Journal of Infection and Chemotherapy最新文献_第6页

Limitations of the AWaRe antibiotic classification during the 2024 Mycoplasma pneumoniae epidemic in Tokyo 2024年东京肺炎支原体流行期间AWaRe抗生素分类的局限性

IF 1.5 4区医学 Q3 INFECTIOUS DISEASES

Journal of Infection and Chemotherapy

Pub Date : 2025-12-04 DOI: 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.

背景：在特定传染病流行期间，AWaRe抗生素分类评估临床抗菌药物管理的效用尚不清楚。本研究旨在研究东京肺炎支原体流行期间使用AWaRe分类的抗生素处方模式。方法从东京所有注册诊所（东京队列）的Tama区域网络（Tama队列）的11家诊所的处方监测系统中获取2024年1月至2025年6月的口服抗生素处方数据。为进行分析，将流行前期、流行期和流行后期分别定义为2024年1 - 6月、2024年7 - 12月和2025年1 - 6月。主要结果是三个时期抗生素使用比例的变化。次要结果是队列间这种变化的差异。结果多摩队列和东京队列共发放抗生素处方8420张和526822张。在Tama队列中，在流行前、流行期和流行后，可获得抗生素的比例分别为64%、48%和75%；东京队列的相应值分别为37%、32%和40%。与东京队列相比，从流行前到流行期，Tama队列的可及性比例估计变化为- 11.7% (95% CI: - 14.2至- 9.2)，从流行期到流行后时期，估计变化为+ 19.0% （95% CI: 16.6至21.5）。结论在2024年肺炎支原体流行期间，可获取比例暂时下降，特别是在Tama队列中，基线可获取比例较高，表明AWaRe指标在流行条件下可能存在局限性。

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引用次数: 0

Pharmacokinetics of daptomycin during low-flow continuous renal replacement therapy in critically ill Japanese patients 日本危重病人低流量连续肾替代治疗期间达托霉素的药代动力学。

IF 1.5 4区医学 Q3 INFECTIOUS DISEASES

Journal of Infection and Chemotherapy

Pub Date : 2025-12-03 DOI: 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.

简介：达托霉素用于治疗接受持续肾替代治疗（CRRT）的危重患者由耐甲氧西林金黄色葡萄球菌引起的全身和危及生命的感染。然而，达托霉素在低流量CRRT中的药代动力学尚未被研究；因此，日本适当的剂量调整仍不确定。方法：采用液相色谱法测定日本接受连续静脉静脉血液滤过（n = 4）和连续静脉静脉血液透析（n = 2）的成年患者血浆和流出液中达托霉素的浓度。对数据进行分析并用于估计药效学暴露和浓度，以描述达托霉素方案。结果：采用双室模型描述了达托霉素的药动学。6例CRRT患者（流出流速0.825±0.038 L/h），参数估计值为：中央室分布容积8.09±3.76 L；外周室分布容积，6.23±2.58 L；室间间隙：4.63±1.98 L/h；总间隙0.439±0.172 L/h；筛分系数，0.0995±0.0295；CRRT外清除率为0.0815±0.0223 L/h；患者本征清除率0.357±0.173 L/h；24 h浓度-时间曲线下面积（AUC）为597.6±196.1 mg·h/L。模拟达托霉素方案暴露目标（AUC≥666 mg·h/L）为5.36±2.46 mg/kg，达到安全目标（最低浓度≤24.3 mg/L）。结论：这些结果有助于确定低流量CRRT期间达托霉素的药代动力学，同时也有助于考虑日本危重患者接受CRRT的给药方案。

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引用次数: 0

RSV epidemiology in Italian adults over 60: a multicenter cross-sectional study 意大利60岁以上成年人RSV流行病学：一项多中心横断面研究。

