A randomized open label study of 'imipenem vs. cefepime' in spontaneous bacterial peritonitis

Liver Int. 2016 May;36(5):677-87. doi: 10.1111/liv.12985. Epub 2015 Nov 21.


Background & aims: Spontaneous bacterial peritonitis (SBP), in the presence of bacterial resistance or failure of third generation cephalosporins (3rd GC) has poor outcome. Empirical antibiotic(s) options are limited in these scenarios.

Methods: Consecutive cirrhotics with SBP because of hospital acquired SBP (>48 h of admission), microbial resistance or non-response (no resolution of SBP at 48 h) were randomized to Cefepime (n = 88) or Imipenem (n = 87) plus standard medical therapy. We assessed for 'response at 48 h' (reduction in ascitic fluid absolute neutrophil count (ANC) by >25% at 48 h), resolution of SBP (<250 cu/mm ANC at day 5) and their clinical outcome.

Results: Of 957 paracentesis in 1200 hospitalized cirrhotics, 253 (26.4%) had SBP and 175 (69.6%) were randomized. Baseline parameters were comparable in two groups. Response at 48 h (58.6% vs. 51.7%; P = 0.4) and resolution of SBP in those with response at 48 h were comparable with no difference in mortality at week 2, month 1 and 3. Patients with 'No response at 48 h' had higher mortality compared with responders (73.8% vs. 25%; P < 0.001). Resolution of SBP was associated with 'response at 48 h' and septic shock, latter being main pre-terminal event. AKI at enrolment [Hazard ratio (HR), 2.6], pneumonia [HR, 2.9], septic shock [HR, 2.2] and response at 48 h [HR, 4.6] predicted poor outcome.

Conclusions: In hospitalized cirrhotics with SBP and risk factors for treatment failure, cefepime showed comparable efficacy and survival to imipenem. Non-response to therapy at 48 h is a reliable predictor of treatment failure and mortality. Antibiotic combinations and novel options are needed for these patients.

Trial registration: ClinicalTrials.gov NCT01852630.

Keywords: acute kidney injury; ascites; cirrhosis; hepatic encephalopathy; liver transplantation; multidrug resistance.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Ascitic Fluid / microbiology
  • Bacterial Infections / drug therapy*
  • Cefepime
  • Cephalosporins / administration & dosage*
  • Cross Infection / drug therapy
  • Drug Resistance, Multiple
  • Drug Therapy, Combination
  • Female
  • Humans
  • Imipenem / administration & dosage*
  • India
  • Liver Cirrhosis / complications
  • Male
  • Middle Aged
  • Paracentesis
  • Peritonitis / drug therapy*
  • Peritonitis / microbiology
  • Risk Factors
  • Severity of Illness Index
  • Survival Analysis
  • Time Factors


  • Anti-Bacterial Agents
  • Cephalosporins
  • Imipenem
  • Cefepime

Associated data

  • ClinicalTrials.gov/NCT01852630