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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.

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., (Copyright © 2021. Published by Elsevier Ltd.)

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., (© 2021. The Author(s).)

Purpose: Antimicrobial use (AMU) is estimated at the national level by using sales data (S-AMU) or insurance claims data (C-AMU). However, these data might be biased by generic drugs that are not sold through wholesalers (direct sales) and therefore not recorded in sales databases, or by claims that are not submitted electronically and therefore not stored in claims databases. We evaluated these effects by comparing S-AMU and C-AMU to ascertain the characteristics and limitations of each kind of data. We also evaluated the interchangeability of these data by assessing their relationship., Methods: We calculated monthly defined daily doses per 1,000 inhabitants per day (DID) using sales and claims data from 2013 to 2017. To assess the effects of non-electronic claim submissions on C-AMU, we evaluated trends in the S-AMU/C-AMU ratio (SCR). To assess the effects of direct sales of S-AMU, we divided AMU into generic and branded drugs and evaluated each SCR in terms of oral versus parenteral drugs. To assess the relationship between S-AMU and C-AMU, we created a linear regression and evaluated its coefficient., Results: Median annual SCRs from 2013 to 2017 were 1.046, 0.993, 0.980, 0.987, and 0.967, respectively. SCRs dropped from 2013 to 2015, and then stabilized. Differences in SCRs between branded and generic drugs were significant for oral drugs (0.820 vs 1.079) but not parenteral drugs (1.200 vs 1.165), suggesting that direct sales of oral generic drugs were omitted in S-AMU. Coefficients of DID between S-AMU and C-AMU were high (generic, 0.90; branded, 0.84) in oral drugs but relatively low (generic, 0.32; branded, 0.52) in parenteral drugs., Conclusions: The omission of direct sales information and non-electronically submitted claims have influenced S-AMU and C-AMU information, respectively. However, these data were well-correlated, and it is considered that both kinds of data are useful depending on the situation., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Regional-level measures can complement national antimicrobial stewardship programs. In Japan, sub-prefectural regions called secondary medical areas (SMAs) provide general inpatient care within their borders, and regional antimicrobial stewardship measures are frequently implemented at this level. There is therefore a need to conduct antimicrobial use (AMU) surveillance at this level to ascertain antimicrobial consumption. However, AMU estimates are generally standardized to residence-based nighttime populations, which do not account for population mobility across regional borders. We examined the impact of population in/outflow on SMA-level AMU estimates by comparing the differences between standardization using daytime and nighttime populations., Methods: We obtained AMU information from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. AMU was quantified at the prefectural and SMA levels using the number of defined daily doses (DDDs) divided by (a) 1,000 nighttime population per day or (b) 1,000 daytime population per day. We identified and characterized the discrepancies between the two types of estimates at the prefectural and SMA levels., Results: The national AMU was 17.21 DDDs per 1,000 population per day. The mean (95% confidence interval) prefectural-level DDDs per 1,000 nighttime and daytime population per day were 17.27 (14.10, 20.44) and 17.41 (14.30, 20.53), respectively. The mean (95% confidence interval) SMA-level DDDs per 1,000 nighttime and daytime population per day were 16.12 (9.84, 22.41) and 16.41 (10.57, 22.26), respectively. The nighttime population-standardized estimates were generally higher than the daytime population-standardized estimates in urban areas, but lower in the adjacent suburbs. Large differences were observed in the main metropolitan hubs in eastern and western Japan., Conclusion: Regional-level AMU estimates, especially of smaller regions such as SMAs, are susceptible to the use of different populations for standardization. This finding indicates that AMU standardization based on population values is not suitable for AMU estimates in small regions., Competing Interests: The authors have declared that no competing interests exist.

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, P for 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.

Background: In 2018, the Japanese medical reimbursement system was revised to introduce a fee for the implementation of an antimicrobial stewardship (AS) fee for pediatric patients. The purpose of this study was to evaluate physicians' prescription behavior following this revision., Methods: We conducted a retrospective observational study from January 1, 2017 to September 30, 2018 of pediatric (< 15 years) outpatients with upper respiratory tract infections (URIs). To assess the pattern of antibiotic prescription for the treatment of pediatric URIs before and after the introduction of the AS fee, we extracted data on pediatric URIs, diagnosed during the study period. Patients were divided based on whether medical facilities claimed AS fees. We defined antibiotic use as the number of antibiotics prescribed, and evaluated the proportion of each class to the total number of antibiotics prescribed. We also recorded the number of medical facilities that each patient visited during the study period., Results: The frequency of antibiotic prescription decreased after AS fee implementation, regardless of whether the facility claimed the AS fee, but tended to be lower in facilities that claimed the fee. Additionally, the frequency of antibiotic prescription decreased in all age groups. Despite the reduced frequency of antibiotic prescription, consultation behavior did not change., Conclusions: The AS fee system, which compensates physicians for limiting antibiotic prescriptions, helped to reduce unnecessary antibiotic prescription and is thus a potentially effective measure against antimicrobial resistance.

