For Doctors in a Hurry
- The clinical impact of rapid antimicrobial susceptibility testing for gram-negative bloodstream infections remains unclear in regions with high resistance.
- Researchers conducted an open-label randomized clinical trial including 850 hospitalized patients to compare rapid phenotypic testing against standard susceptibility testing.
- The probability of a more favorable 30-day clinical outcome ranking with rapid testing was 48.8 percent (95% confidence interval, 45.3% to 52.4%).
- The authors concluded that rapid blood culture susceptibility testing was not statistically superior to standard testing for improving overall patient outcomes.
- While overall outcomes were unchanged, rapid testing accelerated antibiotic adjustments by 14 hours (95% confidence interval, 6 to 22), potentially benefiting highly resistant infections.
Optimizing Antibiotic Selection in Gram-Negative Bacteremia
Gram-negative bacteremia is a significant cause of morbidity and mortality in hospitalized patients, a challenge amplified by the increasing prevalence of multidrug-resistant organisms [1]. International guidelines for managing sepsis underscore the critical importance of administering effective antimicrobial therapy promptly to improve survival [2]. However, conventional culture-based susceptibility testing often requires 48 hours or more, creating a period of diagnostic uncertainty that necessitates the use of broad-spectrum empirical antibiotics. Newer, rapid diagnostic technologies aim to close this gap by providing susceptibility data much faster, with the goal of enabling earlier, targeted therapy [3]. The precise clinical utility of these systems, particularly their effect on patient-centered outcomes within the framework of established antimicrobial stewardship programs, remains an area of active investigation [4].
Evaluating Rapid Diagnostics in High-Resistance Regions
While newer blood culture diagnostics provide rapid antimicrobial susceptibility testing (AST) results for bacteria causing bloodstream infections (BSIs), their actual clinical impact remains unclear. To address this uncertainty, researchers evaluated the clinical outcomes of blood culture testing using a rapid AST method compared with standard AST in patients with BSIs caused by gram-negative bacilli. Because the utility of rapid testing is most critical where standard empiric therapies often fail, the study was conducted in regions with a high prevalence of antimicrobial resistance. The investigators designed an open-label randomized clinical trial that enrolled participants from December 2023 to May 2025, with final follow-up completed on June 18, 2025. The trial took place at 7 medical centers located in Greece (n = 2), India (n = 1), Israel (n = 3), and Spain (n = 1).
Eligible participants included hospitalized patients, encompassing both adults and children, who presented with BSIs caused by gram-negative bacilli. In total, 899 patients were randomized into two distinct diagnostic pathways. One group underwent blood culture evaluation using rapid, phenotypic AST directly from positive blood cultures plus standard susceptibility testing (n = 413), while the control group received standard susceptibility testing alone (n = 437). Of the initial cohort, 850 patients were included in the primary outcome analysis. This analyzed population had a median age of 72 years (interquartile range [IQR], 21 years) and was 43% female.
To ensure the diagnostic data translated into actionable clinical decisions, local antimicrobial stewardship teams reviewed all patients and provided treatment recommendations based on the AST results. This integration reflects real-world hospital workflows, where diagnostic information must be interpreted and acted upon by specialized clinicians to optimize patient care. Following the conclusion of the trial, statistical analysis was conducted from August 2025 to January 2026 to determine whether the accelerated availability of susceptibility data meaningfully altered patient trajectories.
No Superiority in 30-Day Composite Outcomes
To evaluate the clinical impact of the intervention, the researchers established a primary outcome using a desirability of outcome ranking (DOOR) at day 30. This composite metric categorized patients into three distinct clinical states: alive without deleterious events, alive with deleterious events, and death. The overall difference between rapid and standard testing was summarized as the probability that the DOOR outcomes were more desirable in the rapid testing group. To establish statistical success, superiority was concluded if the lower limit of the 95% confidence interval (CI) exceeded 50%.
The analysis demonstrated that the probability that DOOR outcomes were more favorable in the rapid testing group was 48.8% (95% CI, 45.3%-52.4%). Because the lower limit of the confidence interval fell below the required 50% threshold, the investigators determined that among patients with gram-negative bacilli bloodstream infections, rapid blood culture antimicrobial susceptibility testing was not superior to standard testing by DOOR. Although the intervention did not improve this primary composite endpoint, the authors noted that when considered with other efficacy and safety outcomes, these findings may help inform the use of rapid susceptibility testing in clinical practice.
Faster Adjustments and Benefits in Resistant Subgroups
Beyond the primary composite endpoint, the researchers evaluated several secondary outcomes to capture the broader clinical impact of the intervention. These secondary outcomes included 30-day mortality, length of hospitalization, intensive care unit admission, acquisition of hospital-acquired infections, time to effective antibiotic therapy within 3 days, and time to antibiotic escalation or deescalation within 3 days. In the overall as-randomized population, the analysis revealed that there were no differences between the groups in other secondary outcomes. Most notably, the median time to effective antibiotic therapy was not different between the groups in the as-randomized population, indicating that the faster test did not universally translate to quicker administration of the correct initial drugs.
However, the rapid testing intervention did accelerate subsequent clinical decision-making regarding regimen adjustments. The median time to antibiotic escalation or deescalation was faster in the rapid testing group by 14 hours (95% CI, 6 to 22) in the as-randomized population. Furthermore, a clinically relevant signal emerged in a high-risk cohort where delayed treatment carries severe consequences. In the prespecified subgroup with carbapenem-resistant infections, median time to effective therapy was 9.5 hours in the rapid testing group vs 28 hours in the standard testing group. This represented a difference of -18 hours (95% CI, -42 to 6), suggesting that rapid susceptibility testing may offer targeted benefits in expediting appropriate coverage for patients harboring highly resistant pathogens.
References
1. Wisplinghoff H, Bischoff T, Tallent S, Seifert H, Wenzel RP, Edmond MB. Nosocomial Bloodstream Infections in US Hospitals: Analysis of 24,179 Cases from a Prospective Nationwide Surveillance Study. Clinical Infectious Diseases. 2004. doi:10.1086/421946
2. Rhodes A, Evans L, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Critical Care Medicine. 2017. doi:10.1097/ccm.0000000000002255
3. Timbrook TT, Morton J, McConeghy KW, Caffrey AR, Mylonakis E, LaPlante KL. The Effect of Molecular Rapid Diagnostic Testing on Clinical Outcomes in Bloodstream Infections: A Systematic Review and Meta-analysis. Clinical Infectious Diseases. 2016. doi:10.1093/cid/ciw649
4. Nathwani D, Varghese D, Stephens J, Ansari W, Martin S, Charbonneau C. Value of hospital antimicrobial stewardship programs [ASPs]: a systematic review. Antimicrobial Resistance and Infection Control. 2019. doi:10.1186/s13756-019-0471-0
