Spontaneous bacterial peritonitis (SBP) is a common complication of end-stage liver disease. SBP can present with many symptoms such as abdominal pain, fever and altered mental status.1 The diagnosis of SBP is made when ascitic fluid from a paracentesis has an absolute neutrophil count (ANC) more than 250/uL, there is a positive ascitic fluid culture, and no secondary source of infection can be idenitifed.2 However, nearly 60% of patients with SBP have negative fluid cultures.3 These patients can still potentially have SBP and should be treated as such since in-hospital mortality ranges from 20-40%.1,4 Conventional treatment for SBP includes a third-generation cephalosporin for five days, followed by lifetime prophylaxis most commonly with a fluoroquinolone. 5 After 48 hours of antibiotic treatment, a repeat paracentesis should be performed. If the ANC does not decrease by at least 25%, it is considered a therapeutic failure and the antibiotic should be changed.5 With early diagnosis and appropriate antibiotic regimen, SBP is treatable.

When therapy for SBP fails and the ascitic fluid ANC remains elevated, the peritonitis is considered persistent. Persistent peritonitis should raise suspicion for a secondary cause. An increase or lack of a significant decrease in the ANC in follow-up paracentesis should provoke a full work-up for secondary causes of peritonitis.1 Secondary causes include intra-abdominal abscess, bowel perforation, bile leak and malignancy. If a source is not found, persistent peritonitis should be treated with broad-spectrum antibiotics and/or antifungals early on.6 Furthermore, patients with a history of an ICU stay during the previous three months, antibiotic treatment during the previous three months, or a recent intervention in the hospital setting tend to be at higher risk for persistent, difficult to treat peritonitis.7 This includes resistance to third-generation cephalosporins and quinolones, which has been documented in 40-50% of difficult to treat peritonitis cases.7 When patients have complications in their hospital course, difficult to treat peritonitis should be of concern.