Switch to oral antibiotics effective and safe in stable left-sided infective endocarditis

Christina Lau
07 Sep 2018
Switch to oral antibiotics effective and safe in stable left-sided infective endocarditis
Professor Henning Bundgaard presenting results of the POET trial at ESC 2018

In patients with left-sided infective endocarditis in stable condition, switching to oral antibiotics is as effective and safe as continued treatment with intravenous (IV) antibiotics, according to results of the POET trial reported at the European Society of Cardiology (ESC) Congress 2018.

In the noninferiority trial, the primary composite outcome of all-cause mortality, unplanned cardiac surgery, embolic events or relapse of bacteraemia with the primary pathogen occurred in 9 percent of patients who were switched to oral antibiotic therapy, compared with 12.1 percent of patients who continued IV antibiotics (hazard ratio [HR], 0.72; 95 percent confidence interval [CI], 0.39 to 1.33; p=0.4). [N Engl J Med 2018; doi: 10.1056/NEJMoa1808312]

“Analysis of individual components of the primary endpoint showed no significant difference between the oral and IV treatment groups,” reported investigator Professor Henning Bundgaard of Copenhagen University Hospital, Denmark.

In prespecified subgroups of patients stratified by age (≤65.5 or >65.5 years), sex, diabetes, renal disease, bacteria (streptococci, Enterococcus faecalis, Staphylococcus aureus, coagulase-negative staphylococci), surgical treatment, type of heart valve (prosthetic or native), or valve involvement (aortic or mitral), the primary outcome also did not differ significantly between the two groups.

The trial included 400 patients with left-sided infective endocarditis whose condition had become stable after at least 10 days of IV antibiotic therapy (at least 7 days postoperatively for patients who had undergone valve surgery). The patients were randomized to either switch to oral antibiotic therapy (n=201) or continue treatment with IV antibiotics (n=199). Patients in the oral antibiotic group were treated as outpatients if feasible, while those in the IV antibiotic group received treatment as inpatients. The primary outcome was measured from the time of randomization until 6 months after completion of antibiotic treatment.

In terms of safety, in the oral treatment group, subtherapeutic concentration of one of the two antibiotics was detected in seven patients (rifampicin in three patients, moxifloxacin in two patients, linezolid in one patient, and dicloxacillin in one patient). In these seven patients, the plasma concentration of the other simultaneously administered oral antibiotic was appropriate. Importantly, none of the seven patients experienced the primary outcome.

“Adverse effects [AEs] from antibiotics were reported in 6 percent of patients in the IV treatment group compared with 5 percent of patients in the oral treatment group. The most frequently reported AEs were allergy [50 percent], bone marrow suppression [27 percent], and gastrointestinal side effects [14 percent], with no significant difference between the two groups,” said Bundgaard.

“Current guidelines recommend up to 6 weeks of in-hospital IV antibiotic treatment for patients with left-sided infective endocarditis. However, in-hospital complications and mortality associated with endocarditis mainly occur in the early phase of the disease, and hospital stays per se may cause complications,” he continued.

“Based on our findings, more than 50 percent of patients with endocarditis may be candidates for partial oral antibiotic treatment,” he suggested.

“POET is the largest randomized controlled trial of patients with infective endocarditis, and included the leading pathogens of native and prosthetic valve endocarditis. However, caution is needed on the generalizability of the results. Outpatient oral antibiotic therapy is suitable for patients with left-sided infective endocarditis only if they have no heart failure, emboli, arrhythmia or complicating comorbidities and are put under strict monitoring,” commented discussant Professor Chris Gale of the University of Leeds, UK.
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