title: The empirical antibiotic treatment of nosocomial spontaneous bacterial peritonitis: Results of a randomized, controlled clinical trial.
abstract: 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 = 0.01), development of acute kidney injury during hospitalization (HR: 23.2; P = 0.01), and baseline mean arterial pressure (HR: 0.92; P = 0.01) were found to be independent predictors of 90-day TFS.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unit of Hepatic Emergencies and Liver Transplantation, University of Padova, Padova, Italy.|Department of Medicine (DIMED), University of Padova, Padova, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Piano
authors.affiliation: Unit of Hepatic Emergencies and Liver Transplantation, University of Padova, Padova, Italy.|Department of Medicine (DIMED), University of Padova, Padova, Italy.
authors.forename: Silvano
authors.initials: S
authors.lastname: Fasolato
authors.affiliation: Division of Medicine, Private Hospital "Giovanni XXIII" of Monastier, Treviso, Italy.
authors.forename: Freddy
authors.initials: F
authors.lastname: Salinas
authors.affiliation: Department of Medicine (DIMED), University of Padova, Padova, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Romano
authors.affiliation: Unit of Hepatic Emergencies and Liver Transplantation, University of Padova, Padova, Italy.|Department of Medicine (DIMED), University of Padova, Padova, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Tonon
authors.affiliation: Department of Medicine (DIMED), University of Padova, Padova, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Morando
authors.affiliation: Department of Medicine (DIMED), University of Padova, Padova, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Cavallin
authors.affiliation: Department of Medicine (DIMED), University of Padova, Padova, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gola
authors.affiliation: Department of Medicine (DIMED), University of Padova, Padova, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Sticca
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Loregian
authors.affiliation: Department of Molecular Medicine, University of Padova, Padova, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Palù
authors.affiliation: Unit of Hepatobiliary Surgery and Liver Transplantation, University of Padova, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Zanus
authors.affiliation: Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Senzolo
authors.affiliation: Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Burra
authors.affiliation: Unit of Hepatobiliary Surgery and Liver Transplantation, University of Padova, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Cillo
authors.affiliation: Unit of Hepatic Emergencies and Liver Transplantation, University of Padova, Padova, Italy.|Department of Medicine (DIMED), University of Padova, Padova, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Angeli
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001201:Ascites / Q000150:complications / Q000175:diagnosis; D002442:Ceftazidime / Q000008:administration & dosage; D003428:Cross Infection / Q000188:drug therapy* / Q000382:microbiology; D017576:Daptomycin / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D017052:Hospital Mortality; D006785:Hospitals, University; D006801:Humans; D007558:Italy; D008103:Liver Cirrhosis / Q000150:complications / Q000175:diagnosis; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D015999:Multivariate Analysis; D010538:Peritonitis / Q000175:diagnosis* / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D016019:Survival Analysis; D013845:Thienamycins / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D002442:Ceftazidime; D000077731:Meropenem; D017576:Daptomycin