Published online May 27, 2020. doi: 10.4254/wjh.v12.i5.239
Peer-review started: December 9, 2019
First decision: January 6, 2020
Revised: March 26, 2020
Accepted: April 23, 2020
Article in press: April 23, 2020
Published online: May 27, 2020
Processing time: 169 Days and 21.4 Hours
Spontaneous bacterial peritonitis (SBP) confers significant mortality with high rates of recurrence. Prevention is therefore indicated and of great importance in cirrhotic individuals with ascites and either significant hepatic disease, gastrointestinal (GI) bleeding, or history of SBP.
Yet data is sparse regarding the choice of antibiotic when comparing the previous gold standard, norfloxacin, to other agents including ciprofloxacin, trimethoprim-sulfamethoxazole (TMP-SMX), and the GI selective agent rifaximin. The network meta-analysis technique allows us to make indirect comparisons across studies using common comparators.
Our present study uses this technique to rank and evaluate recommended therapies for primary and secondary prophylaxis of SBP.
Thirteen randomized control trials including a total of 1757 patient were analyzed. Individual meta-analyses showed superiority of rifaximin over norfloxacin as well as norfloxacin and TMP-SMX over placebo. Network meta-analysis demonstrated the rank of efficacy in reducing the combined primary and secondary risk of SBP as: Rifaximin, ciprofloxacin, TMP-SMX, norfloxacin, and placebo/no comparator. Rifaximin ranked highest in sensitivity analyses limited to studies of either primary or secondary prophylaxis alone, and in studies reported after 2010. Similarly, rifaximin ranked highest in reducing the risk of death/transplant.
This study provides new evidence for superiority of rifaximin compared to norfloxacin in both primary and secondary SBP prophylaxis. In summary, this conclusion is supported by decreased mortality when rifaximin is used for primary or secondary prophylaxis compared to norfloxacin, ciprofloxacin, and TMP-SMX as shown in individual and network meta-analyses. Other new insights from this study were that rifaximin still performed best in a subgroup analysis of studies done after the year 2010, after the recommendation was made for rifaximin use in hepatic encephalopathy.
Therefore, this study proposes the new hypothesis that the common use of rifaximin for hepatic encephalopathy in decompensated cirrhosis does not decrease its effectiveness in SBP prophylaxis. Additional molecular and biochemical data is needed to explain the beneficial effect of rifaximin. However, our data supports the hypothesis that rifaximin’s selective decontamination of the GI tract, favorable resistance profile, and ability to decrease bacterial translocation across the gut may all contribute to its superiority for prophylaxis. Implications of these results for clinical practice include reconsideration of current AASLD guidelines to recommend rifaximin over norfloxacin as the first line agent for SBP prophylaxis.
The next steps in this area of study should include additional data from large studies with direct comparisons between each antibiotic. Randomized control trial methods should be used in future research studies in order to confirm our meta-analysis findings.