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Background: Evidence about the clinical impact of rapid diagnostic tests (RDTs) for the diagnosis of bloodstream infections is limited, and whether RDT are superior to conventional blood cultures (BCs) embedded within antimicrobial stewardship programs (ASPs) is unknown., Methods: We performed network meta-analyses using results from studies of patients with bloodstream infection with the aim of comparing the clinical impact of RDT (applied on positive BC broth or whole blood) to conventional BC, both assessed with and without ASP with respect to mortality, length of stay (LOS), and time to optimal therapy., Results: Eighty-eight papers were selected, including 25 682 patient encounters. There was an appreciable amount of statistical heterogeneity within each meta-analysis. The network meta-analyses showed a significant reduction in mortality associated with the use of RDT + ASP versus BC alone (odds ratio [OR], 0.72; 95% confidence interval [CI], .59-.87) and with the use of RDT + ASP versus BC + ASP (OR, 0.78; 95% CI, .63-.96). No benefit in survival was found associated with the use of RDT alone nor with BC + ASP compared to BC alone. A reduction in LOS was associated with RDT + ASP versus BC alone (OR, 0.91; 95% CI, .84-.98) whereas no difference in LOS was shown between any other groups. A reduced time to optimal therapy was shown when RDT + ASP was compared to BC alone (-29 hours; 95% CI, -35 to -23), BC + ASP (-18 hours; 95% CI, -27 to -10), and to RDT alone (-12 hours; 95% CI, -20 to -3)., Conclusions: The use of RDT + ASP may lead to a survival benefit even when introduced in settings already adopting effective ASP in association with conventional BC., Competing Interests: Potential conflicts of interest . D. L. P. has research funding from Shionogi, Merck, bioMerieux, BioVersys, and Pfizer and has received consulting fees from the AMR Action Fund, CARB-X, Aurobac, Pfizer, Merck, Cepheid, bioMérieux, and Spero. P. N. A. H. reports research grants from Gilead, has served on advisory boards for OpGen, Merck, and Sandoz, and has received honoraria from OpGen, Sandoz, Pfizer, and bioMerieux. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Early etiological diagnosis and characterization of host response to infection are becoming central in sepsis recognition and management. Still, limitations in conventional diagnosis and patient stratification contribute to the high mortality rates among septic patients, despite new antimicrobials and resuscitation agents. Novel microbiological techniques and omics analyses have led to the development of several tests that are now commercially available or in the pipeline as rapid diagnostic tools. We first reviewed emerging assays for the etiological diagnosis of sepsis starting directly from whole blood, assays based on target-specific polymerase chain reaction or metagenomics. We then investigated results of different omics approaches for both bedside diagnosis of immune dysfunction and detection of patient "signatures" associated with different clinical outcomes or potential response to individualized therapies. Finally, we considered how these novel laboratory tools might be translated into clinical practice, noting that they perform best when integrated within antimicrobial stewardship programs. [ABSTRACT FROM AUTHOR]

Infections due to carbapenem-resistant Gram-negative bacteria are burdened by high mortality and represent an urgent threat to address. Clinicians are currently at a dawn of a new era in which antibiotic resistance in Gram-negative bacilli is being dealt with by the availability of the first new antibiotics in this field for many years. Although new antibiotics have shown promising results in clinical trials, there is still uncertainty over whether their use will improve clinical outcomes in real world practice. Some observational studies have reported a survival benefit in carbapenem-resistant Enterobacteriaceae bloodstream infections using combination therapy, often including "old" antibiotics such as colistin, aminoglycosides, tigecycline, and carbapenems. These regimens, however, are linked to increased risk of antimicrobial resistance, and their efficacy has yet to be compared to new antimicrobial options. While awaiting more definitive evidence, antibiotic stewards need clear direction on how to optimize the use of old and novel antibiotic options. Furthermore, carbapenem-sparing regimens should be carefully considered as a potential tool to reduce selective antimicrobial pressure. • Carbapenem resistance represents one of the biggest challenges for clinicians managing severe Gram-negative infections. • Novel antimicrobials active on carbapenem-resistant Enterobacteriaceae, ceftazidime-avibactam and meropenem-vaborbactam, have been recently approved for clinical use. • Ceftazidime-avibactam and meropenem-vaborbactam showed improved clinical outcomes in the treatment of infections caused by KPC-producing Enterobacteriaceae compared with old antibiotics. • Optimization in the use of old antibiotics (carbapenems, aminoglycosides, fosfomycin, colistin) and careful use of novel compounds currently represent key elements to optimize antimicrobial stewardship programs. [ABSTRACT FROM AUTHOR]