BackgroundCord blood transplantation (CBT) is associated with a high risk of cytomegalovirus (CMV) infection. Letermovir (LTV) is a prophylactic agent against CMV reactivation after CBT, but data on its effectiveness and the incidence of late CMV reactivation after LTV discontinuation are limited. MethodsA single-center retrospective observational study was conducted in 79 adult CMV-seropositive CBT recipients who received their first transplant for acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome from February 2016 to September 2022. Outcomes were compared between 45 patients who received LTV prophylaxis and 34 patients who did not. ResultsThe cumulative incidence of CMV reactivation was significantly lower in patients who received LTV prophylaxis at both day 100 (11.1% vs. 82.4%, p < 0.001) and 1 year (45.3% vs. 82.4%, p < 0.001). The incidence of late CMV reactivation after LTV discontinuation was 34.2%. The cumulative incidence of CMV disease was comparable between patients who received and those who did not (0% vs. 8.8% at day 100, 2.3% vs. 8.8% at 1 year; p = 0.181). Multivariate analysis showed that LTV prophylaxis reduced the cumulative incidence of CMV reactivation (hazard ratio 0.20, 95% confidence interval 0.09 to 0.42, p < 0.001). ConclusionLTV prophylaxis is strongly associated with prevention of CMV reactivation after CBT. Due to the high incidence of late CMV reactivation, close monitoring is required after LTV discontinuation and extension of LTV prophylaxis beyond day 100 should be considered.

This study aimed to clarify the epidemiology and clinical features of tick bites in a Japanese spotted fever (JSF)-endemic area. The clinical records of patients with tick bites were retrospectively reviewed based on a survey conducted at Numakuma Hospital, Fukuyama City, Hiroshima, Japan, from 2016 to 2023. Data on basic characteristics, visit dates, residential address, exposure activities, tick-bite sites, and prophylactic antimicrobial prescriptions for each patient with tick bites were collected at the JSF hotspot hospital. A total of 443 patients with tick bites visited the hospital, of which data on 305 cases (68.8%) were reviewed. The median age of these patients was 71 years, with a higher proportion of women (63.0%). One-third of the patients had a preceding history of working in fields, whereas two-thirds had entered mountains or agricultural fields. Nearly 90% of the patients visited the hospital from April to August, and the most common bite sites were the lower extremities (45.1%). Most patients (76.1%) resided in the southern area of Numakuma Hospital. Nearly all patients were prescribed prophylactic antibiotics (minocycline in 87.8% of cases), and none subsequently developed JSF. Continued surveillance of patients with tick bites is warranted to better understand changes in the clinical impact of tick-borne diseases.

Ensitrelvir received approval in Japan for emergency use in the management of patients with coronavirus disease (COVID-19) in November 2022. A post-marketing surveillance (PMS) was conducted to evaluate the safety and effectiveness of ensitrelvir in Japanese real-world clinical practice, and the interim analysis results (data cutoff: July 20, 2023) have been published. This report describes the final analysis of the PMS for ensitrelvir in a Japanese clinical setting. A continuous survey method was used for this PMS (November 2022 to December 2023), and the observation period was 28 days from the start date of ensitrelvir administration. Patients with COVID-19 who received ensitrelvir for the first time and provided written informed consent to collect and use their data were included in this survey. The outcomes included patient characteristics, adverse drug reactions (ADRs), and time to resolution of COVID-19 symptoms. A total of 3760 and 3638 patients were included in the safety and effectiveness analysis sets, respectively. In the safety analysis set, the mean±standard deviation age was 43.6±17.7 years, 48.5% were male, 97.5% had mild COVID-19, and 73.4% had a vaccination history. Of the 379 ADRs reported, 374 were not serious and 5 were serious. None of the ADRs resulted in sequelae or death. The median time to resolution of fever and all symptoms was 36.0 and 156.0 hours, respectively. This PMS including >3000 patients suggested the safety and effectiveness of ensitrelvir for the treatment of patients with COVID-19 in Japan, with no new safety concern.

