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In this age of antimicrobial resistance (AMR), improving treatment using existing antibiotics is desirable. Extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) are high priority AMR pathogens according to the World Health Organization. Cephamycin-class beta- lactams are tolerant to hydrolysis by ESBL activity and have bactericidal effects on ESBL-E. The aim of the present study was to compare the in vitro minimum inhibitory concentration (MIC) of cefmetazole (CMZ) and flomoxef (FMOX) among ESBL-E strains. This was a retrospective study using microbiology laboratory data from Okayama University Hospital (Japan) from January 2014 to June 2022. The MIC was determined by broth microdilution method and the ESBL phenotypes were determined by double-disk method. Antimicrobial use density (AUD) data for CMZ and FMOX were also gathered. Annual proportions of ESBL-producing organisms in Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae complex were 20.4-30.6%, 3.5-13.7%, and 0-3.1%, respectively. The ESBL-producing bacteria with MIC levels ≤1 µg/mL for CMZ and FMOX ranged from 57 to 84% and 97 to 100%, respectively, for E. coli, and from 50 to 92% and 80 to 100%, respectively, for K. pneumoniae. E. cloacae strains showed MIC levels ≥32 µg/mL for both agents. The AUD ratio for CMZ to FMOX ranged from 5.31 to 12.27, with no apparent upward or downward trend. Proportions of ESBL-producing E. coli and K. pneumoniae strains with MIC ≤1 µg/mL were greater in FMOX than in CMZ. To corroborate the clinical superiority of FMOX in treating ESBL-E infections, a randomized controlled study, as well as pharmacokinetic/pharmacodynamic analysis, is required.

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Globally, the numbers of head and neck cancer (HNC) cases and related deaths have recently increased. In Japan, few studies have examined crude or age-adjusted HNC mortality rates. Therefore, this study aimed to determine the trends in crude and age-adjusted mortality rates for HNC per million individuals in Japan from 1999 to 2019. Data on HNC-associated deaths were extracted from the national death certificate database using the International Classification of Diseases, Tenth Revision (n = 156,742). HNC mortality trends were analysed using joinpoint regression models to estimate annual percentage change (APC) and average APC (AAPC). Among men, no significant change was observed in the age-adjusted death rate trend from 1999 to 2014; however, a marked decrease was observed from 2014 to 2019. No changing point was observed in women. Age-adjusted mortality rates continuously decreased over the 21-year period, with an AAPC of -0.7% in men and -0.6% in women. In conclusion, the overall trend in age-adjusted rates of HNC-associated deaths decreased, particularly among men, in the past 5 years. These results will contribute to the formulation of medical policies to develop targeted screening and prevention programmes for HNC in Japan and determine the direction of treatment strategies.

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BACKGROUND: It is unclear whether the s (-) form of esomeprazole (EPZ) has an improved safety profile when compared with its racemic form omeprazole (OPZ). We assessed the potential complications of these optical isomers when combined with cilostazol, clopidogrel, and prasugrel, which are frequently used concomitant medications. METHODS: Using two adverse event spontaneous reporting databases, Japanese Adverse Drug Event Report (JADER) and FDA Adverse Event Reporting System (FAERS), adverse event names for hemorrhage, venous/arterial embolization, and thrombus were obtained from the Medical Dictionary for Regulatory Activities. Reported odds ratios were calculated using a 2 × 2 contingency table, and a signal was considered present if the lower limit of the 95% confidence interval was >1. RESULTS: In combination with cilostazol, a hemorrhagic signal for OPZ in JADER and arterial emboli and thrombus signals for EPZ were detected in both databases. In combination with clopidogrel, OPZ showed arterial emboli and thrombus signals in JADER and venous/arterial emboli and thrombus signals in FAERS, while EPZ displayed arterial emboli and thrombus signals in FAERS. In contrast, when in combination with prasugrel, there were no adverse event signals in either database. CONCLUSION: This study has confirmed using big data, that EPZ, the optical isomer and racemic form of omeprazole, has the beneficial characteristics of being less sensitive to CYP, as was intended by its design.

