Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. May 27, 2020; 12(5): 239-252
Published online May 27, 2020. doi: 10.4254/wjh.v12.i5.239
Systemic review and network meta-analysis: Prophylactic antibiotic therapy for spontaneous bacterial peritonitis
Nolan Faust, Akihiro Yamada, Haider Haider, Yuga Komaki, Fukiko Komaki, Dejan Micic, Atsushi Sakuraba
Nolan Faust, Department of Medicine, The University of Chicago, Chicago, IL 60637, United States
Akihiro Yamada, Haider Haider, Yuga Komaki, Fukiko Komaki, Dejan Micic, Atsushi Sakuraba, Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, The University of Chicago Medicine, Chicago, IL 60637, United States
Akihiro Yamada, Section of Gastroenterology, Department of Internal Medicine, Toho University Sakura Medical Center, Sakura 2850841, Japan
Yuga Komaki, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan
Author contributions: Faust N and Yamada A analyzed the data and drafted the manuscript; Haider H, Komaki Y, Komaki F and Micic D critical reviewed and approved of manuscript; Sakuraba A made the study concept and design, analyzed the data and wrote the manuscript.
Conflict-of-interest statement: Sakuraba A is the speaker’s bureau for Takeda. The others have no conflict.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Atsushi Sakuraba, MD, PhD, Assistant Professor, Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, The University of Chicago Medicine, 5841 S. Maryland Ave. MC 4076, Chicago, IL 60637, United States.
Received: December 9, 2019
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
Research background

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.

Research motivation

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.

Research objectives

Our present study uses this technique to rank and evaluate recommended therapies for primary and secondary prophylaxis of SBP.

Research methods

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.

Research results

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.

Research conclusions

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.

Research perspectives

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.