IF 1.5 4区医学 Q3 INFECTIOUS DISEASES

Journal of Infection and Chemotherapy

Pub Date : 2025-12-02 DOI: 10.1016/j.jiac.2025.102881

Federica Novazzi , Laura Pellegrinelli , Federica A.M. Giardina , Carla Acciarri , Stefano Menzo , Elisa Vian , Valeria Biscaro , Giulia Piccirilli , Tiziana Lazzarotto , Sara Uceda Renteria , Annapaola Callegaro , Guglielmo Ferrari , Elisabetta Pagani , Elisa Masi , Cristina Galli , Claudia Tiberio , Martina Esposito , Alessandra Pierangeli , Guido Antonelli , Eleonora Lalle , Matteo Fracella

Objective

Respiratory syncytial virus (RSV) infections have a significant impact on public health, particularly among children and the elderly. However, the burden on older adults in Italy is underestimated due to a lack of comprehensive data.

Methods

Data on the molecular detection of RSV in respiratory samples from laboratories across Italy, from north to south, between September 2021 and May 2023 were collected and analyzed.

Results

A total of 138,783 tests were provided by 13 laboratories, with an overall RSV positivity rate of 6.4 %. Among adults aged ≥60 years (35.4 % of the total), the RSV positivity rate was 3.5 %. Two epidemic waves were observed, peaking in December 2021 and January 2023, with the second wave showing a higher number of cases. RSV subtyping revealed that RSV-B was the predominant subtype in both epidemic seasons, compared to RSV-A.

Conclusion

Analyses of RSV circulation in older adults highlight seasonal variability and underscore the importance of testing in this population. These findings may inform surveillance, clinical management, and the development of future preventive strategies, including vaccination.

目的：呼吸道合胞病毒（RSV）感染对公众健康有重大影响，特别是在儿童和老年人中。然而，由于缺乏全面的数据，意大利老年人的负担被低估了。方法：收集和分析2021年9月至2023年5月期间意大利各地实验室呼吸样本中RSV分子检测数据，从北到南。结果：13个实验室共提供138,783份检测报告，RSV总阳性率为6.4%。60岁以上成人（35.4%）RSV阳性率为3.5%；观察到两次流行波，分别于2021年12月和2023年1月达到高峰，第二波病例数更高。RSV亚型分型结果显示，与RSV- a相比，RSV- b是两个流行季节的主要亚型。结论：对老年人RSV循环的分析强调了季节性变异，并强调了在该人群中进行检测的重要性。这些发现可为监测、临床管理和制定包括疫苗接种在内的未来预防策略提供信息。

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引用次数: 0

A comparative study of out-of-pocket expenditure and quality of life in chronic pulmonary aspergillosis and post-tuberculosis lung disease patients 慢性肺曲霉病与结核后肺病患者自费支出与生活质量的比较研究。

IF 1.5 4区医学 Q3 INFECTIOUS DISEASES

Journal of Infection and Chemotherapy

Pub Date : 2025-12-01 DOI: 10.1016/j.jiac.2025.102873

Renuka Titiyal , Sanjukta Sarkar , Megha Priyadarshi , Ved Prakash Meena , Prayas Sethi , G. Rahul Krishnan , Bindu Prakash , Gagandeep Singh , Immaculata Xess , Surabhi Vyas , Neeraj Nischal , Manish Soneja , Sanjeev Sinha , Naveet Wig , Animesh Ray

Background

Chronic pulmonary aspergillosis (CPA) comprises a spectrum of conditions that frequently affect individuals with chronic lung diseases, particularly post-tuberculosis lung disease (PTLD). Both disorders contribute to significant morbidity and impaired quality of life (QoL). In addition, they impose financial burden, much of which is borne directly by patients in low- and middle-income countries. However, data on out-of-pocket expenditure (OOPE) and its relationship with QoL in these groups remain limited.

