Understanding factors influencing vaccine-induced immunity in adolescents is important for optimizing COVID-19 vaccination strategies. Allergic diseases have been hypothesized to alter immune responses through Th2-dominant inflammation, but data regarding their impact on SARS-CoV-2 mRNA vaccine antibody production remain limited in real-world adolescent populations. The purpose of this study is to identify factors affecting SARS-CoV-2 antibody titers after mRNA vaccination in a general population of 16- to 17-year-olds.
Methods
This study analyzed data from 233 participants in the T-CHILD Study, a Japanese general birth cohort, who received their 17-year medical checkup between July 2021 and October 2023. Individuals with a history of COVID-19 or serological evidence of prior infection (positive for both S- and N-antibodies) were excluded. Associations between SARS-CoV-2 S-antibody titers and vaccination history, allergic diseases, and other variables were examined.
Results
Multivariate analysis revealed that only a higher number of vaccine doses was independently associated with higher SARS-CoV-2 antibody titers. No significant associations were found between antibody titers and vaccine type, the interval since the last vaccination, allergic diseases such as asthma, atopic dermatitis (AD), or food allergy, or with total serum IgE levels.
Conclusions
These findings suggest that adolescents with mild allergic diseases can mount sufficient immune responses to SARS-CoV-2 mRNA vaccines, supporting the safety and efficacy of vaccination in this population. (230 words)
{"title":"Does having allergic diseases affect SARS-CoV-2 antibody responses to mRNA vaccination in adolescents?","authors":"Mayako Saito-Abe , Kiwako Yamamoto-Hanada , Tatsuki Fukuie , Kensuke Shoji , Yukihiro Ohya","doi":"10.1016/j.jiac.2025.102893","DOIUrl":"10.1016/j.jiac.2025.102893","url":null,"abstract":"<div><h3>Background</h3><div>Understanding factors influencing vaccine-induced immunity in adolescents is important for optimizing COVID-19 vaccination strategies. Allergic diseases have been hypothesized to alter immune responses through Th2-dominant inflammation, but data regarding their impact on SARS-CoV-2 mRNA vaccine antibody production remain limited in real-world adolescent populations. The purpose of this study is to identify factors affecting SARS-CoV-2 antibody titers after mRNA vaccination in a general population of 16- to 17-year-olds.</div></div><div><h3>Methods</h3><div>This study analyzed data from 233 participants in the T-CHILD Study, a Japanese general birth cohort, who received their 17-year medical checkup between July 2021 and October 2023. Individuals with a history of COVID-19 or serological evidence of prior infection (positive for both S- and N-antibodies) were excluded. Associations between SARS-CoV-2 S-antibody titers and vaccination history, allergic diseases, and other variables were examined.</div></div><div><h3>Results</h3><div>Multivariate analysis revealed that only a higher number of vaccine doses was independently associated with higher SARS-CoV-2 antibody titers. No significant associations were found between antibody titers and vaccine type, the interval since the last vaccination, allergic diseases such as asthma, atopic dermatitis (AD), or food allergy, or with total serum IgE levels.</div></div><div><h3>Conclusions</h3><div>These findings suggest that adolescents with mild allergic diseases can mount sufficient immune responses to SARS-CoV-2 mRNA vaccines, supporting the safety and efficacy of vaccination in this population. (230 words)</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"32 1","pages":"Article 102893"},"PeriodicalIF":1.5,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Measuring vaccination's impact on health-related quality of life (HRQL) is fundamental for cost-effectiveness analyses and health technology assessments, yet pediatric data remain limited. This study measured HRQL impact from reactogenicity symptoms following inactivated influenza vaccination in Japanese children.
Methods
This prospective study used proxy-reported EuroQol-5 dimension youth (EQ-5D-Y) questionnaires to evaluate HRQL daily from pre-vaccination to 7 d post-vaccination per dose in children aged 4–15 years during the 2024–2025 influenza season. Quality-adjusted life day (QALD) loss per dose for the EQ-5D-Y was calculated to quantify the impact of reactogenicity after receiving the inactivated influenza vaccine. The severity of reactogenicity symptoms was classified using the adverse events following immunization (AEFI) grading scale (grades 0–4).
Results
Overall, 218 children received 381 doses of inactivated influenza vaccination. QALD loss (positive score indicates worse post-vaccination states) was −0.032 (first dose) and 0.012 (second dose). The mean QALD loss for first dose recipients was −0.038 (grade 0–1 AEFI) and −0.009 (grade 2–4 AEFI); second dose values were −0.004 (grade 0–1) and 0.085 (grade 2–4).
