What is the treatment approach for refractory Spontaneous Bacterial Peritonitis (SBP)?

From the Guidelines

The treatment approach for refractory Spontaneous Bacterial Peritonitis (SBP) involves escalating antibiotic therapy and addressing underlying complications, with carbapenems (meropenem 1g IV every 8 hours or imipenem 500mg IV every 6 hours) or combinations like piperacillin-tazobactam (4.5g IV every 6-8 hours) being often effective second-line options, as recommended by the most recent guidelines 1. When initial empiric therapy fails, typically after 48-72 hours without clinical improvement, switching to broader-spectrum antibiotics is recommended. Adding an anti-MRSA agent like vancomycin (15-20mg/kg IV every 8-12 hours) may be necessary if resistant gram-positive organisms are suspected. Treatment duration should be extended to 10-14 days for refractory cases. Obtaining repeat paracentesis for culture and sensitivity testing is crucial to guide targeted therapy. Addressing contributing factors is equally important, including albumin supplementation (1.5g/kg on day 1, followed by 1g/kg on day 3) to improve circulatory function, managing hepatorenal syndrome if present, and considering early TIPS (transjugular intrahepatic portosystemic shunt) evaluation in appropriate candidates. Some key points to consider in the management of refractory SBP include:

• The use of carbapenems or other broad-spectrum antibiotics as second-line therapy 1
• The importance of addressing underlying complications, such as hepatorenal syndrome and cirrhosis 1
• The role of albumin supplementation in improving circulatory function and preventing further complications 1
• The need for early consideration of liver transplant evaluation in patients with refractory SBP 1 Refractory SBP carries a poor prognosis and should prompt consideration for liver transplant evaluation. The aggressive approach is necessary because refractory SBP indicates either resistant organisms, inadequate initial therapy, or severe hepatic decompensation that impairs the patient's ability to clear the infection. It is essential to pay close attention to renal function in patients with cirrhosis and an infection, as progressive AKI in this setting portends the poorest prognosis 1. In patients with cirrhosis and an infection, albumin plays a much more important role than as a simple expander of the intravascular volume, and IV albumin improves survival in patients with cirrhosis and SBP 1. Given increasing recent failure rates of initial antibiotic therapy, which may lead to increased mortality, it is recommended that a diagnostic paracentesis (or thoracentesis for SBE) be performed 48 hours after initiating antibiotic therapy to assess response 1. A negative response is defined by a decrease in PMN count <25% from baseline and should lead to broadening the antibiotic spectrum and investigating secondary peritonitis (abdominal imaging studies) 1.

From the Research

Treatment Approach for Refractory Spontaneous Bacterial Peritonitis (SBP)

The treatment approach for refractory SBP involves the use of alternative antibiotic regimens, as first-line therapies may become ineffective.

• The combination of meropenem plus daptomycin has been shown to be more effective than ceftazidime in the treatment of nosocomial SBP 2.
• European recommendations suggest a second-line antibiotic therapy, including meropenem or piperacillin plus tazobactam, for cases where the antibiotic sensitivity to quinolones is low 3.
• Alternative antibiotics such as piperacillin-tazobactam should be considered for patients with nosocomial SBP or for patients who fail to improve on traditional antibiotic regimens 4.

Risk Factors and Predictors of Outcome

Several risk factors and predictors of outcome have been identified in patients with refractory SBP, including:

• Advanced age
• Refractory ascites
• Variceal bleeding
• Renal failure
• Low albumin levels
• Bilirubin over 4 mg/dl
• Child-Pugh class C
• Previous diagnosis of SBP 3
• Ineffective response to first-line treatment 2
• Development of acute kidney injury during hospitalization 2

Diagnostic and Therapeutic Considerations

Diagnostic paracentesis should be performed in all patients with ascites and clinical features with high diagnostic suspicion 5.

• The final diagnosis requires the analysis of ascites and the presence of > 250 mm3 neutrophil polymorphonuclear (PMN) in ascites 5.
• Prompt and effective treatment is required to prevent outcomes, and this becomes challenging as first-line therapies may become ineffective leading to worsening prognosis and increased in-hospital mortality 5.