Methods

This cross-sectional study, conducted at a tertiary referral centre in India, aimed to estimate OOPE (direct and indirect costs) in patients with CPA and PTLD, identify determinants of expenditure, and assess associations with QoL. Data on OOPE, borrowing, and catastrophic health expenditure during the preceding year were collected through structured interviews. QoL was evaluated using the St. George's Respiratory Questionnaire (SGRQ). Results: Both the direct ($406.42 ± 543.95 vs $251.81 ± 245.42, p value: 0.0038) and indirect costs ($49.93 ± 72.07 vs $39.81 ± 123.32, p value: 0.001) were significantly higher in the CPA group compared with the PTLD group. Subgroup analyses revealed higher diagnostic, transport, and food-related expenses in CPA individuals. Catastrophic expenditure was comparable in both groups (CPA: 60.5 %; PTLD: 67.9 %; p:0.325). Hemoptysis independently predicted poorer QoL across groups. QoL was significantly worse in CPA than PTLD (SGRQ total: 37.32 vs 31.16, p: 0.0125) and significant correlation between OOPE and QoL.

Conclusion

CPA imposes a greater financial burden and is associated with a poorer QoL compared with PTLD, underscoring the need for financial protection measures to improve outcomes in these patients.

背景：慢性肺曲霉病（CPA）包括一系列经常影响慢性肺病患者的疾病，特别是结核后肺病（PTLD）。这两种疾病都会导致显著的发病率和生活质量（QoL）受损。此外，它们造成经济负担，其中大部分由低收入和中等收入国家的患者直接承担。然而，关于自费支出（OOPE）及其与这些群体生活质量关系的数据仍然有限。方法：这项横断面研究在印度的一家三级转诊中心进行，旨在估计CPA和PTLD患者的OOPE（直接和间接成本），确定支出的决定因素，并评估与生活质量的关系。通过结构化访谈收集了前一年的对外开放、借款和灾难性卫生支出数据。使用圣乔治呼吸问卷（SGRQ）评估生活质量。结果：CPA组的直接成本（$406.42 + 543.95 vs $251.81 + 245.42， p值：0.0038）和间接成本（$49.93 + 72.07 vs $39.81+ 123.32， p值：0.001）均显著高于PTLD组。亚组分析显示，CPA个体的诊断、运输和食品相关费用较高。两组的灾难性支出具有可比性（CPA: 60.5%; PTLD: 67.9%; p:0.325）。咯血独立预测各组较差的生活质量。CPA患者的生活质量明显差于PTLD患者（SGRQ总分：37.32 vs 31.16, p: 0.0125）， OOPE与生活质量之间存在显著相关性。结论：与PTLD相比，CPA患者的经济负担和生活质量负担更大，需要采取经济保护措施来改善这些患者的预后。

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引用次数: 0

Recurrent familial furunculosis associated with Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus sublineage of the USA300 clone in Tokyo 复发性家族性真菌病与东京USA300克隆的潘通-瓦伦丁白细胞素阳性耐甲氧西林金黄色葡萄球菌亚系相关

IF 1.5 4区医学 Q3 INFECTIOUS DISEASES

Journal of Infection and Chemotherapy

Pub Date : 2025-12-01 DOI: 10.1016/j.jiac.2025.102872

Ayano Fukushima-Nomura , Saeko Takamiyagi , Yoshihiro Ito , Kaede Sawada , Hiroshi Kawasaki , Motoyuki Sugai , Junzo Hisatsune

We report a familial case of recurrent furunculosis caused by Panton-Valentine leukocidin (PVL)-positive community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Tokyo. The index case, a 34-year-old female, and her family members (her husband and their 8-month-old son) were also affected, and all recovered after treatment with oral clindamycin, intranasal mupirocin, and hygiene interventions. Whole-genome sequencing revealed that five isolates from skin and nasal swabs belonged to ST8-IVa-t304, carrying ACME type I and PVL genes. All isolates were resistant to levofloxacin but susceptible to other anti-MRSA agents. Genomic analysis showed the absence of the SaPI5 island and the sek/seq genes. Based on phylogenetic analysis, we concluded that these strains represent a unique USA300-like sublineage that diverged from the closest USA300-NAE lineage. The USA300 clone has emerged globally as a dominant CA-MRSA lineage responsible for severe skin and soft tissue infections. In Japan, PVL-positive USA300-related clones have been increasingly identified in recent years, indicating ongoing diversification of community-associated MRSA lineages. This case illustrates the growing presence of USA300-related clones in Japan and the need for genomic surveillance and early intervention to prevent further spread in community settings.

