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Abstract Background Although there is a growing concern and policy regarding infections or colonization caused by resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), the prognosis of MRSA infections compared to that of methicillin-susceptible Staphylococcus aureus (MSSA) infections remains controversial. Moreover, there have not been any studies comparing both the burden of disease and its impact on the healthcare economy between MRSA infection and colonization while adjusting for confounding factors. These comparisons are crucial for developing effective infection control measures and healthcare policies. We aimed to compare the disease and economic burden between MRSA and MSSA infections and between MRSA infection and colonization. Methods We retrospectively investigated data of 496 in-patients with MRSA or MSSA infections and of 1178 in-patients with MRSA infections or MRSA colonization from a university hospital in Japan from 2016 to 2021. We compared in-hospital mortality, length of stay, and hospital charges between in-patients with MRSA and MSSA infections and those with MRSA infections and MRSA colonization using multiple regressions. We combined surveillance data, including all microbiological test results, data on patients with infections, treatment histories, and clinical outcomes, to create the datasets. Results There was no statistically significant difference in in-hospital mortality rates between matched MRSA vs. MSSA infections and MRSA infection vs. colonization. On the contrary, the adjusted effects of the MRSA infection compared to those of MSSA infection on length of stay and hospital charges were 1.21-fold (95% confidence interval [CI] 1.03–1.42, P = 0.019) and 1.70-fold (95% CI 1.39–2.07, P

ABSTRACTMacrolide antibiotics such as clarithromycin (CLR) and azithromycin are the key drugs used in multidrug therapy for Mycobacterium avium complex (MAC) diseases. For these antibacterial drugs, drug susceptibility has been correlated with clinical response in MAC diseases. We have previously demonstrated the correlation between drug susceptibility and mutations in the 23S rRNA gene, which confers resistance to macrolides. Herein, we developed a rapid detection method using the amplification refractory mutation system (ARMS)–loop-mediated isothermal amplification (LAMP) technique to identify mutations in the 23S rRNA gene of M. avium. We examined the applicability of the ARMS–LAMP method to genomic DNA extracted from six genotypes of M. avium clinical isolates. The M. avium isolates were classified into 21 CLR-resistant and 9 CLR-susceptible strains based on the results of drug susceptibility tests; the 23S rRNA genes of these strains were sequenced and analyzed using the ARMS–LAMP method. Sequence analysis revealed that the 9 CLR-sensitive strains were wild-type strains, whereas the 21 CLR-resistant strains comprised 20 mutant-type strains and one wild-type strain. Using ARMS–LAMP, no amplification from genomic DNAs of the 10 wild-type strains was observed using the mutant-type mismatch primer sets (MTPSs); however, amplification from the 20 mutant-type strain DNAs was observed using the MTPSs. The rapid detection method developed by us integrates ARMS–LAMP with a real-time turbidimeter, which can help determine drug resistance in a few hours. In conclusion, ARMS–LAMP might be a new clinically beneficial technology for rapid detection of mutations.IMPORTANCEMultidrug therapy for pulmonary Mycobacterium avium complex disease is centered on the macrolide antibiotics clarithromycin and azithromycin, and resistance to macrolides is an important prognosticator for clinical aggravation. Therefore, it is important to develop a quick and easy method for detecting resistance to macrolides. Drug resistance is known to be correlated with mutations in macrolide resistance genes. We developed a rapid detection method using amplification refractory mutation system (ARMS)–loop-mediated isothermal amplification (LAMP) to identify a mutation in the 23S rRNA gene, which is a macrolide resistance gene. Furthermore, we examined the applicability of this method using M. avium clinical isolates. The rapid method developed by us for detection of the macrolide resistance gene by integrating ARMS–LAMP and a real-time turbidimeter can help in detection of drug resistance within a few hours. Since this method does not require expensive equipment or special techniques and shows high analytical speed, it would be very useful in clinical practice.

