Stopping Antibiotics Early Gave Heart Infection Patients 13 More Days off Treatment

A shorter, response-tailored course of antibiotics for a serious heart infection left patients a median of 13 more days alive and off antibiotics over six months than the standard four-to-six-week course, but relapses were about three times as common, according to the POET II trial published in the New England Journal of Medicine on Aug. 28.

The open-label trial randomly assigned 508 adults with left-sided infective endocarditis, an infection of the heart's inner lining and valves, to one of two strategies: 255 to response-tailored therapy and 253 to standard duration. All had already received at least two to four weeks of antibiotics and met the trial's criteria for clinical stabilization before randomization, and their infections were caused by Staphylococcus aureus, Enterococcus faecalis or Streptococcus species. Patients in the tailored group then stopped antibiotics; the standard group continued to a total of four to six weeks.

Median time alive without antibiotic treatment within six months of randomization was 183 days in the tailored group and 169 days in the standard group, a difference of 13 days (95% confidence interval, 12 to 13; P<0.001 for superiority), the authors report.

The primary safety endpoint, a composite of death from any cause, unplanned cardiac surgery or symptomatic embolic events within six months, occurred in 21 patients (8.2%) on tailored therapy and 27 (10.7%) on standard therapy, an absolute difference of -2.4 percentage points (95% CI, -7.7 to 2.7). The paper reports that the result met the trial's prespecified noninferiority margin of 7.5 percentage points.

Relapse of bacteremia or endocarditis, a key secondary endpoint, occurred in 13 patients (5.1%) in the tailored group and 4 (1.6%) in the standard group (P=0.04). The authors' own conclusion carries all three results together: a longer time alive off antibiotics, noninferiority on the safety composite, and a higher incidence of relapse.

The paper states that the current recommendation of up to six weeks of therapy rests largely on expert consensus. POET II is registered as NCT03851575; its authors are at hospitals in Denmark, Sweden and the United States.