Background: Antibiotics are often prescribed inappropriately to patients with upper respiratory infection (URI) in ambulatory care settings; however, the economic burden of such prescription has not been quantitatively assessed. Here, we aimed to evaluate the additional cost of antimicrobial prescription for URI at the population level in Japan., Methods: We conducted a retrospective observational survey using longitudinal claims data between 2013 and 2016 obtained from JMDC Claims Database, which contains data from 5·1 million corporate employees and family members under the age of 65 years. Appropriateness of antibiotic prescription was assessed by a panel of six infectious disease physicians according to ICD-10 code in JMDC Claims Database. Total additional cost of antibiotic prescription for URI at the national level was estimated by weighting of age-structured population data., Results: The annual additional cost of inappropriate antibiotic prescription for URI was estimated at 423·6 (95% CI: 416·8-430·5) million USD in 2013, 340·9 (95% CI: 335·7-346·2) million USD in 2014, 349·9 (95% CI: 344·5-355·3) million USD in 2015, and 297·1 (95% CI: 292·4-301·9) million USD in 2016. Three classes of broad-spectrum oral antibiotics (third-generation cephalosporins, macrolides, and fluoroquinolones) accounted for > 90% of the total additional cost., Conclusions: Although a decreasing trend was observed, annual additional costs of inappropriate antibiotic prescriptions for URI could be a substantial economic burden in Japan. Appropriately prescribing broad-spectrum oral antibiotics might be an important issue to reduce unnecessary medical costs in Japanese ambulatory care.

In Japan, there is no national surveillance study of Clostridioides (Clostridium) difficile infection (CDI), and details about the epidemiology and treatment status of CDI are unknown. Additionally, clinical practice guidelines (CPGs) for CDI are published by four different institutions. All CPGs recommend that the antimicrobials, vancomycin (VCM) and metronidazole (MNZ), should be selected according to disease severity. However, the trends for VCM and MNZ use in Japan remain unclear. Therefore, this study was aimed at clarifying the secular trends for VCM and MNZ use based on sales data from 2006 to 2015 and discussing its impact on CDI status and drug costs. This is the first study to clarify the antibiotic use trends for CDI treatment. We found that the total use increased over time (r = 0.0013, P for trend  < 0.0001). While VCM use significantly decreased (r = -0.0003, P for trend  = 0.0002), MNZ use increased (r = 0.0017, P for trend  < 0.0001). These results show that although treatment for CDI was in line with CPGs, CDI incidence might be on an increasing trend. Additionally, despite the increased total use, the total drug costs decreased by 55% ($ 25 million) from 2006 to 2015. It was also surmised that CDI treatment in compliance with CPGs would lead to a reduction in drug costs. Hence, to understand the epidemiology of CDI, it is important to continuously investigate the use of drugs used for CDI therapy.

Patterns of the use of anti-methicillin-resistant Staphylococcus aureus (MRSA) agents in Japan might be influenced by the launch of new anti-MRSA agents, the publication of relevant guidelines, and the increase in the number of generic medicines. However, as anti-MRSA agents are included in multiple anatomical therapeutic chemical classifications, such as glycopeptides and aminoglycosides, the trends of the use of individual anti-MRSA agents remain unclear. Here, we aimed to clarify the trends of anti-MRSA agent use in Japan from 2006 to 2015 based on sales data. Total anti-MRSA agent use was found to have significantly increased from 2006 to 2015 (P for trend  = 0.027, r = 0.00022). Individual trends for vancomycin (VCM), daptomycin, and linezolid (LZD) use showed significant increases, while those for arbekacin (ABK) and teicoplanin (TEIC) showed decreases. In addition, oral LZD use significantly increased, while there was no significant change in intravenous LZD use. The ratio of oral LZD use to total LZD use increased from 25.5% in 2006 to 39.9% in 2015. Meanwhile, TEIC and ABK use decreased, while VCM use increased, following the launch of generic medicines. These results might reflect the status of guideline compliance, the launch of new anti-MRSA agents, and the decline in the sales promotion of the original medicines. It is extremely important to investigate trends for the use of not only different antibiotic groups but also individual antibiotics to develop and implement antimicrobial resistance countermeasures.