Conclusion
QALD loss within 1 week post-vaccination (either first or second dose) was negligible, confirming inactivated influenza vaccine safety in this population.
{"title":"Change of pediatric quality of life following inactivated influenza vaccination using EuroQol-5 dimensions-youth","authors":"Rika Suzuki, Takahiro Mori, Soshi Hachisuka, Tenshin Okubo, Naohiro Yamamoto, Hiroki Nishikawa, Masayuki Onaka, Sayaka Yoshida, Taito Kitano","doi":"10.1016/j.jiac.2025.102890","DOIUrl":"10.1016/j.jiac.2025.102890","url":null,"abstract":"<div><h3>Background</h3><div>Measuring vaccination's impact on health-related quality of life (HRQL) is fundamental for cost-effectiveness analyses and health technology assessments, yet pediatric data remain limited. This study measured HRQL impact from reactogenicity symptoms following inactivated influenza vaccination in Japanese children.</div></div><div><h3>Methods</h3><div>This prospective study used proxy-reported EuroQol-5 dimension youth (EQ-5D-Y) questionnaires to evaluate HRQL daily from pre-vaccination to 7 d post-vaccination per dose in children aged 4–15 years during the 2024–2025 influenza season. Quality-adjusted life day (QALD) loss per dose for the EQ-5D-Y was calculated to quantify the impact of reactogenicity after receiving the inactivated influenza vaccine. The severity of reactogenicity symptoms was classified using the adverse events following immunization (AEFI) grading scale (grades 0–4).</div></div><div><h3>Results</h3><div>Overall, 218 children received 381 doses of inactivated influenza vaccination. QALD loss (positive score indicates worse post-vaccination states) was −0.032 (first dose) and 0.012 (second dose). The mean QALD loss for first dose recipients was −0.038 (grade 0–1 AEFI) and −0.009 (grade 2–4 AEFI); second dose values were −0.004 (grade 0–1) and 0.085 (grade 2–4).</div></div><div><h3>Conclusion</h3><div>QALD loss within 1 week post-vaccination (either first or second dose) was negligible, confirming inactivated influenza vaccine safety in this population.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"32 1","pages":"Article 102890"},"PeriodicalIF":1.5,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145742289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nacubactam is a novel β-lactamase inhibitor with intrinsic antibacterial activity that shows therapeutic potential against carbapenemase-producing Enterobacterales when administered with β-lactam antibiotics. Pharmacokinetics/pharmacodynamics (PK/PD) analyses based on drug concentrations at the site of infection are recommended to better evaluate antibiotic efficacy. A new PD index, the instantaneous minimum inhibitory concentration (MICi), which dynamically reflects the changing susceptibility of β-lactams during co-administration with β-lactamase inhibitors, has recently been proposed. This study aimed to assess the efficacy of cefepime combined with nacubactam in a murine model of pneumonia using MICi-based PK/PD analysis in the lung epithelial lining fluid (ELF).
Methods
In vitro pharmacodynamic testing using the checkerboard method was conducted with two β-lactamase-producing Klebsiella pneumoniae strains. In vivo PK and PD studies were performed in neutropenic mice using both β-lactamase-producing and non-producing strains. Drug concentrations in plasma and ELF were measured, and MICi-based PK/PD analysis was conducted.
Results
In vitro, the MIC of cefepime decreased in a concentration-dependent manner with increasing nacubactam. In the murine model of pneumonia, cefepime monotherapy resulted in bacterial changes of 0.12–4.30 log10 CFU/lung, while the combination therapy reduced bacterial counts by −5.93 to −0.234 log10 CFU/lung. The percentage of time that free cefepime concentrations exceeded MICi (T > MICi) was highly correlated with bacterial reduction. The target T > MICi for maximal effect was estimated to be 29.3 %.
Conclusions
These findings support the utility of MICi-based PK/PD analysis for optimizing combination antibiotic therapy in pneumonia.
