石岡 春彦

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Pulmonary oedema is a feared and difficult to predict complication of severe malaria that can emerge after start of antimalarial treatment. Proinflammatory mediators are thought to play a central role in its pathogenesis.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>An exploratory study was conducted to evaluate the predictive capacity of biomarkers for development of clinical pulmonary oedema in patients with severe falciparum malaria at two hospitals in Bangladesh. Plasma concentrations of interleukin-6 (IL-6), IL-8, tumour necrosis factor (TNF), soluble Receptor of Advanced Glycation End-products (sRAGE), surfactant protein-D (SP-D), club cell secretory protein (CC16), and Krebs von den Lungen-6 (KL-6) on admission were compared with healthy controls. Correlations between these biomarker and plasma lactate and <jats:italic>Plasmodium falciparum</jats:italic> histidine-rich protein 2 (PfHRP2) levels were evaluated. Receiver Operating Characteristic (ROC) curves were constructed to assess the predictive capacity for clinical pulmonary oedema of the biomarkers of interest.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Of 106 screened patients with falciparum malaria, 56 were classified as having severe malaria with a mortality rate of 29%. Nine (16%) patients developed clinical pulmonary oedema after admission. Plasma levels of the biomarkers of interest were higher in patients compared to healthy controls. IL-6, IL-8, TNF, sRAGE, and CC16 levels correlated well with plasma PfHRP2 levels (<jats:italic>r</jats:italic><jats:sub>s</jats:sub> = 0.39; <jats:italic>P</jats:italic> = 0.004, <jats:italic>r</jats:italic><jats:sub>s</jats:sub> = 0.43; <jats:italic>P</jats:italic> = 0.001, <jats:italic>r</jats:italic><jats:sub>s</jats:sub> = 0.54; <jats:italic>P</jats:italic> &lt; 0.001, <jats:italic>r</jats:italic><jats:sub>s</jats:sub> = 0.44; <jats:italic>P</jats:italic> &lt; 0.001, <jats:italic>r</jats:italic><jats:sub>s</jats:sub> = 0.43; <jats:italic>P</jats:italic> = 0.001, respectively). Furthermore, IL-6 and IL-8 levels correlated well with plasma lactate levels (<jats:italic>r</jats:italic><jats:sub>s</jats:sub> = 0.37; <jats:italic>P</jats:italic> = 0.005, <jats:italic>r</jats:italic><jats:sub>s</jats:sub> = 0.47; <jats:italic>P</jats:italic> &lt; 0.001, respectively). None of the biomarkers of interest had predictive capacity for development of clinical pulmonary oedema.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>IL-6, IL-8, TNF, sRAGE, SP-D, CC16 and KL-6 cannot be used in predicting clinical pulmonary oedema in severe malaria patients.</jats:p> </jats:sec>

BACKGROUND: Evaluating the selective pressure of antimicrobials on bacteria is important for promoting antimicrobial stewardship programs (ASPs). The aim of this study was to assess the selective pressure of antimicrobials by evaluating their use (carbapenem [CBP] and CBP-sparing therapy) over time and the detection status of CBP-resistant organisms using multicenter data. METHODS: Among the facilities whose data were registered in the Japan Surveillance for Infection Prevention and Healthcare Epidemiology from 2017 to 2020, those that had data on the use of CBP and CBP-sparing therapy (fluoroquinolones [FQs], cefmetazole [CMZ], piperacillin-tazobactam [PIP/TAZ], ampicillin-sulbactam [ABPC/SBT], ceftriaxone/cefotaxime [CTRX/CTX], CAZ (ceftazidime), cefepime [CFPM], and aminoglycosides [AGs]) as well as on CBP-resistant Enterobacterales (CRE) and CBP-resistant Pseudomonas aeruginosa (CRPA) detection were included. Alcohol-based hand rubbing (ABHR) usage was also analyzed. Regression analyses, including multivariable regression analysis, were performed to evaluate trends. The association of antimicrobial use density (AUD) with CRE and CRPA detection rates was evaluated. RESULTS: In 28 facilities nationwide, CBP, FQ, CAZ, AG, and PIP/TAZ use decreased over the 3-year period, whereas the use of CMZ, ABPC/SBT, CTRX/CTX, CFPM, and ABHR as well as the rates of CRE and CRPA detection increased. The average AUD did not significantly correlate with CRE and CRPA detection rates. The multivariable regression analysis did not reveal any significant correlation between each AUD or ABHR and CRE or CRPA detection. CONCLUSION: CBP and ABHR use showed a decreasing and an increasing trend, respectively, while CRPA and CRE detection rates exhibited a gradual increase. The considerably low CRE and CRPA detection rates suggest that slight differences in numbers may have been observed as excessive trend changes. Further investigation is warranted to evaluate selective pressure while considering the characteristics of ASP and the mechanisms underlying resistance.

