Disclosures: Paolo Angeli – Advisory Committees or Review Panels: Sequana Medica XL765 in vitro The following people have nothing to disclose: Alberto Ferrarese, Alberto
Zanetto, Edoardo Casiglia, Silvano Fasolato, Giovanni Boschetti, Kryssia I. Rodriguez, Elena Nadal, Ilaria Bortoluzzi, Francesco P. Russo, Giacomo Germani, Patrizia Burra, Marco Senzolo BACKGROUND In presence of bacterial resistance and/or failure of first-line antibiotic therapy, ceftriaxone, has poor outcome in patients with SBP. Carbepenems, are often used emperically and may lead to unwarranted drug resistance. The comparative efficacy & safety of Cefepime, compared to car-bepenems is not known in such difficult to treat SBP (DTT-SBP) patients. Such data may prevent emergence of carbanemase resistant strains and develop practice guidelines. PATIENTS Selinexor research buy & METHODS This open label randomized trial (September 2012-December 2013) [Clinical trials- NCT01852630] included decompensated cirrhotics with DTT-SBP, defined as i). hospital acquired SBP (> 48 h of admission), ii). microbial resistance or inadequate response to first-line antibiotic (reduction in ANC by < 25% at 48 h), or iii). recurrence of SBP. These patients were randomized to
Cefepime IV 1g t.i.d (Gr A) or Imipenem IV 1g t.i.d (Gr. B). Diagnostic paracentesis was done at baseline and response tap at 48 h & 5 days for early response (reduction in ANC by > 25% and negative cultures at 48 h) or resolution of SBP (< 250 cu/mm. ANC at day 5) [primary end point]. Persistence of SBP at day 5 constituted treatment failure. Secondary end-point was survival at 3 month. RESULTS Of 957 diagnostic paracentesis among 1200 admitted decompensated cirrhotics, 253 (26.4%) had SBP. 175 (69.2%) with DTT-SBP received Cefepime (Gr..A;n-88) or Imipenem (Gr. B;n-87). Their baseline demographics, etiology, clinical, disease severity and ascitic fluid parameters
selleck kinase inhibitor were comparable. Main cause of DTT-SBP was resistance to first-line antibiotics (39% Gr.A and 48% Gr.B). Both early response (58.6% Gr. A vs. 51.7% Gr. B; p-0.36) and SBP resolution rates (65.5% vs. 60.9%; p-0.53) were comparable, no difference in mortality at week 2, month 1 & 3 (38.6% vs. 37.9%; p-0.92). Early response at 48 h (associated with absence of AKI & septic shock) was only independent predictor of SBP resolution(Odd’s ratio-18.95). Progression of HE & progressive /persistant AKI predicted high mortality & treatment failure. Hospital acquired DTT-SBP had higher mortality than others (39.7% vs.17.3%;p<0.01). Septic shock was main pretermi-nal event (32.3% Gr.A vs.35.6% Gr.B). Patients who died had higher MELD (28 vs 24) and lower SBP resolution rate (p-0.001). Baseline AKI (OR-5.3), pneumonia(OR-7.1),septic shock (OR-6.4) and failure of SBP resolution (OR-14.3) were independent predictors of 3 month mortality.