我们报告一例东京潘通-瓦伦丁白细胞素（PVL）阳性社区相关耐甲氧西林金黄色葡萄球菌（CA-MRSA）引起的复发性肺结核的家族性病例。指示病例为一名34岁女性及其家庭成员（其丈夫及其8个月大的儿子）也受到影响，经口服克林霉素、鼻用莫匹罗星和卫生干预治疗后全部康复。全基因组测序结果显示，来自皮肤和鼻拭子的5株分离株属于ST8-IVa-t304，携带ACME I型和PVL基因。所有分离株均对左氧氟沙星耐药，但对其他抗mrsa药物敏感。基因组分析显示SaPI5岛和sek/seq基因缺失。基于系统发育分析，我们得出结论，这些菌株代表了一个独特的usa300样亚谱系，从最近的USA300-NAE谱系中分化出来。USA300克隆在全球范围内已成为CA-MRSA的主要分支，可导致严重的皮肤和软组织感染。在日本，近年来越来越多地发现pvl阳性usa300相关克隆，这表明社区相关MRSA谱系正在不断多样化。该病例表明，日本出现了越来越多的usa300相关克隆，需要进行基因组监测和早期干预，以防止在社区环境中进一步传播。

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引用次数: 0

Factors associated with TDF-to-TAF switching in chronic hepatitis B: A nationwide cohort study in South Korea 慢性乙型肝炎患者tdf - taf转换相关因素：韩国一项全国性队列研究

IF 1.5 4区医学 Q3 INFECTIOUS DISEASES

Journal of Infection and Chemotherapy

Pub Date : 2025-12-01 DOI: 10.1016/j.jiac.2025.102860

Hyemin Ha , Kwang Il Seo , Nam Kyung Je

Background

Chronic hepatitis B, a primary cause of liver disease and cancer, requires long-term antiviral therapy. Tenofovir alafenamide (TAF), a novel targeted prodrug of tenofovir disoproxil fumarate (TDF), has reduced renal and bone toxicities while delivering comparable antiviral efficacy at a lower dose. This study aimed to identify factors associated with TAF switching within one year of its introduction in patients receiving TDF.

Methods

This retrospective cohort study included adult patients (≥18 years) with chronic hepatitis B who were receiving TDF on the day TAF became reimbursable in Korea, November 1, 2017. Antiviral prescriptions were tracked for one year to identify patients who switched to TAF. Switching rates were calculated as events per 100 person-months. Factors associated with TAF switching were evaluated using Cox proportional hazards models.

Results

Among 95,819 patients receiving TDF on the index date, 1.4 % switched to TAF within one year. Switching was more likely in males, older adults, and those with hypertension, renal disease, or bone disease. Use of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin II receptor blockers (ARBs) was associated with an increased likelihood of switching, whereas nonsteroidal anti-inflammatory drug use and the presence of hepatocellular carcinoma were associated with lower odds. Patients treated in Seoul and at tertiary hospitals had higher switching rates than those in other regions or healthcare settings.

Conclusion

In this nationwide cohort study, the TAF switching rate among patients receiving TDF was 1.4 % within one year of TAF's reimbursement approval in South Korea. Switching was significantly associated with renal disease, bone disease, age ≥60 years, hypertension, and ACEi/ARB use. Although the higher switching rate in patients with renal or bone disease aligns with reimbursement criteria, other at-risk groups not currently covered may benefit from earlier access.