{"title":"Application of epithelial lining fluid drug concentrations to MICi-Based PK/PD modeling of cefepime/nacubactam in a murine model of CPE pneumonia","authors":"Yuki Mizukami , Mishu Takahashi , Kenta Suzuki , Shaoqing Duan , Shintaro Ikegami , Takuma Muraishi , Natsuki Satake , Yuko Okamoto , Yuki Igarashi , Yuki Enoki , Kazuaki Taguchi , Kazuaki Matsumoto","doi":"10.1016/j.jiac.2025.102889","DOIUrl":"10.1016/j.jiac.2025.102889","url":null,"abstract":"<div><h3>Introduction</h3><div>Nacubactam is a novel β-lactamase inhibitor with intrinsic antibacterial activity that shows therapeutic potential against carbapenemase-producing Enterobacterales when administered with β-lactam antibiotics. Pharmacokinetics/pharmacodynamics (PK/PD) analyses based on drug concentrations at the site of infection are recommended to better evaluate antibiotic efficacy. A new PD index, the instantaneous minimum inhibitory concentration (MIC<sub>i</sub>), which dynamically reflects the changing susceptibility of β-lactams during co-administration with β-lactamase inhibitors, has recently been proposed. This study aimed to assess the efficacy of cefepime combined with nacubactam in a murine model of pneumonia using MIC<sub>i</sub>-based PK/PD analysis in the lung epithelial lining fluid (ELF).</div></div><div><h3>Methods</h3><div><em>In vitro</em> pharmacodynamic testing using the checkerboard method was conducted with two β-lactamase-producing <em>Klebsiella pneumoniae</em> strains. <em>In vivo</em> PK and PD studies were performed in neutropenic mice using both β-lactamase-producing and non-producing strains. Drug concentrations in plasma and ELF were measured, and MIC<sub>i</sub>-based PK/PD analysis was conducted.</div></div><div><h3>Results</h3><div><em>In vitro</em>, the MIC of cefepime decreased in a concentration-dependent manner with increasing nacubactam. In the murine model of pneumonia, cefepime monotherapy resulted in bacterial changes of 0.12–4.30 log<sub>10</sub> CFU/lung, while the combination therapy reduced bacterial counts by −5.93 to −0.234 log<sub>10</sub> CFU/lung. The percentage of time that free cefepime concentrations exceeded MIC<sub>i</sub> (T > MIC<sub>i</sub>) was highly correlated with bacterial reduction. The target T > MIC<sub>i</sub> for maximal effect was estimated to be 29.3 %.</div></div><div><h3>Conclusions</h3><div>These findings support the utility of MIC<sub>i</sub>-based PK/PD analysis for optimizing combination antibiotic therapy in pneumonia.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"32 1","pages":"Article 102889"},"PeriodicalIF":1.5,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145723089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Previous reports have suggested an association between cytomegalovirus (CMV) infection and bacterial or fungal infections after allogeneic hematopoietic cell transplantation (HCT). This study aimed to examine the relationship between letermovir (LTV) prophylaxis and the incidence of bacteremia and invasive fungal infections.
Methods
Using a Japanese transplant registry database, we analyzed 19,531 patients who underwent their first allogeneic HCT from 2011 to 2022. Patients who initiated LTV prophylaxis within the first week post-transplantation were classified as the LTV group.
Results
A total of 4915 patients in the LTV group and 14,616 in the No LTV group were analyzed. The incidence of bacteremia by day 100 was significantly lower in the LTV group compared to the No LTV group (17.4 % vs. 21.7 %, P < 0.001). In the multivariate analysis, LTV prophylaxis (HR 0.75, 95 %CI: 0.69–0.81) was found to be significantly associated with a reduced risk of bacteremia, along with neutrophil engraftment. Age >50 years, male, non-remission status, alternative donors, higher values of the hematopoietic cell transplantation-comorbidity index, poor performance status, and grade II–IV acute graft-versus-host disease were associated with an increased risk of bacteremia. LTV was associated with a reduced risk of bacteremia both within 30 days (HR 0.74, 95 %CI: 0.68–0.81) and beyond 30 days (HR 0.76, 95 %CI: 0.66–0.89) after HCT. Conversely, it was not associated with the risk of invasive aspergillosis or candidemia.
Conclusions
LTV prophylaxis significantly reduced the risk of bacteremia. However, it was not associated with the risk of invasive fungal infections.