We have developed circular defects in 2-dimensional photonic crystal lasers that allow current injection for interconnected optical communications. However, when cleaving the sample to measure the output light, the output light intensity changes due to the cleaving position. In a previous study, we proposed a new end face structure called a convex edge structure. In this paper, we design the electron beam lithography patterns to fabricate this structure. With this design, it is possible to eliminate the effect of different cleaving positions and ensure that the cleavage tolerance is larger than the cleavage position error. We also develop the fabrication technology for this structure, fabricate samples, and measure the output light experimentally. The optical properties of the fabricated sample are similar to well-fabricated samples with normal cleavage edge faces. We are assured that these results contribute to future work such as accurate manufacturing and improving the end face configuration to obtain higher outputs.

Objectives: The potential hazards of extended-spectrum antibiotic therapy for patients with community-acquired pneumonia (CAP) with low risk for drug-resistant pathogens (DRPs) remain unclear; however, risk assessment for DRPs is essential to determine the initial antibiotics to be administered. The study objective was to assess the effect of unnecessary extended-spectrum therapy on the mortality of such patients. Methods: A post hoc analysis was conducted after a prospective multicenter observational study for CAP. Multivariable logistic regression analysis was performed to assess the effect of extended-spectrum therapy on 30-day mortality. Three sensitivity analyses, including propensity score analysis to confirm the robustness of findings, were also performed. Results: Among 750 patients with CAP, 416 with CAP with a low risk for DRPs were analyzed; of these, 257 underwent standard therapy and 159 underwent extended-spectrum therapy. The 30-day mortality was 3.9% and 13.8% in the standard and extended-spectrum therapy groups, respectively. Primary analysis revealed that extended-spectrum therapy was associated with increased 30-day mortality compared with standard therapy (adjusted odds ratio 2.82; 95% confidence interval 1.20-6.66). The results of the sensitivity analyses were consistent with those of the primary analysis. Conclusion: Physicians should assess the risk for DRPs when determining the empirical antibiotic therapy and should refrain from administering unnecessary extended-spectrum antibiotics for patients with CAP with a low risk for DRPs.

A non-filter virus inactivation unit was developed that can control the irradiation dose of aerosolized viruses by controlling the lighting pattern of a 280 nm deep-UV (DUV)-LED and the air flowrate. In this study, the inactivation properties of aerosolized SARS-CoV-2 were quantitatively evaluated by controlling the irradiation dose to the virus inside the inactivation unit. The RNA concentration of SARS-CoV-2 remained constant when the total irradiation dose of DUV irradiation to the virus exceeded 16.5 mJ/cm2. This observation suggests that RNA damage may occur in regions below the detection threshold of RT-qPCR assay. However, when the total irradiation dose was less than 16.5 mJ/cm2, the RNA concentration monotonically increased with a decreasing LED irradiation dose. However, the nucleocapsid protein concentration of SARS-CoV-2 was not predominantly dependent on the LED irradiation dose. The plaque assay showed that 99.16% of the virus was inactivated at 8.1 mJ/cm2 of irradiation, and no virus was detected at 12.2 mJ/cm2 of irradiation, resulting in a 99.89% virus inactivation rate. Thus, an irradiation dose of 23% of the maximal irradiation capacity of the virus inactivation unit can activate more than 99% of SARS-CoV-2. These findings are expected to enhance versatility in various applications. The downsizing achieved in our study renders the technology apt for installation in narrow spaces, while the enhanced flowrates establish its viability for implementation in larger facilities.

Abstract The prognostic significance of absolute lymphocyte count (ALC) and absolute neutrophil count (ANC) remains unclear in patients with postoperative pneumonia (POP). The study objectives were to investigate the prognostic effects of ALC and ANC in POP patients, and to evaluate the time courses of ALC and ANC during hospitalization. This post-hoc analysis of a single-center prospective observational study evaluated consecutive POP patients, and comparatively analyzed community-acquired pneumonia (CAP) patients to highlight features of POP. In total, 228 POP patients and 1027 CAP patients were assessed. Severe lymphopenia (ALC 7500 cells/μL) was associated with better survival, whereas CAP patients with neutrophilia tended to have a lower survival rate. Prolonged lymphopenia and delayed increase in neutrophils were characteristic time-course changes of non-survivors in POP. The time courses of ALC and ANC between survivors and non-survivors in POP trended differently from those in CAP. Our study showed that ALC and ANC at pneumonia diagnosis can serve as prognostic factors in POP patients. Differences in time-course changes of ALC and ANC between survivors and non-survivors may provide important information for future immunological research in pneumonia.

