Daptomycin 500mg powder for solution for infusion vials

BackgroundManagement of E faecium bloodstream infections (BSIs) remains debated, particularly the clinical impact of vancomycin resistance, the role of follow-up cultures, and optimal therapeutic regimens. This study aimed to reach expert consensus on these unresolved clinical domains and identify priorities for future research.MethodsWe first conducted a systematic review and meta-analysis in January 20, 204 focusing on four predefined areas: mortality in E faecium BSIs compared with other BSIs, mortality in vancomycin-resistant enterococci (VRE)-BSIs compared with vancomycin-susceptible enterococci-BSIs, management of catheter-related E faecium BSIs, and 4) optimal antibiotic therapy for VRE-BSIs. These results informed a three-round Delphi process involving a panel of experts. An iterative approach was adopted: 16 initial questions developed from the systematic review (6-point Likert scale) were refined across rounds based on expert feedback. Consensus was defined as at least 80% agreement or disagreement.Findings13 statements were generated across three broader domains. Regarding clinical outcomes and diagnostics, experts agreed that mortality is heavily influenced by comorbidities; thus, therapeutic assessment should rely on clinical trends and inflammatory markers, with follow-up blood cultures used to confirm eradication. Catheter-related BSI should be managed with device removal and short-course (9 mg/kg per day) are effective, reserving daptomycin-based combinations for challenging cases (deep-seated infections and/or high Minimum Inhibitory Concentrations). Finally, future trials evaluating the impact of antimicrobial therapy should use Desirability-of-Outcome-Ranking analysis; the in-vitro potential of oritavancin justifies targeted randomized trials to define its clinical efficacy in VRE-BSI.InterpretationThis paper delineates current evidence and expert consensus on management of E faecium BSI while identifying crucial knowledge gaps to guide future clinical research.FundingNone.

Abstract licence: CC BY-NC-ND

Systemic shifts in antimicrobial resistance rates can be due to epidemiologic shifts in microbial susceptibility patterns or artifactual shifts introduced by technical biases in antimicrobial susceptibility testing (AST)-both ultimately leading to changes in antimicrobial prescribing. To reduce technical variability, quality control (QC) criteria for AST are published by manufacturers and standards organizations. However, traditional QC metrics, in isolation, are fallible. In this study, we describe a systematic shift in daptomycin AST results between 2022 and 2025 in isolates tested in two independent health systems. Comprehensive analysis of clinical isolate AST results and retrospective mining of QC data from this period revealed a subtle shift that led to a 5%-22% decrease in overall susceptibility rates for certain organisms, most notably Enterococcus faecium. As daptomycin is a key treatment option for these difficult-to-treat infections, this increase in resistance rates paralleled a decrease in prescribing daptomycin for infections with these organisms. Importantly, this trend was undetectable through routine QC processes and only became apparent through systematic review of patient data. Our findings highlight the opportunity to integrate routine patient data analysis into microbiology QC practices to enhance detection of subtle but clinically relevant changes in AST performance.ImportanceIn this study, we report a critical incident of technical variability using daptomycin gradient diffusion methodology that was undetectable using routine quality control metrics. More broadly, this study underscores the opportunity to incorporate additional modalities, such as clinical patient results, into a comprehensive quality assurance plan to ensure high-quality antimicrobial susceptibility testing results. Given the dynamic spread of multidrug resistance in bacteria, accurate susceptibility testing results are critical to identify and respond to shifts in local epidemiology.

Abstract licence: CC BY