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

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.