Antibiotic treatment for spontaneous bacterial peritonitis in people with advanced liver disease

What is the aim of this Cochrane Review?

To find out the best available antibiotic for spontaneous bacterial peritonitis (fluid collection in the tummy (abdomen), infected with bacteria) in people with advanced liver disease (liver cirrhosis, or late stage scarring of the liver with complications). The abnormal buildup of fluid in people with liver cirrhosis is called ascites. Sometimes, this fluid may get infected with bacteria, with no obvious source of infection. This is called 'spontaneous bacterial peritonitis'. The main treatment of spontaneous bacterial peritonitis is antibiotics, but it is unclear which antibiotic is best for treating it. The authors collected and analysed all relevant studies to answer this question and found 12 randomised clinical trials (participants receive the treatment based on methods similar to a coin toss; this is to ensure that the people who receive the different treatments are similar in all aspects except the treatment, so that any differences in the results between the treatments can be attributed to the treatment rather than differences in the type of people who received the treatment). During the analysis of data, authors used standard Cochrane techniques, which allows comparison of two treatments at a time. Authors also used advanced techniques, that allows comparison of many treatments at the same time (usually referred as 'network meta-analysis' or 'multiple treatment comparisons'). The aim is to gather reliable evidence on the relative benefits and harms of the different antibiotics.

Date of literature search
November 2018.

Key messages
None of the studies were conducted without flaws, and because of the very low certainty in the results, the authors cannot suggest which antibiotic, given alone or in combination to remove the bacteria from one's tummy, is better or worse than other antibiotics in the treatment of spontaneous bacterial peritonitis.

The funding source was unclear in 10 studies; industrial organisations funded two studies.

What was studied in the review?

This review studied people, of any sex, age, and origin, with advanced liver disease due to various causes, and who had developed spontaneous bacterial peritonitis. People were administered different antibiotics for the treatment of spontaneous bacterial peritonitis. The authors excluded studies with liver transplanted participants and bacterial peritonitis due to other causes. The participants' age, when reported, ranged from 42 to 60 years. The number of females, when reported, ranged from 18 to 42 out of 100. The administered antibiotic groups were cephalosporins, penicillins, and quinolones. The review authors wanted to gather and analyse data on death, quality of life, serious and non-serious complications, time to liver transplantation (replacement of a diseased liver with a healthy one), time until disappearance of spontaneous bacterial peritonitis, and disappearance of symptoms.

What were the main results of the review?

The 12 studies included a small number of participants (1278 participants). The study data were sparse; 10 studies with 893 participants provided data for analyses. Follow-up in the trials ranged from one week to three months. The review shows the following.

- Out of the 13 different antibiotics compared in the trials, ceftriaxone and cefotaxime administered into the vein, were most commonly used.

- The type of antibiotic provided may make no difference to the number or percentage of people with serious complications or with any complications; number of (any) complications per person; percentage of people undergoing liver transplantation; or who recovered from spontaneous bacterial peritonitis as per laboratory tests, or other complications of liver cirrhosis.

- Twenty-five out of every 100 people died within three months, and 75 out of every 100 people recovered from spontaneous bacterial peritonitis.

- None of the trials reported health-related quality of life, number of serious adverse events, or symptomatic recovery from spontaneous bacterial peritonitis.

- We have very low confidence in the overall results. Whether some antibiotics may cause important or less important benefits or harms compared to others when given to people with advanced liver disease and spontaneous bacterial peritonitis is questionable.

- We need data from trials of proper design and quality in order to be able to clarify the best antibiotic for spontaneous bacterial peritonitis.

Authors' conclusions: 

Short-term mortality after SBP is about 25%. There is significant uncertainty about which antibiotic therapy is better in people with SBP.

We need adequately powered randomised clinical trials, with adequate blinding, avoiding post-randomisation dropouts (or performing intention-to-treat analysis), and using clinically important outcomes, such as mortality, health-related quality of life, and adverse events.

Read the full abstract...
Background: 

Approximately 2.5% of all hospitalisations in people with cirrhosis are for spontaneous bacterial peritonitis (SBP). Antibiotics, in addition to supportive treatment (fluid and electrolyte balance, treatment of shock), form the mainstay treatments of SBP. Various antibiotics are available for the treatment of SBP, but there is uncertainty regarding the best antibiotic for SBP.

Objectives: 

To compare the benefits and harms of different antibiotic treatments for spontaneous bacterial peritonitis (SBP) in people with decompensated liver cirrhosis.

Search strategy: 

We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until November 2018 to identify randomised clinical trials on people with cirrhosis and SBP.

Selection criteria: 

We included only randomised clinical trials (irrespective of language, blinding, or publication status) in adults with cirrhosis and SBP. We excluded randomised clinical trials in which participants had previously undergone liver transplantation.

Data collection and analysis: 

Two review authors independently identified eligible trials and collected data. The outcomes for this review included mortality, serious adverse events, any adverse events, resolution of SBP, liver transplantation, and other decompensation events. We performed a network meta‐analysis with OpenBUGS using Bayesian methods and calculated the odds ratio, rate ratio, and hazard ratio with 95% credible intervals (CrIs) based on an available‐case analysis, according to the National Institute of Health and Care Excellence (NICE) Decision Support Unit guidance.

Main results: 

We included a total of 12 trials (1278 participants; 13 antibiotics) in the review. Ten trials (893 participants) were included in one or more outcomes in the review. The trials that provided the information included patients having cirrhosis with or without other features of decompensation of varied aetiologies. The follow-up in the trials ranged from one week to three months. All the trials were at high risk of bias. Only one trial was included under each comparison for most of the outcomes. Because of these reasons, there is very low certainty in all the results. The majority of the randomised clinical trials used third-generation cephalosporins, such as intravenous ceftriaxone, cefotaxime, or ciprofloxacin as one of the interventions.

Overall, approximately 75% of trial participants recovered from SBP and 25% of people died within three months. There was no evidence of difference in any of the outcomes for which network meta-analysis was possible: mortality (9 trials; 653 participants), proportion of people with any adverse events (5 trials; 297 participants), resolution of SBP (as per standard definition, 9 trials; 873 participants), or other features of decompensation (6 trials; 535 participants). The effect estimates in the direct comparisons (when available) were very similar to those of network meta-analysis. For the comparisons where network meta-analysis was not possible, there was no evidence of difference in any of the outcomes (proportion of participants with serious adverse events, number of adverse events, and proportion of participants requiring liver transplantation). Due to the wide CrIs and the very low-certainty evidence for all the outcomes, significant benefits or harms of antibiotics are possible.

None of the trials reported health-related quality of life, number of serious adverse events, or symptomatic recovery from SBP.

Funding: the source of funding for two trials were industrial organisations who would benefit from the results of the trial; the source of funding for the remaining 10 trials was unclear.

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