Enhancing carbapenem antimicrobial dosing optimization: synergy of antimicrobial stewardship teams and ward-based clinical pharmacists.

Antimicrobial-product package inserts and insufficient staffing impede routine carbapenem monitoring in the inpatient setting in Japan. The collaboration between antimicrobial stewardship teams and clinical pharmacists was associated with a sustained improvement in carbapenem dosing optimization. Our findings could be of use to countries with inadequate monitoring of carbapenem antimicrobial use.

Characteristics of pediatric patients claimed with acute upper respiratory infection during otorhinolaryngology consultations: A descriptive study of a large Japanese medical claims database.

This study aimed to clarify other diseases claimed simultaneously with acute upper respiratory infection (URI), antibiotic prescriptions, and examinations associated with infectious diseases in pediatric patients with acute URI insurance claims at otorhinolaryngology outpatient visits. Pediatric patients who visited an otolaryngology department between 2019 and 2021 and were definitively diagnosed with URI were selected using a large Japanese medical claims database. Patient backgrounds, antibiotic use, and examinations were descriptively evaluated. In total, 8010 patients were included in the analysis. The median number (interquartile range) of diseases claimed in the same month as acute URI was 4 (3-6). Only 519 (6.5 %) patients were claimed as acute URI alone. Regardless of the prescription of antibiotics, the most commonly redundantly claimed disease in these patients was allergic rhinitis, followed by acute bronchitis, acute sinusitis, and earwax impaction. The frequently prescribed antibiotics were third-generation cephalosporins, macrolides, and penicillins with extended-spectrum, including amoxicillin which was recommended by the Japanese manual; the proportion of patients with examinations was low (2.9-21.7 %). Among patients with acute URI, diagnoses requiring antibiotics were also claimed; therefore, when evaluating acute URI using the Japanese medical claims database, care must be taken in patient selection. Moreover, the implementation rate of examinations necessary for diagnosis was low, so there is an urgent need to develop an environment where examinations can be conducted in outpatient settings.

Relationship between carbapenem use and major diagnostic category in curative care beds: Analysis of a 2020 Japanese national administrative database.

Excessive carbapenem use has contributed to the spread of carbapenem-resistant bacteria. In response, Japan's revised National Action Plan on Antimicrobial Resistance (AMR) 2023-2027 set the goal of a 20 % reduction in carbapenem use. The aim of this study is to reveal the circumstances associated with carbapenem use in diagnosis procedure combination (DPC) community hospitals and fee-for-service hospitals, which account for the majority of the hospitals in Japan. We analyzed publicly available data from the Survey of Discharged Patients conducted by the Ministry of Health, Labour and Welfare in 2020. We used multiple regression analysis to identify the factors associated with carbapenem use in small- to medium-sized hospitals. Considerable carbapenem use was observed in small- to medium-sized hospitals. There was a large difference in carbapenem use among curative care beds in both DPC community hospitals and non-DPC hospitals. Linear regression models showed the significant association of several major diagnostic categories (MDCs) with carbapenem use. In particular, rates of MDC No.02 (eye) and 05 (circulatory system) were potentially associated with excessive or inappropriate carbapenem use. A notable and novel study finding was that there was a large difference in carbapenem consumption as the number of curative care beds increased in both DPC community hospitals and non-DPC hospitals. This may contribute to the identification of carbapenem overuse and toward achieving the goal of the National Action Plan on AMR 2023-2027. Furthermore, identifying factors associated with carbapenem use helps in understanding disease-specific prescribing practices and detecting potential overuse.

Antimicrobial use and combination of resistance phenotypes in bacteraemic Escherichia coli in primary care: a study based on Japanese national data in 2018.

