Liver Abscess, Pyogenic
Conditions
Keywords
Klebsiella pneumoniae
Brief summary
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 (\<1 week) step-down to oral antibiotics, to continuing 4 weeks of intravenous antibiotics, in patients with Klebsiella liver abscess. Methods/Design: The study is designed as a multi-centre randomised 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. Randomisation into intervention or active control arms will be performed with a 1:1 allocation ratio. Participants randomised to the active control arm will receive IV ceftriaxone 2 grams daily to complete a total of 4 weeks of IV antibiotics. Participants randomised to the intervention arm will be immediately converted to oral ciprofloxacin 750mg twice daily. At week 4, all participants will have 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 if treatment with oral antibiotics is less burdensome than prolonged IV antibiotics. Discussion: 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.
Interventions
Sponsors
Tan Tock Seng Hospital
Singapore General Hospital
National University Hospital, Singapore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Inpatient at time of enrollment 2. Age \>= 21 years 3. Computed tomography (CT) or ultrasound (US) within the preceding 7 days suggestive of a liver abscess, as defined by presence of one or more focal areas of hypo- or hyper-attenuation within the liver 4. Klebsiella pneumoniae isolated from abscess fluid or blood collected within the preceding 7 days 5. Able and willing to give informed consent
Exclusion criteria
All subjects meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical cure | Week 12 | The primary endpoint is clinical cure, determined at Week 12 post-randomisation, and defined as CRP\< 20 mg/l, plus absence of documented fever ≥38°C in the preceding week, plus most recent abdominal imaging showing that the maximal diameter of the abscess has reduced. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical response | Week 4 | The main secondary endpoint is clinical response, determined at Week 4 post-randomisation, and defined as CRP \<20 mg/l, plus absence of documented fever ≥38°C in the preceding week, plus most recent abdominal imaging showing that the maximal diameter of the abscess has reduced. |
Other
| Measure | Time frame |
|---|---|
| • unplanned need for drainage after enrolment at any point between randomisation and week 12 (the screening visit will document any plans for elective drainage) | Week 12 |
| • metastatic complications occurring at any point between randomisation and week 12 | Week 12 |
| new K. pneumoniae bacteraemia occurring at any point between the first negative blood culture, and week 12, with the same strain of K. pneumoniae as the original blood culture or abscess fluid culture | Week 12 |
| • length of hospital stay (from the date of randomisation to the end of inpatient stay, censored at week 12) | Week 12 |
| all-cause mortality at any point between randomisation and week 12 | Week 12 |
| • subject quality of life as defined by the WHOQOL-BREF assessed at week 4 and week 12 post-randomisation | Week 12 |
| • overall cost of each treatment strategy from the payer and total societal perspective for the course of the study until the final twelve week follow-up | Week 12 |
| • level of adherence during the entire study period, assessed at twelve weeks. Subject deemed to be compliant if 80% or more of prescribed antibiotics have been taken | Week 12 |
| • length of time the subject requires medical leave following hospital discharge (censored at week 12) | Week 12 |
| • unplanned readmission for any cause at any point between hospital discharge and week 12 | Week 12 |
Countries
Singapore
Outcome results
None listed