Spontaneous bacterial peritonitis (SBP) is a common, life-threatening complication of liver cirrhosis. Third-generation cephalosporins have been considered the first-line treatment of SBP. In 2014, a panel of experts suggested a broader spectrum antibiotic regimen for nosocomial SBP, according to the high rate of bacteria resistant to third-generation cephalosporins found in these patients. However, a broader-spectrum antibiotic regimen has never been compared to third-generation cephalosporins in the treatment of nosocomial SBP. The aim of our study was to compare meropenem plus daptomycin versus ceftazidime in the treatment of nosocomial SBP. Patients with cirrhosis and nosocomial SBP were randomized to receive meropenem (1 g/8 hours) plus daptomycin (6 mg/kg/day) or ceftazidime (2 g/8 hours). A paracentesis was performed after 48 hours of treatment. A reduction in ascitic fluid neutrophil count <25% of pretreatment value was considered a treatment failure. The primary outcome was the efficacy of treatment defined by the resolution of SBP after 7 days of treatment. Thirty-two patients were randomized and 31 were analyzed. The combination of meropenem plus daptomycin was significantly more effective than ceftazidime in the treatment of nosocomial SBP (86.7 vs. 25%; P < 0.001). Ninety-day transplant-free survival (TFS) was not significantly different between the two groups. In the multivariate analysis, ineffective response to first-line treatment (hazard ratio [HR]: 20.6; P 5 0.01), development of acute kidney injury during hospitalization (HR: 23.2; P 5 0.01), and baseline mean arterial pressure (HR: 0.92; P 5 0.01) were found to be independent predictors of 90-day TFS. Conclusion: The combination of meropenem plus daptomycin is more effective than ceftazidime as empirical antibiotic treatment of nosocomial SBP. Efficacy of the empirical antibiotic treatment is a strong predictor of 90-day survival in patients with nosocomial SBP.
In patients with cirrhosis and hepatorenal syndrome (HRS), terlipressin has been used either as continuous intravenous infusion or as intravenous boluses. To date, these two approaches have never been compared. The goal of this study was to compare the administration of terlipressin as continuous intravenous infusion versus intravenous boluses in the treatment of type 1 HRS. Seventy-eight patients were randomly assigned to receive either continuous intravenous infusion (TERLI-INF group) at the initial dose of 2 mg/day or intravenous boluses of terlipressin (TERLI-BOL group) at the initial dose of 0.5 mg every 4 hours. In case of no response, the dose was progressively increased to a final dose of 12 mg/day in both groups. Albumin was given at the same dose in both groups (1 g/kg of body weight at the first day followed by 20-40 g/day). Complete response was defined by decrease of serum creatinine (sCr) from baseline to a final value £ 133 lmol/L, partial response by a decrease 50% of sCr from baseline to a final value >133 lmol/L. The rate of adverse events was lower in the TERLI-INF group (35.29%) than in the TERLI-BOL group (62.16%, P < 0.025). The rate of response to treatment, including both complete and partial response, was not significantly different between the two groups (76.47% versus 64.85%; P value not significant). The mean daily effective dose of terlipressin was lower in the TERLI-INF group than in the TERLI-BOL group (2.23 6 0.65 versus 3.51 6 1.77 mg/day; P < 0.05). Conclusion: Terlipressin given by continuous intravenous infusion is better tolerated than intravenous boluses in the treatment of type 1 HRS. Moreover, it is effective at doses lower than those required for intravenous bolus administration. (HEPATOLOGY 2016;63:983-992)
In a large group of patients with decompensated cirrhosis, we validated the association between AKI stages IA and IB (based on level of sCR) with survival times and AKI progression. We also associated these subgroups of AKI with development of acute-on-chronic liver failure. These findings are important for management of patients with decompensated cirrhosis.
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