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Efficacy and Safety of Metronidazole Monotherapy versus Vancomycin Monotherapy or Combination Therapy in Patients with Clostridium difficile Infection: A Systematic Review and Meta-Analysis.

Li R, Lu L, Lin Y, Wang M, Liu X - PLoS ONE (2015)

Bottom Line: 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.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).Metronidazole and vancomycin are equally effective for the treatment of mild CDI, but vancomycin is superior for the treatment of severe CDI.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Chongqing Medical University, Chongqing, China.

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.

No MeSH data available.


Related in: MedlinePlus

Forest plot of the rate of AEs (a: metronidazole vs. vancomycin; b: monotherapy vs. combination therapy).The vertical line indicates no difference between the groups. ORs are represented by diamond shapes, and 95% CIs are depicted by horizontal lines. Squares indicate point estimates, and the size of each square indicates the weight of the given study in the meta-analysis. M-H, Mantel-Haenszel fixed-effects model.
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pone.0137252.g004: Forest plot of the rate of AEs (a: metronidazole vs. vancomycin; b: monotherapy vs. combination therapy).The vertical line indicates no difference between the groups. ORs are represented by diamond shapes, and 95% CIs are depicted by horizontal lines. Squares indicate point estimates, and the size of each square indicates the weight of the given study in the meta-analysis. M-H, Mantel-Haenszel fixed-effects model.

Mentions: The reported AEs from the included studies consisted of death, colectomy, diarrhea, any complication, ileus, colonic perforation, nausea and vomiting, pseudomembranous colitis, toxic megacolon, rash and severe enterocolitis. We performed subgroup analysis according to the AEs. The meta-analysis results did not show any significant difference in the rate of AEs between metronidazole and vancomycin (the results from 7 studies were separated into six subgroups[13,20,26–30], 1330 patients, OR = 1.18, 95% CI (0.80, 1.74), p = 0.41, I2 = 0%) (Fig 4A). However, the rate of AEs was significantly lower for monotherapy than for combination therapy (the results from 3 studies were separated into eight subgroups [10,28,33], 439 patients, OR = 0.30, 95% CI (0.17, 0.51), p<0.0001, I2 = 0%) (Fig 4B); in fact, this rate was more than 4-fold higher for combination therapy than for monotherapy (46.9% vs.11.1%).


Efficacy and Safety of Metronidazole Monotherapy versus Vancomycin Monotherapy or Combination Therapy in Patients with Clostridium difficile Infection: A Systematic Review and Meta-Analysis.

Li R, Lu L, Lin Y, Wang M, Liu X - PLoS ONE (2015)

Forest plot of the rate of AEs (a: metronidazole vs. vancomycin; b: monotherapy vs. combination therapy).The vertical line indicates no difference between the groups. ORs are represented by diamond shapes, and 95% CIs are depicted by horizontal lines. Squares indicate point estimates, and the size of each square indicates the weight of the given study in the meta-analysis. M-H, Mantel-Haenszel fixed-effects model.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4621873&req=5

pone.0137252.g004: Forest plot of the rate of AEs (a: metronidazole vs. vancomycin; b: monotherapy vs. combination therapy).The vertical line indicates no difference between the groups. ORs are represented by diamond shapes, and 95% CIs are depicted by horizontal lines. Squares indicate point estimates, and the size of each square indicates the weight of the given study in the meta-analysis. M-H, Mantel-Haenszel fixed-effects model.
Mentions: The reported AEs from the included studies consisted of death, colectomy, diarrhea, any complication, ileus, colonic perforation, nausea and vomiting, pseudomembranous colitis, toxic megacolon, rash and severe enterocolitis. We performed subgroup analysis according to the AEs. The meta-analysis results did not show any significant difference in the rate of AEs between metronidazole and vancomycin (the results from 7 studies were separated into six subgroups[13,20,26–30], 1330 patients, OR = 1.18, 95% CI (0.80, 1.74), p = 0.41, I2 = 0%) (Fig 4A). However, the rate of AEs was significantly lower for monotherapy than for combination therapy (the results from 3 studies were separated into eight subgroups [10,28,33], 439 patients, OR = 0.30, 95% CI (0.17, 0.51), p<0.0001, I2 = 0%) (Fig 4B); in fact, this rate was more than 4-fold higher for combination therapy than for monotherapy (46.9% vs.11.1%).

Bottom Line: 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.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).Metronidazole and vancomycin are equally effective for the treatment of mild CDI, but vancomycin is superior for the treatment of severe CDI.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Chongqing Medical University, Chongqing, China.

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.

No MeSH data available.


Related in: MedlinePlus