Seven Days of Antibiotics Matches 14 Days for Uncomplicated Gram-Negative Bacteremia, Evidence Review Concludes
核心洞察
A 2025 systematic review and meta-analysis found 7 days of antibiotics (搜索) noninferior to 14 days for gram-negative bloodstream infections (搜索), with 97.8% probability of noninferiority in intention-to-treat analysis.
No differences emerged in 30- or 90-day all-cause mortality, bacteremia recurrence, hospital length of stay, readmission, infection complications, adverse events, or antibiotic resistance emergence.
Subgroup and post-hoc BALANCE analyses failed to identify any patient group, including those at higher mortality risk, that benefited from a longer antibiotic course.
Clinicians should treat patients with uncomplicated gram-negative bacteremia (搜索) with 7 days of antibiotic therapy rather than 14 days, according to an evidence-based review assigning the recommendation a Strength of Recommendation of A, supported by systematic reviews and meta-analyses of randomized controlled trials.
The conclusion rests largely on a 2025 systematic review and meta-analysis of four randomized controlled trials evaluating whether a 7-day antibiotic course was noninferior to a 14-day course for gram-negative bloodstream infections (搜索). The primary outcome was 90-day all-cause mortality. The meta-analysis included an intention-to-treat population of 3,729 patients and a per-protocol population of 3,126 patients. In the intention-to-treat analysis, median patient age ranged from 67 to 79 years and 51% of patients were female.
Most patients in the meta-analysis were enrolled in the BALANCE (Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness) trial, a 2024 randomized controlled trial that included 2,547 patients with gram-negative bloodstream infections (搜索); the remaining patients came from three earlier randomized trials. The trials had differing exclusion criteria, but shared commonalities including complicated infections—such as those requiring a prolonged antibiotic course, uncontrolled infections, and polymicrobial infections—and severe immunocompromise.
Bayesian Analysis Supports Noninferiority
Both the intention-to-treat and per-protocol analyses used Bayesian statistics to estimate the probability of noninferiority, with each result reported as a risk ratio (RR) and credible interval. For 90-day mortality, 7 days of therapy proved noninferior to 14 days in the intention-to-treat analysis (RR = 0.91; 95% credible interval = 0.69–1.22; probability of noninferiority = 97.8%) and in the per-protocol analysis (RR = 0.93; 95% credible interval = 0.68–1.32; probability of noninferiority = 95.1%).
An earlier 2022 systematic review and meta-analysis, published before the BALANCE trial and encompassing the three prior randomized trials (N = 1,186), examined the same primary outcome of 90-day all-cause mortality alongside multiple secondary outcomes: 30-day all-cause mortality, bacteremia recurrence, length of hospital stay, readmission, infection complications, adverse events, and emergence of antibiotic resistance. No significant differences were found between the 7-day and 14-day groups for 90-day mortality or any secondary outcome.
That review excluded trials addressing infection sources requiring prolonged treatment, including endocarditis, necrotizing fasciitis, osteomyelitis, abdominal abscess, central nervous system infections, empyema, and uncontrolled sources of infection.
No Subgroup Appears to Benefit From Longer Therapy
Investigators also probed whether specific patient populations might still warrant extended treatment. A subgroup analysis in the 2022 review compared outcomes across males versus females, urinary versus nonurinary sources of infection, presence versus absence of hypotension at admission, immunocompromise versus no immunocompromise, and age younger than 65 versus 65 years and older. None of these subgroups showed significant outcome differences between 7 and 14 days of therapy.
A 2025 post-hoc analysis of the BALANCE trial attempted to apply clinical decision rules to identify patients who might benefit from a longer course of 7 days or more. These multifactorial decision tools incorporated clinical and complicating factors such as immunosuppression, unknown infection source, and persistent bacteremia. The tools helped determine which patients were at increased risk of mortality, but did not identify any group with higher 90-day mortality on 7 days of antibiotics (搜索) compared with 14 days. Even among patients at higher mortality risk, 7 days of therapy proved sufficient.
The investigators noted that because the analysis was post-hoc, they were limited to outcomes used in the BALANCE trial and could not assess other endpoints such as 30-day all-cause mortality or infection recurrence.
Pediatric Data Remain Less Definitive
Separate retrospective data in children offer a less conclusive picture on empirical treatment. A study conducted at a single hospital identified 714 children hospitalized with bacteremia between 2004 and 2012; 68% received combination therapy and 32% received monotherapy. However, patients receiving combination therapy were significantly more likely to have been immunocompromised, a baseline imbalance complicating interpretation. An earlier retrospective study at the same hospital found that culture-directed therapy with a β-lactam (搜索) antibiotic plus an aminoglycoside (搜索) showed no survival advantage over β-lactam monotherapy in pediatric gram-negative bacteremia (搜索).
Taken together, the adult evidence supports shortening therapy for uncomplicated gram-negative bacteremia (搜索) to 7 days without compromising mortality, recurrence, length of stay, readmission, infection complications, adverse events, or resistance emergence—a finding with implications for antimicrobial stewardship and reducing unnecessary antibiotic exposure.