BACKGROUND: The cumulative antibiogram is essential to guide empirical therapy for infectious diseases and monitor the trend of antimicrobial resistance. However, the status of antibiogram generation at medical institutions in Japan is uncertain. METHODS: A web-based questionnaire survey was conducted in February 2023 on the status of antibiogram preparation among facilities participating in the Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE), an infection control surveillance system in Japan. RESULTS: The questionnaire collection rate was 19.6% (379/1931). Of all facilities, 47% (178/379) performed microbiological tests mainly in-house, while 53% (201/379) performed microbiological tests mainly outsourced. Of all facilities, 78% (296/379) prepared antibiograms. Of those without antibiograms, 33% (27/83) were considering the development in the future. Some facilities cited staff shortage as a barrier to preparing antibiograms. Of the 214 facilities with antibiograms that could use the J-SIPHE system to prepare antibiograms, 19% (41/214) were using the J-SIPHE system to prepare their antibiograms. CONCLUSIONS: One-quarter of the facilities that responded to the survey had not prepared antibiograms. Technical support for surveillance and awareness activity for using cumulative antibiograms might promote antibiogram preparation in Japan, which may improve antimicrobial stewardship and antimicrobial resistance measures.

The impact of the COVID-19 pandemic on the incidence of microbial infections and other metrics related to antimicrobial resistance (AMR) has not yet been fully described. Using data from Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE), a national surveillance database system that routinely collects clinical and epidemiological data on microbial infections, infection control practices, antimicrobial use, and AMR emergence from participating institutions in Japan, we assessed the temporal changes in AMR-related metrics before and after the start of the COVID-19 pandemic. We found that an apparent decrease in the incidence of microbial infections in 2020 compared with 2019 may have been driven primarily by a reduction in bed occupancy, although the incidence showed a constant or even slightly increasing trend after adjusting for bed occupancy. Meanwhile, we found that the incidence of Streptococcus pneumoniae dramatically decreased from April 2020 onward, probably due to stringent non-pharmaceutical interventions against COVID-19. Antimicrobial use showed a weak increasing trend, while the use of hand sanitiser at the included medical institutions increased by about 50% in 2020 compared with 2019.

The main objective of the study is to assess the impact of regional heterogeneity on the severity of COVID-19 in Japan. We included 27,865 cases registered between January 2020 and February 2021 in the COVID-19 Registry of Japan, to examine the relationship between the National Early Warning Score (NEWS) of COVID-19 patients on the day of admission and the prefecture where the patients live. A hierarchical Bayesian model was used to examine the random effect of each prefecture in addition to the patients' backgrounds. Additionally, we compared the results of two models; one model included the number of beds secured for COVID-19 patients in each prefecture as one of the fixed effects, and the other model did not. The results indicated that the prefecture had a substantial impact on the severity of COVID-19 on admission, even when considering the effect of the number of beds separately. Our analysis revealed a possible association between regional heterogeneity and increased/decreased risk of severe COVID-19 infection on admission. This heterogeneity was derived not only from the number of beds secured in each prefecture but also from other factors.