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Objective Amid the global spread of antimicrobial resistance, antimicrobial stewardship should be further promoted in the clinical setting. Our previous study suggested an intra-week disproportion of discontinuation of broad-spectrum antibiotics. We therefore explored the generalization of this prescription trend by investigating the use of all intravenous antibiotics. Methods A retrospective, observational study. Patients Between January 1, 2018, and December 31, 2020, we collected data on the initiation and discontinuation of intravenous antimicrobials on each day of the week and on days after holidays at Okayama University Hospital, Japan. We compared the monthly antimicrobial prescription initiation and discontinuation using the Kruskal-Wallis test and Mann-Whitney U-test with Bonferroni correction as a post-hoc procedure. Results Data from 15,293 hospitalized cases were analyzed. The initiation of antimicrobials differed slightly among days of the week, although this trend was clinically insignificant. Compared with the initiations, antimicrobial discontinuations were disproportionately biased among the weekdays, tending to occur on Mondays (p<0.001) about twice as often as on other days. Similarly, antimicrobials were unevenly discontinued on the day after holidays compared to other days (p<0.001), with an approximately 2-fold difference. The use of antimicrobials in the hospital was thus unequally terminated on weekdays. Conclusion To further promote antimicrobial stewardship, clinicians should be aware of the influence of behavioral, environmental, and social factors on antimicrobial prescription, which is seemingly beyond medical indications.

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AIM: Amid the global aging, an establishment of healthcare policies for the aged population is a common issue to be addressed. However, few studies on centenarians have reported place and cause of death (PoD and CoD, respectively) as indicators of end-of-life care quality. This study aimed to analyze trends in PoD and CoD among centenarians in Japan. METHODS: Data from death certificates from Japanese vital statistics were analyzed; 205 513 deaths occurred among centenarians (aged ≥100 years) in Japan during the period from 2006 to 2016. PoD prevalence was calculated for each CoD. Trends in PoD prevalence were analyzed using the Joinpoint regression model. Changing points, annual percentage changes, and average annual percentage changes (AAPCs) were calculated to examine trends. RESULTS: The number of deaths more than doubled from 10 340 in 2006 to 26 427 in 2016. PoDs were composed of hospitals (52.7%), nursing homes (31.4%), own homes (13.6%) and others (2.2%). Dementia and old age increased rapidly as CoD. Proportions of hospital and home deaths decreased, with AAPCs of -2.3% (95% confidence interval [CI], -2.6 to -1.9) and -2.3% (95% CI, -3.2 to -1.4), respectively. Conversely, the proportion of deaths in nursing homes rapidly increased, with an AAPC of 6.8% (95% CI, 6.0-7.7). CONCLUSIONS: The results revealed changes in PoD among centenarians in Japan. Understanding these transitions is indispensable for health policy in aging societies. Geriatr Gerontol Int 2022; 22: 675-680.

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Febrile neutropenia (FN) is a serious side effect in patients undergoing cancer chemotherapy and frequently proves fatal. Since infection control is crucial in the management of FN, the antimicrobial agent cefozopran (CZOP) has been recommended but not approved for routine use in clinical care of FN in Japan. However, few studies of CZOP in the management of FN have used a thrice daily dose schedule. The aim of this study was to retrospectively compare the efficacy and safety of CZOP at a dose of 1 g three times daily to those of cefepime (CFPM) in the treatment of FN in our lung cancer patients. The response rates of the CZOP and CFPM groups were 89.5% (17/19 cases) and 83.0% (39/47 cases), respectively, with no significant difference between the two groups. The median duration of antimicrobial treatment was 6 days (4-10 days) in the CZOP group and 7 days (3-13 days) in the CFPM group, with no significant difference between groups. The incidence rates of adverse events were 21.1% (4/19 cases) in the CZOP group and 19.1% (9/47 cases) in the CFPM group. No adverse events of Grade 3 or higher were observed in either group. The findings of the present study suggest that CZOP administration at a dose of 1 g three times per day as an antimicrobial treatment alternative against FN.

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To promote antimicrobial stewardship, we studied antimicrobial prescription rates for uncomplicated cystitis, a common outpatient disease requiring antibiotic treatment. This multicenter retrospective study was performed from January 1, 2018, to December 31, 2020, in Japan, targeting outpatients aged ≥ 20 years whose medical records revealed International Classification of Diseases (ICD-10) codes suggesting uncomplicated cystitis (N300). The data of 1445 patients were collected and that of 902 patients were analyzed. The overall median patient age was 71 years and a proportion of those aged less than 50 years was 18.8% with a female dominance (82.6%). Antimicrobials were prescribed for 884 patients (98.0%) and a total of 623 patients (69.1%) were treated with broad-spectrum drugs, including fluoroquinolones (36.0%), third-generation cephalosporins (29.9%) and faropenem (3.1%). A logistic regression model revealed that the broad-spectrum agents were significantly prescribed for the older patients, male patients, and those who visited internists. Recurrence was observed in 37 (4.1%) cases, and the multivariate analysis suggested any of age, sex, or antimicrobial types were not associated with the recurrence. Collectively, approximately two-thirds of antimicrobials prescribed for uncomplicated cystitis were broad-spectrum agents. The present data would be an indicator for antimicrobial prescriptions in uncomplicated cystitis in Japan.

