Table 1.
Main characteristics of the studies included in this meta-analysis
| Cunney et al [19] | Do et al [30] | Morris et al [20] | Yousuf et al [13] | Henrich et al [31] | |
| Country | Ireland | Canada | USA | USA | USA |
| Study design | Cohort study | Case-control study | Cohort study | Cohort study | Cohort study |
| Year | 1998 | 1998 | 2002 | 2002 | 2009 |
| Total number | 32 | 59 | 147 | 77 | 336 |
| Study sample | Hospital-based; inpatients with CDI admitted in a nephrology unit | Hospital-based; inpatients with CDI | Hospital-based; inpatients with CDI | Hospital-based; inpatients and outpatients with CDI | Hospital-based; inpatients with CDI |
| CDI detection | C. difficile toxin A in stool using EIA, stool culture of C. difficile, histologic examination of colonic biopsies and diarrhea | C. Difficile-positive stool culture and diarrhea | Positive stool test for toxin A and/or B using EIA and hospital discharge code for CDI | C. difficile toxin A in stool using EIA and diarrhea | Positive stool test for C. difficile toxin using Cytotoxic assay or toxin A and B ELISA |
| Chronic kidney disease definition and ascertainment | Chronic renal failure (not defined); medical record review | Chronic renal insufficiency, defined as baseline SCr of 1.5 mg/dL | Renal disease and/or diabetes mellitus; medical record review | Chronic renal insufficiency, defined as persistently elevated SCr of ≥1.5 mg/dL for ≥ 3 months | Renal disease; physician-documented medical condition |
| Definition of severe/complicated CDI | N/A | N/A | N/A | N/A | CDI that resulted in death within 30 days after diagnosis, required ICU admission, colectomy or other surgery or led to intestinal perforation |
| OR for severe/complicated CDI | N/A | N/A | N/A | N/A | Renal disease 0.84 (0.37–1.91) |
| OR for mortality | 5 (0.99–25.3) | N/A | 0.82 (0.26–2.61) | 6.15 (2.14–17.66) | N/A |
| OR for recurrence | N/A | 6.5 (1.4–32.3) | N/A | 12.75 (2.45–66.26) | N/A |
| Confounder adjusted | None | None | none | None | Renal disease: none Hemodialysis: Age, sex, antimicrobial use, malignancy, chemotherapy, steroid use, WBC, glucose, ALT, albumin, SCr |
| Quality assessment (Newcastle-Ottawa scale) | Selection: 2 Comparability: 0 Outcome: 2 |
Selection: 2 Comparability: 0 Exposure: 2 |
Selection: 3 Comparability: 0 Outcome: 3 |
Selection: 3 Comparability: 0 Outcome: 3 |
Selection: 3 Comparability: 2 Outcome: 3 |
| Dudukgian et al [14] | Pepin et al [23] | Wilson et al [22] | Fujitani et al [32] | Bauer et al [33] | |
| Country | USA | Canada | UK | USA | Europe |
| Study design | Cohort study | Cohort study | Cohort study | Cohort study | Cohort study |
| Year | 2009 | 2009 | 2010 | 2011 | 2011 |
| Total number | 398 | 130 | 128 | 184 | 496 |
| Study sample | Hospital-based; inpatients with CDC | Multi-center; inpatients with fulminant CDI requiring an emergency colectomy | Hospital-based; inpatients with CDI | Multi-center; inpatients with CDI | Multi-center; outpatient and inpatients with CDI |
| CDI detection | Discharge diagnosis of CDC (ICD-9 008.45) and positive toxin ELISA or biopsy consistent with pseudomembranous colitis | Positive C. difficile cytotoxin assay, endoscopic or histopathologic evidence of pseudomembranous colitis | Positive stool test for toxin A or B using ELISA and diarrhea | Positive stool test for C. difficile toxin A and B and diarrhea | positive stool test for toxin A, B or both using EIA, cytotoxicity test or PCR or stool culture for toxin-producing C. difficile and diarrhea |
| Chronic kidney disease definition and ascertainment | Renal insufficiency (not defined); medical record review | Chronic renal failure, defined as baseline SCr ≥1.5 mg/dL | Renal failure (not clearly defined); medical record review | Chronic renal insufficiency/end-stage renal disease (not defined); medical record review | Chronic dialysis; APACHE II |
| Definition of severe/complicated CDI | CDI requiring surgery or resulting in death | N/A | N/A | CDI that required ICU admission, surgery for toxic megacolon, large-bowel perforation or refractory colitis or resulted in death within 30 days after diagnosis | CDI that contributed or caused ICU admission or death or led to colectomy |
| OR for severe/complicated CDI | 1.90 (0.98–3.69) | N/A | N/A | 1.78 (0.64–4.97) | 0.29 (0.04–2.35) |
| OR for mortality | 2.64 (1.32–5.27) | 1.75 (0.85–3.60) | 1.65 (0.77–3.54) | N/A | N/A |
| OR for recurrence | N/A | N/A | N/A | N/A | 2.23 (0.59–8.37) |
| Confounder adjusted | None | None | None | None | Complicated: none Recurrence: Age, health-care association, pulmonary disease, previous antibiotics use, recent CDI, C. difficile strain |
| Quality assessment (Newcastle-Ottawa scale) | Selection: 3 Comparability: 0 Outcome: 3 |
Selection: 3 Comparability: 0 Outcome: 3 |
Selection: 3 Comparability: 0 Outcome: 3 |
Selection: 4 Comparability: 0 Outcome: 3 |
Selection: 4 Comparability: 2 Outcome: 3 |
| Manek et al [34] | Stewart et al [24] | Welfare et al [15] | Kim et al [36] | Pant et al [18] | |
