The optimal dosing strategy of antimicrobial agents in critically ill patients receiving extracorporeal membrane oxygenation (ECMO) is unknown. We conducted comprehensive review of existing literature on effect of ECMO on pharmacokinetics and pharmacodynamics of antimicrobials, including antibacterials, antifungals, and antivirals that are commonly used in critically ill patients. We aim to provide practical guidance to clinicians on empiric dosing strategy for these patients. Finally, we discuss importance of therapeutic drug monitoring, limitations of current literature, and future research directions.
17 February 2025 in Open Forum Infectious Diseases
Background: Infective endocarditis (IE) is a life-threatening infection often challenging to diagnose, particularly in culture-negative cases. Plasma microbial cell-free DNA (mcfDNA) sequencing has shown potential for detecting pathogens in IE. However, its clinical utility, diagnostic impact, and limitations remain debated. This study evaluates its use in diagnosing and managing IE in a tertiary care setting. Methods: This single-center retrospective cohort study included adult patients (≥18 years) who underwent mcfDNA sequencing via the Karius test for suspected IE at Mayo Clinic Rochester between December 2019 and February 2024. Diagnostic classification followed the 2023 Duke–International Society of Cardiovascular Infectious Diseases criteria. Data on demographics, clinical features, routine microbiologic workup, and mcfDNA sequencing results were collected. Statistical analysis was conducted to evaluate diagnostic utility and treatment impact. Results: Among 141 patients, 66 had a diagnosis of IE, with mcfDNA sequencing identifying pathogens in 60.6% of them, compared with 39.4% with routine workup. mcfDNA sequencing was the sole microbiologic test with positive results in 33.3% of patients, leading to antimicrobial adjustments in 50.0% of that group. Clinically insignificant mcfDNA sequence detection occurred in 28.6% of patients without a diagnosis of IE. Conclusions: mcfDNA sequencing is a valuable adjunctive tool for diagnosing culture-negative IE and guiding antimicrobial therapy when clinical suspicion is high. However, its utility depends on appropriate clinical context, highlighting the need for careful test interpretation and further prospective studies to assess patient-centered outcomes and cost-effectiveness.
Infective endocarditis (IE) remains a diagnostic challenge, particularly in cases where microbiological diagnosis is not established. Advances in molecular diagnostics have expanded the ability to identify causative pathogens beyond traditional culture-based methods. This review explores the role of molecular assays, including pathogen-specific PCR, multiplex PCR, broad-range PCR, and shotgun metagenomic sequencing, in diagnosing IE. These molecular techniques enhance pathogen detection, especially in patients with prior antibiotic exposure, and improve diagnostic accuracy in culture-negative IE. Broad-range PCR assays and metagenomic sequencing offer the untargeted detection of a wide spectrum of organisms. Despite their advantages, limitations such as availability, interpretation challenges, and a lack of antimicrobial susceptibility testing remain. A multimodal approach integrating molecular diagnostics with conventional methods is essential to optimize patient management. Further research is needed to refine diagnostic algorithms and improve cost-effectiveness in clinical practice.
The COVID-19 Omicron variant has imposed a tremendous burden on healthcare services. We characterized the types of the Omicron variant-associated hospitalizations and their associations with clinical outcomes. Consecutive adults hospitalized with COVID-19 during the Omicron variant surge period of 1–14 January 2022, were classified into one of three groups based on their clinical presentations on admission: Group 1—primary COVID-19; Group 2—extrapulmonary manifestations of COVID-19; and Group 3—incidental COVID-19. Of the 500 patients who were hospitalized, 51.4% fell into Group 1, 16.4% into Group 2, and 32.2% into Group 3. The patients in Groups 1 and 2 were older, with higher proportions of comorbidities than patients in Group 3. The Group 1 patients had the highest mortality rate (15.6%), followed by Group 2 (8.5%), and Group 3 (0.6%), with adjusted odds ratios (OR) of 22.65 (95% confidence interval [CI], 2.75–239.46; p = 0.004) and 10.95 (95% CI, 1.02–117.28; p = 0.048), respectively, compared to Group 3. Those in Group 1 showed a greater utilization of intensive care services (15.9%), followed by Group 2 (10.9%), and Group 3 (2.5%), with adjusted ORs of 7.95 (95% CI, 2.52–25.08; p < 0.001) and 5.07 (95% CI, 1.34–19.15; p = 0.017), respectively, compared to Group 3. The patients in Groups 1 and 2 had longer hospitalization stays than the patients in Group 3 (p < 0.001 and p = 0.002, respectively). Older age (≥65 years) was an independent factor associated with longer hospital stays (OR = 1.72, 95% CI, 1.07–2.77). These findings can help hospitals prioritize patient care and service planning for future SARS-CoV-2 variants.