ABSTRACT: Objectives: The dissemination of difficult-to-treat carbapenem-resistant Enterobacterales (CRE) is of great concern. We clarified the risk factors underlying CRE infection mortality in Japan. Methods: We conducted a retrospective, multicentre, observational cohort study of patients with CRE infections at 28 university hospitals from September 2014 to December 2016, using the Japanese National Surveillance criteria. Clinical information, including patient background, type of infection, antibiotic treatment, and treatment outcome, was collected. The carbapenemase genotype was determined using PCR sequencing. Multivariate analysis was performed to identify the risk factors for 28-day mortality. Results: Among the 179 patients enrolled, 65 patients (36.3%) had bloodstream infections, with 37 (20.7%) infections occurring due to carbapenemase-producing Enterobacterales (CPE); all carbapenemases were of IMP-type (IMP-1: 32, IMP-6: 5). Two-thirds of CPE were identified as Enterobacter cloacae complex. Combination therapy was administered only in 46 patients (25.7%), and the 28-day mortality rate was 14.3%. Univariate analysis showed that solid metastatic cancer, Charlson Comorbidity Index ≥3, bloodstream infection, pneumonia, or empyema, central venous catheters, mechanical ventilation, and prior use of quinolones were significant risk factors for mortality. Multivariate analysis revealed that mechanical ventilation (OR: 6.71 [1.42–31.6], P = 0.016), solid metastatic cancers (OR: 5.63 [1.38–23.0], P = 0.016), and bloodstream infections (OR: 3.49 [1.02–12.0], P = 0.046) were independent risk factors for 28-day mortality. Conclusion: The significant risk factors for 28-day mortality in patients with CRE infections in Japan are mechanical ventilation, solid metastatic cancers, and bloodstream infections.

We report a case of a woman presenting with an erythematous finger nodule, with a history of exposure to tropical fish. The erythematous nodules subsequently spread proximally from the finger. Initial treatment with oral amoxicillin-clavulanate was unsuccessful, and she developed a drug eruption. Treatment with oral minocycline and thermotherapy was initiated, as we suspected infection with Mycobacterium marinum (M. marinum) from her history and clinical features. A culture from a skin biopsy from the finger grew M. marinum, confirming the diagnosis. There is no established treatment regimen for skin infections caused by M. marinum. In this case, it took time for cultures to confirm the diagnosis of nontuberculous mycobacterial infection. While it would be ideal to await culture results, we felt it was better for the patient to initiate treatment, and in M. marinum infections, minocycline is considered particularly effective. However, it was envisaged that this would result in a prolonged treatment course, leading to potential resistance. Thermotherapy was added in an attempt to shorten the treatment period. This regime was successful, and the patient has remained free of recurrence since. The early initiation of treatment for cutaneous non-tuberculous mycobacterial infection requires aggressive suspicion. Also, testing, including adequate sampling and culturing, is essential for an accurate diagnosis. Slow-growing mycobacteria may take several months to be definitively diagnosed, as they grow only under certain conditions. Therefore, thorough clinical history-taking and information sharing with the microbiology team are essential. Our case illustrates this, and we believe this has important educational value. [ABSTRACT FROM AUTHOR]

Abstract Background Prediction of inpatients with community-acquired pneumonia (CAP) at high risk for severe adverse events (SAEs) requiring higher-intensity treatment is critical. However, evidence regarding prediction rules applicable to all patients with CAP including those with healthcare-associated pneumonia (HCAP) is limited. The objective of this study is to develop and validate a new prediction system for SAEs in inpatients with CAP. Methods Logistic regression analysis was performed in 1334 inpatients of a prospective multicenter study to develop a multivariate model predicting SAEs (death, requirement of mechanical ventilation, and vasopressor support within 30 days after diagnosis). The developed ALL-COP-SCORE rule based on the multivariate model was validated in 643 inpatients in another prospective multicenter study. Results The ALL-COP SCORE rule included albumin ( 45 mmHg, 2 points), HCO3 − ( 2/3, 2 points; 1/2–2/3, 1 point). Patients with 4–5, 6–7, and ≥ 8 points had 17%, 35%, and 52% increase in the probability of SAEs, respectively, whereas the probability of SAEs was 3% in patients with ≤ 3 points. The ALL-COP SCORE rule exhibited a higher area under the receiver operating characteristic curve (0.85) compared with the other predictive models, and an ALL-COP SCORE threshold of ≥ 4 points exhibited 92% sensitivity and 60% specificity. Conclusions ALL-COP SCORE rule can be useful to predict SAEs and aid in decision-making on treatment intensity for all inpatients with CAP including those with HCAP. Higher-intensity treatment should be considered in patients with CAP and an ALL-COP SCORE threshold of ≥ 4 points. Trial registration This study was registered with the University Medical Information Network in Japan, registration numbers UMIN000003306 and UMIN000009837.

