We aimed to assess the frequency of acute kidney injury (AKI) in different areas under the concentration–time curve (AUC) values of vancomycin (VAN) using a two-point blood collection method, allowing for accurate AUC assessment in critically ill patients. This multicenter retrospective observational study was conducted in eight hospitals. We retrospectively analyzed the data of patients who had received VAN in an intensive care unit (ICU) between January 2020 and December 2022. The primary outcome was the incidence of AKI. Patients were classified into three groups according to the AUC _24–48h at the initial therapeutic drug monitoring (TDM) as follows: <500, 500–600, and ≥600 µg·h/mL. The AUC _24–48h values were calculated using the Bayesian estimation software Practical AUC-guided TDM. Among 146 patients [median age (interquartile range), 67 (56–78) years; 39% women], the AUC _24–48h <500 µg·h/mL had an AKI rate of 6.5% (7/107), the AUC _24–48h 500–600 µg·h/mL had an AKI rate of 28.0% (7/25), and the AUC _24–48h ≥600 µg·h/mL had an AKI rate of 42.9% (6/14). In multivariate Cox proportional hazard analysis, the AUC _24–48h 500–600 µg·h/mL [hazard ratio 5.4, 95% confidence interval (CI) 1.64–17.63] and the AUC _24–48h ≥600 μg·h/mL (hazard ratio 7.0, 95% CI 2.31–21.18) significantly correlated with a higher incidence of AKI compared with the AUC _24-48h <500 μg·h/mL. In conclusion, we identified an association between AUC on day 2 and the risk of AKI in ICU patients, suggesting that not only AUCs above 600 µg·h/mL but also those between 500 and 600 µg·h/mL pose a risk for AKI. IMPORTANCE: Vancomycin (VAN) is a glycopeptide antibiotic and one of the most commonly used antibiotics for severe infections caused by methicillin-resistant Staphylococcus aureus . However, higher VAN concentrations have been associated with an increased risk of acute kidney injury (AKI). Herein, we aimed to assess the frequency of AKI in different areas under the concentration–time curve (AUC) values of VAN using a two-point blood collection method, allowing for accurate AUC assessment in critically ill patients. We identified an association between AUC on day 2 and the risk of AKI in intensive care unit patients, suggesting that not only AUCs above 600 µg·h/mL but also those between 500 and 600 µg·h/mL pose a risk for AKI. Therefore, individualized dosing is feasible, with pharmacists being able to optimize VAN doses to attain appropriate targets.

The therapeutic drug monitoring (TDM) of vancomycin (VCM) in critically ill patients often results in the estimated area being under the concentration–time curve (AUC) values that deviate from individual observations. In this study, we investigated the factors influencing the achievement of the target AUC of VCM at steady-state in critically ill patients. We retrospectively collected data from patients treated with VCM in an intensive care unit (ICU). Multivariate analysis was used to adjust for significant factors with p < 0.05 and identify new factors affecting the achievement of the target AUC at steady-state for VCM. Among the 113 patients included in this study, 72 (64%) were in the 1-point group (trough only), whereas 41 (36%) were in the 2-point group (trough/peak). The percentage of patients achieving the target AUC at the follow-up TDM evaluation was significantly higher in the two-point group. Multivariate analysis showed that being in the 2-point group and those with a 20% or more increase (or decrease) in creatinine clearance (CCr) were both significantly associated with the success rate of achieving the target AUC at the follow-up TDM. Novel findings revealed that in patients admitted to the ICU, changes in renal function were a predictor of AUC deviation, with a 20% or more increase (or decrease) in CCr being an indicator. We believe the indicators obtained in this study are simple and can be applied clinically in many facilities. If changes in renal function are anticipated, we recommend an AUC evaluation of VCM with a two-point blood collection, close monitoring of renal function, and dose adjustment based on reanalyzing the serum concentrations of VCM.

The efficacy and safety of linaclotide in elderly patients are poorly understood. Herein, we aimed to assess the efficacy and safety of linaclotide in elderly patients in real-world setting. We retrospectively enrolled consecutive patients who started linaclotide therapy at Sapporo Medical University Hospital from October 1, 2017 to December 31, 2019. The efficacy and safety of linaclotide were examined in relation to various factors, including age (<65 or ≥65 years) and dose (0.25 or 0.5 mg/d). Fifty-two patients were enrolled, 60% of whom were over 65 years old and 40% were female. Thirty-six patients received a linaclotide dose of 0.25 mg/d. The most common side effect was diarrhea, but there was no difference in the incidence of diarrhea between the elderly (64.5%) and non-elderly patients (42.9%, p=0.130). No significant difference was observed with respect to improvement in constipation in the elderly (83.9%) and non-elderly patients (71.4%, p=0.318). Additionally, the difference in efficacy of linaclotide in patients who received a reduced dose (80.6%) vs. those who received the recommended dose (75.0%) was not statistically significant (p=0.719). Multivariate analysis revealed that age, gender, and dose were not associated with diarrhea induced by linaclotide treatment. However, concurrent treatment with constipation-inducing medications [odds ratio (OR) 5.79, p=0.047] and linaclotide monotherapy (OR 11.1, p=0.040) were both risk factors contributing to diarrhea. Linaclotide is effective and safe for use in elderly patients. The incidence of diarrhea may increase when linaclotide is administered alone or concurrently used with medications that cause constipation.