背景：慢性乙型肝炎是肝脏疾病和癌症的主要原因，需要长期抗病毒治疗。替诺福韦alafenamide （TAF）是富马酸替诺福韦二氧吡酯（TDF）的一种新型靶向前药，在降低肾脏和骨骼毒性的同时，以较低剂量提供相当的抗病毒效果。本研究旨在确定在接受TDF的患者引入TAF后一年内与TAF转换相关的因素。方法：这项回顾性队列研究纳入了2017年11月1日在韩国TAF可报销当日接受TDF治疗的成年慢性乙型肝炎患者（≥18岁）。抗病毒药物的处方被追踪了一年，以确定那些转而使用TAF的患者。转换率以每100人月的事件数计算。使用Cox比例风险模型评估与TAF转换相关的因素。结果：在指标日接受TDF的95,819例患者中，1.4%的患者在一年内转为TAF。在男性、老年人、高血压、肾病或骨病患者中更有可能发生转换。血管紧张素转换酶抑制剂(ACEis)/血管紧张素受体阻滞剂（ARBs）的使用与转换的可能性增加相关，而非甾体抗炎药的使用和肝细胞癌的存在与转换的可能性较低相关。在首尔和三级医院接受治疗的患者的转换率高于其他地区或医疗机构。结论：在这项全国性队列研究中，韩国接受TDF的患者在TAF报销批准后一年内的TAF转换率为1.4%。转换与肾脏疾病、骨病、年龄≥60岁、高血压和ACEi/ARB使用显著相关。虽然肾病或骨病患者较高的转换率符合报销标准，但目前未覆盖的其他高危人群可能会从早期准入中受益。

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引用次数: 0

Corrigendum to "Development of traceable international standard materials using sequence-customized lentivirus, modeled on SARS-CoV-2 nucleic acid amplification tests, and validation through a pilot external quality assessment" [J Infect Chemother 31 (5) 2025 102694]. 基于SARS-CoV-2核酸扩增试验的序列定制慢病毒可溯源国际标准材料开发及外部质量试点评估验证[j].感染与化疗杂志，第31卷，第5期，2025,102694。

IF 1.5 4区医学 Q3 INFECTIOUS DISEASES

Journal of Infection and Chemotherapy

Pub Date : 2025-12-01 DOI: 10.1016/j.jiac.2025.102880

Mizuki Itano, Kotaro Aoki, Haruka Nakagawa Kamura, Yoshikazu Ishii, Kazuhiro Tateda

引用次数: 0

The current status of neonatal echovirus 11 infections in Japan: A comparison to the global situation 日本新生儿埃可病毒11型感染现状：与全球比较

IF 1.5 4区医学 Q3 INFECTIOUS DISEASES

Journal of Infection and Chemotherapy

Pub Date : 2025-12-01 DOI: 10.1016/j.jiac.2025.102879

Takanori Funaki , Kensuke Shoji

Enteroviruses (EVs) are one of the most common causes of severe neonatal infections. The spectrum of diseases varies with age, sex, and immune status. As molecular methods have evolved, several new EVs have been identified, bringing the total number of serotypes to over 100. Since 2022, the World Health Organization has published Disease Outbreak News on echovirus 11 (E11) infections due to an increase in severe neonatal E11 infections in several European countries. In Japan, several life-threatening neonatal cases were also reported in the summer of 2024. Clinical characteristics of severe cases include rapid clinical deterioration with multiorgan failure, hemophagocytic lymphohistiocytosis-like inflammatory features, and a high mortality rate. Male infants are likely to experience severe outcomes, specifically in neonates, onset soon after birth, and possible maternal peripartum infection. Meanwhile, older infants with aseptic meningitis often show mild, self-limited disease. Genomic characteristics indicate that a new recombinant genotype D5 is the predominant circulating E11 lineage worldwide. Recent severe neonatal cases linked to a closely related genetic variant that may have increased pathogenicity. This evidence suggests both viral evolution and immature neonatal immunity may contribute to the disease severity. Given the newly initiated nationwide surveillance in Japan, enhanced EV surveillance and rapid genomic characterization are crucial for early identification of severe E11 infection in neonates.

