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Table 1.  

Characteristic Total Recurrent CDI, n = 515 No recurrent CDI, n = 3,786 p value
Year of incident CDI       0.002
   2015 751 (17.5) 115 (22.3) 636 (16.8) 0.002
   2016 744 (17.3) 86 (16.7) 658 (17.4) NS
   2017 685 (15.9) 68 (13.2) 617 (16.3) NS
   2018 789 (18.3) 77 (15.0) 712 (18.8) 0.03
   2019 632 (14.7) 68 (13.2) 564 (14.9) NS
   2020 700 (16.3) 101 (19.6) 599 (15.8) 0.03
Age, y, median (IQR) 65.0 (26.0) 70.0 (23.0) 64.0 (26.0) <0.001
Sex       0.04
   M 1,640 (38.1) 175 (34.0) 1,465 (38.7)  
   F 2,661 (61.9) 340 (66.0) 2,321 (61.3)  
Race
   White 3,169 (73.7) 419 (81.4) 2,750 (72.6) <0.001
   Black 430 (10.0) 34 (6.6) 396 (10.5) 0.006
   Asian, American Indian, or Pacific Islander 38 (0.9) 1 (0.2) 37 (1.0) NS
   Mixed race or unknown 664 (15.4) 61 (11.8) 603 (15.9) 0.02
Ethnicity
   Hispanic 327 (8.4) 31 (6.5) 296 (8.7) NS
   Non-Hispanic 3,556 (91.6) 448 (93.5) 3,108 (91.3) 0.006

Table 1. Demographic characteristics of persons with incident CDI, stratified by occurrence of recurrent CDI, New Haven County, Connecticut, USA, 2015–2020*

*Values are no. (%) except as indicated. CDI, Clostridioides difficile infection; IQR, interquartile range; NS, not significant.

Table 2.  

Characteristic Total Recurrent CDI, n = 515 No recurrent CDI, n = 3,786 p value
Epidemiologic class
   HCFO 610 (14.2) 83 (16.1) 527 (13.9) NS
   CO-HCFA 1,234 (28.7) 174 (33.8) 1,060 (28.0) 0.006
   CA 2,457 (57.1) 258 (50.1) 2,199 (58.1) <0.001
Medical history
   Previous CDI 837 (19.5) 101 (19.6) 736 (19.4) NS
   Immunocompromised 1,397 (32.5) 182 (35.3) 1,215 (32.1) NS
   Cerebrovascular accident 320 (7.4) 48 (9.3) 272 (7.2) NS
   Cognitive impairment or dementia 337 (7.8) 49 (9.5) 288 (7.6) NS
   Malignancy 903 (21.0) 144 (28.0) 759 (20.1) <0.001
   HIV without AIDS 32 (0.7) 7 (1.4) 25 (0.7) NS
   Diabetes mellitus 1,024 (23.8) 127 (24.7) 897 (23.7) NS
   Chronic obstructive pulmonary disease 790 (18.4) 88 (17.1) 702 (18.5) NS
   Chronic liver disease 229 (5.3) 27 (5.2) 202 (5.3) NS
   Heart failure 544 (12.7) 67 (13.0) 477 (12.6) NS
   Myocardial infarction 261 (6.1) 39 (7.6) 222 (5.9) NS
   Peripheral vascular disease 213 (5.0) 33 (6.4) 180 (4.8) NS
   Connective tissue disease 184 (4.3) 21 (4.1) 163 (4.3) NS
   Gastrointestinal disease 809 (18.8) 88 (17.1) 721 (19.0) NS
   Peptic ulcer disease 71 (1.7) 8 (1.6) 63 (1.7) NS
   Morbid obesity 149 (3.5) 20 (3.9) 129 (3.4) NS
Medication history prior to incident CDI
   Proton pump inhibitors 1,487 (39.9) 190 (41.0) 1,297 (39.7) NS
   Histamine 2 receptor blockers 598 (16.1) 85 (18.5) 513 (15.8) NS
   Antibiotics 2,931 (68.2) 375 (72.8) 2,556 (67.5) 0.015
      Penicillins 1,033 (24.0) 115 (22.3) 918 (24.3) NS
      Cephalosporins 1,274 (29.6) 179 (34.8) 1,095 (28.9) 0.007
      Tetracyclines 191 (4.4) 32 (6.2) 159 (4.2) 0.037
      Nitroimidazole 614 (14.3) 88 (17.1) 526 (13.9) 0.052
      Nitrofurantoin 99 (2.3) 21 (4.1) 78 (2.1) 0.004
   Immunotherapeutic agents 1,707 (39.7) 190 (36.9) 1,517 (40.1) NS
      Steroids 811 (18.9) 101 (19.6) 710 (18.8) NS
      Chemotherapy 334 (7.8) 49 (9.5) 285 (7.5) NS
Clinical exposures prior to incident CDI
   Admitted 2,194 (51.1) 264 (51.4) 1,930 (51.0) NS
      CDI as reason for admission 1,098 (50.1) 143 (54.4) 955 (49.5) NS
   Emergency department visit 1,579 (37.7) 216 (43.5) 1,363 (36.9) 0.005
   Dialysis 191 (4.6) 29 (5.8) 162 (4.4) NS
   Surgery 561 (13.4) 77 (15.5) 484 (13.1) NS
   Death 163 (3.8) 1 (0.2) 162 (4.3) <0.001
Treatment of incident CDI
   Total no. cases during 2018–2020 2,121 246 1,875  
   Received treatment 1,890 (89.1) 218 (88.6) 1,672 (89.2) NS
      Vancomycin 1,344 (63.4) 162 (65.9) 1,182 (63.0) NS
      Metronidazole 479 (22.6) 47 (19.1) 432 (23.0) NS
      Fidaxomicin 28 (1.3) 3 (1.2) 25 (1.3) NS
      Other antibiotic 7 (0.3) 1 (0.4) 6 (0.3) NS
      Stool transplant 9 (0.4) 1 (0.4) 8 (0.4) NS
      Probiotics 383 (18.1) 40 (16.2) 343 (18.3) NS
      >1 treatment course duration 458 (21.6) 55 (22.4) 403 (21.5) NS

