Antibiotics for Klebsiella Liver Abscess Study
Information source: National University Hospital, Singapore
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Liver Abscess, Pyogenic
Intervention: Ciprofloxacin (Drug); Ceftriaxone (Drug); Trimethoprim/sulfamethoxazole (Drug); Ertapenem (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: National University Hospital, Singapore Official(s) and/or principal investigator(s): Sophia Archuleta, MD, Principal Investigator, Affiliation: National University Hospital, Singapore
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.
Clinical Details
Official title: A Multi-centre Randomised Open-label Active Comparator-controlled Non-inferiority Trial Comparing Oral to Intravenous Antibiotics in the Early Management of Klebsiella Pneumoniae Liver Abscess
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Clinical cure
Secondary outcome: Clinical response
Eligibility
Minimum age: 21 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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 exclusion criteria at baseline will be excluded
from participation:
1) Polymicrobial abscess - additional organisms isolated from blood or abscess fluid
within the preceding 7 days 2a) Klebsiella pneumoniae resistant to Ceftriaxone AND
Ertapenem 2b) Klebsiella pneumoniae resistant to Ciprofloxacin AND Cotrimoxazole 3)
On effective* IV antibiotics > 7 days 4a) Hypersensitivity to cephalosporins AND
carbapenems; as defined by history of rash, urticaria, angiodema, bronchospasm or
circulatory collapse following prior administration.
4b) Hypersensitivity to fluoroquinolones AND sulpha drugs; as defined by history of
rash, urticaria, angioedema, bronchospasm or circulatory collapse following prior
administration.
4c) History of penicillin anaphylaxis (angioedema, bronchospasm or circulatory
collapse). Subjects with a history of only rash or urticaria or unknown reaction to
penicillin can be included.
5) Inability to take oral medications for any reason 6) Severe sepsis or septic shock
defined as unresolved hypotension (MAP<70) or tachycardia (HR>110), or requirement of
inotropic support or ventilation at time of eligibility. Should the subject's hypotension
or tachycardia subsequently resolve, and they cease to require inotropes and ventilation
within 7 days, they may be reconsidered for eligibility.
7) Established endophthalmitis at time of screening (patients with visual symptoms
should have ophthalmology review prior to enrollment) 8) Established central nervous
system abscess at time of screening (patients with focal neurology should have CT head
prior to enrollment) 9) Women who are pregnant or breastfeeding 10)
Inability to obtain consent from subject 11) Patients on tizanidine or theophylline
12) Patients on concomitant drugs that can result in prolongation of the QT interval
(e. g., class IA or class III antiarrhythmics) or with risk factors for torsade de pointes
(e. g., known QT prolongation, uncorrected hypokalemia) 13) Patients whose K. pneumoniae
tests resistant to ciprofloxacin, and those with contraindications to ciprofloxacin will
be tested for G6PD deficiency, and excluded if deficient 14) Severe immunocompromise
(e. g., active leukemia or lymphoma, generalized malignancy, aplastic anemia, solid organ
transplant, bone marrow transplant within 2 years of transplantation, or transplants of
longer duration still on immunosuppressive drugs or with graft-versus-host disease,
congenital immunodeficiency, current radiation therapy, HIV/AIDS with CD4 lymphocyte count
<200 and patients or on immunosuppressant medications) 15) Creatinine clearance <15
ml/min
*defined as antibiotics to which the Klebsiella pneumoniae isolate in blood or abscess
fluid is susceptible
Locations and Contacts
National University Hospital, Singapore, Singapore; Recruiting Sophia Archuleta, Email: sophia@nus.edu.sg
Singapore General Hospital, Singapore, Singapore; Not yet recruiting Phone: Thuan Tong Tan, Email: tan.thuan.tong@sgh.com.sg
Tan Tock Seng Hospital, Singapore, Singapore; Recruiting David Lye, Email: david_lye@ttsh.com.sg
Additional Information
Related publications: 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.
Starting date: November 2013
Last updated: December 2, 2013
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