A study of trends and factors associated with therapeutic drug monitoring (TDM) implementation for arbekacin treatment using a large Japanese medical claims database.

INTRODUCTION: Reimbursements for pharmacist interventions and infectious disease teams have recently been introduced in Japan. Arbekacin (ABK) is used to treat pneumonia and sepsis caused by methicillin-resistant Staphylococcus aureus, and therapeutic drug monitoring (TDM) is recommended. This study aimed to clarify the trend in TDM implementation for ABK over time and the factors associated with TDM implementation using a claims database. METHODS: Data of patients aged ≥15 years who received ABK for ≥3 consecutive days between 2010 and 2019 were extracted from a large Japanese medical claims database. The proportion of reimbursements claimed for TDM, pharmacist interventions, and the setup of infectious disease teams for each year were calculated. The factors associated with TDM implementation were identified using multivariate logistic regression analysis. RESULTS: The proportion of TDM implementation for ABK increased by 9.1% from 2010 to 2019, but it remained less than 40% throughout this period. The proportion of TDM implementation was higher in patients who claimed reimbursements for pharmacist interventions than in patients who did not. Logistic regression analysis showed that the stationing of pharmacists in wards and long-term ABK treatment were significantly associated with TDM implementation. CONCLUSIONS: From 2010 to 2019, the proportion of TDM implementation for ABK was significantly low. Moreover, the factors associated with TDM implementation were clarified. An environment wherein pharmacists can help implement TDM for patients receiving ABK would be beneficial.

Trends in healthcare visits and antimicrobial prescriptions for acute infectious diarrhea in individuals aged 65 years or younger in Japan from 2013 to 2018 based on administrative claims database: a retrospective observational study.

BACKGROUND: The inappropriate use of antimicrobials for acute infectious diarrhea is widespread and leads to the problem of antimicrobial resistance. To improve the use of antimicrobials, it is first necessary to understand the actual situation of diarrheal disease and to identify potential targets for intervention. This study aimed to investigate the recent epidemiological characteristics of and antimicrobial prescriptions for acute infectious diarrhea in Japan. METHODS: This was a retrospective observational study of outpatients aged 0-65 years, separated into children (age 0-17 years) and adults (age 18-65 years), diagnosed with acute infectious diarrhea, using the administrative claims database of the Japan Medical Data Center from 2013 to 2018. We evaluated the number of eligible visits/number of database registrants (defined as the visit rate). The analysis of the antimicrobial prescription rate was restricted to otherwise healthy individuals diagnosed with acute infectious diarrhea alone by excluding patients with multiple disease diagnoses and with medical backgrounds of chronic bowel diseases or immunocompromised conditions. We further classified them by diagnosis of bacterial or nonbacterial acute infectious diarrhea. RESULTS: The total number of eligible visits for acute infectious diarrhea was 2,600,065. The visit rate, calculated based on the number of eligible visits by database registrants, was higher in children (boys, 0.264; girls, 0.229) than in adults (men, 0.070; women, 0.079), with peaks in early summer and winter. The peaks for visits in adults lagged those of children. In total, 482,484 visits were analyzed to determine the antimicrobial prescription rate; 456,655 (94.6%) were diagnosed with nonbacterial acute infectious diarrhea. Compared with children (boys, 0.305; girls, 0.304), the antimicrobial prescription rate was higher in adults, and there were differences between sexes in adults (men, 0.465; women, 0.408). Fosfomycin and fluoroquinolone were most frequently used for nonbacterial acute infectious diarrhea in children (44.1%) and adults (50.3%), respectively. CONCLUSIONS: These results revealed overprescription of antimicrobials for acute infectious diarrhea in this administrative claims database in Japan and contribute to the development of antimicrobial stewardship strategies and the identification of targets for efficiently reducing inappropriate antimicrobial use.

Impact of adjuvant lorazepam with granisetron on chemotherapy-induced nausea and vomiting in pediatric patients with acute lymphoblastic leukemia.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) affects quality of life for patients with cancer undergoing chemotherapy. We aimed to assess the effect of lorazepam with granisetron on CINV in children with acute lymphoblastic leukemia (ALL). METHODS: We reviewed the records of 71 consecutive patients with newly diagnosed ALL who received chemotherapy including vincristine, anthracycline, and systemic steroids between January 2011 and December 2016 in our hospital. The number of chemotherapy cycles reviewed was 164. All patients received granisetron as CINV prophylaxis. RESULTS: Nausea was observed in 51/71 patients (72%) and 93/164 cycles (57%). Vomiting was observed in 47/71 patients (66%) and 79/164 cycles (48%). Age and gender distribution were not significantly different between patients who received lorazepam at the initiation of the chemotherapy cycle (LZP group, n = 30) and those who did not receive lorazepam (non-LZP group, n = 134). There were no significant differences in the incidence of CIN and CIV between the LZP group and non-LZP group (CIN, 67% vs. 57%, P = 0.31; CIV, 53% vs. 47%, P = 0.98). In multivariate logistic regression, female gender and older age (> 5 years) were significant risk factors for CIV (female, odds ratio (OR) 2.5, 95% confidence interval (CI) 1.3-5.0, P = 0.007; older age, OR 2.5, CI 1.3-4.8, P = 0.008). CONCLUSIONS: We found no beneficial effect of providing lorazepam as adjuvant antiemetic for prevention of CINV in children with ALL.

Investigation of oral macrolide prescriptions in Japan using a retrospective claims database, 2013-2018.

