Comparative Effectiveness of Piperacillin-Tazobactam or Fluoroquinolones Versus Third-Generation Cephalosporins in Spontaneous Bacterial Peritonitis: A Systematic Review and Meta-Analysis

Spontaneous bacterial peritonitis (SBP) remains a significant cause of morbidity and mortality among patients with cirrhosis. Third-generation cephalosporins (TGCs) have long been considered standard empiric therapy in major guidelines such as the British Society of Gastroenterology (BSG), the European Association for the Study of the Liver (EASL), and the American Association for the Study of Liver Diseases (AASLD). However, rising resistance patterns have led to increased use of piperacillin-tazobactam within the National Health Service (NHS). We aimed to evaluate the current evidence on the use of piperacillin-tazobactam and fluoroquinolones (FQs) in SBP through a systematic review of randomised controlled trials (RCTs) and observational studies. The study followed Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines. MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (Cochrane CENTRAL) were searched from inception. The primary outcome was resolution of infection, with the secondary outcome being mortality (in-hospital or 30-day). Meta-analysis was performed where appropriate. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) and the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tools, and evidence certainty was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. Nine studies (n = 2034) met the inclusion criteria. There was no difference between FQs and TGCs in terms of resolution of infection (odds ratio (OR) 0.95 (0.67-1.34), P = 0.90, I² = 0%) and mortality (OR 0.76 (0.46- 1.24), P = 0.27, I² = 0). Resolution of infection data for piperacillin-tazobactam versus TGCs was narratively reviewed, showing non-inferiority in a cohort and higher microbiological coverage in a culture-positive SBP cohort. The certainty of the evidence was very low according to the GRADE framework. No study directly reported mortality for piperacillin-tazobactam in SBP. One included study examined purely nosocomial SBP and showed a significantly higher rate of infection resolution with meropenem plus daptomycin versus ceftazidime. In summary, in community-acquired SBP, FQs are comparable to TGCs in terms of resolution of infection and mortality. Piperacillin-tazobactam may provide non-inferior clinical efficacy and broader microbiological coverage in settings with a higher prevalence of resistant or nosocomial organisms. Wider-spectrum coverage should be considered for nosocomial infections or patients with severe disease, guided by local antibiotic resistance patterns. However, no study reported mortality outcomes specifically for piperacillin-tazobactam. The low certainty of evidence for piperacillin-tazobactam versus TGCs highlights the need for well-powered RCTs.