Table 2. Clinical characteristics of persons with incident CDI, stratified by occurrence of recurrent CDI, New Haven County, Connecticut, USA, 2015–2020*

*Values are no. (%) except as indicated. CA, community-associated; CDI, Clostridioides difficile infection; CO-HCFA, community-onset healthcare facility–associated; HCFO, healthcare facility–onset; NS, not significant.

Table 3.  

Characteristic Total Epidemiologic class p value
HCFO, n = 83 CO-HCFA, n = 174 CA, n = 258
Year of recurrent CDI         <0.001
   2015 115 (22.3) 17 (20.5) 36 (20.7) 62 (24.0)  
   2016 86 (16.7) 6 (7.2) 31 (17.8) 49 (19.0)  
   2017 68 (13.2) 9 (10.8) 22 (12.6) 37 (14.3)  
   2018 77 (15.0) 10 (12.1) 31 (17.8) 36 (14.0)  
   2019 68 (13.2) 5 (6.0) 29 (16.7) 34 (13.2)  
   2020 101 (19.6) 36 (43.4) 25 (14.4) 40 (15.5)  
Age, y, median (IQR) 70.0 (23.0) 74.0 (20.0) 71.0 (23.0) 68.0 (26.0) 0.002
Sex         0.083
   M 175 (34.0) 36 (43.4) 61 (35.1) 78 (30.2)  
   F 340 (66.0) 47 (56.6) 113 (64.9) 180 (69.8)  
Race         <0.001
   White 419 (81.4) 70 (84.3) 134 (77.0) 215 (83.3)  
   Black 34 (6.6) 5 (6.0) 13 (7.5) 16 (6.2)  
   Asian, American Indian, or Pacific Islander 1 (0.2) 0 1 (0.6) 0  
   Mixed race or unknown 61 (11.8) 8 (9.6) 26 (14.9) 27 (10.5)  
Ethnicity         0.007
   Hispanic 31 (6.5) 2 (2.5) 14 (8.7) 15 (6.3)  
   Non-Hispanic 448 (93.5) 77 (97.5) 147 (91.3) 224 (93.7)  
Medical history
   Previous CDI 101 (19.6) 19 (22.9) 29 (16.7) 53 (20.5) 0.435
   Immunocompromised 182 (35.3) 47 (56.6) 71 (40.1) 64 (24.8) <0.001
   Cerebrovascular accident 48 (9.3) 13 (15.7) 19 (10.9) 16 (6.2) 0.024
   Cognitive impairment or dementia 49 (9.5) 17 (20.5) 19 (10.9) 13 (5.0) <0.001
   Malignancy 144 (28.0) 22 (26.5) 67 (38.5) 55 (21.3) <0.001
Medication history
   Proton pump inhibitors 190 (41.0) 47 (58.0) 74 (45.4) 69 (31.5) <0.001
   Histamine 2 receptor blockers 85 (18.5) 19 (23.5) 37 (22.7) 29 (13.4) 0.031
   Antibiotics 375 (72.8) 73 (88.0) 145 (83.3) 157 (60.9) <0.001
      Penicillins 115 (22.3) 28 (33.7) 61 (35.1) 26 (10.1) <0.001
      Cephalosporins 179 (34.8) 56 (67.5) 87 (50.0) 36 (14.0) <0.001
      Tetracyclines 32 (6.2) 7 (8.4) 17 (9.8) 8 (3.1) 0.013
      Nitroimidazole 88 (17.1) 19 (22.9) 45 (25.9) 24 (9.3) <0.001
      Nitrofurantoin 21 (4.1) 1 (1.2) 10 (5.8) 10 (3.9) 0.012
   Immunotherapeutic agents 190 (36.9) 35 (42.2) 68 (39.1) 87 (33.7) 0.292
Clinical exposures
   Admitted 264 (51.4) 57 (68.7) 113 (65.3) 94 (36.4) <0.001
      CDI as reason for admission 143 (54.4) 18 (31.6) 69 (61.6) 56 (59.6) <0.001
   Emergency department visit 216 (43.5) 45 (54.9) 102 (59.0) 69 (28.5) <0.001
   Dialysis 29 (5.8) 9 (11.0) 14 (8.1) 6 (2.5) 0.005
   Surgery 77 (15.5) 22 (26.8) 45 (26.0) 10 (4.2) <0.001