BACKGROUND: Antimicrobial use (AMU) in primary care is a contributing factor to the emergence of antimicrobial-resistant bacteria. We assessed the potential effects of AMU on the prevalence of a combination of resistance phenotypes in bacteraemic Escherichia coli in outpatient care settings between primary care facilities ('clinics') and hospitals. METHODS: Population-weighted total AMU calculated from the national database was expressed as DDDs per 1000 inhabitants per day (DID). National data for all routine microbiological test results were exported from the databases of a major commercial clinical laboratory, including 16 484 clinics, and the Japan Nosocomial Infections Surveillance, including 1947 hospitals. AMU and the prevalence of combinations of resistance phenotypes in bacteraemic E. coli isolates were compared between clinics and hospitals. RESULTS: The five most common bacteria isolated from patients with bacteraemia were the same in clinics, outpatient settings and inpatient settings in hospitals, with E. coli as the most frequent. Oral third-generation cephalosporins and fluoroquinolones were the top two AMU outpatient drugs, except for macrolides, and resulted in at least three times higher AMU in clinics than in hospitals. The percentage of E. coli isolates resistant to both drugs in clinics (18.7%) was 5.6% higher than that in hospitals (13.1%) (P < 10-8). CONCLUSIONS: Significant AMU, specifically of oral third-generation cephalosporins and fluoroquinolones, in clinics is associated with a higher prevalence of E. coli isolates resistant to both drugs. This study provides a basis for national interventions to reduce inappropriate AMU in primary care settings.

Comparative effectiveness of cefmetazole versus carbapenems and piperacillin/tazobactam as initial therapy for bacteremic acute cholangitis: A retrospective study.

INTRODUCTION: Carbapenems and piperacillin/tazobactam (PIPC/TAZ) are commonly used as the initial therapy to treat extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales in acute cholangitis. However, the overuse of these antibiotics contributes to the spread of antimicrobial resistance. Cefmetazole (CMZ) is stable to hydrolysis by ESBLs, so it may be an alternative to carbapenems and PIPC/TAZ. However, the effectiveness of CMZ compared with that of carbapenems and PIPC/TAZ as the initial therapy for acute cholangitis is unknown. METHODS: We conducted a retrospective cohort study at a university hospital between April 1, 2014, and December 31, 2022. Patients with bacteremic acute cholangitis who received CMZ, carbapenems, or PIPC/TAZ as the initial therapy were included. The patients were divided into a CMZ group and a carbapenems or PIPC/TAZ (CP) group to compare patient outcomes. RESULTS: A total of 99 patients (54 in the CMZ group and 45 in the CP group) were analyzed. The baseline characteristics of the patients were similar and 30-day mortality did not differ between groups (4% vs. 7%, P = 0.66). However, the CMZ group had a shorter length of stay (LOS) (8 days vs. 15 days, P < 0.001) and lower mean antibiotic cost (98.92 USD vs. 269.49 USD, P < 0.001) than the CP group. CONCLUSIONS: In bacteremic acute cholangitis, initial therapy with CMZ may contribute to a shorter LOS and lower antibiotic costs than treatment with carbapenems and PIPC/TAZ, without worsening patient outcomes.

Relationship between antihypertensive drug use and number of people with high blood pressure in FY 2018: a descriptive epidemiological study based on the National Database of Health Insurance Claims and Specific Health Checkups of Japan open data.

