A new study investigating the appropriate duration of antibiotics for staphylococcal bloodstream infections has found that use of an algorithm to guide treatment could aid antibiotic stewardship efforts.

The results of the randomized clinical trial, published today in JAMA, showed that use of the algorithm, when compared with the usual standard of care, resulted in a non-inferior rate of clinical success in patients with staphylococcal bacteremia, and was not significantly associated with more infection-related serious adverse events. In patients with simple and uncomplicated infections, the duration of antibiotic therapy was reduced by nearly 2 days compared with usual care.

The authors of the study note that while staphylococci are the most commonly identified pathogens in bloodstream infections, the optimal duration of antibiotic therapy for bacteremia caused by Staphylococcus aureus or coagulase-negative staphylococci is unknown, and current treatment recommendations are based on limited evidence. As a result, treatment practices vary considerably, which can in some cases lead to unnecessarily prolonged antibiotic use.

“Any reductions in the use of antibiotics to treat these infections would be a significant benefit in our effort to fight antibiotic resistance, particularly when these measures can be undertaken without harm to patients,” lead author Thomas Holland, MD, of Duke University Medical Center said in a hospital press release.

Algorithm-guided care vs. usual care

The study included 509 patients with staph bloodstream infections at 16 hospitals in the United States and Spain who were randomly assigned to algorithm-guided antibiotic therapy or treatment based on usual practice, in which the treating physician determined the antibiotic and the duration of therapy.

In the algorithm-based therapy group, antibiotic selection and duration of therapy were predefined, with clinical criteria—including blood culture results, echocardiogram results, and signs of a spreading infection—being used to determine whether the infection was simple, uncomplicated, or complicated.

According to the algorithm, patients with simple or uncomplicated coagulase-negative staphylococcal bacteremia received up to 3 days or 5 days of antibiotic therapy, respectively, while patients with uncomplicated S aureus bacteremia received 14 days of therapy. Complicated cases received 28 to 42 days of antibiotic treatment. S aureus bacteremia cases receive longer antibiotic treatment than those caused by coagulase-negative staphylococci because they are associated with higher morbidity and mortality.

The primary outcomes of the study were success rate at the test-of-cure evaluation and serious adverse events rate in the two groups. A secondary outcome was antibiotic days in the per-protocol population with simple or uncomplicated staphylococcal bacteremia.

The clinical success rate in the two groups was similar, with 209 of 255 patients in the algorithm group and 207 of 254 in the usual-care group achieving clinical success (82% vs. 81.5%; difference, 0.5% [1-sided 97.5% confidence interval [CI], −6.2% to ∞]). Serious adverse events occurred in 32.5% of the algorithm-group patients, compared with 28.3% of the usual-care patients (difference, 4.2%; 95% CI, −3.8% to 12.2%). The 4.2% difference in serious adverse events was deemed non-significant, but the

Staph NIH photo

authors note that this interpretation was limited by wide confidence intervals.

Among the patients who had simple or uncomplicated bacteremia, duration of therapy for the algorithm-based therapy patients was 1.8 days shorter (4.4 vs. 6.2 days; 95% CI, −3.1 to −0.6), with the difference primarily attributable to fewer days of therapy in patients who had uncomplicated coagulase-negative staphylococcal bacteremia. Antibiotic duration for this group was reduced by 3.1 days.

That finding is highlighted in a commentary that accompanies the study. “Given that vancomycin is the most commonly prescribed antibiotic in US acute care hospitals, a 3-day reduction for a high-incidence condition such as uncomplicated coagulase-negative staphylococcus bacteremia could have a sizable public health effect,” internal medicine and infectious disease specialists Eli Perencevich, MD, and Preeti Malani, MD, of the University of Iowa and the University of Michigan, write.

Perencevich and Malani say the results will likely influence the next iteration of treatment guidelines for staphylococcal bacteremia.

See also:

Sep 25 JAMA study

Sep 25 JAMA commentary

Sep 25 Duke University Medical Center press release