Effect of nitazoxanide on diarrhea: A systematic review and network meta-analysis of randomized controlled trials

We aimed to systematically review evidence pertaining to the safety and efficacy of nitazoxanide in treating infectious diarrhea. On September 21, 2017, we identified relevant studies using 12 databases. The estimates of the included studies were pooled as a risk ratio (RR). We conducted a network and pairwise random-effects meta-analysis for both direct and indirect comparisons of different organisms that are known to cause diarrhea. The primary and secondary analysis outcomes were clinical response until cessation of illness, parasitological response and adverse events. We included 18 studies in our analysis. In cryptosporidiosis, the overall estimate favored nitazoxanide in its clinical response in comparison with placebo RR 1.46 [95% CI 1.22-1.74; P-value <0.0001]. Network meta-analysis among patients with Giardia intestinalis showed an increase in the probability of diarrheal cessation and parasitological responses in comparison with placebo, RR 1.69 [95% CI 1.08-2.64, P-score 0.27] and RR 2.91 [95% CI 1.72-4.91, P-score 0.55] respectively. In Clostridium difficile infection, the network meta-analysis revealed a non-significantly superior clinical response effect of nitazoxanide to metronidazole 31 days after treatment RR 1.21 [95% CI 0.87-1.69, P-score 0.26]. In Entamoeba histolytica, the overall estimate significantly favored nitazoxanide in parasitological response with placebo RR 1.80 [95% CI 1.35-2.40, P-value < 0.001]. We highlighted the effectiveness of nitazoxanide in the cessation of diarrhea caused by Cryptosporidium, Giardia intestinalis and Entamoeba histolytica infection. We also found significant superiority of NTZ to metronidazole in improving the clinical response to G. intestinalis, thus it may be a suitable candidate for treating infection-induced diarrhea. To prove the superiority of NTZ during a C. difficile infection may warrant a larger-scale clinical trial since its superiority was deemed insignificant. We recommend nitazoxanide as an appropriate option for treating infectious diarrhea.