Tazobactam/ceftolozane (TAZ/CTLZ) and relebactam/imipenem/cilastatin (REL/IPM/CS) are expected to be effective for treating patients with antimicrobial-resistant infections, particularly gram-negative pathogens, but nationwide surveillance of these has not been investigated thoroughly in Japan. Pseudomonas aeruginosa (n=164), Klebsiella pneumoniae (n=141), and Haemophilus influenzae (n=156) isolated from respiratory infected patients in Japan from June 2019 through December 2020 provided by the Japanese Surveillance Committee were used. Antimicrobial susceptibility testing for TAZ/CTLZ, REL/IPM and comparator agents against isolates were carried out by broth microdilution methods according to the Clinical and Laboratory Standards Institute standard. The MIC50/90 of TAZ/CTLZ against P. aeruginosa and K. pneumoniae were 0.5/1 μg/mL and 0.25/0.5 μg/mL, those of REL/IPM were 0.25/1 μg/mL and 0.25/0.5 μg/mL, respectively, and all isolates were susceptible to both drugs. Susceptible rates for P. aeruginosa to IPM, ceftazidime (CAZ), and levofloxacin (LVFX) were 84.1, 87.8, and 76.8%, and those of K. pneumoniae to tazobactam/piperacillin, CAZ, and LVFX were 98.6, 98.6, and 95.0%, respectively. The MIC50/90 of TAZ/CTLZ for H. influenzae were 0.5/2 μg/mL, comparable to those of cefepime (CFPM), 1/2 μg/mL, but susceptible rate to TAZ/CTLZ and CFPM differed at 50.6 and 100%, respectively. This difference was estimated from the different clinical breakpoints between TAZ/CTLZ (0.5 μg/mL) and CFPM (2 μg/mL) and the epidemiological prevalence of β-lactamase negative ampicillin resistance (BLNAR), which is high in Japan but rare in the US/EU. Excellent in vitro activities for TAZ/CTLZ and REL/IPM against major causative gram-negative bacteria in RTI patients were observed.

BackgroundThe optimal timing and selection for blood culture collection in patients with acute cholangitis remains unclear. The relationship between common bile duct (CBD) diameter and the incidence of bacteremia in patients with CBD stones was elucidated. MethodsThis single-center retrospective observational study included patients with symptomatic CBD stones who presented to the emergency department between January 2019 and December 2021. The primary endpoint was the incidence of bacteremia. The patients were divided into two groups based on bacteremia complications. The patient characteristics and CBD diameters were compared between the two groups to identify factors associated with bacteremia. ResultsIn total, 270 patients were analyzed, with bacteremia identified in 134 patients (50 %), and the median CBD diameter was 10.7 mm (IQR, 8.7–13.7). The CBD diameter was significantly larger in patients with bacteremia (median 12.4 mm [IQR, 9.9–15.7] vs. 9.7 mm [IQR, 8.2–11.7], P < 0.001) in univariate analysis. Multivariable analysis revealed that the CBD diameter was significantly associated with bacteremia (OR: 1.25, 95 % CI: 1.14–1.38, P < 0.010). The area under the ROC curves, representing the diagnostic accuracy of CBD diameter for indicating bacteremia, was 0.72 (95 % CI, 0.66–0.78) with a cut-off value of 11.2 mm. ConclusionCBD dilation in patients with symptomatic CBD stones is significantly correlated with bacteremia. The CBD diameter cannot be assessed as the sole tool for detecting bacteremia; however, CBD dilation could be an indicator of bacteremia, assisting in the treatment strategy, regardless of the initial severity of cholangitis.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe illness and mortality in patients with immunodeficiency. Although vaccination has been recommended, the induction of protective antibodies by immunization, and thus the disease-preventive effect, has proven insufficient in immunodeficient patients, especially in those with predominantly antibody deficiency. A monoclonal antibody combination of tixagevimab and cilgavimab (TIX/CIL) was developed as a pre-exposure prophylaxis (PrEP). In this study, we investigated the post-PrEP increase in antiviral antibody titers and detailed the breakthrough infections that occurred despite PrEP in Japanese immunodeficient patients who had received TIX/CIL. MethodsBlood samples were collected before and after TIX/CIL administration between November 2022 and August 2023. Antibody titers against the S-protein of SARS-CoV-2 were measured to evaluate TIX/CIL-induced protection. Information regarding breakthrough infection, as evidenced by positive antigen and/or PCR tests, was collected. ResultsA significant increase in the anti-S antibody titer was observed in all 89 immunodeficient patients who had received TIX/CIL. However, 14 (16%) patients experienced breakthrough SARS-CoV-2 infections, of which one died of respiratory failure. ConclusionThe shift in the SARS-CoV-2 circulating strain might have reduced the efficacy of TIX/CIL, leading to an increased number of breakthrough infections.

