422
Scott Anjewierden et al
Records identified through database searching (n=2032)
Additional records identified through other sources (n=1)
Records after duplicates removed (n=1373)
Records screened (n=127)
Records excluded (n=72)
Full-text articles assessed for eligibility (n=56)
Full-text articles excluded: 42 • Includes outpatient data: 13 • Combined adult and pediatric data: 13
Studies that met inclusion criteria (n=14)
• Primarily children < 1: 4 • ≤ 10 cases of C. diff: 3 • Appropriate data missing: 4 • CDI recurrence only: 2 • Duplicate data source: 2 • Studied 1 risk factor: 1
Studies included in quantitative synthesis (meta-analysis) (n=9)
Figure 1. Flow chart for study inclusion in the systematic review and meta-analysis.
Figure 2. Forest plot of the association between antibiotic use and CDI. Vertical line corresponds to no difference point between the 2 groups. Squares correspond to risk ratios. Horizontal lines represent the 95% confidence intervals. The diamond indicates the pooled relative risk ratios. Note. df, degrees of freedom; M-H, Mantel-Haenszel.
Meta-analyses of risk factors for CDI
Exposure to antibiotics A total of 7 studies reported data on prior antibiotic exposure (5 unadjusted and 2 adjusted studies). Because<3 studies provided adjusted data, we combined studies reporting the adjusted and unadjusted data. Meta-analysis of the 7 studies demonstrated a sig- nificantly increased risk of CDI with prior exposure to any antibi- otic class (OR, 2.14; 95% CI, 1.31–3.52; P=.003) (Fig. 2). There was moderate heterogeneity among these studies (I2 = 57%). We also performed subgroup analysis for the adjusted and unadjusted stud- ies. The meta-analysis of the unadjusted studies showed a signifi- cantly increased risk of CDI with prior exposure to any antibiotic class (OR, 2.34; 95% CI, 1.27–4.31; P=.006). There was significant heterogeneity among these studies (I2 = 68%). The meta-analysis of the adjusted studies also showed an increased risk of CDI with
prior exposure to antibiotics, but the results were not statistically significant (OR, 1.49; 95% CI, 0.66–3.34; P = .34). There was low heterogeneity between the 2 adjusted studies (I2=1%). Risk factors for CDI with individual antibiotic subclasses were not reported by >2 studies and were therefore not included in the meta-analysis.
Gastric acid suppression We identified 4 studies that reported adjusted data on PPI use as a risk factor for CDI. Meta-analysis of the 4 studies showed increased risk of CDI with PPI use (OR, 1.33; 95% CI, 1.07–1.64; P = .01) (Fig. 3). There was moderate heterogeneity among these studies (I2 = 36%). Adjusted data for the risk of CDI with H2 receptor antagonist (H2RA) use was obtained from 3 studies. Meta-analysis of the 3 studies examining H2RA use also showed increased risk of CDI associated with H2RA use, but the result was not statistically
Included
Eligibility
Screening
Identification
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