Background: Inappropriate antibiotic prescribing is a cause of antimicrobial resistance. Acute Respiratory Tract Infections (ARTI) are common diseases for those antibiotics are most likely prescribed in outpatient setting., Objectives: To clarify factors associated with antibiotic prescribing for non-bacterial acute respiratory tract infections (NB-ARTI) and identify targets for reducing inappropriate prescribing for NB-ARTI in Japan., Methods: We conducted a retrospective, observational study using longitudinal claims data between April 2012 and June 2017. We assessed the rate of and factors associated with inappropriate antibiotic prescribing in outpatient settings for all NB-ARTI consultations included in the database., Results: The mean monthly antibiotic prescribing rate per 100 NB-ARTI consultations during the study period was 31.65. The monthly antibiotic prescribing rate per 100 NB-ARTI consultations decreased by 19.2% from April 2012 to June 2017. Adolescents (13-18 years) and adults of working age (19-29 and 30-39 years) were more likely prescribed antibiotics compared with elderly patients ≥ 60 years (aOR: 1.493 [95%CI: 1.482-1.503], 1.585 [95%CI: 1.575-1.595], and 1.507 [95%CI: 1.498-1.516], respectively). Outpatient clinics registered as internal medicine or ear, nose, and throat specialty were more likely to prescribe antibiotics than those of paediatric specialty or other specialties. Among health facility type, clinics without beds (aOR 2.123 [95%CI: 2.113-2.133]) and clinics with beds (aOR: 1.752 [95%CI: 1.7371-1.767]) prescribed significantly more antibiotics for NB-ARTI than outpatient departments inside general hospitals., Conclusions: Inappropriate antibiotic prescribing for NB-ARTI is common in Japan. Although the antibiotic prescribing rate has decreased, further interventions are required to promote antimicrobial stewardship (ASP). Education and awareness for adults and promotion of ASP among physicians in clinics without beds are key drivers to reduce inappropriate antibiotic prescribing in Japan., Competing Interests: The authors have declared that no competing interests exist.

The National Action Plan on Antimicrobial Resistance in Japan aims to achieve a 50% reduction in the use of broad-spectrum oral antimicrobials (cephalosporins, macrolides, and quinolones) from 2013 to 2020. Based on the national sales data for antimicrobials, we estimated the regional antimicrobial use (AMU) from 2013-2016 and evaluated the differences in the use of broad-spectrum oral antimicrobials among three regions in which differences had been identified previously. The AMU was standardized based on the defined daily dose (DDD) and described as the DDDs/1,000 inhabitants/day (DID). Annual combined total oral and parenteral AMU during 2013-2016 was 14.9, 14.5, 14.7, and 14.6 DID, respectively. The change in mean ± standard deviation in the total AMU at the prefectural level was - 0.2 ± 0.8 DID. Among the 47 prefectures, decreasing trends were observed in 34, while in the remaining 13 prefectures increasing trends were recorded. In 2016, no significant differences in the mean usage of oral cephalosporins among the three regions were observed. The mean usage of oral macrolides in the eastern (4.1 DID) was significantly lower than that in the central region (4.7 DID) (p = 0.009) and the western (4.8 DID) (p = 0.002). The mean usage of oral quinolones in the western (3.2 DID) was significantly higher than that in the eastern (2.3 DID) (p ＜ 0.001) and central (2.7 DID) (p = 0.001) regions. To determine appropriate targets for the implementation of antimicrobial stewardship for reducting the use of broad-spectrum oral antimicrobials, further studies are required to identify the reasons underlying these differences.

Bacteremic urinary tract infection (UTI) caused by Stenotrophomonas maltophilia rarely occurs in pediatric patients. We report a case of bacteremic UTI caused by S. maltophilia in an 8-month-old boy with a congenital ureteropelvic junction obstruction on the left side. The patient was brought to our hospital with a chief complaint of fever. He had undergone a nephrostomy tube insertion 4 months previously, and the tube had been removed 2 weeks before presentation at our hospital. He had a white blood cell count of 6,100/μL and a serum C-reactive protein level of 4.51 mg/dL. A microscopic urinalysis and Gram stain showed numerous Gram-negative bacilli and many leukocytes, and an ultrasonography showed grade 4 hydronephrosis of the left kidney. Based on these findings, we diagnosed the infant as having a complex UTI and started the intravenous administration of piperacillin/tazobactam. After 2 days, a urine culture showed Gram-negative bacilli (107 CFU/mL). Gram-negative bacilli were also cultured from two blood samples that were taken from different vessels at the time of admission. The Gram-negative bacilli were identified as S. maltophilia via the automated bacterial identification system. The patient recovered after a 2-week intravenous piperacillin/tazobactam treatment and subsequent oral treatment with trimethoprim-sulfamethoxazole. Since medical devices are susceptible to contamination with S. maltophilia, we suspect that the nephrostomy tube was the most likely source of infection.