{"title":"Letermovir prophylaxis and risk of bacterial or fungal infection after allogeneic hematopoietic cell transplantation","authors":"Shun-ichi Kimura , Shunto Kawamura , Takashi Toya , Keiji Okinaka , Hiroki Hosoi , Naoyuki Uchida , Noriko Doki , Tetsuya Nishida , Masatsugu Tanaka , Yuta Hasegawa , Yoshinobu Kanda , Noboru Asada , Naoki Kurita , Hirohisa Nakamae , Tetsuya Eto , Makoto Yoshimitsu , Makoto Onizuka , Takahiro Fukuda , Marie Ohbiki , Yoshiko Atsuta , Kimikazu Yakushijin","doi":"10.1016/j.jiac.2025.102888","DOIUrl":"10.1016/j.jiac.2025.102888","url":null,"abstract":"<div><h3>Background</h3><div>Previous reports have suggested an association between cytomegalovirus (CMV) infection and bacterial or fungal infections after allogeneic hematopoietic cell transplantation (HCT). This study aimed to examine the relationship between letermovir (LTV) prophylaxis and the incidence of bacteremia and invasive fungal infections.</div></div><div><h3>Methods</h3><div>Using a Japanese transplant registry database, we analyzed 19,531 patients who underwent their first allogeneic HCT from 2011 to 2022. Patients who initiated LTV prophylaxis within the first week post-transplantation were classified as the LTV group.</div></div><div><h3>Results</h3><div>A total of 4915 patients in the LTV group and 14,616 in the No LTV group were analyzed. The incidence of bacteremia by day 100 was significantly lower in the LTV group compared to the No LTV group (17.4 % vs. 21.7 %, <em>P</em> < 0.001). In the multivariate analysis, LTV prophylaxis (HR 0.75, 95 %CI: 0.69–0.81) was found to be significantly associated with a reduced risk of bacteremia, along with neutrophil engraftment. Age >50 years, male, non-remission status, alternative donors, higher values of the hematopoietic cell transplantation-comorbidity index, poor performance status, and grade II–IV acute graft-versus-host disease were associated with an increased risk of bacteremia. LTV was associated with a reduced risk of bacteremia both within 30 days (HR 0.74, 95 %CI: 0.68–0.81) and beyond 30 days (HR 0.76, 95 %CI: 0.66–0.89) after HCT. Conversely, it was not associated with the risk of invasive aspergillosis or candidemia.</div></div><div><h3>Conclusions</h3><div>LTV prophylaxis significantly reduced the risk of bacteremia. However, it was not associated with the risk of invasive fungal infections.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"32 1","pages":"Article 102888"},"PeriodicalIF":1.5,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145723056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Listeria monocytogenes infection, known as listeriosis, is relatively uncommon. However, in elderly or immunocompromised patients, it can lead to severe manifestations such as meningitis and bacteremia, making it a clinically important disease. The primary route of transmission is through ingestion of contaminated food, and since a wide range of food items may be involved, close collaboration with public health authorities is essential for effective source identification.
Case report
We encountered 11 cases of Listeria monocytogenes bacteremia within a limited region over the course of one month. Whole-genome sequencing revealed that the isolates were highly genetically related. Notably, the patients resided in different municipalities, suggesting exposure to a widely distributed food source. However, under the current Japanese legal framework, bacteremia is not a notifiable condition, which hindered timely identification of the infection source.
Conclusion
This case series underscores challenges in both clinical practice and the public health system in Japan, highlighting how such rare, genetically related clusters of bacteremia, occurring within a short period and across multiple municipalities, can easily be overlooked under the current surveillance framework.
{"title":"A cluster of 11 cases of Listeria monocytogenes bacteremia in Kyoto, Japan","authors":"Hajime Tsuboi , Shin Matsubara , Yoshiyuki Kawahara , Kenji Konaka , Kaori Tamai , Daisuke Yokoi , Yoshihiro Tanabe , Naohisa Fujita , Satoru Shikata","doi":"10.1016/j.jiac.2025.102887","DOIUrl":"10.1016/j.jiac.2025.102887","url":null,"abstract":"<div><h3>Background</h3><div><em>Listeria monocytogenes</em> infection, known as listeriosis, is relatively uncommon. However, in elderly or immunocompromised patients, it can lead to severe manifestations such as meningitis and bacteremia, making it a clinically important disease. The primary route of transmission is through ingestion of contaminated food, and since a wide range of food items may be involved, close collaboration with public health authorities is essential for effective source identification.</div></div><div><h3>Case report</h3><div>We encountered 11 cases of <em>Listeria monocytogenes</em> bacteremia within a limited region over the course of one month. Whole-genome sequencing revealed that the isolates were highly genetically related. Notably, the patients resided in different municipalities, suggesting exposure to a widely distributed food source. However, under the current Japanese legal framework, bacteremia is not a notifiable condition, which hindered timely identification of the infection source.</div></div><div><h3>Conclusion</h3><div>This case series underscores challenges in both clinical practice and the public health system in Japan, highlighting how such rare, genetically related clusters of bacteremia, occurring within a short period and across multiple municipalities, can easily be overlooked under the current surveillance framework.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"32 1","pages":"Article 102887"},"PeriodicalIF":1.5,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-05DOI: 10.1016/j.jiac.2025.102886
Makoto Hayashi , Takuya Yokoe , Satoshi Matsukura
The clinical outcomes of nontuberculous mycobacterial pulmonary disease (NTM-PD) are largely influenced by nutritional status. However, specific nutritional intervention strategies for NTM-PD have not been established, making management challenging. This narrative review summarizes the immunopathology associated with mycobacterial infection and the effects of malnutrition on immune responses. It further examines the clinical impact of malnutrition and the nutritional characteristics of patients with NTM-PD, highlighting the significance of nutritional intervention. Additionally, we review the current knowledge on nutritional therapy for NTM-PD, drawing insights from approaches used in related conditions. Although nutritional support may improve patient outcomes and is clearly needed, evidence regarding its effectiveness remains limited. Consequently, incorporating nutritional assessment and individualized intervention into comprehensive care currently represents the best clinical practice.
