Possible reluctance to shorten antibiotic duration in Gram-negative bacteremia and limitations of mortality-based outcomes: the need to prioritize clinical-microbiologic recurrence in future trials—Insights from the “Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness” (BALANCE) Trial

Abstract

Shorter antibiotic durations (≤7 days) have demonstrated non-inferiority to longer courses for several bacterial infections, but evidence for bacteremia remains limited. Trials often exclude patients with bacteremia, focus on uncomplicated cases, or lack sufficient power to detect clinically significant effects. The recent Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) trial, a multicenter study spanning 74 hospitals, investigated 7 versus 14 days of antibiotic therapy for bloodstream infections, showing non-inferiority in 90-day all-cause mortality. Despite these findings, a possible reluctance to adopt shorter durations persists, as seen in high exclusion rates and protocol deviations. BALANCE highlights the importance of source control in managing bloodstream infections resulting in the relatively low 7-day mortality. However, reliance on 90-day mortality may underestimate clinical failure, with outcomes like suppurative or distant complications and recurrence being more relevant. The trial predominantly included non-severely immunocompromised patients with community-acquired Gram-negative bacteremia, limiting generalizability to multidrug-resistant or hospital-acquired infections. The BALANCE trial, along with the previous three randomized control trials comparing short- versus longer-duration antibiotics for Gram-negative bacteremia, supports guideline recommendations for shorter antibiotic courses in cases involving non-multidrug-resistant organisms, non-severely immunocompromised patients, and effective source control. It also highlights the importance of future trials prioritizing clinically meaningful outcomes and underrepresented populations.