| BACKGROUND: Clostridium difficile infection(CDI) has become a global epidemiological problem for both hospitalized patients and outpatients. The incidence and severity of CDI appear to be on the rise. The most commonly used drugs to treat CDI are metronidazole and vancomycin.OBJECTIVE: The aim of this study was to compare the efficacy and safety of metronidazole monotherapy with vancomycin monotherapy and combination therapy in CDI patients.METHODS: Clinical trials comparing metronidazole with vancomycin for the treatment of CDI published in Pub Med, Embase, Cochrane library, Web of Science, China National Knowledge Infrastructure(CNKI), Chinese Scientific Journals Database(VIP), WANFANG DATA(another Chinese database) and academic dissertations full-text retrieval platform(Pro Quest) were searched. Designed the inclusion criteria and exclusion criteria for screening documents, studies were included if they met the inclusion criteria, reviewers independently abstracted data from each eligible study and the included studies independently appraised for methodological quality. The quality of each included study was evaluated according to the modified Jadad score and the risk of bias. In addition, potential publication bias was assessed by visual inspection of asymmetry in Begg’s funnel plots, and Egger’s test was then used to provide statistical evidence of funnel plot symmetry. All of these analyses were performed using Review Manager software(Rev Man, version 5.1, Oxford, UK; The Cochrane Collaboration, 2008) and STATA software(version 12.0, Stata Corp, College Station, TX, USA). Both I2 and Q statistics were considered, pooled odds ratios(ORs) and 95% confidence intervals(CIs) were also used in the meta-analysis. In our analyses, we used the I2 statistic to quantitatively describe heterogeneity across studies, the Mantel-Haenszel fixed-effects model(FEM) or Mantel-Haenszel randomed-effects model(REM) was used for all analysis group according to the I2 value. Subgroup analysis was used to reduce the influence of heterogeneity on the results of the analysis and through sensitivity analysis to explore underlying sources of heterogeneity.RESULTS: Thirteen articles with 2501 patients were included in this meta-analysis. For the efficacy, there was no statistically significant differences in the rate of clinical cure between metronidazole and vancomycin for mild CDI(OR=0.67, 95% CI(0.45, 1.00), p=0.05); however, for severe CDI, the rate of clinical cure was lower for metronidazole than for vancomycin(OR=0.46, 95% CI(0.26, 0.80), p=0.006). No statistically significant differences in the rate of CDI recurrence was found between metronidazole and vancomycin for mild CDI(OR=0.99, 95% CI(0.40, 2.45), p=0.98) or for severe CDI(OR=0.98, 95% CI(0.63, 1.53), p=0.94). No statistically significant difference in the rate of clinical cure(OR=1.07, 95% CI(0.58, 1.96), p=0.83) or CDI recurrence(OR=0.91, 95% CI(0.66, 1.26), p=0.56) was found between monotherapy and combination therapy. For the safety, there was no significant difference in the rate of adverse effects(AEs)(OR=1.18, 95% CI(0.80, 1.74), p=0.41) between metronidazole and vancomycin. In contrast, the rate of AEs(OR=0.30, 95% CI(0.17, 0.51), p<0.0001) was found to be significantly lower for monotherapy than for combination therapy; in fact, this rate was over 4 times higher for the latter(11.1% vs. 46.9%).CONCLUSIONS: The meta-analysis has revealed that metronidazole and vancomycin are equally effective for the treatment of mild CDI but that vancomycin is superior for treatment of patients with severe CDI. Combination therapy is not superior to monotherapy because it might be associated with an increase in the rate of AEs. |
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