BACKGROUND: In most countries barring Japan, antihypertensive drug use has been reported using the defined daily doses/1000 inhabitants/day (DID). Although DID has been shown to allow for the assessment of the number of patients treated with a particular drug, the relationship between DID and the number of patients with hypertension has not been clarified. This study aimed to clarify the relationship between antihypertensive drug use and the number of people with high blood pressure based on the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) open data. METHODS: DID was calculated by extracting the use of oral antihypertensive drugs from outpatient prescriptions in the NDB Open Data in FY 2018. The number of people with high blood pressure was calculated using the number of enrollees in each sex-age group for systolic and diastolic blood pressure in the 40-74 years age group. The correlation between the DID of antihypertensive drugs and the number of people with high blood pressure by sex and age class was evaluated using Spearman's rank correlation coefficient. RESULTS: The use of antihypertensive drugs increased with age in both men and women. Furthermore, in both sexes, dihydropyridine derivatives, calcium antagonists, and angiotensin II receptor blockers were the main drugs used from the age of 20 years onward. In addition, a very strong positive correlation was found between the number of people with high systolic blood pressure and DID in both sexes (men: r = 1, P < 0.05; women: r = 1, P < 0.05). In contrast, there was no significant correlation between the number of people with high diastolic blood pressure and DID in both sexes (men: r = - 0.214, P > 0.05; women: r = 0.393, P > 0.05). CONCLUSIONS: To our knowledge, this study is the first to investigate the use of oral antihypertensive drugs in outpatient settings in Japan. In addition, the DID of antihypertensive drugs can be used as an alternative indicator of the number of people with high systolic blood pressure.

Trends in Implementation of Loading Dose of Voriconazole from 2010 to 2019 and Influencing Factors of Loading Dose Based on a Japanese Administrative Claim Database: A Retrospective Cohort Study.

A loading dose of voriconazole (VRCZ) is recommended to increase its blood concentration at an early stage. However, the trends in the implementation of the loading dose in VRCZ in Japan has not yet been clarified. In addition, although pharmacists play many important roles in antimicrobial stewardship, the effect of pharmacist intervention on the implementation of a loading dose of VRCZ has not yet been reported. Therefore, this study aimed to clarify the implementation of loading dose of VRCZ and the influencing factors of loading dose. This study used an administrative claims database that included patients who received injectable VRCZ between 2010 and 2019. The implementation of loading doses in the VRCZ was evaluated annually. Multivariate logistic regression analysis was performed to identify the factors influencing loading dose. Overall, 2197 patients were included. The implementation rate of the loading dose remained below 65% throughout the study period. Among medical fees that can be calculated through pharmacist intervention, only the infection prevention and control premium significantly increased the implementation of loading dose of VRCZ (odds ratio: 1.587, 95% confidence interval: 1.053-2.392). In conclusion, antifungal stewardship may have been promoted at medical institutions that established infection prevention and control. In the future, pharmacists will need to intervene more actively from the beginning of VRCZ administration.

Trends in teicoplanin loading dose implementation from 2010 to 2019 and evaluation of safety and efficacy factors: a retrospective cohort study based on a Japanese administrative claims database.

BACKGROUND: The loading dose of teicoplanin (TEIC) is recommended for implementation. However, there is significant discrepancy between the dose settings in the package insert and, in the guidelines, and the actual status of loading doses in Japan is unclear. Furthermore, TEIC causes liver injury as side effect. Although the risk of developing liver injury has not been reported to be increased following a loading dose based on the guidelines, there is a lack of reports in large populations. Therefore, we evaluated the trend in the loading dose and factors affecting the efficacy and safety of TEIC administration. METHODS: A Japanese administrative claims database was used in this study. Trends in loading doses were evaluated in target populations administered TEIC between 2010 and 2019. Patient characteristics were adjusted by propensity score matching based on the guideline group (total dose of 3 days > 1,600 mg) and non-guideline group (≤ 1,600 mg) of the loading dose. Finally, univariable and multivariable conditional logistic regression analysis was performed to evaluate factors affecting 30-day mortality and liver injury. RESULTS: A total of 10,030 patients were selected based on these criteria. The proportion of loading doses based on the recommended guidelines showed an increase over time, regardless of the implementation of therapeutic drug monitoring (TDM), but especially so in cases where TDM was implemented, the loading doses were administered in accordance with the recommendations of the guidelines. Conditional logistic regression analysis showed a relationship between drug management and guidance fees (odds ratio [OR]: 0.45, 95% confidence interval [CI]: 0.36‒0.55), a reimbursement indicating pharmacist intervention, and a reduction in 30-day mortality. In addition, loading doses based on the recommended guidelines had no influence on liver injury, and other factors were not significantly associated with increased incidence of liver injury. CONCLUSION: Thus, this study implies the benefits of pharmacological management as indicated by drug management and guidance fee and supports the implementation of loading doses based on the guideline on TEIC administration.

