Holland TL, et al. - In this cohort of 509 adults with staphylococcal bacteremia, researchers assessed whether an algorithm used to define treatment duration for staphylococcal bacteremia vs standard of care provides noninferior efficacy without increasing severe adverse events (AEs). Findings revealed that the use of an algorithm to guide testing and treatment vs usual care brought about a noninferior rate of clinical success among individuals with staphylococcal bacteremia. Interpretation was limited by wide confidence intervals, although there was not a significant difference in serious AEs.

Methods

• Eligibility study participants included adults with staphylococcal bacteremia who were aged ≥ 18 years, had ≥ 1 blood cultures positive for Staphylococcus aureus or coagulase-negative staphylococci, and did not have any known or suspected complicated infection at the time of randomization.
• The study was conducted at 16 academic medical centers in the US (n=15) and Spain (n=1) from April 2011 to March 2017.
• The participants were followed up for 42 days beyond end of therapy for those with S. aureus and 28 days for those with coagulase-negative staphylococcal bacteremia.
• Participants were randomized to algorithm-based therapy (n=255) or usual practice (n=254).
• Diagnostic evaluation, antibiotic selection, and duration of therapy were predefined for the algorithm group.
• Clinicians caring for study participants in the usual practice group had unrestricted choice of antibiotics, duration, and other aspects of clinical care.
• Coprimary outcomes were:
• Clinical success, as determined by a blinded adjudication committee and tested for noninferiority within a 15% margin, and
• Serious AE rates in the intention-to-treat population, tested for superiority.
• Among per-protocol participants with simple or uncomplicated bacteremia, the prespecified secondary outcome measure, tested for superiority, was antibiotic days.

Results

• Among eligible study participants, 480 (94.3%) completed the trial.
• Findings revealed that clinical success was documented in 209 of 255 participants assigned to algorithm-based therapy and in 207 of 254 participants randomized to usual practice (82.0% vs 81.5%; difference: 0.5% [one-sided 97.5% CI: -6.2% to ∞]).
• Researchers reported serious AEs in 32.5% of algorithm-based therapy participants and 28.3% of usual practice participants (difference: 4.2% [95% CI: -3.8% to 12.2%]).
• Mean duration of therapy was 4.4 days for algorithm-based therapy vs 6.2 days for usual practice (difference: -1.8 days [95% CI: -3.1 to -0.6]) among per-protocol participants with simple or uncomplicated bacteremia.