A general-purpose virus inactivation unit that can inactivate viruses was developed using deep ultraviolet (DUV) LEDs that emit DUV rays with a wavelength of 280 nm. The inside of the virus inactivation unit is a rectangular conduit with a sharp turn of 180° (sharp-turned rectangular conduit). Virus inactivation is attempted by directly irradiating the air passing through the conduit with DUV rays. The flow characteristics of air and virus particles inside the virus inactivation unit were investigated using numerical simulations. The air was locally accelerated at the sharp turn parts and flowed along the partition plate in the sharp-turned rectangular conduit. The aerosol particles moving in the sharp-turned rectangular conduit were greatly bent in orbit at the sharp turn parts, and then rapidly approached the partition plate at the lower part of the conduit. Consequently, many particles collided with the partition plates behind the sharp-turn parts. SARS-CoV-2 virus was nebulized in the virus inactivation unit, and the RNA concentration and virus inactivation rate with and without the emission of DUV-LEDs were measured in the experiment. The concentration of SARS-CoV-2 RNA was reduced to 60% through DUV-LED irradiation. In addition, SARS-CoV-2 passing through the virus inactivation unit was inactivated below the detection limit by the emission of DUV-LEDs. The virus inactivation rate and the value of the detection limit corresponded to 99.38% and 35.36 TCID50/mL, respectively.

Abstract Background In a previous retrospective observational study, a 3-day regimen of oseltamivir as post-exposure prophylaxis (PEP) for preventing transmission of influenza in wards was shown to be comparable to 7- to 10-day regimens provided index cases were immediately separated from close contacts. In order to confirm the efficacy of a 3-day regimen, we started to conduct a prospective, multi-center, single-arm trial. Methods This study is a prospective, multi-center, single-arm study designed by the Sectional Meeting of Clinical Study, Japan Infection Prevention and Control Conference for National and Public University Hospitals. Index patients with influenza are prescribed a neuraminidase inhibitor and are discharged immediately or transferred to isolation rooms. The close contacts are given oseltamivir as 75 mg capsules once daily for adults or 2 mg/kg (maximum of 75 mg) once daily for children for 3 days as PEP. All close contacts are monitored for development of influenza for 7 days after starting PEP. Discussion A 3-day regimen of oseltamivir as PEP has advantages over 7- to 10-day regimens in terms of costs, medication adherence and adverse effects. Trial registration The Institutional Review Board of Hokkaido University Hospital for Clinical Research, 015-0518, registered on November 11, 2016. UMIN Clinical Trials Registry, UMIN000024458, disclosed on October 31, 2016. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027881 . Japan Registry of Clinical Trials, jRCTs011180015, disclosed on March 14, 2019. https://jrct.niph.go.jp/latest-detail/jRCTs011180015

Intracortical microstimulation to the visual cortex is thought to be a feasible technique for inducing localized phosphenes in patients with acquired blindness, and thereby for visual prosthesis. In order to design effective stimuli for the prosthesis, it is important to elucidate relationships between the spatio-temporal patterns of stimuli and the resulting neural responses and phosphenes through pre-clinical animal studies. However, the physiological basis of effective spatial patterns of the stimuli for the prosthesis has been little investigated in the literature, at least partly because that the previously developed multi-channel stimulation systems were designed specifically for the clinical use. In the present, a 64-channel stimulation module was developed as a scalable tool for animal experiments. The operations of the module were verified by not only dry-bench tests but also physiological animal experiments in vivo. The results demonstrated its usefulness for examining the stimulus-response relationships in a quantitative manner, and for inducing the multi-site neural excitations with a multi-electrode array. In addition, this stimulation module could be used to generate spatially patterned stimuli with up to 4,096 channels in a dynamic way, in which the stimulus patterns can be updated at a certain frame rate in accordance with the incoming visual scene. The present study demonstrated that our stimulation module is applicable to the physiological and other future studies in animals on the cortical prostheses.