肠病毒（ev）是严重新生儿感染的最常见原因之一。疾病的范围因年龄、性别和免疫状况而异。随着分子方法的发展，已经发现了几种新的ev，使血清型总数超过100种。自2022年以来，世界卫生组织发布了关于埃可病毒11 （E11）感染的疾病暴发新闻，原因是几个欧洲国家新生儿严重感染E11的病例有所增加。在日本，2024年夏天也报告了几例危及生命的新生儿病例。重症病例的临床特点为临床迅速恶化，伴多器官功能衰竭，有噬血细胞淋巴组织细胞病样炎症特征，病死率高。男性婴儿可能会经历严重的后果，特别是新生儿，出生后不久发病，并可能出现母体围产期感染。同时，年龄较大的无菌性脑膜炎患儿通常表现为轻度、自限性疾病。基因组特征表明，新的重组基因型D5是世界范围内主要的循环E11谱系。最近的严重新生儿病例与一种密切相关的基因变异有关，这种变异可能增加了致病性。这一证据表明，病毒进化和不成熟的新生儿免疫都可能导致疾病的严重程度。鉴于日本新启动的全国监测，加强EV监测和快速基因组鉴定对于早期识别新生儿严重E11感染至关重要。

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引用次数: 0

Multi-biomarker integration in predicting bedaquiline treatment response among diabetic MDR-TB patients 多生物标志物整合预测糖尿病耐多药结核病患者贝达喹啉治疗反应。

IF 1.5 4区医学 Q3 INFECTIOUS DISEASES

Journal of Infection and Chemotherapy

Pub Date : 2025-11-26 DOI: 10.1016/j.jiac.2025.102878

Liqing Zhu , Mengmeng Li , Zhongjian Wang

Background

Diabetes mellitus significantly complicates multidrug-resistant tuberculosis (MDR-TB) treatment outcomes. This study investigated the predictive value of integrating bedaquiline pharmacokinetics, inflammatory markers, and glycemic parameters for treatment response in diabetic MDR-TB patients.

Methods

We conducted a retrospective cohort study of 186 patients with MDR-TB and diabetes mellitus receiving bedaquiline-containing regimens from January 2019 to December 2023. Bedaquiline trough concentrations, inflammatory markers (CRP, IL-6, TNF-α), and glycemic indices (HbA1c, fasting glucose) were measured at baseline and during follow-up. The primary outcome was sputum culture conversion or clinical improvement at 6 months. Multivariate logistic regression identified predictors of treatment response, and a predictive model was developed using 70 % training and 30 % validation cohorts.

Results

Overall treatment response rate was 72.0 %. Responders demonstrated significantly higher bedaquiline trough concentrations and better glycemic control. The integrated predictive model incorporating bedaquiline concentration, baseline CRP, HbA1c, and HbA1c change achieved superior discrimination compared to individual biomarkers. Subgroup analysis revealed a critical interaction between glycemic control and drug exposure, with poor glycemic control patients showing 0 % response in the lowest bedaquiline quartile but 100 % response in higher quartiles.

Conclusions

Multi-biomarker integration effectively predicts bedaquiline treatment response in diabetic MDR-TB patients. The synergistic relationship between adequate drug exposure and glycemic control underscores the necessity for integrated therapeutic drug monitoring and diabetes management strategies in this high-risk population.

