Systemic review and network meta-analysis: Prophylactic antibiotic therapy for spontaneous bacterial peritonitis

Abstract

Background: Spontaneous bacterial peritonitis (SBP) is an important prognostic factor for outcomes in patients with cirrhosis. Antibiotic prophylaxis is recommended in patients at high risk for developing SBP, but the choice of antibiotics remains unclear.

Aim: To evaluate the efficacy of various antibiotics for prophylaxis of SBP based on randomized control trials (RCTs).

Methods: Electronic databases were searched through November 2018 for RCTs evaluating the efficacy of therapies for primary or secondary prophylaxis of SBP. The primary outcome was the development of SBP. Sensitivity analyses limited to studies of primary or secondary prophylaxis and studies reported after 2010 were performed. The secondary outcome was the risk of all-cause mortality or transplant. The outcomes were assessed by rank of therapies based on network meta-analyses. Individual meta-analyses were also performed.

Results: Thirteen RCTs (1742 patients) including norfloxacin, ciprofloxacin, rifaximin, trimethoprim-sulfamethoxazole (TMP-SMX), or placebo/no comparator were identified. 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 risk of SBP as: Rifaximin, ciprofloxacin, TMP-SMX, norfloxacin, and placebo/no comparator. Rifaximin ranked highest in sensitivity analyses limited to studies of primary or secondary prophylaxis and studies reported after 2010. Similarly, rifaximin ranked highest in reducing the risk of death/transplant.

Conclusion: The present comprehensive network meta-analysis provides RCT based evidence for superior efficacy of rifaximin compared to other antibiotics for the prophylaxis of SBP and reducing risk of death/transplant. Further RCTs are warranted to confirm our findings.

Keywords: Antibiotics; Cirrhosis; Network meta-analysis; Prophylaxis; Spontaneous bacterial peritonitis; Systemic review.

Figure 1

Flow chart of assessment of studies identified in the network meta-analysis.

Figure 2

Network meta-analysis of studies assessing the risk of spontaneous bacterial peritonitis. A: Network of treatment comparisons between antibiotics. Numbers indicate the number of studies comparing the two connected treatment arms; B: Relative effects of between each treatment. The numbers in the cell represent the odds ratio (95%CI) of the column defining modality relative to the row defining treatment; C: Rank probability (consistency model) for each antibiotic. Indicated is the possibility of each rank (No. 5 is the best). The overall rank interpreted by surface under the cumulative ranking technique is shown in the table. surface under the cumulative rankings in the table are reordered in the conventional ascending sequence. CPFX: Ciprofloxacin; NFX: Norfloxacin; RFX: Rifaximin; TMPSMX: Trimethoprim-sulfamethoxazole; SUCRA: Surface under the cumulative ranking.

Figure 3

Network meta-analysis of studies assessing the risk of death/transplant. A: Network of treatment comparisons between antibiotics. Numbers indicate the number of studies comparing the two connected treatment arms; B: Relative effects of between each treatment. The numbers in the cell represent the odds ratio (95%CI) of the column defining modality relative to the row defining treatment; C: Rank probability (consistency model) for each antibiotic. Indicated is the possibility of each rank (No. 5 is the best). The overall rank interpreted by surface under the cumulative ranking technique is shown in the table. surface under the cumulative rankings in the table are reordered in the conventional ascending sequence. CPFX: Ciprofloxacin; NFX: Norfloxacin; RFX: Rifaximin; TMPSMX: Trimethoprim-sulfamethoxazole; SUCRA: Surface under the cumulative ranking.