Journal of Infection and Chemotherapy最新文献

Background: Severe 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.

Methods: Blood 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.

Results: A 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.

Conclusion: The shift in the SARS-CoV-2 circulating strain might have reduced the efficacy of TIX/CIL, leading to an increased number of breakthrough infections.

Introduction: We 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.

Methods: Serum 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.

Results: Before 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.

Conclusion: The 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.

Background and objective: Inappropriate initial antimicrobial therapy has been associated with high mortality in patients with gram-negative bacilli bloodstream infections during febrile neutropenia following chemotherapy for hematological malignancies. The aim of this study is to determine this association in our hospital.

Methods: A single center, retrospective, cohort study of bloodstream infection due to gram-negative bacilli and febrile neutropenia was conducted. Clinical characteristics, microbiological etiology, antimicrobial resistance profile, empirical and targeted antibiotic therapy, intensive care unit admission, persistent bacteremia and mortality were analyzed.

Results: Of the 171 episodes of bloodstream infection due to gram-negative bacilli, empirical antimicrobial therapy was inappropriate in 43 episodes (25.1 %). There was a significant difference in mortality at 7 and 30 days between patients who received appropriate versus inappropriate empirical treatment (4.6 % versus 13.9 %, p = 0.04; 15.6 % versus 32.5 %, p = 0.016). Inappropriate empirical treatment (RR, 2.97 [95 % CI, 1.01-8.74]), shock at the time of febrile neutropenia diagnosis (RR, 6.5 [95 % CI, 1.83-23.05]) carbapenem-resistant microorganism (RR, 3.73 [95 % CI, 1.14-12.24]) and persistent bacteremia (RR, 84.6 [95 % CI, 11.3-629.4]) were associated with an increased mortality at 7 and 30 days. In the multivariate analysis, shock (RR, 4.85 [95 % CI, 2.10-11.65]) was independently associated with increased 30-day mortality, but inappropriate empirical antimicrobial therapy was not an independent prognostic determinant (RR, 1.66 [0.53-4.82]).

Conclusion: Shock at the time of febrile neutropenia diagnosis contributes to mortality in patients with gram-negative bacilli bloodstream infection, in this scenario, appropriate empirical antimicrobial therapy should be encouraged.

The term "hydatid disease" refers to echinococcosis. Echinococcosis is a zoonotic disease caused by the larval stage of the Echinococcus parasite. The disease is widespread in regions where the parasite is endemic, particularly in developing nations like India. However, there are only a couple of documented case studies of echinococcosis associated with hematological malignancy in the literature. We present an extremely uncommon case of a 36-year-old male who had liver hydatidosis and was diagnosed with acute myeloid leukemia (AML)-M1. The patient received treatment for acute myeloid leukemia (daunomycin, cytarabine, and 5-azacytidine), followed by management of hydatid disease after complete remission of acute leukemia. The patient underwent periodic evaluations for one year and exhibited satisfactory improvement.

This study aimed to clarify changes in antimicrobial prescribing trends in pediatric clinics before and after the chronic shortage of amoxicillin and amoxicillin-clavulanic acid from 2023 in Japan. Amoxicillin and amoxicillin-clavulanic acid have been in chronic short supply since May 24, 2023 due to increased demand. It is unclear whether this situation has changed the type of oral antimicrobials prescribed by clinics. A retrospective observational study was conducted to analyze antimicrobial prescriptions in pediatric clinics between January and December 2023. The data was collected using information available on a new platform, the Online Monitoring System for Antimicrobial Stewardship at Clinics (OASCIS). The period from March to May was defined as the pre-shortage period, and the period from June to August was defined as the post-shortage period. Antimicrobials were classified using the AWaRe classification proposed by the World Health Organization. The average prescription rate per AWaRe classification in the three months before and after the shortage was compared. A total of 28,888 oral antimicrobial prescriptions were collected. Due to the chronic shortage, the proportion of Access antimicrobials decreased from 53.9 % in the pre-shortage period to 46.8 % in the post-shortage period (p < 0.001). The proportion of Watch antimicrobials increased from 45.9 % to 52.8 % (p < 0.001). Among the Watch antimicrobials, prescriptions for third-generation cephalosporins increased from 18.8 % to 24.7 % (p < 0.001). The chronic shortage of amoxicillin and amoxicillin-clavulanic acid has led to the use of broad-spectrum antimicrobial agents for patients in pediatric clinics.

Biological false-positive reactions to non-treponemal syphilis tests occur under various conditions, including in patients with infectious mononucleosis. However, false-positive treponemal test results are rarely reported. We present three cases of Epstein-Barr virus-associated infectious mononucleosis that exhibited concurrent false-positive results in both treponemal and non-treponemal tests, effectively imitating syphilis serology. Notably, the false-positive treponemal test results were transient and persisted for more than 6 months before reverting to negative. This is atypical for true Treponema pallidum infection (syphilis), in which treponemal tests usually remain positive for life. This case series highlights the potential for misdiagnosis and emphasizes the importance of careful interpretation of syphilis serology results in the context of infectious mononucleosis. This is particularly important when typical syphilis symptoms are absent, as in our patients. The similarity in the clinical manifestations between infectious mononucleosis and syphilis, including sore throat, lymphadenopathy, rash, and hepatitis, further complicates the diagnostic process. Clinicians should consider recent Epstein-Barr virus-associated infectious mononucleosis when interpreting positive syphilis serology, especially in young adults presenting with mononucleosis-like symptoms. Follow-up serological testing is useful to avoid unnecessary treatment and potential patient mismanagement.