A desktop-type air curtain system (DACS) capable of being installed on a desk to protect healthcare workers from infectious diseases was developed. Pseudo-exhaled air containing aerosol particles emitted from a mannequin was blown toward the air curtain generated by the DACS. The aerosol blocking effect of the DACS was investigated using particle image velocimetry measurements. A scenario in which the arm of a patient in the blood collection room is placed on the gate of the DACS was also investigated. Air curtain flow was maintained inside the gate of the DACS. The aerosol particles approaching the DACS were observed to bend abruptly toward the suction port without passing through the gate, signifying that the aerosol particles were blocked by the air curtain flow. When the arm of the patient was placed on the gate of the DACS during blood collection, the airflow above the arm was disrupted. However, the aerosol blocking performance remained unaffected. We envisage that this system will be useful as an indirect barrier not only in the medical field but also in situations where sufficient physical distance cannot be maintained, such as at the reception counter.

Abstract 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 (

Abstract Background To clarify the molecular epidemiology of carbapenem-resistant Enterobacter cloacae complex (CREC) and the risk factors for acquisition of carbapenemase-producing E. cloacae complex (CPEC). Methods Using clinical CREC isolates detected in a Japanese university hospital over 4 years, carbapenemase production was screened with phenotypic methods. Carbapenemase genes were analysed by PCR and sequencing. Molecular epidemiological analyses were conducted with repetitive extragenic palindromic (REP)-PCR and multilocus sequence typing (MLST). CRECs were identified to the subspecies level by hsp60 sequencing. Whole-genome sequencing of plasmids was conducted. A case-control study was performed to identify risk factors for acquisition of CPEC among patients with CREC. Results Thirty-nine CRECs including 20 CPECs carrying bla IMP-1 were identified. Patients with CPEC had longer hospital stay before detection (26.5 days vs. 12 days, p = 0.008), a urinary catheter (odds ratio [OR], 5.36; 95% confidence interval [CI], 1.14–30.9; p = 0.023), or intubation (OR, 7.53; 95% CI, 1.47–53.8; p = 0.008) compared to patients without CPEC. Four genetically closely related CPEC clusters were observed, which showed that three of four CPEC clusters corresponded to E. asburiae (ST 53), E. hormaechei subsp. steigerwaltii (ST 113 and ST 1047) and E. cloacae subsp. cloacae (ST 513) by MLST and hsp60 sequencing. Seven representative plasmids shared structures with class I integron containing bla IMP-1 and IncHI2A replicon type. Conclusions A longer hospital stay, presence of a urinary catheter, and intubation are risk factors for CPEC acquisition. In addition to horizontal transmission of genetically indistinguishable CPECs, IncHI2A plasmid carrying bla IMP-1 appeared to be transferred among genetically different ECs.

Abstract Bloodstream infection (BSI) is a severe complication in immunocompromised patients. Next-generation sequencing (NGS) allows us to analyze comprehensively and quantitatively all microorganisms present in a clinical sample. Thirty-five pediatric patients (12 with BSI and 23 with suspected BSI/negative blood culture) were enrolled. Plasma/serum samples were used for sequencing and the results were compared with those from blood culture. Sequencing reads of bacteria isolated in blood culture were identified by NGS in all plasma/serum samples at disease onset. Bacteria isolated in blood culture were identical to the dominant bacteria by NGS in 8 of 12 patients. Bacterial reads per million reads of the sequence depth (BR) > 200 and relative importance values of the dominant bacteria (P1) > 0.5 were employed to determine causative pathogens. Causative pathogens were detected using these criteria in 7 of 12 patients with BSI. Additionally, causative bacteria were detected in the plasma/serum at 7 days before disease onset in two patients with catheter-related BSI. Causative pathogens, including virus, were identified in three patients with suspected BSI. Lastly, a total of 62 resistance genes were detected by NGS. In conclusion, NGS is a new method to identify causative microorganisms in BSI and may predict BSI in some patients.