients.³⁷ In non-IBD patients, metronidazole remains a viable option for treating mild infections when vancomycin and fidaxomicin are unavailable; however, it should not be used for severe CDI.^36–38 Moreover, among the patients with IBD, metronidazole should not be used even in non-severe CDI, as vancomycin seems to decrease the rate of colectomy and shorten the length of hospital stay compared to metronidazole.^29,39 After the first CDI episode, rCDI is found in 20%–30% of patients, and recurrent rates increase with subsequent episodes.¹⁴ Besides antibiotics, fecal microbiota transplantation (FMT) is an established treatment for rCDI with cure rates up to 90% in non-IBD patients.⁴⁰ This therapy has also been effective in IBD patients. The popularity of metronidazole in our study may be reflected by the data collected from 2008 onward when the European guidelines favored metronidazole for CDI treatment, as well as the high cost of other antibiotics and the tendency to favor FMT in Finland.

In this study, the recurrence of CDI is defined as a symptomatic episode occurring at least 14 days after a previous positive sample. Previous studies have used various definitions for infection interval and cutoffs between positive samples, using time frames of 4, 8, or 12 weeks, as there is no established consensus on the appropriate interval.^41–44 We established a cutoff of 90 days between CDI episodes to distinguish recurrent infections from re-infections; otherwise, CDI recurrent infections would not be comparable. Among the IBD subtypes, recurrent infections were frequently seen in UC patients with or without the cutoff time limit.

The strength of our study lies in its relatively young study population with limited confounding comorbidities, a large cohort size, a well-documented CDI episode, and a higher number of IBD patients receiving biological treatments compared to most previous studies. Based on well-characterized clinical data, including FC levels, we evaluated the effect of IBD activity on the occurrence of CDI and the impact of CDI on IBD activity. The limitations of our study include its retrospective design, the lack of matched medications and IBD subtypes between cases and controls, and the absence of endoscopically confirmed disease activity. In addition, data on FC were missing for half of the patients, and we lacked activity scores and laboratory tests prior to CDI. Furthermore, the long duration of data collection involved changing treatment models for IBD and CDI.

Tips for clinicians

Our data suggest that IBD patients with signs of disease activity or a short duration of IBD are more susceptible to CDI. Corticosteroids appear to predispose patients to CDI, as their use often precedes CDI episodes. However, advanced therapies were not associated with CDI episodes. CDI further leads IBD patients to hospitalization, but CDI was not clearly connected with major outcomes (e.g., colectomy). IBD patients with elevated FC levels during CDI were seemingly more susceptible to rCDI and would thus benefit from effective treatment of CDI, including FMT, after the first CDI episode. Currently, alternatives to metronidazole are recommended for CDI infections in IBD patients.

Conclusion

This study identifies the risk factors for CDI and its recurrent infections. The major risk factors associated with CDI in IBD patients include active disease before infection, recent diagnosis of IBD, corticosteroid use, and previous hospitalization. In addition, IBD patients with elevated FC levels during CDI appear to be more susceptible to rCDI. Biologicals seem to be relatively safe in IBD patients regarding infections. The prior use of corticosteroids, hospitalization, and the presence of GI symptoms before CDI likely indicate an underlying IBD flare, suggesting that inadequate disease control may contribute to the risk of CDI.

Thus, patients with signs of active IBD and a short duration of the disease may benefit from proactive treatment of IBD and more frequent monitoring in the early stages, as these patients appear to be at higher risk of developing CDI.

Supplemental Material

sj-docx-2-tag-10.1177_17562848251318292 – Supplemental material for Higher disease activity of inflammatory bowel disease predisposes to Clostridioides difficile infection

Supplemental material, sj-docx-2-tag-10.1177_17562848251318292 for Higher disease activity of inflammatory bowel disease predisposes to Clostridioides difficile infection by Krista Vitikainen, Merit Kase, Leo Meriranta, Pauliina Molander, Clas-Göran af Björkesten, Veli-Jukka Anttila and Perttu Arkkila in Therapeutic Advances in Gastroenterology

Supplemental Material

sj-eps-1-tag-10.1177_17562848251318292 – Supplemental material for Higher disease activity of inflammatory bowel disease predisposes to Clostridioides difficile infection

Supplemental material, sj-eps-1-tag-10.1177_17562848251318292 for Higher disease activity of inflammatory bowel disease predisposes to Clostridioides difficile infection by Krista Vitikainen, Merit Kase, Leo Meriranta, Pauliina Molander, Clas-Göran af Björkesten, Veli-Jukka Anttila and Perttu Arkkila in Therapeutic Advances in Gastroenterology

Footnotes

Acknowledgements

None.

Declarations

ORCID iDs

Krista Vitikainen

Pauliina Molander

Supplemental material

Supplemental material for this article is available online.

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