{"title":"Nutrition in nontuberculous mycobacterial pulmonary disease: A narrative review","authors":"Makoto Hayashi , Takuya Yokoe , Satoshi Matsukura","doi":"10.1016/j.jiac.2025.102886","DOIUrl":"10.1016/j.jiac.2025.102886","url":null,"abstract":"<div><div>The clinical outcomes of nontuberculous mycobacterial pulmonary disease (NTM-PD) are largely influenced by nutritional status. However, specific nutritional intervention strategies for NTM-PD have not been established, making management challenging. This narrative review summarizes the immunopathology associated with mycobacterial infection and the effects of malnutrition on immune responses. It further examines the clinical impact of malnutrition and the nutritional characteristics of patients with NTM-PD, highlighting the significance of nutritional intervention. Additionally, we review the current knowledge on nutritional therapy for NTM-PD, drawing insights from approaches used in related conditions. Although nutritional support may improve patient outcomes and is clearly needed, evidence regarding its effectiveness remains limited. Consequently, incorporating nutritional assessment and individualized intervention into comprehensive care currently represents the best clinical practice.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"32 1","pages":"Article 102886"},"PeriodicalIF":1.5,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antibiotic-associated encephalopathy (AAE) is a rare but significant neurological complication of β-lactam antibiotics, particularly in patients with renal impairment. While cefepime, ceftazidime, and ceftriaxone are well-documented causes, cefmetazole (CMZ) has not been widely recognized for neurotoxicity. We report an 82-year-old Japanese man with end-stage renal disease on chronic hemodialysis who developed altered mental status and myoclonus five days after starting intravenous CMZ for prostatic abscess. Electroencephalography (EEG) revealed triphasic waves consistent with non-convulsive status epilepticus. Neuroimaging and cerebrospinal fluid analysis showed no evidence of infection or stroke. Symptoms resolved within 48 hours of CMZ discontinuation. A Naranjo score of 5 supported a diagnosis of CMZ-induced AAE. This case underscores the potential neurotoxicity of CMZ and emphasizes the importance of early recognition of AAE in patients with renal dysfunction.
{"title":"Antibiotic-associated encephalopathy induced by cefmetazole in a hemodialysis patient: Case report","authors":"Toshiyuki Nakanishi , Taku Harada , Satoshi Kutsuna","doi":"10.1016/j.jiac.2025.102882","DOIUrl":"10.1016/j.jiac.2025.102882","url":null,"abstract":"<div><div>Antibiotic-associated encephalopathy (AAE) is a rare but significant neurological complication of β-lactam antibiotics, particularly in patients with renal impairment. While cefepime, ceftazidime, and ceftriaxone are well-documented causes, cefmetazole (CMZ) has not been widely recognized for neurotoxicity. We report an 82-year-old Japanese man with end-stage renal disease on chronic hemodialysis who developed altered mental status and myoclonus five days after starting intravenous CMZ for prostatic abscess. Electroencephalography (EEG) revealed triphasic waves consistent with non-convulsive status epilepticus. Neuroimaging and cerebrospinal fluid analysis showed no evidence of infection or stroke. Symptoms resolved within 48 hours of CMZ discontinuation. A Naranjo score of 5 supported a diagnosis of CMZ-induced AAE. This case underscores the potential neurotoxicity of CMZ and emphasizes the importance of early recognition of AAE in patients with renal dysfunction.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"32 1","pages":"Article 102882"},"PeriodicalIF":1.5,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peripheral parenteral nutrition (PPN), administered via a peripheral intravenous catheter (PVC), can occasionally lead to bloodstream infections (BSIs). We previously reported that a prolonged daily infusion time of PPN and all intravenous fluids were risk factors for BSI development. In response, our institution implemented a recommendation to limit the average daily infusion time of PPN to <12 h and that of all intravenous fluids to <18 h. The aim of this study was to investigate whether the incidence of BSI in patients receiving PPN decreased following the implementation of these recommendations.