Table 3. Characteristics of participants with recurrent CDI, stratified by epidemiologic class, New Haven County, Connecticut, USA, 2015–2020*

*Values are no. (%) except as indicated. CA, community-associated; CDI, Clostridioides difficile infection; CO-HCFA, community-onset healthcare facility–associated; HCFO, healthcare facility–onset; IQR, interquartile range.

Table 4.  

Factor OR (95% CI)
Model 1* Model 2† Model 3‡
Year of recurrent CDI
   2016 0.73 (0.54–1.00)† 0.68 (0.44–1.05) 0.68 (0.44–1.06)
   2017 0.59 (0.42–0.83)† 0.43 (0.26–0.72)‡ 0.43 (0.26–0.73)§
   2018 0.69 (0.50–0.96)† 0.59 (0.37–0.95)‡ 0.60 (0.37–0.97)§
   2019 0.69 (0.49–0.97)† 0.50 (0.30–0.84)‡ 0.50 (0.30–0.84)§
   2020 0.98 (0.72–1.32) 0.72 (0.46–1.12) 0.73 (0.46–1.16)
Age 1.02 (1.01–1.02)† 1.01 (1.00–1.02) 1.01 (1.00–1.02)
Female sex 1.20 (0.98–1.46) 1.22 (0.92–1.63) 1.22 (0.92–1.63)
Race or ethnicity
   Black 0.61(0.42–0.89)† 0.50 (0.31–0.83)‡ 0.50 (0.30–0.83)§
   Asian/American Indian/Pacific Islander 0.27 (0.04–1.98) <0.01 (<0.01 to >999.99) <0.01 (<0.01 to >999.99)
   Mixed/Unknown race 0.97 (0.54–1.75) 1.36 (0.58–3.20) 1.36 (0.58–3.19)
Hispanic 0.90 (0.51–1.58) 0.64 (0.28–1.50) 0.65 (0.28–1.51)
Medication history
   Proton pump inhibitors   0.85 (0.64–1.13) 0.85 (0.64–1.13)
   Histamine 2 receptor blockers   0.98 (0.68–1.41) 0.97 (0.67–1.39)
   Antibiotics   1.21 (0.80–1.81) 1.21 (0.81–1.81)
      Penicillins   1.03 (0.74–1.44) 1.02 (0.73–1.42)
      Cephalosporins   1.13 (0.81–1.57) 1.10 (0.79–1.54)
      Tetracyclines   1.05 (0.60–1.85) 1.05 (0.60–1.85)
      Nitroimidazole   0.93 (0.64–1.35) 0.93 (0.65–1.34)
      Nitrofurantoin   2.38 (1.23–4.59)‡ 2.37 (1.23–4.58)§
   Immunotherapeutic agents   0.86 (0.62–1.18) 0.85 (0.62–1.17)
Clinical history
   Previous CDI   1.03 (0.74–1.44) 1.03 (0.74–1.44)
   Immunocompromised   1.20 (0.89–1.61) 1.19 (0.88–1.60)
   Cerebrovascular accident   0.91 (0.58–1.43) 0.90 (0.57–1.41)
   Cognitive Impairment or dementia   0.91 (0.58–1.42) 0.91 (0.58–1.42)
   Malignancy   1.52 (1.11–2.08)‡ 1.51 (1.11–2.07)§
Clinical exposures
   CDI as reason for admission   1.48 (1.10–2.01)‡ 1.46 (1.07–12.01)§
   Emergency department visit   1.32 (1.00–1.76) 1.28 (0.95–1.71)
   Dialysis   1.45 (0.85–2.47) 1.44 (0.85–2.46)
   Surgery   1.14 (0.80–1.64) 1.11 (0.77–1.59)
Epidemiologic class
   CO-HCFA     1.10 (0.74–1.63)
   CA     0.93 (0.61–1.42)

