Yohei Doi

PURPOSE: The aim of this study was to evaluate the effectiveness of remdesivir among vulnerable patients hospitalized with a primary diagnosis of coronavirus disease 2019 (COVID-19). METHODS: In this retrospective study, data from the Premier Healthcare Database compiled from December 2021 to December 2024 were examined. Four cohorts were analyzed: overall (≥18 years of age), elderly (≥65 years of age), those with pneumonia due to COVID-19, and those with chronic obstructive pulmonary disease (COPD). Analyses were stratified by supplemental oxygen requirements upon admission. Patients treated with remdesivir within the first 2 days of hospitalization were matched to those not treated with remdesivir during hospitalization, using 1:1 propensity score matching without replacement. Outcomes of interest were 14- and 28-day all-cause inpatient mortality. RESULTS: A total of 220,677 patients met the eligibility criteria; of these, 123,388 (55.9%) were treated with remdesivir within the first 2 days of hospitalization. Overall, treatment with remdesivir was associated with significantly lower 14- and 28-day mortality rates compared to rates in patients who did not receive remdesivir (adjusted hazard ratio [95% CI], 0.76 [0.73-0.79] and 0.78 [0.75-0.81], respectively; P < 0.0001). Similar results were observed across all patient groups irrespective of supplemental oxygen requirements and across early (December 2021-December 2022) and later (January 2023-December 2024) Omicron periods. CONCLUSIONS: These results build on previous research highlighting the effectiveness of early treatment initiation with remdesivir in vulnerable patients hospitalized due to SARS-CoV-2 infection.

Evidence regarding the diagnostic value of quantitative interferon-gamma release assay (IGRA) results in elderly populations is limited, and large-scale data for QuantiFERON-TB Gold Plus (QFT-Plus) are scarce. We evaluated QFT-Plus and T-SPOT.TB (T-SPOT) for distinguishing active tuberculosis (ATB) from latent infection (LTBI) in elderly individuals in Japan, a super-aged country. We conducted a retrospective, cross-sectional diagnostic accuracy study of patients ≥65 years who underwent IGRA testing between 2015 and 2024 at two hospitals: a tuberculosis referral center (QFT-Plus and T-SPOT) and a tertiary hospital (T-SPOT only). ATB was defined as microbiologically confirmed TB. Quantitative IGRA values were compared between ATB and LTBI in all patients and in IGRA-positive subsets. Receiver operating characteristic (ROC) curves assessed discriminatory performance. Among 10,745 elderly patients (ATB: n = 310; LTBI: n = 1,158), values showed substantial overlap. For T-SPOT, the area under the curves (AUCs) improved at Tosei General Hospital (TGH) (ESAT-6: 0.679, CFP-10: 0.670) in IGRA-positive cases. In contrast, all-patient AUCs at Fujita Health University Hospital (FHUH) were low (ESAT-6: 0.367, CFP-10: 0.362), demonstrating an inverse association, though they improved (ESAT-6: 0.607 and CFP-10: 0.554) in IGRA-positive cases. For QFT-Plus, all-patient AUCs were low (TB1 antigen: 0.462, TB2 antigen: 0.470), but improved in the IGRA-positive cohort (TB1 antigen: 0.630, TB2 antigen: 0.645). The optimal quantitative cutoffs in IGRA-positive cases provided modest diagnostic accuracy. In elderly individuals, quantitative IGRA values alone have limited ability to distinguish ATB from LTBI, but QFT-Plus and T-SPOT show modest improvement in IGRA-positive cases. Although not suitable as a stand-alone diagnostic, quantitative IGRA may assist risk stratification and decision-making in selected scenarios.IMPORTANCETuberculosis remains a major health concern in aging societies, such as Japan, where most patients are elderly adults with impaired immune function. Interferon-gamma release assays (IGRA) are widely used for detecting infection, but the role of their quantitative values in differentiating active tuberculosis from latent tuberculosis infection has been uncertain. Our study is the first to evaluate the quantitative performance of the latest QuantiFERON-TB Gold Plus and T-SPOT.TB specifically in elderly patients, across both a tuberculosis referral hospital and a university hospital. Although absolute separation between active and latent disease was not achieved, we found that, in test-positive individuals, active cases tended to yield higher values, particularly with T-SPOT.TB. This indicates that quantitative information, when interpreted within the clinical context, can assist physicians in assessing risk and guiding further diagnostic steps, offering practical value for improving decision-making in the care of vulnerable elderly patients.

