Journal of Infection最新文献_第3页

A non-randomized pragmatic historically controlled trial evaluating the effectiveness and safety of a bedaquiline or a linezolid-based short regimen for rifampicin-resistant tuberculosis 一项非随机实用历史对照试验，评估了贝达喹啉或利奈唑胺短期疗法治疗耐利福平结核病的有效性和安全性。

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-10-18 DOI: 10.1016/j.jinf.2024.106291

Background

Short all-oral regimens for Rifampicin-resistant tuberculosis (ShORRT) have been a turning point in the treatment of drug-resistant tuberculosis. Despite this, access to drugs, stockouts, or adverse effects may limit the use of the recommended regimens.

Methods

Pragmatic non-randomized trial evaluating the efficacy and safety of a ShORRT strategy for the treatment of rifampicin-resistant Tuberculosis (RR-TB) at the Hospital Nossa Senhora da Paz (Angola). The strategy assigned participants to receive a bedaquiline (BDQ) or a linezolid-based (LZF) regimen supplemented with levofloxacin, clofazimine, and cycloserine for up to 9 months.

Results

One hundred and twenty-one participants with pulmonary RR-TB were treated with the ShORRT strategy; 69 received the bedaquiline- and 52 the linezolid-based regimen. Overall, 98 (81%) participants had successful treatment outcomes, which was significantly higher compared to a 20-month historical injectable-based regimen (successful outcome rate including cure and treatment completed: 53.7%) (p < 0.001). No significant differences between treatment success rates (85.5% vs. 75.0%), treatment failure (0.0% vs. 1.9%), death (5.8% vs. 13.5%), or lost to follow-up (LTFU) (8.7% vs. 9.6%) were seen between the BDQ and the LZF-based regimen. Globally, 72 adverse events (AE) occurred in 36 (29.7%) participants. Eighteen (14.9%) of these were grade ≥3 and were more frequently observed in those receiving the LZD-based regimen (p = 0.02).

Conclusion

The ShORRT strategy with a nine-month BDQ- or LZD-based regimen supports the efficacy of shorter all-oral regimens for the treatment of RR-TB and presents real-world data from schemes without bedaquiline, nitroimidazole, or injectables.

背景：治疗耐利福平结核病的全口服短程疗法（ShORRT）是耐药结核病治疗的一个转折点。尽管如此，药物的获取、缺货或不良反应可能会限制推荐方案的使用：方法：在安哥拉帕斯圣母医院（Hospital Nossa Senhora da Paz）开展务实的非随机试验，评估ShORRT策略治疗耐利福平结核病（RR-TB）的有效性和安全性。该策略分配参与者接受贝达喹啉（BDQ）或利奈唑烷（LZF）为基础并辅以左氧氟沙星、氯法齐明和环丝氨酸的治疗方案，疗程长达9个月：121名肺部RR-TB患者接受了ShORRT疗法，其中69人接受了贝达喹啉疗法，52人接受了利奈唑胺疗法。总体而言，98 名参与者（81%）获得了成功的治疗结果，与以往为期 20 个月的注射疗法相比，成功率显著提高（成功率包括治愈率和治疗完成率：53.7%）（p < 0.001）。在治疗成功率（85.5% vs. 75.0%）、治疗失败率（0.0% vs. 1.9%）、死亡率（5.8% vs. 13.5%）或失去随访（LTFU）率（8.7% vs. 9.6%）方面，BDQ疗法与LZF疗法之间无明显差异。在全球范围内，有36名参与者（29.7%）发生了72起不良事件（AE）。其中18例（14.9%）为≥3级，在接受LZD方案的患者中发生率更高（P =0.02）：采用为期 9 个月的 BDQ 或 LZD 方案的 ShORRT 策略支持缩短全口服方案治疗 RR-TB 的疗效，并提供了不使用贝达喹啉、硝基咪唑或注射剂的方案的实际数据。

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引用次数: 0

Novel imported clades accelerated the RSV surge in Beijing, China, 2023-2024 2023-2024 年，新的输入支系加速了中国北京 RSV 的激增。

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-10-18 DOI: 10.1016/j.jinf.2024.106321

Objectives

Despite the optimization of the zero-COVID policy in late 2022, there was a subsequent increase noted in the number of respiratory syncytial virus (RSV) cases in Northern China. In this study, we investigated and characterized the dynamics of this surge at the genomic level in Beijing, China.