Table 4. Factors associated with recurrent CDI identified in 3 models, New Haven County, Connecticut, USA, 2015–2020*

*Model 1 contains year of incident CDI diagnosis, age, sex, race, and ethnicity. Model 2 contains, in addition to model 1 variables, use of proton pump inhibitors, histamine 2 receptor blocker, antibiotics, penicillin, cephalosporin, tetracycline, nitroimidazole, nitroimidazoles, nitrofurans, immunotherapeutic agents, previous CDI, immunocompromised states, cerebrovascular accident, cognitive impairment or dementia, malignancy, admission because of CDI, emergency department visit, dialysis, and surgery. Model 3 contains, in addition to variables in model 2, the epidemiologic class of cases. CA, community-associated; CDI, Clostridioides difficile infection; CO-HCFA, community-onset healthcare facility–associated; OR, odds ratio.
†Statistically significant in the first model.
‡Statistically significant in the second model.
§Statistically significant in the final model.

CME / ABIM MOC

Trends in and Risk Factors for Recurrent Clostridioides difficile Infection, New Haven County, Connecticut, USA, 2015–2020

  • Authors: Chinenye M. Okafor, MD, MPH; Paula Clogher, MPH, CHES; Danyel Olson MS, MPH; Linda Niccolai, PhD; James Hadler, MD, MPH
  • CME / ABIM MOC Released: 4/13/2023
  • Valid for credit through: 4/13/2024
Start Activity

  • Credits Available

    Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 1.00 ABIM MOC points

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for primary care clinicians, infectious disease specialists, gastroenterologists, and other healthcare professionals who treat and manage patients at risk for Clostridioides difficile infection.

The goal of this activity is for learners to be better able to assess the prevalence and risk factors for recurrent Clostridioides difficile infection.

Upon completion of this activity, participants will:

  • Assess trends in the epidemiology of Clostridioides difficile infection
  • Analyze race and study year as risk factors for recurrent Clostridioides difficile infection
  • Evaluate chronic health conditions as risk factors for recurrent Clostridioides difficile infection
  • Evaluate specific medications or medication classes as risk factors for recurrent Clostridioides difficile infection


Disclosures

Medscape, LLC requires every individual in a position to control educational content to disclose all financial relationships with ineligible companies that have occurred within the past 24 months. Ineligible companies are organizations whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

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Faculty

  • Chinenye M. Okafor, MD, MPH

    Yale School of Public Health
    New Haven, Connecticut

  • Paula Clogher, MPH, CHES

    Connecticut Emerging Infections Program
    New Haven, Connecticut

  • Danyel Olson MS, MPH

    Connecticut Emerging Infections Program
    New Haven, Connecticut

  • Linda Niccolai, PhD

    Yale School of Public Health
    Connecticut Emerging Infections Program
    Yale Institute of Global Health
    New Haven, Connecticut
     

  • James Hadler, MD, MPH

    Yale School of Public Health
    Connecticut Emerging Infections Program
    New Haven, Connecticut

CME Author

  • Charles P. Vega, MD

    Health Sciences Clinical Professor of Family Medicine
    University of California, Irvine School of Medicine

    Disclosures

    Charles P. Vega, MD, has the following relevant financial relationships:
    Consultant or advisor for: Boehringer Ingelheim Pharmaceuticals, Inc.; GlaxoSmithKline; Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Editor

  • Jude Rutledge, BA

    Copyeditor

    Emerging Infectious Diseases 

Compliance Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Amanda Jett, PharmD, BCACP, has no relevant financial relationships.