INTRODUCTION: Carbapenem-resistant Gram-negative bacteria (CRGNB) pose a major clinical threat. This study evaluated the in vitro activity of cefiderocol and other recently approved β-lactam/β-lactamase inhibitor combinations against major CRGNB. MATERIALS AND METHODS: A total of 292 CRGNB clinical isolates were analyzed, comprising 146 Enterobacterales, 106 Pseudomonas aeruginosa, and 40 Stenotrophomonas maltophilia, all collected from hospitals across Japan. Antimicrobial susceptibility testing was performed by broth microdilution (BMD). Disk diffusion testing was also conducted for cefiderocol, and categorical agreement with BMD was assessed. Whole-genome sequencing (WGS) was used for species confirmation and characterization of resistance determinants. RESULTS: Carbapenemase producers accounted for 64.4 % of Enterobacterales (94/146) and 8.5 % of P. aeruginosa (9/106), with metallo-β-lactamase (MBL) producers comprising 92.6 % (87/94) and 77.8 % (7/9), respectively. Based on CLSI breakpoints, 94.5 % (276/292) of isolates were susceptible to cefiderocol, including 91.8 % of Enterobacterales, 99.1 % of P. aeruginosa, and 92.5 % of S. maltophilia. Ceftolozane-tazobactam, ceftazidime-avibactam, and imipenem-relebactam were active against 12.3 %, 44.5 % and 45.9 % of Enterobacterales, and 89.6 %, 86.8 % and 72.6 % of P. aeruginosa, respectively. Categorical agreement between cefiderocol disk diffusion and BMD exceeded 92 % across all groups, although very major errors occurred in Enterobacterales (n = 2) and S. maltophilia (n = 3). Cefiderocol-non-susceptible Enterobacterales isolates frequently harbored carbapenemase and extended-spectrum β-lactamase (ESBL) genes, together with mutations in ftsI (encoding PBP3), ompK35, or siderophore receptor genes (cirA, tonB). DISCUSSION: Cefiderocol showed potent in vitro activity against CRGNB in Japan, including MBL producers. Disk diffusion correlated well with BMD results; however, confirmatory BMD testing should be considered when resistance is clinically suspected.

OBJECTIVES: Advances in critical care have increased antimicrobial use in intensive care units (ICUs), often extending to end-of-life patients without clear clinical benefit. This systematic review and meta-analysis investigated antimicrobial use in critically ill ICU patients with end-of-life care status. METHODS: A comprehensive search of Medline (PubMed) and Embase identified articles published from January 2000 through August 2023. Interventional and observational studies focusing on antimicrobial use for critically ill ICU patients with end-of-life status were included. Study types, demographics, clinical characteristics, and antimicrobial use (i.e., continuation or discontinuation) were extracted. A meta-analysis was conducted to estimate the proportion of antimicrobial use, with subgroup analyses by region and national income status. RESULTS: From 13,542 publications, 26 studies met the inclusion criteria; no randomized or prospective studies were identified. Thirteen studies (50.0%) reported antimicrobial use and were included in the quantitative synthesis. The pooled proportion of antimicrobial prescriptions was 0.35 (95% CI, 0.18-0.54) with significant heterogeneity (I2=99.7%, P<0.01). Subgroup analysis revealed regional differences: 0.50 (95% CI, 0.11-0.89) in North America, 0.40 (95% CI, 0.10-0.76) in Europe, and 0.24 (95% CI, 0.10-0.76) in the Asia-Pacific region. CONCLUSIONS: Despite increasing emphasis on judicious antimicrobial use, studies comprehensively assessing antimicrobial prescribing in ICU patients with end-of-life care status remain scarce. Based on the limited available evidence, approximately one-third of such patients received antimicrobials. Regional differences in prescribing patterns were also observed, potentially influencing overall antimicrobial consumption in ICUs.