title: Efficacy and Safety of Metronidazole Monotherapy versus Vancomycin Monotherapy or Combination Therapy in Patients with Clostridium difficile Infection: A Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  Clostridium difficile infection (CDI) has become a global epidemiological problem for both hospitalized patients and outpatients. The most commonly used drugs to treat CDI are metronidazole and vancomycin. 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
  A comprehensive search without publication status or other restrictions was conducted. Studies comparing metronidazole monotherapy with vancomycin monotherapy or combination therapy in patients with CDI were considered eligible. Meta-analysis was performed using the Mantel-Haenszel fixed-effects model, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated and reported.
  
  
  RESULTS
  Of the 1910 records identified, seventeen studies from thirteen articles (n = 2501 patients) were included. No statistically significant difference in the rate of clinical cure was found between metronidazole and vancomycin for mild CDI (OR = 0.67, 95% CI (0.45, 1.00), p = 0.05) or between either monotherapy and combination therapy for CDI (OR = 1.07, 95% CI (0.58, 1.96), p = 0.83); however, the rate of clinical cure was lower for metronidazole than for vancomycin for severe CDI (OR = 0.46, 95% CI (0.26, 0.80), p = 0.006). No statistically significant difference 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 severe CDI (OR = 0.98, 95% CI (0.63, 1.53), p = 0.94) or between either monotherapy and combination therapy for CDI (OR = 0.91, 95% CI (0.66, 1.26), p = 0.56). In addition, there was no significant difference in the rate of adverse events (AEs) between metronidazole and vancomycin (OR = 1.18, 95% CI (0.80, 1.74), p = 0.41). In contrast, the rate of AEs was significantly lower for either monotherapy than for combination therapy (OR = 0.30, 95% CI (0.17, 0.51), p < 0.0001).
  
  
  CONCLUSIONS
  Metronidazole and vancomycin are equally effective for the treatment of mild CDI, but vancomycin is superior for the treatment of severe CDI. Combination therapy is not superior to monotherapy because it appears to be associated with an increase in the rate of AEs.
authors.affiliation: College of Pharmacy, Chongqing Medical University, Chongqing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Third Affiliated Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Laichun
authors.initials: L
authors.lastname: Lu
authors.affiliation: College of Pharmacy, Chongqing Medical University, Chongqing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lin
authors.affiliation: College of Pharmacy, Chongqing Medical University, Chongqing, China.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Chongqing Medical University, Chongqing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D016360:Clostridioides difficile / Q000187:drug effects*; D004359:Drug Therapy, Combination; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D016896:Treatment Outcome; D014640:Vancomycin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D008795:Metronidazole; D014640:Vancomycin