In-Hospital Mortality, Outcomes, and Cost Analysis of Hospitalized C. difficile Patients With Inflammatory Bowel Disease: A Nationwide Sample Study

Introduction: Clostridioides difficile (C. diff) is the leading cause of nosocomial diarrhea and has been shown to impact about 13 in every 1000 hospitalized patients. The occurrence of C. diff and Inflammatory bowel disease (IBD) have been linked to disruption of the gut microbiota (dysbiosis) which may explain the parallel rise of C. diff infection in IBD patients. Our study aimed to analyze the cost burden and clinical outcomes of hospitalized IBD patients with C. diff infections. Methods: 240,550 adults hospitalized with Crohn’s disease or Ulcerative colitis were analyzed using the NIS data from 2016-2019. Patients were classified into a group with C. diff and a group without C. diff and variables like Age, gender, race, diabetes mellitus, nicotine use, anemia, end-stage renal disease (ESRD), thrombocytopenia, albumin abnormality, peritoneal abscess, toxic megacolon, gastrointestinal bleed, vesicovaginal fistula, anorectal fistula, vesicointestinal fistula, mortality, and hospitalization cost were analyzed using the 2-sample t test, chi-square test, and multiple linear regression. P value < 0.05 was considered statistically significant. Results: We found that compared to men, women hospitalized with IBD are more likely to get infected with C. diff (4.2% vs 4.5%, P = < 0.001). Older IBD patients (Mean age of 53.1) are at risk compared to other age groups (P = < 0.001). Whites had the least C. diff rates compared to blacks, Hispanics, Asians, Native America, and others (4.2% vs 4.7% vs 5.6% vs 5.3% vs 4.4% vs 4.5%, P = < 0.001). IBD patients with anemia and thrombocytopenia had a significantly higher rate of C. diff infection (P = < 0.001). Interestingly, nicotine dependence and peritoneal abscess protected against C. diff infection (P = < 0.001 and 0.008). The average total hospital cost among IBD patients with C. diff was $20,254 higher compared to those without C. diff after controlling the effects of the variables - age, gender, race, nicotine status, anemia, ESRD, peritoneal abscess, thrombocytopenia, gastrointestinal bleed, and vesicovaginal fistula. The odds of mortality among IBD patients with C. diff was more than twice compared to those without C. diff (OR = 2.1, P = < 0.001) (Table 1). Conclusion: IBD patients remain at increased risk of C. diff infection and more hospital expenses. Hence, clinicians should rule out C. diff infection first in every IBD patient presenting with disease flare-ups or diarrhea. Table 1. - (A): Descriptive summary of patients with ulcerative colitis and Crohn's disease. (B): Univariate analysis- Clostridioides difficile vs other variables. (C): Multiple linear regression of total hospital cost on Clostridioides difficile. (D): Multiple logistic regression analysis of mortality on Clostridioides difficile A Variables Mean Std Err Age in years at admission 52.4 0.05 Total charges 56650.6 201.75 Total Sample size (n) =28476826 n=240550 % Gender (female) 135183 56.21 Race White 182555 78.39 Black 26630 11.44 Hispanic 14607 6.27 Asian or Pacific Islander 2794 1.2 Native American 881 0.38 Others 5410 2.32 Clostridioides difficile 10487 4.36 