Does Rapid Antimicrobial Testing for Gram-Negative Bacteremia Improve Outcomes?

A tool for better antibiotic stewardship did not improve clinical outcomes in hospitalized patients with gram-negative bacterial bloodstream infections, according to the international FAST trial.

The randomized study found that rapid antimicrobial susceptibility testing (AST) had just a 48.8% (95% CI 45.3-52.4) probability of being better than standard AST in a desirability of outcome ranking that comprised being alive without or with deleterious events or death at 30 days, reported researchers led by Ritu Banerjee, MD, PhD, of Vanderbilt University Medical Center in Nashville, Tennessee.

Secondary outcomes were similar at that point, including all-cause mortality (24.2% vs 22.7%, respectively), intensive care unit (ICU) admission (3.4% vs 3.7%), acquisition of multidrug-resistant organisms (13.3% vs 11.7%), and remaining in the hospital at 30 days (9.2% vs 13.3%).

There was, however, some evidence supporting the premise that faster AST results would at least yield faster optimization of antibiotic therapy, according to findings published in JAMA and presented at the European Society of Clinical Microbiology and Infectious Diseases congress in Munich.

For example, time to first antibiotic escalation or de-escalation within 3 days of randomization was faster both for patients with cephalosporin-resistant (12 vs 35 hours) and carbapenem-resistant (13 vs 47 hours) infections. The difference for the overall patient cohort was also significant (22 vs 36 hours).

Moreover, among those with carbapenem-resistant organisms, rapid AST resulted in a median 3 days shorter hospitalization. At 30 days, nearly half as many of these patients remained in hospital (15.1% vs 28% with standard AST).

Despite falling short of superiority for the primary endpoint, the authors noted that “rapid AST was associated with improvements in more timely antibiotic modifications and targeted antibiotic therapy in certain subsets of patients, more frequent guidance from antimicrobial stewardship teams, and greater acceptance of stewardship recommendations.”

“When considered with other efficacy and safety outcomes, these findings may help inform the use of rapid susceptibility testing in clinical practice,” they concluded.

Banerjee’s group had tested rapid AST using the Vitek Reveal system. This commercially available device allows users to determine antibiotic susceptibility directly from a positive blood culture within hours, approximately 1 day earlier than with standard AST, which requires organisms to be grown and then tested after isolation from blood culture samples.

“While awaiting this crucial information, clinicians are faced with a difficult dilemma: choose potentially excessively broad-spectrum antibiotics and risk potentially preventable adverse events or risk ineffective therapy,” wrote Arjun Srinivasan, MD, of the Joint Commission in Oakbrook Terrace, Illinois, in an accompanying editorial. “In nearly all cases, clinicians will choose the former, helping fuel the downward spiral of antimicrobial resistance because broad-spectrum antibiotics increase the selective pressure for resistant organisms, which, in turn, require even broader-spectrum antibiotics.”

Faster antibiotic susceptibility results could give clinicians a chance to optimize therapy sooner and potentially change patient outcomes, according to Srinivasan.

“The FAST trial should move hospitals firmly in the direction of implementing rapid AST,” he argued. “If we have a tool that will help antibiotic stewardship programs support clinicians in optimizing therapy faster, an outcome that is consistent across all studies of rapid AST, should we not work toward making that tool available?”

Why didn’t rapid AST deliver clearer clinical benefits in the FAST trial? Sample size could have been an issue, Srinivasan said. Rapid AST may deliver a mortality benefit in patients with severe infections such as sepsis who were receiving ineffective empiric therapy, he noted — but only about one-quarter of FAST’s patients had septic shock.

What’s more, the study authors noted that participating trial sites did not always have the most effective antibiotics at their disposal.

“This treatment gap, which has been described in low- and middle-income countries, may contribute to rapid AST not affecting clinical outcomes; it is likely that rapid AST may have had greater benefit if first-line, effective antibiotics had been available at all sites,” wrote Banerjee and colleagues.

FAST enrolled patients from December 2023 to May 2025 at seven medical centers in Greece, India, Israel, and Spain, all of which had a high prevalence of multidrug-resistant gram-negative bacteria. Study participants were hospitalized patients of any age who had gram-negative bacilli in blood cultures taken while hospitalized.

Those randomized to rapid and standard AST alike had blood culture organism identification determined using mass spectrometry. For participants randomized to the rapid testing group, AST was determined by directly testing positive blood culture bottle contents using Vitek Reveal; standard AST was performed on subcultured bacteria using methods that varied by site.

At baseline, participants had a median age of 72-73 years, a majority were men, 17% were in the ICU, and 62% were receiving effective antibiotic therapy. A Quick Pitt bacteremia score ≥2 was calculated for just under one in four patients.

Other findings showed that the likelihood of effective antibiotic therapy within 3 days was similar between groups (88.4% for rapid vs 85.6% for standard AST). Overall length of stay was virtually unchanged (8 days for both groups).

Study limitations included the study sites’ heterogeneous antimicrobial resistance, baseline clinical and microbiology practices, and intervention implementation. Institution-specific factors may also impact the effect of blood culture diagnostics, which may make the findings not generalizable. In addition, nearly 20% of patients had infections with organisms that were off panel.