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.

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.

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.

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 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.

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.

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.

Long-term use of foscarnet is associated with an increased incidence of acute kidney injury in hematopoietic stem cell transplant patients: A retrospective observational study.

BACKGROUND: Foscarnet is an important drug for the treatment of cytomegalovirus infection in patients undergoing hematopoietic stem cell transplantation (HSCT). Foscarnet is often discontinued because of the development of acute kidney injury (AKI). Thus, the identification of factors leading to the development of AKI is beneficial. This study aimed to investigate the incidence of AKI and the factors influencing AKI development in HSCT patients treated with foscarnet. METHODS: This was a retrospective observational study. Patients who underwent HSCT and received foscarnet at the Department of Hematology, Osaka City University Hospital, were identified from medical records. The patients were classified into AKI and non-AKI groups, and the risk factors associated with AKI were evaluated. For continuous variables, receiver-operating characteristic (ROC) curve analysis was used to calculate the optimal cutoff value. RESULTS: Thirty-five patients (47 cases) were assigned to the AKI (51.1%, 24/47) and non-AKI groups (48.9%, 23/47). The AKI group had a significantly longer foscarnet administration period than the non-AKI group (p = 0.049). The appropriate cutoff value for the foscarnet administration period using the ROC curve was 27 days. The incidence of AKI was significantly higher in cases who received foscarnet for more than 27 days (11/14, 78.6%) compared to those who received less than 27 days (13/33, 39.4%) (odds ratio: 5.64, 95% confidence interval 1.32-24.2, p = 0.024). CONCLUSION: The incidence of AKI was 51.1% in HSCT patients treated with foscarnet, and foscarnet administration for more than 27 days may be associated with the incidence of AKI.

The Use of Topical Antibiotics Based on the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) Open Data in 2017.

The national action plan on antimicrobial resistance (AMR) in Japan emphasizes the importance of understanding antimicrobial use (AMU). Some studies have been conducted on oral and parenteral AMU in Japan. However, there are few studies on the use of topical antimicrobials, such as in dermatology and ophthalmology. Therefore, the purpose of this study was to investigate the use of topical AMU in Japan. Data on AMU in dermatology and ophthalmology were obtained from the 2017 National Database of Health Insurance Claims and Specific Health Checkups of Japan Open Data. The number of dermatological products used was 58,396,530 in 2017. The proportions of betamethasone/gentamicin and gentamicin used were 50.5% and 16.7%, respectively, whereas that of the ingredient quantity in gentamicin was 7.8%. It has been suggested that topical AMU should be evaluated based on the number of products being used. The number of ophthalmological products used was 24,655,653 in 2017, and the proportion of quinolones used was 95.9%. The high prescription rate of quinolones may cause an increase in quinolone resistance in the ophthalmologic field. Topical AMU, which is a potential "blind spot" in the measures against AMR, needs to be continuously monitored, together with systemic AMU.

The intended purpose and regional patterns of use of antibiotics for managing Clostridioides (Clostridium) difficile infections: An analysis of the National Database of Health Insurance Claims and Specific Health Checkups data of Japan.

INTRODUCTION: We previously showed the trend of antimicrobial use (AMU) for Clostridioides (Clostridium) difficile infection (CDI) using sales data. However, the details of the prescribing medical institutions and regional characteristics are unknown. Therefore, the purpose of this study was to clarify the details of the medical institutions where antibiotics for CDI were prescribed, and evaluate the AMU for CDI and the regional characteristics. METHODS: Antibiotics for CDI, including oral vancomycin (VCM), oral metronidazole (MNZ), and intravenous (IV) MNZ, were collected from the National Database of Health Insurance Claims and Specific Health Checkups (NDB) between 2013 and 2016. The PID (patients/1000 inhabitants/day) was used as an evaluation index for AMU. The PID was calculated using the claim types: inpatient, outpatient, dental, and pharmacy. The PID of each prefecture was calculated for inpatient claims in 2016. RESULTS: The AMU of oral VCM and IV MNZ were observed mainly in the inpatient claims. For oral MNZ, the total AMU in the outpatient and pharmacy claims accounted for approximately 80% per year throughout the study period. For inpatient claims of each prefecture in 2016, the PID of the antibiotics used for CDIs was approximately 3.5 times the difference between the highest and lowest prefectures. CONCLUSIONS: The AMU for CDI that takes into account the purpose of use was clarified by using the information of the prescribed medical institutions that were included in the NDB. Oral MNZ was used frequently in outpatients, and attention should be paid to the acquisition of resistance.

Bibliometric analysis of pharmacist's research on antimicrobial stewardship in Japan: an interrupted time series analysis on the implementation of the certification system for infection control pharmacists.