| Country | Canada | USA | UK | Korea | USA |
| Study design | Cohort study | Cohort study | Cohort study | Cohort study | Cohort study |
| Year | 2011 | 2011 | 2011 | 2012 | 2012 |
| Total number | 365 | 41207 | 2761 | 198 | 64944 |
| Study sample | Hospital-based; inpatients with CDI | Nationwide Inpatient Sample (NIS) 2007 database; inpatients with CDC in US hospitals | Hospital-based; inpatients with CDI | Hospital-based; inpatients who recovered from CDI | Nationwide Inpatient Sample (NIS) 2009 database; inpatients with CDC in US hospitals |
| CDI detection | Positive stool test for C. difficile toxin A and B using EIAand diarrhea, visualization of pseudomembrane on endoscopy or histopathology | ICD-9 code of 008.45 | Positive stool test for C. difficile toxin A and B immunoassay and diarrhea | Positive stool test for C. difficile toxin A and B and diarrhea | ICD-9 code of 008.45 |
| Chronic kidney disease definition and ascertainment | Renal disease (not defined); medical record review | Renal failure (not defined; AHRQ comorbidity indicators | Renal disease; ICD-10 code of N00–N28 | Renal disease (not defined); medical record review | End-stage renal disease; discharge diagnosis based on ICD-9 code of 585.6 |
| Definition of severe/complicated CDI | CDI that caused severe hypokalemia, toxic megacolon, bowel perforation, lower GI bleeding requiring blood transfusion, ICU transfer or death before treatment completion | N/A | N/A | - | N/A |
| OR for severe/complicated CDI | 1.76 (0.71–4.39) | N/A | N/A | - | N/A |
| OR for mortality | N/A | 0.93 (0.91–0.95) | 1.96 (1.62–2.38) | - | 1.56 (1.43–1.70) |
| OR for recurrence | N/A | N/A | N/A | 2.14 (0.45–10.26) | N/A |
| Confounder adjusted | none | Yes but not clearly specified | Age and comorbidities | Age, sex, treatment, additional use of antibiotics, underlying disease | None |
| Quality assessment (Newcastle-Ottawa scale) | Selection: 3 Comparability: 0 Outcome: 3 |
Selection: 4 Comparability: 1 Outcome: 3 |
Selection: 3 Comparability: 2 Outcome: 3 |
Selection: 4 Comparability: 2 Outcome: 3 |
Selection: 4 Comparability: 0 Outcome: 3 |
| Halabi et al [16] | Mullane et al [21] | Samie et al [35] | Lee et al [17] | |
| Country | USA | United, Canada and Europe | Germany | USA |
| Study design | Cohort study | Cohort study | Cohort study | Cohort study |
| Year | 2013 | 2013 | 2013 | 2014 |
| Total number | 3900 | 1054 | 124 | 335 |
| Study sample | Nationwide Inpatient Sample (NIS) 2001–2010 database; inpatients with CDC who underwent total or subtotal colectomy for CDC in US hospitals | Multi-center; patients with CDI enrolled in randomized controlled trial | Hospital-based; inpatients with CDI | ACS-NSQIP database 2005–2010; inpatients underwent emergent open colectomy for CDC |
| CDI detection | ICD-9 code of 008.45 | Positive stool test for C. difficile toxin A and/or B and diarrhea | positive stool test for toxin A, B or positive stool culture for C. difficile and diarrhea | ICD-9 code of 008.45 |
| Chronic kidney disease definition and ascertainment | Chronic kidney disease (not defined); NIS dataset | Chronic kidney disease stage 3–4, defined as CrCl < 60 ml/min/1.73 m2; Estimated CrCl was calculated using Cockcroft-Gault formula | Chronic kidney disease stage 3–4 defined as a GFR < 60 ml/min; GFR was calculated using Cockcroft-Gault formula | Dialysis dependence, defined as acute or chronic within 2 weeks before surgery; ACS-NSQIP database |
| Definition of severe/complicated CDI | N/A | N/A | N/A | N/A |
| OR for severe/complicated CDI | N/A | N/A | N/A | N/A |
| OR for mortality | 1.63 (1.50–1.76) | 1.72 (0.75–3.97) | N/A | 2.3 (1.1–4.8) |
| OR for recurrence | N/A | 1.80 (1.08–2.98) | 1.52 (0.51–4.53) | N/A |
| Confounder adjusted | none | Age, treatment, fever WBCs, albumin, concomitant antibiotics | C-reactive protein, leukocytosis, PPI use, DM, glucocorticoid therapy, cerebral insult, cirrhosis | Age, preoperative septic shock, severe COPD, postoperative cardiac arrest, would classification, preoperative platelet, INR and BUN |
| Quality assessment (Newcastle-Ottawa scale) | Selection: 4 Comparability: 0 Outcome: 3 |
Selection: 4 Comparability: 2 Outcome: 3 |
Selection: 3 Comparability: 2 Outcome: 3 |
Selection: 4 Comparability: 2 Outcome: 3 |
Abbreviations: ALT, alanine transaminase; EIA, enzyme immunoassay; ELISA, enzyme-linked immunosorbent assay; CDI, Clostridium difficile infection; ICU, intensive care unit; N/A, not available; SCr, serum creatinine; WBC, white blood cell.
Abbreviations: CDC, Clostridium difficile colitis; AHRQ, Agency for Health Care Research and Quality
Abbreviations: ICU, intensive care unit; ACS-NSQIP, American College of Surgeons – National Surgical Quality Improvement Program.
Abbreviations: BUN, blood urea nitrogen; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus; INR, international normalized ratio; K, Potassium; PPI, proton pump inhibitor; WBC, white blood cell.