Primary prevention
Antibiotics for primary prophylaxis, the prevention of a first episode of SBP, should be used judiciously, taking into account adverse effects and risk of promoting resistance.[61] The potential benefit of antibiotic prophylaxis must be balanced against the increased likelihood of risks from long-term antibiotics, and decisions should be individualised according to patient characteristics, current evidence, and drug availability.[61][62][63]
Primary prophylaxis for SBP should be considered in patients at highest risk of infection which includes patients with cirrhosis and acute upper gastrointestinal bleeding, and patients found to have low total protein content in ascitic fluid plus evidence of liver or kidney impairment.[61][64] The most recent 2021 AASLD guidelines do note that several of the studies looking at giving antibiotics for primary prophylaxis of SBP have been considered to be of variable quality and considered insufficient to make a consensus recommendation for primary prophylaxis, other than in patients with advanced cirrhosis and at high risk of infection, such as in the clinical scenarios above. A low concentration of ascitic protein (<15 g/L [<1.5 g/dL]) has been demonstrated as a risk factor for the development of SBP and systematic reviews have found that oral antibiotic prophylaxis in this patient population reduces the rate of first-episode SBP and other bacterial infections, and results in reduced mortality.[65][66] The greater the degree of liver and kidney dysfunction, also the greater the benefit of prophylaxis. In patients with low concentration of ascitic protein and either severe liver dysfunction (Child-Turcotte-Pugh score ≥9, with serum bilirubin ≥51.31 micromol/L [≥3 mg/dL]) or kidney dysfunction (serum creatinine level ≥106 micromol/L [≥1.2 mg/dL], urea ≥8.92 mmol/L [≥25 mg/dL], or serum sodium level ≤130 mmol/L [≤130 mEq/L]) , prophylaxis with norfloxacin was associated with a decreased 6-month SBP rate and hepatorenal syndrome rate.[67]
While most studies have been done with norfloxacin, which has been discontinued in some countries (including the US), prophylaxis with ciprofloxacin, trimethoprim/sulfamethoxazole, or rifaximin have also shown benefit. Rifaximin, a poorly absorbed oral antibiotic with broad-spectrum activity against both gram-positive and gram-negative intestinal bacteria, has been studied as a means of primary prevention of SBP. In meta-analyses, rifaximin appeared to reduce the risk of first-episode SBP in people with cirrhosis.[68][69][70][71] In terms of which antibiotic regimen is more efficacious, the AASLD does not recommend any antibiotic, but two more recent meta-analyses (one that has been published since those guidelines) have suggested rifaximin as potentially being more efficacious.[71][72]
Beta-blockers
Evidence for the use of non-selective beta-blockers for SBP prophylaxis is conflicting.[61] One meta-analysis of three randomised controlled trials (one on primary prevention; two on secondary prevention) found that propranolol and nadolol may prevent new episodes of SBP in patients with cirrhosis and ascites.[73] A subsequent randomised controlled trial in patients with compensated cirrhosis showed that use of a non-selective beta-blocker was associated with a reduced incidence of decompensated cirrhosis or death, suggesting that their use in early cirrhosis may be beneficial.[74]
However, continued use of a non-selective beta-blocker in patients with cirrhosis and established SBP was associated with reduced (transplant-free) survival, increased hospital stay, and higher rates of hepatorenal syndrome and acute kidney injury.[75] Later studies demonstrated that this was likely limited to patients with reduced mean arterial pressure.[76][77] Therefore, the AASLD advises to not continue the drug in hypotensive patients, while it can be resumed when the mean arterial pressure normalises.[61]
Secondary prevention
Antibiotics for secondary prophylaxis against SBP should be considered in patients following an episode of SBP.[61][117][130][158] The 1-year cumulative recurrence rate is around 70% in those that survive SBP.[117] Treatment should continue until ascites resolves, the patient becomes critically ill, or liver transplantation takes place.[51] See Primary Prevention for more information on prophylaxis in patients with no history of SBP.
One systematic review and network meta-analysis (where different antibiotic prophylaxes were treated as different interventions) of antibiotic prophylaxis for the prevention of SBP in people with cirrhosis found no evidence of difference in mortality or serious adverse events in any of the direct comparisons or network meta‐analysis.[159] There was no evidence of difference based on whether the prophylaxis was primary or secondary. Overall quality of evidence was low or very low.[159]
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Local bacterial resistance patterns should be considered when selecting the most appropriate antibiotic.
Rifaximin
One meta-analysis of studies of rifaximin for primary and secondary prevention of SBP suggested a protective effect; in subgroup analysis, rifaximin reduced the risk of SBP by 74% compared with systemic antibiotics for secondary prophylaxis.[68]
Beta-blockers
Evidence for the use of non-selective beta-blockers for SBP prophylaxis is conflicting.[61] One meta-analysis of three randomised controlled trials (one on primary prevention; two on secondary prevention) found that propranolol and nadolol may prevent new episodes of SBP in patients with cirrhosis and ascites.[73] A subsequent randomised controlled trial in patients with compensated cirrhosis showed that use of a non-selective beta-blocker was associated with a reduced incidence of decompensated cirrhosis or death, suggesting that their use in early cirrhosis may be beneficial.[74]
However, continued use of a non-selective beta-blocker in patients with cirrhosis and established SBP was associated with reduced (transplant-free) survival, increased hospital stay, and higher rates of hepatorenal syndrome and acute kidney injury.[75] Consideration should be given to stopping non-selective beta-blockers if SBP develops. Further randomised controlled studies using hard end points are required to establish the benefits of beta-blockers in patients with refractory ascites, and the American Association for the Study of Liver Diseases advises caution if their use is considered for patients with hypotension, hyponatraemia, or acute kidney injury.[61]
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