Methods
We retrospectively collected data from 714 patients who underwent PPN therapy via PVC at Fukujuji Hospital from August 2022 to July 2025. We compared the incidence of BSI during PPN therapy between the preintervention and postintervention periods.
Results
Among the 714 patients, 507 were in the preintervention group, and 207 were in the postintervention group. The proportion of patients who developed BSIs was significantly lower in the postintervention group than in the preintervention group (n = 2 [1.0 %] vs. n = 27 [5.3 %], p = 0.006). The crude BSI incidence rate decreased from 3.59 to 0.73 per 1000 infusion days. A multivariable Poisson regression model revealed that the postintervention period was associated with a significantly lower BSI incidence rate (adjusted incidence rate ratio: 0.190; 95 % confidence interval: 0.045–0.804; p = 0.024), corresponding to an approximately 81 % reduction in BSI incidence.
Conclusion
Shortening the average daily infusion time of PPN and all intravenous fluids may help prevent the development of BSIs.
外周静脉营养（PPN）通过外周静脉导管（PVC）给予，偶尔会导致血流感染（bsi）。我们之前报道过PPN每日输注时间延长和所有静脉输液是BSI发展的危险因素。作为回应，我们的机构实施了一项建议，将PPN的平均每日输注时间限制在12小时，所有静脉输液的平均每日输注时间限制在18小时。本研究的目的是调查在实施这些建议后，接受PPN的患者BSI的发生率是否降低。方法回顾性收集2022年8月至2025年7月在福大医院经PVC行PPN治疗的714例患者的资料。我们比较了干预前和干预后PPN治疗期间BSI的发生率。结果714例患者中干预前组507例，干预后组207例。干预后组发生脑梗死的患者比例显著低于干预前组（n = 2 [1.0%] vs. n = 27 [5.3%], p = 0.006）。粗BSI发生率从每1000天3.59下降到0.73。多变量泊松回归模型显示，干预后期间BSI发病率显著降低（调整后的发病率比：0.190；95%可信区间：0.045-0.804;p = 0.024），相当于BSI发病率降低了约81%。结论缩短PPN及所有静脉输液的平均每日输注时间有助于预防脑梗死的发生。
{"title":"Reducing the daily infusion time of peripheral parenteral nutrition to prevent bloodstream infection in hospitalized patients","authors":"Masafumi Shimoda, Yoshiaki Tanaka, Hiroyuki Kokutou, Takashi Yoshiyama, Kozo Morimoto, Kozo Yoshimori, Shoji Kudoh","doi":"10.1016/j.jiac.2025.102884","DOIUrl":"10.1016/j.jiac.2025.102884","url":null,"abstract":"<div><h3>Introduction</h3><div>Peripheral parenteral nutrition (PPN), administered via a peripheral intravenous catheter (PVC), can occasionally lead to bloodstream infections (BSIs). We previously reported that a prolonged daily infusion time of PPN and all intravenous fluids were risk factors for BSI development. In response, our institution implemented a recommendation to limit the average daily infusion time of PPN to <12 h and that of all intravenous fluids to <18 h. The aim of this study was to investigate whether the incidence of BSI in patients receiving PPN decreased following the implementation of these recommendations.</div></div><div><h3>Methods</h3><div>We retrospectively collected data from 714 patients who underwent PPN therapy via PVC at Fukujuji Hospital from August 2022 to July 2025. We compared the incidence of BSI during PPN therapy between the preintervention and postintervention periods.</div></div><div><h3>Results</h3><div>Among the 714 patients, 507 were in the preintervention group, and 207 were in the postintervention group. The proportion of patients who developed BSIs was significantly lower in the postintervention group than in the preintervention group (n = 2 [1.0 %] vs. n = 27 [5.3 %], <em>p</em> = 0.006). The crude BSI incidence rate decreased from 3.59 to 0.73 per 1000 infusion days. A multivariable Poisson regression model revealed that the postintervention period was associated with a significantly lower BSI incidence rate (adjusted incidence rate ratio: 0.190; 95 % confidence interval: 0.045–0.804; <em>p</em> = 0.024), corresponding to an approximately 81 % reduction in BSI incidence.</div></div><div><h3>Conclusion</h3><div>Shortening the average daily infusion time of PPN and all intravenous fluids may help prevent the development of BSIs.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"32 1","pages":"Article 102884"},"PeriodicalIF":1.5,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-04DOI: 10.1016/j.jiac.2025.102885
Yuto Otsubo , Rentaro Oda , Yo Murata , Funato Sato , Shogo Akahoshi , Hiroshi Sakiyama , Yuho Horikoshi
Background
The utility of AWaRe antibiotic classification for evaluating antimicrobial stewardship in clinics during epidemics of specific, infectious diseases remains unknown. This study aimed to examine antibiotic prescribing patterns using the AWaRe classification during a Mycoplasma pneumoniae epidemic in Tokyo.