Necessity for a System Implementing Therapeutic Drug Monitoring in Outpatient Settings Based on the Actual Use of Voriconazole Using the National Database of Health Insurance Claims and Specific Health Checkups of Japan: A Descriptive Epidemiological Study.

Voriconazole (VRCZ) is an antifungal drug that necessitates therapeutic monitoring (TDM). Typically, TDM is recommended for patients undergoing long-term outpatient treatment. However, in Japan, insurance reimbursement for TDM is only permitted for inpatients. There is a concern that VRCZ use is growing among outpatients, although information regarding this issue remains unavailable. Therefore, we aimed to clarify the use of VRCZ by utilizing data from the National Database of Health Insurance Claims and Specific Health Checkups in Japan. The use of branded and generic oral VRCZ from 2013 to 2019 was calculated using the defined daily doses/1000 inhabitants/d (DID) for each receipt type. Oral VRCZ was used more frequently in the outpatient setting than that in the inpatient setting, with use increasing over time. The use of generic drugs began in 2016 and accounted for 52.5% of the use in 2019 among outpatients. Considering outpatient prescriptions, 76.4-81.0% were dispensed at insurance pharmacies, indicating the need for community pharmacist involvement. Accordingly, the appropriate use of VRCZ in ambulatory care should be promoted in collaboration with community pharmacists, and a reimbursement system should be established to implement TDM in ambulatory care.

Risks of malignant lymphoma in rheumatoid arthritis patients receiving methotrexate-alone and in combination therapy compared with the general population: A study based on a Japanese medical claims database.

OBJECTIVE: The risk of malignancy in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX) and biological disease-modifying antirheumatic drug (bDMARD) combination therapy is unknown. This study aimed to clarify the incidence of malignancy and the recommended monitoring period in patients receiving this combination therapy. MATERIALS AND METHODS: A retrospective, observational study based on a large Japanese medical claims database was conducted between April 2013 and February 2020. Patients with RA were classified into MTX-alone and combination therapy groups, and the standardized incidence rates (SIR) of malignancy were calculated. The time of onset of malignancy in both groups was calculated. RESULTS: In total, 2,052 patients received MTX-alone and 782 received combination therapy. The incidence of malignant lymphoma was significantly higher with MTX-alone therapy (SIR: 6.09, 95% confidence interval (CI): 1.58 - 10.61) and combination therapy (SIR: 20.86, 95% CI: 8.53 - 33.19) than in the general Japanese population. Furthermore, the combination therapy had a significantly higher risk of malignant lymphoma than the MTX-alone therapy (adjusted odds ratio: 4.27, 95% CI: 1.64 - 11.12). The median time from MTX prescription to the onset of malignant lymphoma was 3.58 years (interquartile range (IQR): 2.00 - 5.34 years) for MTX-alone and 3.42 years (IQR: 1.25 - 4.92 years) for combination therapy. CONCLUSION: The incidence of malignant lymphoma in the combination therapy group was extensively higher than that in the general Japanese population. Special attention is required for early symptoms of malignant lymphoma, particularly in the 3rd - 4th year after initiating MTX therapy.

Evaluation of the meropenem dosage and administration schedule in patients with bacteremia initial therapy.