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BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of nosocomial and community infections, and vancomycin (VCM) is widely recommended as a first-line therapeutic drug. Minimum inhibitory concentrations (MICs) of VCM ≤2 µg/mL are defined as susceptible, but increases in these levels, known as "VCM MIC creep" have been reported. The aim of this study was to investigate VCM MIC creep during the promotion of a national antimicrobial stewardship campaign. METHODS: We collected data from 2013 to 2020 on S. aureus isolated at the clinical microbiology laboratory at Okayama University Hospital, Japan. We calculated the annual proportions of MRSA isolation rates by MIC levels for nosocomial and community samples and estimated annual percentage changes in the antimicrobial use density of the VCM. RESULTS: Of the 1,716 MRSA isolates, no strains showed intermediate or resistant ranges of VCM MIC levels. By 2020, the proportion of MRSA with an MIC of ≤0.5 µg/mL decreased to 35.4%, while that with an MIC of 1 µg/mL increased to 64.1% over time. The annual percentage changes of the VCM antimicrobial use density significantly increased without any trend change point (average 8.1%, p = 0.035). There was no clear correlation between the VCM AUD and annual proportion of nosocomial MRSA with MIC 1 µg/mL (correlation coefficient 0.48; p value = 0.24). CONCLUSION: We demonstrated a deteriorating situation of VCM MIC creep among MRSA strains isolated at our university hospital during the national antimicrobial stewardship campaign.

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To encourage and guide antimicrobial stewardship team (AST) activity and promote appropriate antibiotic use, we studied the impact of day of the week on the initiation and discontinuation of antibiotic administration. This was a multicenter observational study conducted at 8 Japanese hospitals from April 1 to September 30, 2019, targeting patients who underwent treatment with broad-spectrum antibiotics, such as anti-methicillin-resistant Staphylococcus aureus agents and anti-pseudomonal agents. We compared the weekly numbers of initiations and discontinuations of antibiotic prescription on each day of the week or on the days after a holiday. There was no statistical difference in the number of antibiotic initiations on both weekdays and the day after a holiday. However, antibiotic discontinuation was significantly higher from Tuesday onward than Monday and from the second day than the first day after a holiday. Similar trends were observed regardless of the categories of antibiotics, hospital and admission ward, and AST activity. This study suggests that broad-spectrum antibiotics tend to be continued during weekends and holidays and are most likely to be discontinued on Tuesday or the second day after a holiday. This was probably due to behavioral factors beyond medical indications, requiring further antimicrobial stewardship efforts in the future.

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In Japan, clinical and experimental studies addressing COVID-19 have been increasing in number since early February 2020, with many case reports being published. Concurrently, many notifications and guidelines have been issued from the government and academic societies. Taking optimal measures at the prefectural level as well as the national level is necessary to prevent the spread of COVID-19. Surveying and analyzing details of the incidences of infected persons in each prefecture is extremely important. This report describes the epidemiological characteristics of COVID-19 observed in Okayama Prefecture, followed by discussion of the direction of public health actions to be taken in the future. We reiterate the crucial importance of reinforcing and maintaining current public health measures, including rapid and detailed compilation of information related to infected persons and their surroundings, appropriate blocking of viral transmission, and early containment of infected persons, to minimize the spread of infection especially during the overlapping epidemic period of influenza in Okayama Prefecture.

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BACKGROUND: Osimertinib is an essential drug to treat non-small-cell lung cancer (NSCLC) harboring the epidermal growth factor receptor (EGFR) T790M mutation, and rebiopsy is necessary to detect this mutation. However, the significance of repeat rebiopsy in NSCLC patients whose first rebiopsy was T790M-negative remains unclear. We used a retrospective cohort to clarify this issue. METHODS: We reviewed the medical records of patients with NSCLC harboring EGFR mutations who underwent EGFR tyrosine kinase inhibitor (TKI) treatment at Okayama University Hospital between January 2015 and January 2017. RESULTS: Of 102 patients with EGFR-mutant NSCLC, 55 underwent rebiopsy after acquired resistance to prior EGFR TKIs. Pre-existing activating EGFR mutations were found in all 55 rebiopsied samples. Of the 55 samples, 25 were T790M-positive (45%). Among the remaining 30 patients (T790M-negative on the first rebiopsy), 21 underwent additional rebiopsies following interval therapy. Of the 21 patients, 11 were T790M-positive on the second rebiopsy and 1 on the third. We also evaluated the efficacy of osimertinib in patients who needed a repeat rebiopsy to detect the T790M mutation. Osimertinib showed good activity with an objective response rate of 50%. CONCLUSIONS: Repeat rebiopsy increases the ability to detect a secondary mutation (T790M) in EGFR.