背景：糖尿病严重影响耐多药结核病（MDR-TB）的治疗结果。本研究探讨了整合贝达喹啉药代动力学、炎症标志物和血糖参数对糖尿病耐多药结核病患者治疗反应的预测价值。方法：我们对2019年1月至2023年12月接受含贝达喹啉方案治疗的186例耐多药结核病和糖尿病患者进行了回顾性队列研究。在基线和随访期间测量贝达喹啉谷浓度、炎症标志物（CRP、IL-6、TNF-α）和血糖指数（HbA1c、空腹血糖）。主要结果为6个月时痰培养转化或临床改善。多变量逻辑回归确定了治疗反应的预测因素，并使用70%的训练队列和30%的验证队列建立了预测模型。结果：总有效率为72.0%。反应者表现出明显更高的贝达喹啉谷浓度和更好的血糖控制。与单个生物标志物相比，结合贝达喹啉浓度、基线CRP、HbA1c和HbA1c变化的综合预测模型具有更好的辨别能力。亚组分析显示血糖控制和药物暴露之间存在关键的相互作用，血糖控制较差的患者在最低的贝达喹啉四分位数中显示0%的应答，而在较高的四分位数中显示100%的应答。结论：多生物标志物整合可有效预测糖尿病耐多药结核病患者贝达喹啉治疗反应。充分的药物暴露和血糖控制之间的协同关系强调了在这一高危人群中进行综合治疗药物监测和糖尿病管理策略的必要性。

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引用次数: 0

Chronic pulmonary coccidioidomycosis complicated with meningitis: A case report 慢性肺球虫菌病合并脑膜炎1例。

IF 1.5 4区医学 Q3 INFECTIOUS DISEASES

Journal of Infection and Chemotherapy

Pub Date : 2025-11-22 DOI: 10.1016/j.jiac.2025.102870

Ryo Mizushima , Yuki Moriyama , Akira Watanabe , Keigo Ueno , Takayuki Shinohara , Yoshitsugu Miyazaki , Norio Ohmagari

We encountered a case of chronic pulmonary coccidioidomycosis complicated with meningitis in a 53-year-old African-American veteran with a history of staying in Arizona, United States of America. The patient was referred from another hospital with complaints of cough, blood-stained phlegm, hemoptysis, and headache. Chronic pulmonary coccidioidomycosis was suspected based on the presence of multiple pulmonary cavity lesions on computed tomography (CT) and a relevant exposure history, and the diagnosis was confirmed by serological antibody tests (coccidioidomycosis IgG, positive; coccidioidomycosis IgM, negative). Treatment was initiated with oral fluconazole (FLCZ) 400 mg daily, but there was no improvement in symptoms, and CT revealed gradual enlargement of the pulmonary cavitary lesions. Therefore, the oral FLCZ dose was increased to 800 mg; however, the patient developed worsening headache, and subsequent cerebrospinal fluid analysis revealed a slight increase in cell count with positive IgG, negative IgM, and negative polymerase chain reaction results. Suspecting meningitis, the oral FLCZ dose was further increased to 1200 mg, leading to marked improvement in symptoms at the following visit. In coccidioidomycosis, an increase in any antibody titer should be considered an indicator of active infection. In addition, if headache develops during the course of the disease, appropriate treatment for meningitis should be initiated even if cerebrospinal fluid findings are minimal.

我们遇到了一例慢性肺球虫菌病合并脑膜炎的病例，患者是一位53岁的非裔美国退伍军人，曾在美国亚利桑那州居住。患者从另一家医院转诊，主诉为咳嗽、痰染血、咯血和头痛。基于计算机断层扫描（CT）显示肺部多腔病变及相关暴露史，怀疑为慢性肺球孢子菌病，并通过血清学抗体检测（球孢子菌病IgG阳性，球孢子菌病IgM阴性）确认诊断。治疗开始时口服氟康唑（FLCZ） 400mg，每日，但症状没有改善，CT显示肺空洞病变逐渐扩大。因此，口服FLCZ剂量增加至800 mg；然而，患者头痛加重，随后的脑脊液分析显示细胞计数轻微增加，IgG阳性，IgM阴性，聚合酶链反应阴性。怀疑是脑膜炎，口服氟氯联苯剂量进一步增加到1200毫克，导致在接下来的访问中症状明显改善。在球孢子菌病中，任何抗体滴度的增加都应被视为活动性感染的指标。此外，如果在疾病过程中出现头痛，即使脑脊液发现很少，也应开始适当的脑膜炎治疗。

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