BACKGROUND: The standard meropenem (MEPM) regimen allowed by insurance in Japan is 0.5 g two or three times a day. Differences in dosages and administration schedules in Japan were evaluated. METHODS: Patients with bacteremia for whom MEPM was used as the initial treatment at our institution between 2016 and 2021 were included. We retrospectively investigated patients classified into two groups: those treated according to severe infections (high-dose groupand others (low-dose group). After propensity score matching, we compared the probability of achieving free drug blood levels above the minimum inhibitory concentration (MIC) in 24 h (%fT > MIC) and outcomes. RESULTS: The probability of 100% fT > MIC was significantly higher in the high-dose group (96.4% vs 74.5%, odds ratio [OR] = 0.3, 95% confidence interval [CI] = 0.2-0.4, P = < 0.001). Regarding outcomes, the 30-day mortality rate was significantly lower in the high-dose group (1.4% vs. 11.4%, OR = 8.0, 95% CI = 1.5-43.7, P = 0.019). CONCLUSIONS: To improve outcomes in patients with bacteremia treated with MEPM, support for appropriate antimicrobial use is necessary for compliance with the dosage and administration schedule according to severe infections in initial treatment.

Effectiveness of Noncertified Pharmacist-Led Antimicrobial Stewardship Programs in a Medium-Sized Hospital Without an Infectious Disease Specialist: A Retrospective Pre-Post Study.

Background: Few studies have reported the outcomes of antimicrobial stewardship programs (ASPs) implemented without infectious disease (ID) physician or pharmacist specialists. We implemented interventions that included providing antimicrobial optimization recommendations through a pharmacist-led team using prospective audit and feedback. This study evaluated different types of interventions and their impact on the outcomes of ASPs in a medium-sized hospital without ID specialists. Methods: This retrospective pre-post study included adult inpatients treated with intravenous antimicrobials between April 2016 and March 2020. Outcome (eg, length of hospital stay [LOS], drug cost) and process measures (eg, type of intervention, length of therapy) were compared between 2 time periods: pre-ASP (April 2016-March 2018) and post-ASP (April 2018-March 2020). Results: We included 5419 and 5634 patients in the pre- and post-ASP periods, respectively. The most common types of interventions were adjusting length of therapy (49.5%), additional laboratory tests (27.1%), antimicrobial change (16.2%), and dosage of antimicrobial (7.1%). After ASP implementation, LOS significantly decreased (14.8 vs 13.8 days, P < .01), along with the length of therapy, empirical use of antipseudomonal and anti-methicillin-resistant Staphylococcus aureus drugs, and number of days to de-escalation. No significant differences were noted in 30-day mortality, 30-day readmission, or de-escalation rates. On average, the antimicrobial cost per hospitalization decreased from US$173.03 to US$120.66. Conclusions: Pharmacist-led ASP interventions that focus on the length of therapy have the potential to reduce LOS in hospitals without ID specialists. Overall, this study showed that ASPs can be effectively implemented in medium-sized hospitals without ID specialists.

Risk of a second cancer and infection in patients with indolent B-cell lymphoma exposed to first-line bendamustine plus rituximab: A retrospective analysis of an administrative claims database.

Bendamustine has a potent immunosuppressive effect because it causes T-cell lymphopenia, which might lead to a second primary malignancy (SPM) and would increase the risk of infection. Using the Medical Data Vision administrative claims database, we compared the cumulative incidence of SPM, infections within 6 months, and overall survival (OS) among untreated patients with indolent B-cell lymphomas (iBCL) who received rituximab-based chemotherapy between 2009 and 2020. Patients with grade 3b follicular lymphoma or a previous history of malignancy were excluded. Eligible 5234 patients were assigned to three cohorts: rituximab monotherapy (N = 780), RCHOP/RCVP/RTHPCOP (doxorubicin replaced with pirarubicin) (N = 2298), or bendamustine/rituximab (BR) (N = 2156). There were 589 recorded SPMs, of which myelodysplastic syndromes were the most common (1.7%). The cumulative incidence of SPM was significantly higher in patients treated with BR than in those treated with rituximab monotherapy (p < 0.01) or RCHOP/RCVP/RTHPCOP (p < 0.0001): the 5-year cumulative incidence function was 18.1%, 12.5%, and 12.9%, respectively. In the Fine-Gray subdistribution hazards model, BR showed a significantly higher cumulative incidence of SPM than RCHOP/RCVP/RTHPCOP (subhazard ratio, 1.33; 95% confidence interval [CI], 1.10-1.61). Furthermore, in sensitivity analysis, a nested case-control study using an entire cohort showed consistent results: the SPM odds ratios (95% CI) of first-line bendamustine, bendamustine after first-line, and any-line bendamustine were 1.43 (1.14-1.78), 1.26 (0.96-1.64), and 1.33 (1.09-1.62), respectively. Regarding infections, adjusted odds ratios (95% CI) of BR compared to RCHOP/RCVP/RTHPCOP were as follows: cytomegalovirus infection, 13.7 (4.88-38.4); bacterial pneumonia, 0.63 (0.50-0.78); and pneumocystis pneumonia, 0.24 (0.11-0.53). There was no significant difference in OS between RCHOP/RCVP/RTHPCOP and BR in patients with follicular, mantle cell, marginal zone, or lymphoplasmacytic lymphomas. In conclusion, treatment strategies that consider the risk of SPM and infections after chemotherapy are warranted in patients with iBCL.

