Monday, June 5, 2023
| 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.
| 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.
| 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.
| 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.
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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.
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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.
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.