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CME / ABIM MOC

Trends in and Risk Factors for Recurrent Clostridioides difficile Infection, New Haven County, Connecticut, USA, 2015–2020

Authors: Chinenye M. Okafor, MD, MPH; Paula Clogher, MPH, CHES; Danyel Olson MS, MPH; Linda Niccolai, PhD; James Hadler, MD, MPHFaculty and Disclosures

CME / ABIM MOC Released: 4/13/2023

Valid for credit through: 4/13/2024

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Abstract and Introduction

Absract

Recurrent Clostridioides difficile infection (RCDI) causes an increased burden on the healthcare system. We calculated RCDI incidence and identified factors associated with RCDI cases in New Haven County, Connecticut, USA, during 2015–2020 by using data from population-based laboratory surveillance. A subset of C. difficile cases had complete chart reviews conducted for RCDI and potentially associated variables. RCDI was defined as a positive C. difficile specimen occurring 2–8 weeks after incident C. difficile infection. We compared cases with and without RCDI by using multiple regression. RCDI occurred in 12.0% of 4,301 chart-reviewed C. difficile cases, showing a U-shaped time trend with a sharp increase in 2020, mostly because of an increase in hospital-onset cases. Malignancy (odds ratio 1.51 [95% CI 1.11–2.07]) and antecedent nitrofurantoin use (odds ratio 2.37 [95% CI 1.23–4.58]) were medical risk factors for RCDI. The 2020 increase may reflect the impact of the COVID-19 pandemic.

Introduction

Clostridioides difficile infection (CDI) is one of the most common causes of healthcare-associated infection[1] and can result in serious illness and death[2]. CDI is classified into 3 types on the basis of epidemiology: healthcare facility–onset (HCFO), community-onset healthcare facility–associated (CO-HCFA), and community-associated (CA) CDI[1]. Both HCFO and CO-HCFA are healthcare-associated CDIs, differing in where a person is located at symptom onset. Despite evidence of decreasing healthcare-associated CDI cases in the United States, CA-CDI incidence appears to be stable[3].

Recurrent CDI (RCDI), defined as an episode of symptom onset and a positive assay result after an episode with a positive assay result in the previous 2–8 weeks[4], is associated with increased burden on the healthcare system and increased medical costs[2]. As many as an estimated 30% of CDI case-patients will experience a first recurrence, with increasing risk for recurrence after the previous episode[2]. Specific to RCDI, studies have demonstrated that older age and female sex increase the risk for recurrence[2]. CDI episodes have been shown to have worse outcomes with each subsequent recurring episode[2,5]. Prior studies have described the possible factors that may increase the risk for recurrence as microbiologic factors[6–9], clinical characteristics[5,10–15], or epidemiologic factors[15]. Studies mostly limited to older populations also describe social factors, such as living environment, that may be linked to RCDI[16] and readmission[17], as well as receipt of additional antibiotics[16] after CDI. An increasing percentage of cases that are CA-CDI[3] could potentially mean an increase in RCDI attributable to the community despite evidence of overall reduction in RCDI cases[2].

Determining trends in RCDI and both predisposing and treatment factors associated with recurrence will provide insight into the effectiveness of measures to prevent RCDI, especially given its burden on the healthcare system. Observations from previous studies of increasing cases of RCDI among CA incident cases while RCDI decreases among healthcare-associated incident CDI[3] may require a reexamination of the measures for managing CDI among those with CA-CDI. Because of the COVID-19 pandemic and the consequent increase in hospital admissions[18], an increase in RCDI is expected among those with healthcare-associated CDI, but the extent and associated factors are largely unexplored. We aimed to describe the sociodemographic characteristics, clinical underlying conditions and medical history, and medication history up to the point of incident CDI of the population with RCDI in New Haven County, Connecticut, USA, during 2015–2020. Additional objectives were to examine trends in RCDI stratified by epidemiologic class (HCFO, CO-HCFA, or CA) and identify possible factors associated with RCDI in the study population.