Type 1 Diabetes 613 0.25 Type 2 Diabetes 8004 3.33 Nicotine 33671 14 Anemia 26752 11.12 End Stage Renal Disease 4603 1.91 Thrombocytopenia 7634 3.17 Albumin Abnormality 13 0.01 Peritoneal Abscess 3511 1.46 Toxic Megacolon 73 0.03 Gastrointestinal Hemorrhage 3038 1.26 Vesicovaginal fFistula 25 0.01 Anorectal Fistula 159 0.07 Vesicointestinal Fistula 700 0.29 Death 3558 1.48 B Variables No Clostridioides difficile Clostridioides difficile P value** Age 52.34 (0.05) 53.1 (0.25) 0.002 Total Cost 55775.7 (200.0) 75866.9 () < 0.001 Gender < 0.001 Male 100925 (95.8) 4390 (4.2) Female 129089 (95.5) 6094 (4.5) Race < 0.001 White 174879 (95.8) 7676 (4.2) Black 25382 (95.3) 1248 (4.7) Hispanic 13795 (94.4) 812 (5.6) Asian or Pacific Islander 2645 (94.7) 149 (5.3) Native American 842 (95.6) 39 (4.4) Others 5165 (95.5) 245 (4.5) Type 1 Diabetes 0.957 No 229477 (95.6) 10460 (4.4) Yes 586 (95.6) 27 (4.4) Type 2 Diabetes 0.619 No 222399 (95.6) 10147 (4.4) Yes 7664 (95.8) 340 (4.3) Nicotine < 0.001 No 197659 (95.5) 9220 (4.5) Yes 32404 (96.2) 1267 (3.8) Anemia < 0.001 No 204759 (95.8) 9039 (4.2) Yes 25304 (94.6) 1448 (5.4) End Stage renal disease < 0.001 No 225781 (95.7) 10166 (4.3) Yes 4282 (93) 321 (7) Thrombocytopenia < 0.001 No 222840 (95.7) 10076 (4.3) Yes 7223 (94.6) 411 (5.4) Albumin Abnormality 0.440 No 230051 (95.6) 10486 (4.4) Yes 12 (92.3) 1 (7.7) Peritoneal Abscess 0.008 No 226673 (95.6) 10366 (4.4) Yes 3390 (96.6) 121 (3.5) Toxic Megacolon 0.252 No 229995 (95.6) 10482 (4.4) Yes 68 (93.2) 5 (6.9) Gastrointestinal Hemorrhage < 0.001 No 227217 (95.7) 10295 (4.3) Yes 2846 (93.7) 192 (6.3) Vesicovaginal Fistula 0.022 No 230042 (95.6) 10483 (4.4) Yes 21 (84) 4 (16) Anorectal Fistula 0.118 No 229915 (95.6) 10476 (4.4) Yes 148 (93.1) 11 (6.9) Vesicointestinal Fistula 0.306 No 229388 (95.6) 10462 (4.4) Yes 675 (96.4) 25 (3.6) Died during Hospitalization < 0.001 No 226731 (98.6) 10140 (96.7) Yes 3215 (1.4) 343 (3.3) C Variables Estimate P-value Clostridioides difficile Yes 20253.8 < .0001 No Reference . Age 190.0 < .0001 Gender Female -6793.7 < .0001 Male Reference Race Black 1360.8 0.077 Hispanic 15715.7 < .0001 Asian or Pacific Islander 21532.2 < .0001 Native American 10162.3 0.010 Others 10524.4 < .0001 Whites Reference Nicotine Yes -10003.1 < .0001 No Reference Anemia Yes 3677.0 < .0001 No Reference Renal Yes 35980.5 < .0001 No Reference Peritoneal Abscess Yes 97785.2 < 0.001 No Reference Thrombocytopenia Yes 35875.9 < .0001 No Reference Gastrointestinal Hemorrhage Yes 18041.1 < .0001 No Reference Vesicovaginal Fistula Yes 84031.3 < .0001 No Reference D Variables OR (CI) P-value Clostridioides difficile, Yes vs No 2.1 (1.8, 2.4) < .0001 Age 1 (1.0, 1.1) < .0001 Female vs Male 0.8 (0.8, 0.9) < .0001 Race Black vs White 1.1 (1, 1.3) 0.1262 Hispanic vs White 1.3 (1.1, 1.5) 0.8211 Asian Pacific Islander vs White 1.4 (1.0, 1.9) 0.468 Native American vs White 1.7 (0.9, 3) 0.2633 Others vs White 1.2 (0.9, 1.6) 0.6915 Nicotine user vs non-user 0.9 (0.8, 1) 0.0926 Anemia vs no 1.1 (1, 1.2) 0.1634 Peritoneal Abscess vs no 2.3 (2, 2.7) < .0001 Renal disease vs no disease 2.4 (1.8,3.2) < .0001 Thrombocytopenia vs no 2.8 (2.4, 3.2) < .0001 Gastrointestinal Hemorrhage vs no 3 (2.5, 3.7) < .0001 Vesicovaginal fistula vs no 6 (1.3, 27.9) 0.0217