Macrolide usage in Japan exceeds that in Europe and the United States. Investigating the actual conditions in which macrolides are used is important for identifying further interventions for appropriate antimicrobial use; however, this situation has not been evaluated in Japan. Therefore, we aimed to clarify the number of macrolide prescriptions and their changes before and after implementation of the Antimicrobial Resistance (AMR) Action Plan. In addition, we also investigated the names of diseases for which macrolides have been prescribed and the number of days of prescription. A retrospective observational study was conducted using JMDC claims data from January 2013 to December 2018. The proportion of all oral antimicrobials and macrolides used during this period and the diseases for which macrolides were used in the 3 years before and after the AMR Action Plan were determined separately for acute (< 14 prescription days) and chronic (> 14 prescription days) diseases. The number of prescriptions for macrolides constituted approximately 30% of those for all oral antimicrobials; of these, clarithromycin accounted for approximately 60%. Most prescriptions for acute diseases were for common cold, whereas allergic and dermatological diseases were included among chronic diseases. The names of these illnesses did not change before and after the AMR Action Plan. Overall, these results indicate that appropriate macrolide use involves a review of their use for common cold along with appropriate evaluation of their long-term use for skin and allergic diseases. They also indicate the need for further fact-finding studies and ongoing AMR measures.

Antimicrobial Use Fell Substantially in Japan in 2020-The COVID-19 Pandemic May Have Played a Role.

This study investigated the impact of the COVID-19 pandemic on antimicrobial use (AU) trends in Japan in 2020 and explored its potential effects on appropriate AU. Using nationwide antimicrobial sales data, we examined the annual and monthly trends in AU from 2016-2020 according to the AWaRe classification (Access and Watch categories) and administration route (oral and injectable). To analyze the possible impact of the COVID-19 pandemic on AU, seasonal autoregressive integrated moving average (SARIMA) models were used to predict AU in 2020 (based on the trends from 2016-2019) under the assumption that the pandemic did not occur. We observed a substantial reduction in AU in 2020 compared with preceding years. In addition, the reductions in AU for total antimicrobials and Watch category antimicrobials were greater than predicted regardless of administration route. These results suggest that the COVID-19 pandemic contributed to the observed reductions in AU, but it is also possible that the changes reflect recent efforts to improve AU. Continued AU surveillance and research are needed to optimize prescribing practices through appropriate antimicrobial stewardship.

Influence of pharmacists and infection control teams or antimicrobial stewardship teams on the safety and efficacy of vancomycin: A Japanese administrative claims database study.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) has a high mortality and requires effective treatment with anti-MRSA agents such as vancomycin (VCM). Management of the efficacy and safety of VCM has been implemented with the assignment of pharmacists in hospital wards and the establishment of teams related to infectious diseases. However, there are no reports evaluating the association between these factors and the efficacy and safety of VCM in large populations. METHODS: This study used the Japanese administrative claims database accumulated from 2010 to 2019. The population was divided into two groups, therapeutic drug monitoring (TDM) group and non-TDM group, and adjusted by propensity score matching. We performed multivariate logistic regression analysis to determine the influence of pharmacists and infection control teams or antimicrobial stewardship teams on acute kidney injury (AKI) and 30-day mortality. RESULTS: The total number of patients was 73 478 (TDM group, n = 55 269; non-TDM group, n = 18 209). After propensity score matching, 18 196 patients were matched in each group. Multivariate logistic regression analysis showed that pharmacological management for each patient contributed to the reduction of AKI (odds ratio [OR]: 0.812, 95% confidence interval [CI]: 0.723‒0.912) and 30-day mortality (OR: 0.538, 95% CI: 0.503‒0.575). However, the establishment of infectious disease associated team in facilities and the assignment of pharmacists in the hospital wards had no effect on AKI and 30-day mortality. In addition, TDM did not affect the reduction in AKI (OR: 1.061, 95% CI: 0.948‒1.187), but reduced 30-day mortality (OR: 0.873, 95% CI: 0.821‒0.929). CONCLUSION: Pharmacologic management for individual patients, rather than assignment systems at facilities, is effective to reduce AKI and 30-day mortality with VCM administration.

The first national survey of antimicrobial use among dentists in Japan from 2015 to 2017 based on the national database of health insurance claims and specific health checkups of Japan.

PURPOSE: To counter the global health threat of antimicrobial resistance, effective antimicrobial stewardship programs are needed to improve antimicrobial use (AMU) among dentists in addition to physicians. This study aimed to investigate the nationwide epidemiology of AMU among Japanese dentists to facilitate the development of dentist-centered programs. METHODS: We conducted a retrospective population-based study using the National Database of Health Insurance Claims and Specific Health Checkups of Japan to analyze the AMU among Japanese dentists between 2015 and 2017. AMU was quantified as the defined daily doses per 1,000 inhabitants per day (DID). The trends in dentist-prescribed AMU were examined according to antimicrobial category and administration route. We also compared outpatient oral AMU between dentists and physicians as well as between on-site and off-site dispensing. RESULTS: The DID values of dentist-prescribed AMU were 1.23 in 2015, 1.22 in 2016, and 1.21 in 2017. During this study period, outpatient oral antimicrobials comprised the majority (approximately 99%) of dentist-prescribed AMU, and cephalosporins were the most frequently prescribed antimicrobials (>60% of all antimicrobials). The DID values of outpatient oral AMU were 1.21 for dentists and 12.11 for physicians. The DID value for on-site dispensing was 0.89 in 2017, in which cephalosporins were the predominantly used antimicrobials (DID: 0.60). CONCLUSIONS: Interventions that target dentists in Japan should focus on on-site dispensing of oral antimicrobials (especially cephalosporins) for outpatients. Further studies are needed to ascertain the underlying factors of oral cephalosporin prescriptions to guide the development of effective antimicrobial stewardship programs.