James S Molton1,2, Monica Chan3,4, Shirin Kalimuddin5,6, Jolene Oon1,2, Barnaby E Young3,4,7, Jenny G Low5,6, Brenda M A Salada1, Tau Hong Lee3,4, Limin Wijaya5,6, Dale A Fisher1,2, Ezlyn Izharuddin3, Tse Hsien Koh6,8, Jeanette W P Teo9, Prabha Unny Krishnan7,10, Bien Peng Tan11, Winston W L Woon12, Ying Ding3,4, Yuan Wei13, Rachel Phillips14, Rajesh Moorakonda13, Kah Hung Yuen15, Boon Piang Cher15, Joanne Yoong16,17, David C Lye2,3,4,7, Sophia Archuleta1,2,4. 1. Division of Infectious Diseases, University Medicine Cluster, National University Hospital, Singapore. 2. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 3. Infectious Diseases Department, Tan Tock Seng Hospital, Singapore. 4. National Centre for Infectious Diseases, Singapore. 5. Department of Infectious Diseases, Singapore General Hospital, Singapore. 6. Duke-NUS Medical School, Singapore. 7. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. 8. Department of Microbiology, Singapore General Hospital, Singapore. 9. Department of Laboratory Medicine, Microbiology Unit, National University Hospital, Singapore. 10. Department of Laboratory Medicine, Microbiology Section, Singapore. 11. Diagnostic Radiology, Tan Tock Seng Hospital, Singapore. 12. Hepato-Pancreato-Biliary Surgery Service, Tan Tock Seng Hospital, Singapore. 13. Singapore Clinical Research Institute, Singapore. 14. School of Public Health, Imperial College London, London, United Kingdom. 15. Saw Swee Hock School of Public Health, National University of Singapore, Singapore. 16. Center for Economic and Social Research, University of Southern California, Los Angeles, California. 17. Dean's Office, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Abstract
BACKGROUND:Klebsiella pneumoniae liver abscess (KLA) is emerging worldwide due to hypermucoviscous strains with a propensity for metastatic infection. Treatment includes drainage and prolonged intravenous antibiotics. We aimed to determine whether oral antibiotics were noninferior to continued intravenous antibiotics for KLA. METHODS: This noninferiority, parallel group, randomized, clinical trial recruited hospitalized adults with liver abscess and K. pneumoniae isolated from blood or abscess fluid who had received ≤7 days of effective antibiotics at 3 sites in Singapore. Patients were randomized 1:1 to oral (ciprofloxacin) or intravenous (ceftriaxone) antibiotics for 28 days. If day 28 clinical response criteria were not met, further oral antibiotics were prescribed until clinical response was met. The primary endpoint was clinical cure assessed at week 12 and included a composite of absence of fever in the preceding week, C-reactive protein <20 mg/L, and reduction in abscess size. A noninferiority margin of 12% was used. RESULTS:Between November 2013 and October 2017, 152 patients (mean age, 58.7 years; 25.7% women) were recruited, following a median 5 days of effective intravenous antibiotics. A total of 106 (69.7%) underwent abscess drainage; 71/74 (95.9%) randomized to oral antibiotics met the primary endpoint compared with 72/78 (92.3%) randomized to intravenous antibiotics (risk difference, 3.6%; 2-sided 95% confidence interval, -4.9% to 12.8%). Effects were consistent in the per-protocol population. Nonfatal serious adverse events occurred in 12/72 (16.7%) in the oral group and 13/77 (16.9%) in the intravenous group. CONCLUSIONS: Oral antibiotics were noninferior to intravenous antibiotics for the early treatment of KLA. CLINICAL TRIALS REGISTRATION: NCT01723150.
RCT Entities:
BACKGROUND:Klebsiella pneumoniae liver abscess (KLA) is emerging worldwide due to hypermucoviscous strains with a propensity for metastatic infection. Treatment includes drainage and prolonged intravenous antibiotics. We aimed to determine whether oral antibiotics were noninferior to continued intravenous antibiotics for KLA. METHODS: This noninferiority, parallel group, randomized, clinical trial recruited hospitalized adults with liver abscess and K. pneumoniae isolated from blood or abscess fluid who had received ≤7 days of effective antibiotics at 3 sites in Singapore. Patients were randomized 1:1 to oral (ciprofloxacin) or intravenous (ceftriaxone) antibiotics for 28 days. If day 28 clinical response criteria were not met, further oral antibiotics were prescribed until clinical response was met. The primary endpoint was clinical cure assessed at week 12 and included a composite of absence of fever in the preceding week, C-reactive protein <20 mg/L, and reduction in abscess size. A noninferiority margin of 12% was used. RESULTS: Between November 2013 and October 2017, 152 patients (mean age, 58.7 years; 25.7% women) were recruited, following a median 5 days of effective intravenous antibiotics. A total of 106 (69.7%) underwent abscess drainage; 71/74 (95.9%) randomized to oral antibiotics met the primary endpoint compared with 72/78 (92.3%) randomized to intravenous antibiotics (risk difference, 3.6%; 2-sided 95% confidence interval, -4.9% to 12.8%). Effects were consistent in the per-protocol population. Nonfatal serious adverse events occurred in 12/72 (16.7%) in the oral group and 13/77 (16.9%) in the intravenous group. CONCLUSIONS: Oral antibiotics were noninferior to intravenous antibiotics for the early treatment of KLA. CLINICAL TRIALS REGISTRATION: NCT01723150.
Authors: N Deborah Friedman; Seok M Lim; Rodney James; Robyn Ingram; Mary O'Reilly; James G D Pollard; Sonia Koning; Catherine George; Arjun Rajkhowa; Douglas F Johnson; Kirsty L Buising Journal: JAC Antimicrob Resist Date: 2020-08-06