BACKGROUND: Pharmacist plays an integral role in promoting antimicrobial stewardship (AS) strategies by committing to the evidence-based activities in this field. The present study aims to document trends in actual achievements through bibliometric analysis and identify the future direction of pharmacists with expertise in AS by describing the characteristics of articles on AS written by Japanese pharmacists. METHODS: The study searched for articles written in Japanese and English on Ichushi-Web and MEDLINE, respectively, until December 2020 for published articles relevant to AS. The articles were classified into the seven groups according to content. Interrupted time series analysis (ITSA) was performed to identify the effect of the certification system for infection control pharmacy specialists (ICPSs) on the number of articles in Japanese. RESULTS: The study retrieved 476 and 145 titles from Ichushi-Web and MEDLINE, respectively, out of which 383 and 123 articles written in Japanese and English, respectively, were considered relevant to AS. A continued publication was found for Japanese articles written by pharmacists assigned to large-sized hospitals since 1998, whereas few articles in English were published until 2017. The most frequent content of articles in both languages was intervention (56.7 and 59.0%, respectively). ITSA indicated that the number of publication slightly increased before [ß1 = 1.33, 95% confidence interval (CI): - 0.62-3.28; P = 0.169] the implementation of the system. Moreover, the level (ß2 = 11.41, 95%CI: - 0.23-23.05; P = 0.054) increased after the implementation of the system, whereas the slope decreased (ß3 = - 2.07, 95%CI: - 4.16-0.03; P = 0.053). However, the changes were not statistically significant. CONCLUSION: The study identified the contribution of pharmacists by documenting trends in AS practice and by conducting bibliometric analysis. The implementation of the ICPS certification system positively influenced the trend of publications. Therefore, the study recommends that policymakers and stakeholders should promote and support the evidence-based activities for AS for pharmacists in small- to medium-sized hospitals.

Incidence of acute kidney injury after teicoplanin- or vancomycin- and piperacillin/tazobactam combination therapy: A comparative study using propensity score matching analysis.

INTRODUCTION: Combination therapy with vancomycin (VCM) and piperacillin/tazobactam (PIPC/TAZ) increases the risk of acute kidney injury (AKI). Teicoplanin (TEIC) has a lower risk of AKI than VCM. Currently, the difference in AKI risk after TEIC-PIPC/TAZ combination therapy and VCM-PIPC/TAZ combination therapy is controversial. This study aimed to compare AKI incidence after treatment with these two drug combinations using propensity score matching analysis. METHODS: This single-center cohort study used data extracted from patients' medical records. We included patients who received TEIC-PIPC/TAZ therapy (TEIC group) or VCM-PIPC/TAZ therapy (VCM group). After propensity score matching, AKI incidence, AKI stage, 30-day mortality, and time to AKI incidence were compared between the groups. RESULTS: After propensity score matching, 94 patients were matched in each group. AKI incidence was significantly lower in the TEIC group than in the VCM group (10.6% vs. 23.4%, odds ratio [95% confidence interval]: 0.39 [0.17-0.88], p = 0.03). AKI stage, 30-day mortality, and time to AKI incidence were not significantly different between the groups. CONCLUSIONS: This study suggested that AKI incidence may be lower in patients undergoing combination therapy with TEIC-PIPC/TAZ than in those receiving therapy with VCM-PIPC/TAZ. To prevent the occurrence of AKI, clinicians may need to choose TEIC instead of VCM for patients receiving PIPC/TAZ.

Trends in Antipseudomonal Agent Use Based on the 2006 to 2015 Sales Data in Japan.

Pseudomonas aeruginosa resistance is a major issue worldwide. Drug resistance is related to inappropriate antibiotic use. Because antipseudomonal agents have a wide spectrum, they must be used appropriately. The purpose of this study was to clarify the trends in antipseudomonal agent use in Japan based on sales data from 2006 to 2015. The total antipseudomonal agent use was increased significantly (r = 0.10, Pfor trend = 0.00040). The proportion of fluoroquinolones use was the highest throughout the year, accounting for 88.6-91.4%. The use of piperacillin/tazobactam significantly increased. The increased use of these drugs may be due to the launch of higher doses and additional indications. On the other hand, for antipseudomonal agents, parenteral carbapenems use was 2.7-3.7%, but it has remained unchanged over the years. In Japan, permit and notification systems have been introduced to prevent the inappropriate use of parenteral carbapenems in medical institutions. It was speculated that these efforts suppressed the inappropriate use of parenteral carbapenems. This study clarified the trend of antipseudomonal agent use in Japan from 2006 to 2015. It is important to continue monitoring antipseudomonal agents use to conduct appropriate antimicrobial resistance measures.

An alternative index for evaluating AMU and anti-methicillin-resistant Staphylococcus aureus agent use: A study based on the National Database of Health Insurance Claims and Specific Health Checkups data of Japan.

INTRODUCTION: Anti-methicillin-resistant Staphylococcus aureus (MRSA) agents have different doses and administration periods. Thus, it is difficult to evaluate antimicrobial use (AMU) of anti-MRSA agents using defined daily doses per 1000 inhabitants per day (DID) or days of therapy per 1000 inhabitants per day (DOTID). This study aimed to evaluate the relationship between anti-MRSA agent use and resistant bacteria using the number of patients per 1000 inhabitants per day (PID) as an alternative index of AMU. METHODS: AMU data for anti-MRSA agents were collected from the National Database of Health Insurance Claims and Specific Health Checkups (NDB) in 2016. The relationship between PID and DID or DOTID was evaluated. The number of patients with MRSA isolated was obtained from Japan Nosocomial Infections Surveillance, and their correlation with PID was analyzed. The rate of anti-MRSA agent use in each prefecture was investigated. RESULTS: PID showed a significant linear relationship with both DID and DOTID (all p < 0.0001). PID was significantly correlated with the number of patients with MRSA isolated. Additionally, the rate of anti-MRSA agent use was markedly different in each region. CONCLUSIONS: PID is not affected by doses and administration periods, and thus may be an alternative index for the selective pressure of antibiotics. Evaluating AMU using PID based on NDB data will help in the development of effective antimicrobial resistance measures.