title: Oral versus intravenous antibiotics for patients with Klebsiella pneumoniae liver abscess: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Klebsiella pneumoniae liver abscess is the most common etiology of liver abscess in Singapore and much of Asia, and its incidence is increasing. Current management includes prolonged intravenous antibiotic therapy, but there is limited evidence to guide oral conversion. The implicated K1/K2 capsule strain of Klebsiella pneumoniae is almost universally susceptible to ciprofloxacin, an antibiotic with high oral bioavailability. Our primary aim is to compare the efficacy of early (< one week) step-down to oral antibiotics, to continuing four weeks of intravenous antibiotics, in patients with Klebsiella liver abscess.
  
  
  METHODS
  The study is designed as a multi-center randomized open-label active comparator-controlled non-inferiority trial, with a non-inferiority margin of 12%. Eligible participants will be inpatients over the age of 21 with a CT or ultrasound scan suggestive of a liver abscess, and Klebsiella pneumoniae isolated from abscess fluid or blood. Randomization into intervention or active control arms will be performed with a 1:1 allocation ratio. Participants randomized to active control will receive IV ceftriaxone 2 grams daily to complete a total of four weeks of IV antibiotics. Participants randomized to intervention will be immediately converted to oral ciprofloxacin 750 mg twice daily. At Week four, all participants will undergo abdominal imaging and be assessed for clinical response (CRP < 20 mg/l, absence of fever, plus scan showing that the maximal diameter of the abscess has reduced). If criteria are met, antibiotics are stopped; if not, oral antibiotics are continued, with reassessment for clinical response fortnightly. If criteria for clinical response are met by Week 12, the primary endpoint of clinical cure is met. A cost analysis will be performed to assess the cost saving of early conversion to oral antibiotics, and a quality of life analysis will be performed to assess whether treatment with oral antibiotics is less burdensome than prolonged IV antibiotics.
  
  
  CONCLUSIONS
  Our results would help inform local and international practice guidelines regarding the optimal antibiotic management of Klebsiella liver abscess. A finding of non-inferiority may translate to the wider adoption of a more cost-effective strategy that reduces hospital length of stay and improves patient-centered outcomes and satisfaction.
  
  
  BACKGROUND
  Clinical trials gov NCT01723150.
authors.forename: James
authors.initials: J
authors.lastname: Molton
authors.forename: Rachel
authors.initials: R
authors.lastname: Phillips
authors.forename: Mihir
authors.initials: M
authors.lastname: Gandhi
authors.forename: Joanne
authors.initials: J
authors.lastname: Yoong
authors.forename: David
authors.initials: D
authors.lastname: Lye
authors.forename: Thuan Tong
authors.initials: TT
authors.lastname: Tan
authors.forename: Dale
authors.initials: D
authors.lastname: Fisher
authors.affiliation: Division of Infectious Diseases, University Medicine Cluster, National University Health System, Singapore, Singapore. sophia@nus.edu.sg.
authors.forename: Sophia
authors.initials: S
authors.lastname: Archuleta
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000191:economics; D002443:Ceftriaxone / Q000008:administration & dosage* / Q000191:economics; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000191:economics; D002985:Clinical Protocols; D003362:Cost-Benefit Analysis; D004334:Drug Administration Schedule; D016527:Drug Costs; D017721:Hospital Costs; D006784:Hospitals, Teaching; D006801:Humans; D007710:Klebsiella Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000302:isolation & purification; D008100:Liver Abscess / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics / Q000382:microbiology; D011788:Quality of Life; D012107:Research Design; D012846:Singapore; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin; D002443:Ceftriaxone