乌鸦传媒

NEW ORLEANS -- For stabilized patients with left-sided endocarditis, oral antibiotic treatment topped intravenous therapy for safety and efficacy in long-term results reported here from a randomized trial.

Out of 400 patients enrolled, 26.4% of those receiving partial oral treatment had one of the events included in a composite primary endpoint -- unplanned cardiac surgery, all-cause mortality, embolic events, or relapse of the positive blood culture with the primary pathogen -- compared with 38.2% of patients assigned to full IV therapy (HR 0.64, 95% CI 0.45-0.91), in the Danish trial.

Oral therapy also reduced mortality, occurring in 16.4% of patients treated with oral medications and 27.1% of those in the IV arm for a total of 87 deaths (HR 0.57 95% CI 0.37-0.87), reported Henning Bundgaard, MD, PhD, DMSc, of the National University Hospital in Copenhagen at the American College of Cardiology annual meeting.

There were no significant differences in endpoints for embolic events, relapse of infection, or unplanned cardiac surgery, he added. Results were also published as a brief letter in the .

The investigators reported short-term results last summer. "Efficacy and safety of changing to oral antibiotic treatment was non-inferior to continued intravenous antibiotic treatment in the short term, and now, we see very reassuring results in the long term up to 3.5 years," Bundgaard said.

It is widely accepted that treating infectious endocarditis can take up to 6 weeks using antibiotics intravenously. The condition is also linked with high in-hospital complication and mortality rates, but these complications are mainly seen in the early phase of the disease. After patients are stabilized, the main reason for staying in the hospital is to receive IV antibiotics, noted Bundgaard.

Intravenous antibiotics were selected based on European Society of Cardiology guidelines. Oral antibiotic regimens were developed specifically for this study. The investigators chose antibiotics with moderate to high bioavailability. In all cases, the researchers gave the patients two different antibiotics, from different drug classes with different mechanisms of action and metabolization. Bundgaard's group determined minimal inhibitory concentration, and they also measured plasma-antibiotics for safety reasons in order to adjust dosages if necessary, Bundgaard continued.

When it comes to clinical practice, "this new treatment may halve the hospital stays of patients with a heart valve injection," Bundgaard emphasized.

"In most stabilized patients with even serious infections of heart valves, treatment with antibiotics as tablets is as good as presently used injections of antibiotics," he continued.

"The main question that this trial presents is how do we extrapolate this data from this trial to a real life population, especially in the United States because this study was done in Denmark," said Gurusher Panjrath, MD, of George Washington University Hospital in Washington, as a discussant during a press conference on the study.

While the POET results are a great first step, clinicians need more information before jumping in to apply these findings, Panjrath continued.

This study is very timely in light of the growing opioid epidemic in hopes that this data may actually help us to shorten length of stay, and reduce complications in this very complex population. There are caveats in terms of extrapolating from the Danish cohort to the US population as the patients in the oral study arm were seen 2 to 3 time a week, which might be hard to pull off in US academic health centers, session panel discussant David Mushatt, MD, MPH, of Tulane University in New Orleans, emphasized.

He also pointed out that the composite and death outcomes trended significantly lower in the oral arm in the long term follow up after a year, especially given the decrease in cardiovascular death.

Study details

Patients were randomized 1:1 to the oral antibiotic treatment group (n=201) and to conventional IV therapy (n=199) at all Danish heart centers nationwide. In all patients, treatment began with 10 days of IV therapy; oral treatment followed in those assigned to that group, while IV medications were continued in the other arm. About three-quarters of participants were men and patients' mean age was 67.

Inclusion criteria were:

• Temperature below 38.0 °C for at least 2 days
• Within 48 hours of randomization there could be no sign of abscess formation by transesophageal echocardiography
• Having left-sided endocarditis according to the modified Duke criteria caused by enterococcus faecalis, streptococci, staphylococcus aureus, or coagulase-negative staphylococci
• White blood cell count under 15 x 10⁹/L
• 10 days or longer of IV antibiotic treatment or 1 week or longer following valve surgery
• C-reactive had to be less than 25% of peak value or under 20 mg/L

Patients taking oral antibiotics were eligible for outpatient care and in most cases, they received it. Patients often required close monitoring and intensive care during the initial treatment phase. Most intravenously treated patients remained in the hospital for the course of their treatment, which was generally a median of about 19 days, Bundgaard said, as it was hard to navigate the logistics of intravenous antibiotics.

Comment