Methods
Oral antibiotic prescription data from January 2024 to June 2025 were obtained from the prescription surveillance system of 11 clinics in the Tama regional network (Tama cohort), a subset of all registered clinics in Tokyo (Tokyo cohort). For analysis, the pre-epidemic period, epidemic period, and post-epidemic period were defined as January–June 2024, July–December 2024, and January–June 2025, respectively. The primary outcome was the change in Access antibiotic proportions across the three periods. The secondary outcome was the difference in this change between cohorts.
Results
In total, 8,420 and 526,822 antibiotic prescriptions were issued by the Tama cohort and the Tokyo cohort, respectively. In the Tama cohort, Access antibiotic proportions were 64 %, 48 %, and 75 % during the pre-epidemic, epidemic, and post-epidemic periods, respectively; the corresponding values in the Tokyo cohort were 37 %, 32 %, and 40 %. Compared with the Tokyo cohort, estimated changes in Access proportions in the Tama cohort were −11.7 % (95 % CI: −14.2 to −9.2) from pre-epidemic to epidemic period, and +19.0 % (95 % CI: 16.6 to 21.5) from epidemic to post-epidemic period.
Conclusions
Access proportions temporarily decreased during the 2024 M. pneumoniae epidemic, particularly in the Tama cohort, where the baseline Access proportion was high, indicating potential limitation of AWaRe indicators under epidemic conditions.
{"title":"Limitations of the AWaRe antibiotic classification during the 2024 Mycoplasma pneumoniae epidemic in Tokyo","authors":"Yuto Otsubo , Rentaro Oda , Yo Murata , Funato Sato , Shogo Akahoshi , Hiroshi Sakiyama , Yuho Horikoshi","doi":"10.1016/j.jiac.2025.102885","DOIUrl":"10.1016/j.jiac.2025.102885","url":null,"abstract":"<div><h3>Background</h3><div>The utility of AWaRe antibiotic classification for evaluating antimicrobial stewardship in clinics during epidemics of specific, infectious diseases remains unknown. This study aimed to examine antibiotic prescribing patterns using the AWaRe classification during a <em>Mycoplasma pneumoniae</em> epidemic in Tokyo.</div></div><div><h3>Methods</h3><div>Oral antibiotic prescription data from January 2024 to June 2025 were obtained from the prescription surveillance system of 11 clinics in the Tama regional network (Tama cohort), a subset of all registered clinics in Tokyo (Tokyo cohort). For analysis, the pre-epidemic period, epidemic period, and post-epidemic period were defined as January–June 2024, July–December 2024, and January–June 2025, respectively. The primary outcome was the change in Access antibiotic proportions across the three periods. The secondary outcome was the difference in this change between cohorts.</div></div><div><h3>Results</h3><div>In total, 8,420 and 526,822 antibiotic prescriptions were issued by the Tama cohort and the Tokyo cohort, respectively. In the Tama cohort, Access antibiotic proportions were 64 %, 48 %, and 75 % during the pre-epidemic, epidemic, and post-epidemic periods, respectively; the corresponding values in the Tokyo cohort were 37 %, 32 %, and 40 %. Compared with the Tokyo cohort, estimated changes in Access proportions in the Tama cohort were −11.7 % (95 % CI: −14.2 to −9.2) from pre-epidemic to epidemic period, and +19.0 % (95 % CI: 16.6 to 21.5) from epidemic to post-epidemic period.</div></div><div><h3>Conclusions</h3><div>Access proportions temporarily decreased during the 2024 <em>M. pneumoniae</em> epidemic, particularly in the Tama cohort, where the baseline Access proportion was high, indicating potential limitation of AWaRe indicators under epidemic conditions.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"32 1","pages":"Article 102885"},"PeriodicalIF":1.5,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-03DOI: 10.1016/j.jiac.2025.102883
Kazuro Ikawa , Mana Taguchi , Takeshi Ide , Norifumi Morikawa , Kenta Takeda
Introduction
Daptomycin is used to treat systemic and life-threatening infections caused by methicillin-resistant Staphylococcus aureus in critically ill patients receiving continuous renal replacement therapy (CRRT). However, the pharmacokinetics of daptomycin during low-flow CRRT have not been examined; thus, the appropriate dosing adjustment in Japan remains uncertain.
