Relationship between nephrotoxicity and area under the concentration-time curve of vancomycin in critically ill patients: a multicenter retrospective study.

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 AUC24-48h at the initial therapeutic drug monitoring (TDM) as follows: <500, 500-600, and ≥600 µg·h/mL. The AUC24-48h 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 AUC24-48h <500 µg·h/mL had an AKI rate of 6.5% (7/107), the AUC24-48h 500-600 µg·h/mL had an AKI rate of 28.0% (7/25), and the AUC24-48h ≥600 µg·h/mL had an AKI rate of 42.9% (6/14). In multivariate Cox proportional hazard analysis, the AUC24-48h 500-600 µg·h/mL [hazard ratio 5.4, 95% confidence interval (CI) 1.64-17.63] and the AUC24-48h ≥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 AUC24-48h <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.

Flowchart for predicting achieving the target area under the concentration-time curve of vancomycin in critically ill Japanese patients: A multicenter retrospective study.

INTRODUCTION: In therapeutic drug monitoring (TDM) of vancomycin (VCM), the area under the concentration-time curve (AUC) is related to the clinical efficacy and toxicity. Therefore, herein, we examined the factors associated with achieving the target AUC at follow-up and developed a decision flowchart for achieving the target AUC in critically ill patients. METHODS: This multicenter retrospective observational study was conducted at eight hospitals. We retrospectively analyzed data from patients who had received VCM in the intensive care unit from January 2020 to December 2022. Decision-tree (DT) analysis was performed using factors with p < 0.1 in univariate analysis as the independent variables. Case data were split up to two times, and four subgroups were included. The primary endpoint was achieving the target AUC at the follow-up TDM (AUCfollow-up) and target AUCfollow-up achievement was defined as an AUC of 400-600 µg‧h/mL. The initial AUC values were calculated with the 2-point concentrations (peak and trough) using the Bayesian estimation software Practical AUC-guided TDM (PAT). RESULTS: Among 70 patients (median age [interquartile range], 66 [56, 79] years; 50 % women), the AUCfollow-up was achieved in 70 % (49/70). Three factors were selected for the decision flow chart: predicted AUCfollow-up of 400-600 µg‧h/mL, dosing at 12-h intervals, and CCr of 130 mL/min/1.73 m2 or higher; the accuracy was adequate (92 %, R2 0.52). CONCLUSION: We successfully identified the factors associated with achieving the target AUC of VCM at follow-up TDM and developed a simple-to-use DT model. However, the validity of the findings needs to be evaluated.

Antimicrobial Stewardship Program for Patients in the Hematological Department Receiving Carbapenem Therapy: A Single-Center and Interrupted Time Series Analysis.

As antibiotic resistance has become a global problem, the intervention of an antimicrobial stewardship team (AST) is warranted. In hematological disorders, infectious complications are crucial owing to abnormal neutrophil function and decreased cell-mediated immunity. Despite the widespread implementation of AST intervention, the effectiveness of stewardship practices for immunocompromised patients remains uncertain. We determined the effect of AST interventions on carbapenem therapy in the department of hematology. Patients admitted to the department and undergoing carbapenem therapy were enrolled. We compared carbapenem use between the pre-AST (April 2016-March 2018) and post-AST (April 2018-March 2021) periods. Factors associated with long-term carbapenem therapy were investigated. Overall, 515 episodes of carbapenem therapy in 264 patients in the department were evaluated. According to the interrupted time series analysis, the number of days of therapy decreased with AST intervention (ß = -0.263, p = 0.011). In multivariate analysis, predictive factors associated with long-term carbapenem therapy (>8 days) were outpatient onset, chronic obstructive pulmonary disease, acute myeloid leukemia, multiple myeloma, and infection with resistant bacteria (such as extended spectrum ß-lactamases and AmpC) (95% confidence interval, 1.030-2.818, 1.067-66.667, 1.057-2.782, 0.168-0.742, and 1.382-5.750, respectively). The AST intervention reduced carbapenem use in patients with hematological disorders.

Development and evaluation of a formula for predicting introduction of medication self-management in stroke patients in the Kaifukuki rehabilitation ward.

BACKGROUND: Medication self-management in stroke patients is important to prevent further progression of disease and incidence of side effects. The purpose of this study was to create a formula for predicting medication self-management introduction in stroke patients using functional independence measure items and patient data, including medication-related information. METHODS: This was a retrospective analysis of 104 patients (cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage) discharged from the Kaifukuki rehabilitation ward at Showa University Fujigaoka Rehabilitation Hospital from January to December 2012. Multivariate analysis was performed to develop a formula for predicting achievement of medication self-management. RESULTS: Of the 104 patients, 39 (37.5%) achieved medication self-management. In the logistic regression analysis, number of drugs, age, walk/wheelchair mobility FIM, and memory FIM were extracted as significant factors independently contributing to achievement of medication self-management (p < 0.05). The prediction formula was [4.404 - 0.229 × number of drugs at admission + 0.470 × walk/wheelchair mobility FIM at admission + 0.416 × memory FIM at admission - 0.112 × age]. CONCLUSIONS: In the future, this formula may be used as an index to predict success of medication self-management in stroke patients.

[Expected Duties of Pharmacists and Potential Needs of Physicians and Nurses on a Kaifukuki Rehabilitation Ward].

This study investigated the required duties of pharmacists in a kaifukuki rehabilitation ward from the viewpoint of the ward physicians and nurses. A questionnaire survey was distributed to 27 facilities with kaifukuki rehabilitation wards. The questionnaire examined which duties the physicians and nurses expected from pharmacists while on the ward (4 areas, 10 items), as well as the time required for pharmacists to carry out those duties. Multivariate analysis was used to investigate which types of work took the most time for pharmacists on kaifukuki rehabilitation wards. Responses were received from 43 physicians and 184 nurses who worked on the kaifukuki rehabilitation wards of 19 facilities. The results revealed that the essential duties performed by pharmacists were the management of medical supplies, instruction on the use of self-medicating drugs at the time of introduction, and monitoring drug side effects. Furthermore, some duties, such as the distribution of medicines and changing or suggesting new drugs, required pharmacists to spend extended time on the ward. The responses indicated that physicians and nurses recognized the necessity for pharmacists to perform ward duties along with their routine work. This study shows that physicians and nurses working in kaifukuki rehabilitation wards demand proactive participation from pharmacists in appropriate medical therapy, such as instruction in the administration of medications and assessment at the time of prescription changes.

Effect of 2,5-dimethylpyrazine on uterine contraction in late stage of pregnant female rats.

Effect of 2,5-dimethylpyrazine (2,5-DMP) on oxytocic agent-induced late pregnant uterine contraction in female rats was studied. Oxytocic agents induced-hypercontraction in the late phase of pregnant uterine movements were inhibited by administration of 2,5-DMP. The inhibition of uterine contraction was obtained more strengthening by presence of a low dose of ritodrine hydrochloride than 2,5-DMP alone. These results suggests that 2,5-DMP has an inhibitory action on uterine hypercontraction induced by oxytocic agent through the beta2-adrenoceptor in the pregnant uterus and supports the applicability of relaxing drugs for oxytocic agent-induced accidents.