Effects of population age structure on parenteral antimicrobial use estimations.

Antimicrobial use (AMU) is conventionally reported as unadjusted defined daily doses (DDDs) or population-adjusted DDDs per 1000 inhabitants per day (DID). DID is frequently used to monitor national AMU trends, this metric does not intrinsically take temporal changes in population age structure into account. We examined the effects of population age structure on DID estimates of parenteral AMU in Japan, and predicted future trends in DDDs based on population projections. Parenteral AMU data from 2013 to 2018 were acquired from a national claims database. We assessed temporal trends in parenteral AMU by age group (children aged < 15 years, working-age persons aged 15-64 years, and older persons aged ≥ 65 years) using both DID and DDDs. In addition, we modeled DDD predictions based on age-specific population projections from 2019 to 2030. DID values for older persons were 8.08-10.15 times and 5.43-5.63 times higher than in children and working-age persons, respectively. DID was stable, but DDDs increased in older persons. The prediction models showed that DDDs will continue to increase until 2030 if DID remains steady or decreases. DID estimates were skewed by the older population. More rigorous antimicrobial stewardship efforts targeting geriatric care are needed to counter the aging-associated increase in AMU.

Association between Carbapenem Consumption and Clinical Outcomes in an In-Hospital Setting: Analysis of a Japanese Nationwide Administrative Database in 2020.

This study aimed to clarify the relationship between carbapenem consumption and clinical outcome using the diagnosis procedure combination (DPC) payment system database (2020) published by the Ministry of Health, Labour, and Welfare of Japan. This study divided 5316 medical facilities subject to aggregation into five facilities and calculated the median values, including facility characteristics, clinical outcomes, and carbapenem consumption. Next, a correlation analysis was performed between carbapenem consumption and clinical outcome, as well as a multiple regression analysis between carbapenem consumption as the dependent variable and clinical outcome, bed size, and proportion of patients by disease as independent variables. Additionally, three clinical outcomes available from the DPC payment system database were selected, including cure, readmission within 4 weeks, and the average length of stay. This study revealed no relationship between carbapenem consumption and clinical outcome in university hospitals and university hospital-equivalent community hospitals; however, a relationship was suggested in the community, DPC-prepared, and non-DPC hospitals. University hospitals and university hospital-equivalent community hospitals with a high consumption of carbapenems may need to reconsider the classification because of the limited number of facilities in this classification.

Cost and healthcare utilization of methicillin-resistant Staphylococcus aureus bacteremia estimated from linked antimicrobial resistance surveillance and hospital claims data in Japan.

