title: Efficacy and safety of alternating norfloxacin and rifaximin as primary prophylaxis for spontaneous bacterial peritonitis in cirrhotic ascites: a prospective randomized open-label comparative multicenter study.
abstract: OBJECTIVE
  Primary prevention of spontaneous bacterial peritonitis (SBP) is an important strategy to reduce morbidity and mortality in cirrhotic patients with ascites. Efficacy and safety of alternating rifaximin and norfloxacin as primary prophylaxis is questionable.
  
  
  METHODS
  Three hundred thirty-four cirrhotic patients with high SAAG (≥1.1) ascites, protein level in ascitic fluid less than 1.5 g/dL with advanced liver disease (Child-Pugh score >9 points with serum bilirubin level >3 mg/dL) or renal impairment (serum creatinine level >1.2 mg/dL, blood urea nitrogen level >25 mg/dL, or serum sodium level <130 mEq/L) were included in an open-label, randomized study aimed at comparing alternating use of norfloxacin and rifaximin vs. norfloxacin or rifaximin alone as primary prophylaxis for SBP. Both intention-to-treat and per-protocol efficacy analyses were done after 6 months of treatment by assessment of ascitic fluid neutrophil count. Safety analysis was done for all intention-to-treat populations.
  
  
  RESULTS
  Alternating norfloxacin and rifaximin showed superior prophylaxis by intention-to-treat (74.7 vs. 56.4% vs. 68.3%, p < 0.048). Pairwise analysis showed that alternating regimen had lower probability to develop SBP when compared to a norfloxacin-based regimen in intention-to-treat (p = 0.016) and per protocol analysis (p = 0.039). There was no difference among the studied groups regarding the incidence and severity of adverse events reported.
  
  
  CONCLUSIONS
  Alternating norfloxacin- and rifaximin-based primary prophylaxis for SBP showed higher efficacy with the same safety profile when compared with monotherapy of norfloxacin.
authors.affiliation: Hepatology Department, National Liver Institute, Menoufia University, Shebeen El Koom, Menoufia, 52311, Egypt. medassem68@yahoo.com.
authors.forename: M
authors.initials: M
authors.lastname: Assem
authors.affiliation: Hepatology Department, National Liver Institute, Menoufia University, Shebeen El Koom, Menoufia, 52311, Egypt.
authors.forename: M
authors.initials: M
authors.lastname: Elsabaawy
authors.affiliation: Internal Medicine Department, Al Noor Hospital, M.O.H, Mecca, Saudi Arabia.
authors.forename: M
authors.initials: M
authors.lastname: Abdelrashed
authors.affiliation: Tropical Medicine Department, King Khalid Hospital, M.O.H, Tabuk, Saudi Arabia.
authors.forename: S
authors.initials: S
authors.lastname: Elemam
authors.affiliation: Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
authors.forename: S
authors.initials: S
authors.lastname: Khodeer
authors.affiliation: Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: W
authors.initials: W
authors.lastname: Hamed
authors.affiliation: Clinical Pathology Department, National Liver Institute, Menoufia University, Shebeen El Koom, Menoufia, 52311, Egypt.
authors.forename: A
authors.initials: A
authors.lastname: Abdelaziz
authors.affiliation: Hepatology Department, National Liver Institute, Menoufia University, Shebeen El Koom, Menoufia, 52311, Egypt.
authors.forename: G
authors.initials: G
authors.lastname: El-Azab
mesh_terms: D000328:Adult; D000368:Aged; D019072:Antibiotic Prophylaxis / Q000379:methods*; D001424:Bacterial Infections / Q000517:prevention & control*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009643:Norfloxacin / Q000008:administration & dosage* / Q000009:adverse effects; D010538:Peritonitis / Q000382:microbiology / Q000517:prevention & control*; D011446:Prospective Studies; D012294:Rifamycins / Q000008:administration & dosage* / Q000009:adverse effects; D000078262:Rifaximin; D016896:Treatment Outcome
chemical_list: D012294:Rifamycins; D000078262:Rifaximin; D009643:Norfloxacin
keywords: Norfloxacin; Primary prophylaxis; Rifaximin; Spontaneous bacterial peritonitis