Antibiotics for Klebsiella Liver Abscess Study
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.
Timeline
- Start
- 2013-11-05
- Primary completion
- 2018-01-16
- Completion
- 2018-01-16
Outcome
Met primary endpoint
paper 71/74 (95.9%) randomized to oral antibiotics met the primary endpoint compared with 72/78 (92.3%) randomized to intravenous antibiotics PMID 31641767 ↗
paper (risk difference, 3.6%; 2-sided 95% confidence interval, -4.9% to 12.8%). PMID 31641767 ↗
paper Oral antibiotics were noninferior to intravenous antibiotics for the early treatment of KLA. PMID 31641767 ↗
Publications
- Background Molton J, Phillips R, Gandhi M, Yoong J, Lye D, Tan TT, Fisher D, Archuleta S. Oral versus intravenous antibiotics for patients with Klebsiella pneumoniae liver abscess: study protocol for a randomized controlled trial. Trials. 2013 Oct 31;14:364. doi: 10.1186/1745-6215-14-364.
- Yoong J, Yuen KH, Molton JS, Ding Y, Cher BP, Chan M, Kalimuddin S, Oon J, Young B, Low J, Salada BMA, Lee TH, Wijaya LM, Fisher D, Izharuddin E, Wei Y, Phillips R, Moorakonda R, Lye DC, Archuleta S. Cost-minimization analysis of oral versus intravenous antibiotic treatment for Klebsiella pneumoniae liver abscess. Sci Rep. 2023 Jun 16;13(1):9774. doi: 10.1038/s41598-023-36530-5.
- Molton JS, Chan M, Kalimuddin S, Oon J, Young BE, Low JG, Salada BMA, Lee TH, Wijaya L, Fisher DA, Izharuddin E, Koh TH, Teo JWP, Krishnan PU, Tan BP, Woon WWL, Ding Y, Wei Y, Phillips R, Moorakonda R, Yuen KH, Cher BP, Yoong J, Lye DC, Archuleta S. Oral vs Intravenous Antibiotics for Patients With Klebsiella pneumoniae Liver Abscess: A Randomized, Controlled Noninferiority Study. Clin Infect Dis. 2020 Aug 14;71(4):952-959. doi: 10.1093/cid/ciz881.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Ceftriaxone | Other / unclassified | 2 g | Intravenous |
| Subject | Ciprofloxacin | Small molecule | 750 mg | Oral |
| Comparator | Ertapenem | Small molecule | — | Intravenous |
| Subject | Trimethoprim/sulfamethoxazole | Unknown | — | Oral |