2026 Southeastern Residency Conference

Background: Spontaneous bacterial peritonitis (SBP) is the most common bacterial infection among patients with decompensated cirrhosis. Ceftriaxone remains a widely used first line empiric therapy; however, shifts in epidemiology and rising antimicrobial resistance have raised concerns regarding treatment failure in this population. A key challenge in SBP management is that up to 60% of cases are culture negative, necessitating reliance on peritoneal fluid cytology for diagnosis and assessment of therapeutic response. In patients with culture negative SBP who fail to respond to ceftriaxone, evidence-based guidance for antibiotic escalation is lacking, resulting in substantial variability in clinical practice. Evaluation of outcomes in patients with culture negative SBP empirically treated with ceftriaxone may help identify risk factors for treatment failure and inform the effectiveness of commonly employed escalation strategies.
Objective: This study aims to determine the success rates of the following antibiotic escalation strategies used after ceftriaxone failure: carbapenem-sparing regimens (cefepime, or piperacillin-tazobactam), carbapenem regimens, carbapenem-sparing + broad gram-positive coverage (vancomycin, linezolid, or daptomycin), or carbapenem + broad gram-positive coverage. A secondary aim is to identify risk factors associated with ceftriaxone treatment failure in the patient population.
Methods: This is a retrospective cohort study conducted at a tertiary referral hospital from June 2022 to December 2025. Adult patients were included if they had culture negative SBP, defined as an ascitic polymorphonuclear (PMN) count ≥250 cells/µL, were primarily treated with ceftriaxone, and underwent a repeat paracentesis ≥48 hours later to assess treatment response (or had resolution of ascites). Patients were excluded if they had secondary peritonitis, non-cirrhotic peritonitis, or received ≥ 24 hours of alternative antibiotics prior to ceftriaxone. For the primary outcome, we evaluated response rates across the 4 antibiotic escalation groups. Treatment success was defined as a ≥25% reduction in PMN count on repeat paracentesis. For the secondary endpoint, we planned to evaluate risk factors associated with treatment failure and compare patient outcomes.
Results: A total of 69 patients with culture-negative SBP were included. The median age was 55 years (IQR 47–66), 67% were male, and the most common etiology of cirrhosis was alcohol-related (41%). Median MELD-Na score was 22 (IQR 17–28). The median time from admission to SBP diagnosis was 20 hours (IQR 1–69), and 86% of patients received ceftriaxone 2g. Ceftriaxone failure occurred in 5 patients (7.2%). All five received antibiotic escalation: four were treated with a carbapenem-based regimen, and one received cefepime with metronidazole. Among patients with documented PMN response data, reductions ranged from 31% to 89%. Two patients in the ceftriaxone failure group died in-hospital (40%) compared to 4 patients (6%) in the success group. Median hospital length of stay was longer in the failure group (14 days [IQR 10–16] vs. 8 days [IQR 6–18]), as was duration of antibiotic therapy (9 days [IQR 7–13] vs. 5 days [IQR 4–6]). In an exploratory analysis of potential risk factors, nosocomial SBP was identified in 20% of failures and 27% of successes. Prior anti-pseudomonal antibiotic exposure within 90 days was more prevalent among ceftriaxone failures compared to successes (40% vs. 23%). The small sample size precluded formal statistical comparison for all outcomes.
Conclusion: Ceftriaxone failure was uncommon in our cohort of culture-negative SBP, occurring in approximately 7% of patients. Ceftriaxone failure was associated with prolonged hospitalization, extended antibiotic exposure, and higher in-hospital mortality. Prior broad-spectrum antibiotic use emerged as a potential risk factor warranting further investigation in larger cohorts. These findings underscore the need for larger prospective studies to establish evidence-based escalation strategies.