Methods
The daptomycin concentrations in plasma and effluent samples of adult Japanese patients receiving continuous venovenous hemodiafiltration (n = 4) and continuous venovenous hemodialysis (n = 2) were measured by liquid chromatography. The data were analyzed and used to estimate pharmacodynamic exposure and concentrations to profile daptomycin regimens.
Results
The pharmacokinetics of daptomycin was described using two-compartment model. In the six CRRT patients (effluent flow rate, 0.825 ± 0.038 L/h), the parameter estimates were: volume of distribution of the central compartment, 8.09 ± 3.76 L; volume of distribution of the peripheral compartment, 6.23 ± 2.58 L; intercompartmental clearance, 4.63 ± 1.98 L/h; total clearance, 0.439 ± 0.172 L/h; sieving coefficient, 0.0995 ± 0.0295; extrinsic clearance by CRRT, 0.0815 ± 0.0223 L/h; intrinsic clearance of the patient, 0.357 ± 0.173 L/h; area under the concentration-time curve (AUC) for 24 h, 597.6 ± 196.1 mg‧h/L. Simulated daptomycin regimen for the exposure target (AUC ≥666 mg‧h/L) was 5.36 ± 2.46 mg/kg every 24 h, achieving the safety target (the minimum concentration ≤24.3 mg/L).
Conclusion
These results help to define the pharmacokinetics of daptomycin during low-flow CRRT, while also helping to consider dosing regimens for critically ill Japanese patients receiving CRRT.
{"title":"Pharmacokinetics of daptomycin during low-flow continuous renal replacement therapy in critically ill Japanese patients","authors":"Kazuro Ikawa , Mana Taguchi , Takeshi Ide , Norifumi Morikawa , Kenta Takeda","doi":"10.1016/j.jiac.2025.102883","DOIUrl":"10.1016/j.jiac.2025.102883","url":null,"abstract":"<div><h3>Introduction</h3><div>Daptomycin is used to treat systemic and life-threatening infections caused by methicillin-resistant <em>Staphylococcus aureus</em> in critically ill patients receiving continuous renal replacement therapy (CRRT). However, the pharmacokinetics of daptomycin during low-flow CRRT have not been examined; thus, the appropriate dosing adjustment in Japan remains uncertain.</div></div><div><h3>Methods</h3><div>The daptomycin concentrations in plasma and effluent samples of adult Japanese patients receiving continuous venovenous hemodiafiltration (n = 4) and continuous venovenous hemodialysis (n = 2) were measured by liquid chromatography. The data were analyzed and used to estimate pharmacodynamic exposure and concentrations to profile daptomycin regimens.</div></div><div><h3>Results</h3><div>The pharmacokinetics of daptomycin was described using two-compartment model. In the six CRRT patients (effluent flow rate, 0.825 ± 0.038 L/h), the parameter estimates were: volume of distribution of the central compartment, 8.09 ± 3.76 L; volume of distribution of the peripheral compartment, 6.23 ± 2.58 L; intercompartmental clearance, 4.63 ± 1.98 L/h; total clearance, 0.439 ± 0.172 L/h; sieving coefficient, 0.0995 ± 0.0295; extrinsic clearance by CRRT, 0.0815 ± 0.0223 L/h; intrinsic clearance of the patient, 0.357 ± 0.173 L/h; area under the concentration-time curve (AUC) for 24 h, 597.6 ± 196.1 mg‧h/L. Simulated daptomycin regimen for the exposure target (AUC ≥666 mg‧h/L) was 5.36 ± 2.46 mg/kg every 24 h, achieving the safety target (the minimum concentration ≤24.3 mg/L).</div></div><div><h3>Conclusion</h3><div>These results help to define the pharmacokinetics of daptomycin during low-flow CRRT, while also helping to consider dosing regimens for critically ill Japanese patients receiving CRRT.</div></div>","PeriodicalId":16103,"journal":{"name":"Journal of Infection and Chemotherapy","volume":"32 1","pages":"Article 102883"},"PeriodicalIF":1.5,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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