IntroductionCorynebacterium species potentially develop high-level daptomycin resistance (HLDR) shortly after daptomycin (DAP) administration. We aimed to investigate the clinical and microbiological characteristics of HLDR Corynebacterium infections. MethodsWe first presented a clinical case accompanied by the results of a comprehensive genetic analysis of the isolate, and then performed a systematic scoping review. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, we searched for articles with related keywords, including “Corynebacterium”, “Daptomycin", and "Resistance”, in the MEDLINE and Web of Science databases from the database inception to October 25, 2024. Clinical case reports and research articles documenting the isolation of HLDR Corynebacterium species, defined by a minimum inhibitory concentration of DAP at ≥256 μg/mL, were deemed eligible for this review. ResultsOf 80 articles screened, seven case reports detailing eight cases of HLDR Corynebacterium infections, as well as five research articles, were included. C. striatum was the most common species (7/9 cases, 77.8%), and prosthetic device-associated infections accounted for 66.7% of the cases. Duration of DAP administration before the emergence of HLDR isolates ranged from 5 days to 3 months; three-quarters of the cases developed within 17 days. Three HLDR isolates were genetically confirmed to have an alteration in pgsA2. The majority of the patients were treated with either glycopeptides or linezolid, with favorable outcomes. In vitro experiments confirmed that C. striatum strains acquire the HLDR phenotype at higher rates (71% to 100%) within 24 hours of incubation, compared to other Corynebacterium strains ConclusionDAP monotherapy, especially for prosthetic device-associated infections, can result in the development of HLDR Corynebacterium. Additional research is warranted to investigate the clinical implications of this potentially proliferating antimicrobial resistant pathogen.

IntroductionWe evaluated the application of a newly improved enzyme immunoassay (EIA) kit, Mumps IgG Seiken®, by comparing antibody responses to different EIA kits, and neutralization tests (NTs), using clinical samples. MethodsSerum samples were collected before and 4-6 weeks after vaccination from 128 children who had no history of mumps or mumps vaccination. Using three different EIA kits, Mumps IgG Seiken®, a commercial kit from Enzygnost®, and an in-house kit, mumps-specific IgG antibodies were measured. Anti-mumps antibody responses between each of the EIA kits and NTs were evaluated. ResultsBefore vaccination, all samples were seronegative, except for three serum samples measured by Mumps IgG Seiken®, which exhibited equivocal. The antibody-positivity rates and equivocal rates of Mumps IgG Seiken® post-vaccination (71.1% and 23.4%, respectively) were comparable to those of Enzygnost® (74.2% and 19.5%, respectively). However, antibody-positivity and equivocal rates were significantly higher and lower than those of in-house kit (51.6% and 40.6%, respectively) (p<0.05). The concordance rates of the kit (68.7%) were comparable to those of Enzygnost® (71.1%) and higher than those of in-house-developed kit (58.6%) (p<0.05). The area under curve of the three EIA kits were 0.801, 0.804, and 0.859; however, the differences did not reach significance. Correlations of the values obtained using three EIA kits with NTs were 0.71, 0.61, and 0.78. ConclusionThe newly approved Mumps IgG Seiken® showed good correlation with NTs and had lower equivocal rates compared to in-house kit, comparable to Enzygnost®. This kit may be clinically acceptable for the evaluation of vaccine immunogenicity.

Patients with acute myeloid leukemia (AML) are at high risk of developing invasive fungal disease (IFD) with high morbidity and attributable mortality, including those who were received Venetoclax treatment. Patients with acute myeloid leukemia (AML) who were received Venetoclax treatment are at high risk of developing invasive fungal disease (IFD) with high morbidity and attributable mortality. Especially those Venetoclax, a new oral Bcl-2 inhibitor, targets tumor cells' ability to induce apoptosis. It is the only one which is approved by Food and Drug Administration (FDA) for treating newly diagnosed AML patients who are 75 years of age or older and are ineligible for intensive induction chemotherapy due to existing comorbidities. It has been shown that venetoclax-based regimens raise the risk of invasive fungal diseases (IFD) for AML patients in clinical practice. Because it can lead to prolonged and profound neutropenia in AML patients, with IFD incidence rates ranging from 5.1% to 32%, resulting in higher mortality rates. Because of drug-drug interactions between Venetoclax and partial antifungal agents, to choose anti-fungal prophylaxis and to adjust the dosage of agents rationally for AML patients seems crucial to physicians to those who are undergoing venetoclax-based chemotherapy. Therefore, this review aims to summary the mechanism and characteristic of IFD in AML patients and provide practical clinical suggestions and details for the prophylaxis of IFD in AML patients suffering Venetoclax-based treatment.