Oral vs Intravenous Antibiotics for Patients With Klebsiella pneumoniae Liver Abscess: A Randomized, Controlled Noninferiority Study

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.

Current Positioning against Severe Infections Due to Klebsiella pneumoniae in Hospitalized Adults

“…Liver abscess due to K. pneumoniae is a disease that has increased in prevalence in the last few decades, especially in Asia but also in the USA [ 70 ]. The clinical picture is a set of fever, chills and right upper quadrant pain, with laboratory abnormalities, including elevated white blood cell count and alkaline phosphatase [ 71 ].…”

“…The clinical picture is a set of fever, chills and right upper quadrant pain, with laboratory abnormalities, including elevated white blood cell count and alkaline phosphatase [ 71 ]. A combination of drainage and antibiotics is the standard treatment, especially in patients with larger abscesses [ 70 ].…”

Antibiotic Stewardship (ABS) im Krankenhaus: ein Update

“…Randomisierte Studien zur oralen Therapie schwerer Infektionen gibt es mittlerweile zu Knochen-und Gelenkinfektionen [23], Bakteriämien, intraabdominellen Infektionen (z. B. Leberabszess [24]) und sogar der (teilweisen oralen Behandlung der) Endokarditis [25]. Die meisten klinischen Infektiologen sind aber in Bezug auf eine orale Therapie der Endokarditis und der S.-aureus-Bakteriämie noch sehr zurückhaltend.…”

An 82-Year-Old Male With a Liver Abscess

“…The choice of antimicrobial is based on the susceptibility profile of the pathogen. In a recent open-label randomized clinical trial, oral antimicrobial therapy was found to be noninferior to intravenous therapy in the treatment of liver abscesses caused by K. pneumoniae [ 15 ]. Recurrent infection (relapse or reinfection) has been reported following treatment of K. pneumoniae liver abscess in a minority of cases, and clinicians should be aware of this possibility [ 4 , 10 , 16 ].…”