Objective: To compare the incremental costs and healthcare utilization of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with those of methicillin-susceptible S. aureus (MSSA) bacteremia. Design: Retrospective cohort study using data from April 2014 to March 2015. Setting: Antimicrobial resistance surveillance and hospital claims data from 16 Japanese hospitals. Patients: The study included 73 patients with S. aureus bacteremia: 23 with MRSA and 50 with MSSA. Methods: MRSA bacteremia was identified using blood cultures and drug-susceptibility tests. MRSA- and MSSA-related medical practices were evaluated. The costs were calculated and compared. All the medical costs were classified into empirical and definitive therapy periods and expressed in Japanese yen (JPY, 1 USD = 106 JPY). Additionally, costs at aggressive and passive bacterial test-performing facilities were compared. Results: No significant differences existed in MRSA-related resource use per patient episode between MRSA and MSSA bacteremia during empirical therapy. However, during definitive therapy, in MRSA bacteremia compared with MSSA bacteremia, this difference was higher. The average MRSA-related costs of empirical therapy for MRSA and MSSA were 13,380 and 9,140 JPY (126 and 86 USD) per patient, and for definitive therapy, they were 69,810 and 29,510 JPY (659 and 278 USD) per patient, respectively. No significant differences were noted. Conversely, the average examination costs during definitive therapy differed significantly: 9,740 vs 3,850 JPY (92 vs 36 USD), respectively (P = .0294). Furthermore, the incremental costs in aggressive facilities were lower for the definitive therapy period than those in passive facilities. Conclusions: In the definitive therapy period, MRSA bacteremia had higher incremental costs and greater use of healthcare resources. In addition, the incremental costs in aggressive facilities were lower than those in passive facilities.

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.

Search for Indexes to Evaluate Trends in Antibiotic Use in the Sub-Prefectural Regions Using the National Database of Health Insurance Claims and Specific Health Checkups of Japan.

The evaluation indexes of antimicrobial use (AMU) in sub-prefectural regions have not been established because these regional units are susceptible to the effects of population inflows and outflows. We defined the difference in AMU calculated each year as a new evaluation index and compared the AMU of secondary medical areas with those already reported for Japan and each prefecture. Patients/1000 inhabitants/day (PID) for oral antibiotics in 2013 and 2016 were calculated using the National Database of Health Insurance Claims and Specific Health Checkups. ΔPID was defined as the difference between the PIDs in 2013 and 2016. Differences in AMUs for Japan and prefectures that have already been published were also calculated, and the concordance rate with ΔPID in each secondary medical area was evaluated. Antibiotics and age groups with less than 50% concordance between secondary medical area and previously reported AMU changes were observed. This revealed that even at the secondary medical area level, which is more detailed than the prefectural level, the AMU changes were not consistent. Therefore, in order to appropriately promote measures against antimicrobial resistance, we suggest the necessity of not only surveying AMU at the national or prefectural levels but also examining sub-prefectural trends in AMU.

Exploration of Trends in Antimicrobial Use and Their Determinants Based on Dispensing Information Collected from Pharmacies throughout Japan: A First Report.

The purpose of this study was to evaluate the defined daily doses (DDD)/1000 prescriptions/month (DPM) as a new indicator that can be used in pharmacies, and to describe antimicrobial use patterns in pharmacies nationwide in Japan. Dispensing volumes, number of prescriptions received, and facility information were obtained from 2638 pharmacies that participated in a survey. DPM was calculated based on the dispensing volume and number of prescriptions, which are routinely collected data that are simple to use. Use of third-generation cephalosporins, quinolones, and macrolides in pharmacies that received prescriptions primarily from hospitals or clinics decreased from January 2019 to January 2021. In particular, the antimicrobial use was higher in otorhinolaryngology departments than in other departments, despite a decrease in the antimicrobial use. In the linear multiple regression analysis, otorhinolaryngology department was independently associated with the third-generation cephalosporin, quinolone, and macrolide prescription in all periods. This study reveals for the first-time trends in antimicrobial use through a new indicator using the volume of drugs dispensed in pharmacies throughout Japan. Antimicrobial use differed by the medical department, suggesting the need to target interventions according to the department type.

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.