Objectives: There are limited information that need to do appropriate treatment including duration of antibiotic treatments, timing of urinary drainage and pathogenesis of bacteria in calculous pyelonephritis. In the present study, we investigated real-world data on clinical features and succeeded treatment strategies in calculous pyelonephritis cases in our hospital, then, aimed to make predictive model estimating duration of intravenous antibiotics treatment.

Methods: Participants were 163 consecutive patients diagnosed with calculous pyelonephritis who underwent antibiotics treatments between 2017 and 2023 in our in-patients' clinic. Candidates for explanatory variables that may affect duration of antibiotic treatments were age, gender, body mass index, stone location, stone size, septic status, blood culture, urine drainage, indwelling urethral catheter, diabetes mellitus and steroid intake.

Results: Duration of intravenous antibiotics treatment was 6 days in median (IQR: 4-8 days). Indwelling DJ stent or percutaneous nephrostomy were undergone in 74 (45.4 %) patients. Multiple regression analysis revealed that gender, age, indwelling urethral catheter, septic status and management of urine drainage independently affected essential duration of intravenous antibiotics treatment and regression coefficient estimates of those factors respectively were 0.998, 0.890, 2.487, 1.462, 1.293 with constant of 2.464.

Conclusions: Our preliminary multiple regression models for predicting duration of intravenous antibiotics treatment may be useful to judge the timing of changing treatment strategies for patients who would not improve at around estimated intravenous antibiotics treatment periods. If vital signs were stable, it may be acceptable to judge urine drainage from above the urinary stone at around two days after intravenous antibiotic treatments.

Background: Vaccination is the primary method of preventing influenza infection and complications in young children. We evaluated the efficacy and safety of a single dose of MEDI3250 (intranasal, quadrivalent, live attenuated influenza vaccine) in healthy Japanese children during the 2016/17 influenza season.

Methods: In this multicenter, randomized, double-blind, phase 3 study (jRCT2080223345), participants aged 2-18 years received MEDI3250 or placebo (2:1), stratified by age (2-6 years, 7-18 years). The primary and secondary endpoints were the incidence of confirmed symptomatic onset of influenza caused by a circulating wild-type strain or by a vaccine-matched strain, respectively. Safety outcomes included the incidence of adverse events (AEs) and vaccine-related AEs.

Results: Overall, 910 participants received MEDI3250 (n = 608) or placebo (n = 302). For the primary endpoint (regardless of the influenza subtype), the incidence of influenza onset was 25.5 % (MEDI3250) and 35.9 % (placebo); relative risk reduction, 28.8 % (95 % confidence interval, 12.5 %, 42.0 %). For the secondary endpoint (vaccine-matched strain), the incidence was 10.9 % (MEDI3250) and 17.2 % (placebo); relative risk reduction, 36.6 % (95 % confidence interval, 6.5 %, 56.8 %). Solicited AEs occurred in 67.6 % (MEDI3250) and 63.6 % (placebo). Most events were mild; nasal discharge was most common (59.2 % [MEDI3250] and 52.6 % [placebo]). Unsolicited AEs occurred in 36.0 % (MEDI3250) and 33.1 % (placebo). The most common unsolicited vaccine-related AE was diarrhea (2.3 %, both groups).

Conclusions: MEDI3250 had a greater preventive effect against influenza onset in Japanese children than placebo; no new safety signals were observed relative to previous clinical and post-marketing studies of MEDI3250.

Background: Few interventional studies of catheter-associated urinary tract infection (CAUTI) have been conducted to optimize indwelling urinary catheter (IUC) use in Japan.

Methods: The nurse-led, before-after study was conducted at a tertiary care center from June 2018 through May 2022. The intervention included 1) the provision of appropriate indications for IUC use, 2) prospective feedback to the primary care providers by ward nurses on unnecessary/inappropriate IUC use with two, separate interventional phases, the first involving intensive care units (ICU) only, the second involving ICU and general wards, and 3) proactive feedback by Infectious diseases physicians in the Infection Control department to the primary care providers regarding IUC discontinuation upon discharge from the ICU.

Results: During the first phase involving the implementation of the intervention only in the ICU, the indwelling urinary catheter-device utilization ratio (IUC-DUR) trend in the general wards decreased by 1.5 % (P = 0.01). However, the addition of the intervention to the general wards in the second phase led to a 2 % increase in the trend (P = 0.010). The CAUTI incidence in neither the ICU nor the general wards changed significantly.

Conclusions: Although providing feedback on IUC removal at discharge from the ICU and appropriate indications for urinary catheter insertion can reduce inappropriate urinary catheter use, the nurse-led intervention alone was inadequate for reducing the CAUTI incidence.

Introduction: Corynebacterium 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.

Methods: We 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.

Results: Of 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 %-100 %) within 24 h of incubation, compared to other Corynebacterium strains.

Conclusion: DAP 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.