Early treatment of disseminated intravascular coagulation (DIC) can be associated with improved patient outcomes. The Japanese Ministry of Health and Welfare (JMHW) and the International Society on Thrombosis and Haemostasis (ISTH) criteria are the most specific for diagnosis of septic DIC. The revised Japanese Association for Acute Medicine (JAAM) criteria are able to diagnose sepsis-induced DIC in the early stage. Recombinant human soluble thrombomodulin (rhTM) has recently been used for treating DIC. Previous studies have shown a benefit of using rhTM for D,IC diagnosed by the JMHW or ISTH criteria, but not the JAAM criteria. The purpose of this study was to sequentially evaluate coagulation biomarkers and the DIC score after giving rhTM treatment to patients with sepsis-induced DIC diagnosed according to the JAAM criteria. We performed a retrospective cohort study. Critically ill patients were included if diagnosed with sepsis-induced DIC according to the JAAM criteria. They were either treated without rhTM (control group) or with rhTM (treatment group). The primary outcome was the DIC score on day 7. The secondary outcome was 28-day mortality from the start of DIC treatment. Changes in the results of coagulation tests were assessed over time from the start of treatment to day 7. Twelve and 23 patients were assigned to the treatment and control groups, respectively. The DIC score on day 7 was significantly higher in the treatment group (3.3 ± 1.4) than in the control group (4.9 ± 1.8, p < 0.05). Estimated survival showed lower in treatment group than control group. There was significant difference between the control group and the treatment group (p < 0.05). The D-dimer level on day 7 was significantly lower in the treatment group (7.5 ± 4.1 μg/mL) than in the control group (30.9 ± 33.6 μg/mL, p < 0.05). Life-threatening bleeding did not occur. Our results indicated that rhTM improved sepsis-induced DIC and mortality. Recombinant human soluble thrombomodulin may improve sepsis-induced DIC diagnosed according to the JAAM criteria without an increased bleeding risk.

Disseminated intravascular coagulation (DIC) is associated with high mortality in patients with sepsis. Several studies reporting that recombinant human soluble thrombomodulin (rhTM) reduced mortality in sepsis patients. This retrospective cohort study aimed to evaluate the efficacy of rhTM for patients with mild coagulopathy compared with those with severe coagulopathy. We evaluated about 90-day mortality and SOFA score. SOFA score was also evaluated for the following components: respiratory, cardiovascular, hepatic, renal and coagulation. All 69 patients were diagnosed with sepsis, fulfilled Japanese Association for Acute Medicine criteria for DIC, and were treated with rhTM. Patients were assigned to either the mild coagulopathy group (did not fulfill the International Society on Thrombosis and Haemostasis overt DIC criteria) or the severe coagulopathy group (fulfilled overt DIC criteria). The 90-day mortality was significant lower in severe coagulopathy group than mild coagulopathy group (P = 0.029). Although the SOFA scores did not decrease in the mild coagulopathy group, SOFA scores decreased significantly in the severe coagulopathy group. Furthermore the respiratory component of the SOFA score significant decreased in severe coagulopathy group compared with mild coagulopathy group. rhTM administration may reduce mortality by improving organ dysfunction especially for respiratory in septic patients with severe coagulopathy.

Background/Objectives: The combination drug sulfamethoxazole/trimethoprim (ST) is a broad-spectrum antibiotic used against various infections; however, it is associated with several serious adverse events. The ST package inserts contain warnings about these adverse events. However, warnings vary internationally, and specific measures to address ST-related adverse events are unclear. Therefore, we aimed to comprehensively evaluate ST-related adverse events using the Japanese Adverse Drug Event Report (JADER) database and analyze the onset time for each event. Methods: Adverse events due to ST were analyzed using the JADER database between April 2004 and June 2023. The reported odds ratio and 95% confidence interval (95% confidence interval [CI]) were calculated, with a signal detected if the 95% CI lower limit exceeded 1. The Weibull distribution was used to characterize the onset time of adverse events with detected signals. Results: The total number of cases in the JADER database during the study period was 862,952, and the number of adverse events involving ST as a suspected drug was 4203. Adverse events associated with ST include hyperkalemia, syndrome of inappropriate antidiuretic hormone secretion, hematopoietic cytopenia, acute renal failure, hypoglycemia, disseminated intravascular coagulation syndrome, hepatic disorder, and the Stevens–Johnson syndrome/toxic epidermal necrolysis. Conclusions: Weibull analysis indicated an early failure-type onset time for all adverse events, suggesting the need for intensive adverse event monitoring of ST, especially in the first month of use. These findings may support revising drug package inserts in Japan to better reflect the identified risks.

Infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-Es) pose a significant global threat with notable increases in prevalence worldwide. Carbapenems are often used as the first line of treatment. However, their overuse accelerates resistance development, highlighting the urgent need for clinically viable carbapenem-sparing strategies. Cefmetazole (CMZ) and flomoxef (FMOX) are parenteral antibiotics that are widely used in Japan and have emerged as potential carbapenem alternatives. Repositioning these agents effectively addresses the clinical need for carbapenem-sparing strategies and outpatient ESBL-E management. This review aims to reposition CMZ and FMOX for real-world clinical practice by synthesizing basic research, clinical studies, and pharmacokinetics/pharmacodynamics (PKs/PDs) analyses, which suggest that these agents may be effective in treating ESBL-E infections—particularly urinary tract infections, as evidenced by their minimum inhibitory concentration (MIC) values. The clinical outcomes of these interventions have been comparable to those of carbapenems, which support their role in antimicrobial stewardship. Their PK/PD characteristics emphasize the importance of dose optimization to ensure therapeutic efficacy, whereas recent insights into resistance mechanisms provide a foundation for appropriate use. As novel antibiotic development takes substantial time, revisiting existing options is increasingly important. Notably, the Infectious Diseases Society of America’s 2024 guidance on antimicrobial resistance has omitted CMZ and FMOX, owing to which clinicians have limited guidance on their use, particularly in regions like Japan where these antibiotics are widely employed. By addressing this knowledge gap, the present review offers a comprehensive evaluation of these drugs and highlights their potential as intravenous agents in ESBL-E management. Furthermore, it highlights the ongoing challenge of ensuring effective oral step-down therapy in an outpatient setting to reinforce the global relevance of CMZ and FMOX in a broader treatment framework, underscoring their potential for outpatient administration where clinically appropriate.

Background/Objectives: Voriconazole (VRCZ) use requires accurate monitoring to avoid suboptimal drug levels and adverse effects. In addition, the appearance of resistant fungal strains is a problem that needs attention. Blood concentration measurement is the monitoring technique of choice; however, it is slow, limiting its clinical application. This study aimed to evaluate the clinical utility of rapid therapeutic drug monitoring (TDM) for VRCZ using high-performance liquid chromatography with ultraviolet detection (HPLC-UV) compared to conventional outsourced liquid chromatography–tandem mass spectrometry (LC-MS/MS) testing in outpatient care. Methods: VRCZ blood concentrations were measured using HPLC-UV and LC-MS/MS. Reporting times, accuracy, and clinical outcomes were assessed for outpatients receiving VRCZ treatment. Safety was monitored for renal, hepatic, and visual toxicities. Results: HPLC-UV significantly reduced reporting times (0.433 h vs. 74.3 h, p < 0.001), and Deming’s regression analyses showed a strong correlation with LC-MS/MS results (Pearson’s r = 0.988). Bland–Altman analysis showed an average difference of 0.025 μg/mL between HPLC-UV and LC-MS/MS. Prospective monitoring of three outpatients revealed no adverse events, enabling safe and effective VRCZ dosing. Conclusions: Rapid VRCZ TDM using HPLC-UV is a cost-effective and feasible approach for outpatient care, significantly improving reporting times and patient safety. Further studies and cross-facility collaboration are needed to expand its application.

The optimal starting dose of tolvaptan to effectively improve fluid retention in patients with heart failure (HF) is unknown. This study explored the factors affecting the pharmacokinetics (PKs) and pharmacodynamics of tolvaptan in patients with decompensated HF. We prospectively enrolled patients who were slated to receive tolvaptan because of volume overload associated with chronic HF. Blood samples were collected to measure tolvaptan concentrations before and 4, 8, 12–15, 24, and 144 h after administration. Additionally, demographic parameters, coadministered drugs, and body fluid composition were evaluated. Multiple regression analysis to detect PK parameters for the prediction of body weight (BW) loss at day 7 after the initiation of tolvaptan treatment and PK analysis to explore the factors affecting the PKs of tolvaptan were performed. In total, 165 blood samples were obtained from 37 patients. The predictors of weight loss on day 7 were area under the curve (AUC_0–∞) of tolvaptan. PK analysis of the data revealed a strong correlation between CL/F and Vd/F, but no correlation between CL/F and kel (r = .95 and .06, respectively). A significant correlation was observed between total body fluid and Vd/F, and this correlation remained statistically significant even after adjusting for BW (r = .49, p < .05). Fat was also significantly correlated with Vd/F before adjusting for BW, on the other the correlation disappeared after adjusting BW. The optimal dose of tolvaptan based on total body fluid levels in individual patients could result in the alleviation of fluid retention in patients with HF.