Methods

Patients with acute respiratory tract infections (ARTIs) were enrolled from 35 sentinel hospitals in Beijing, China. Epidemiological investigations, G gene amplification, and whole-genome sequencing were performed, followed by epidemiological analysis, imported clade detection, and mutation identification. We also combined global data to illustrate the biological and epidemiological characteristics of the emerging clades.

Results

A total of 60,423 patients with ARTIs were recruited between January 2015 and January 2024. The RSV peak observed in the winter of 2023 was the highest in the past 9 years. Two novel imported clades, A.D.5.2 and B.D.E.1, were detected for the first time in China. This surge was mainly driven by B.D.E.1, which exhibited a significantly higher proportion of older individuals both in Beijing and globally. Seven non-synonymous mutations in B.D.E.1 were found in Beijing. B.D.E.1 had more sites suffering from positive selection than its parent.

Conclusions

The novel imported clade B.D.E.1 accelerated an unprecedented RSV surge in Beijing, presenting noteworthy epidemiological and biological characteristics. Continuous RSV genome monitoring has important implications for RSV outbreak identification, genetic diversity tracking, vaccine development, and strategy implementation.

目标：尽管 2022 年末优化了零感染病例政策，但随后发现华北地区呼吸道合胞病毒（RSV）病例数量有所增加。在本研究中，我们在基因组水平上调查并描述了中国北京这一激增的动态：方法：从中国北京的 35 家哨点医院招募急性呼吸道感染（ARTI）患者。进行流行病学调查、G 基因扩增和全基因组测序，然后进行流行病学分析、进口支系检测和突变鉴定。我们还结合全球数据说明了新出现支系的生物学和流行病学特征：结果：2015 年 1 月至 2024 年 1 月期间，共招募了 60423 名 ARTIs 患者。2023年冬季观察到的RSV高峰是过去9年中最高的。中国首次检测到两个新的输入支系：A.D.5.2 和 B.D.E.1。这种激增主要是由 B.D.E.1 推动的，它在北京和全球都表现出明显较高的老年个体比例。在北京，B.D.E.1 中发现了 7 个非同义突变。B.D.E.1比其父本有更多的位点受到正选择：结论：B.D.E.1新输入支系加速了北京前所未有的RSV飙升，呈现出值得注意的流行病学和生物学特征。持续的 RSV 基因组监测对 RSV 疫情识别、遗传多样性追踪、疫苗开发和策略实施具有重要意义。

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引用次数: 0

Inflammatory cytokine responses in pediatric tuberculosis with or without SARS-CoV-2 seropositivity 伴有或不伴有 SARS-CoV-2 血清阳性反应的小儿结核病的炎症细胞因子反应

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-10-18 DOI: 10.1016/j.jinf.2024.106314

Objectives

To characterize the inflammatory cytokine profiles in children with TB in the presence and absence of SARS-CoV2 seropositivity.

Methods

This study evaluated cytokine responses in two groups of children with TB: CoV2+ (TB and SARS-CoV2 seropositive) and CoV2- (TB and SARS-CoV2 seronegative). Each group had 30 children, and cytokine levels were measured at baseline, months 3 and 6.

Results

At baseline, CoV2+ children exhibited significantly elevated levels of cytokines, including IFN-γ, IL-2, TNFα, IL-1α, and IL-6, and reduced levels of IL-1β and IL-18, compared to CoV2- children. No significant differences in cytokine levels between the groups were observed at months 3 and 6. Additionally, a general decline in cytokine levels was noted over the course of treatment in both groups. A positive correlation was found between most cytokines and SARS-CoV2 IgG spike protein levels at baseline and at month 3 in the CoV2+ group.

Conclusions

This study is one of the first studies to characterize the systemic inflammatory responses in SARS-CoV2 seropositive and seronegative children with TB from a TB endemic country. The findings enhance our understanding of the immunopathogenesis of TB and SARS-CoV2 seropositivity in children and may inform future therapeutic strategies

目的描述结核病患儿在 SARS-CoV2 血清阳性和非 SARS-CoV2 血清阳性情况下的炎症细胞因子特征：本研究评估了两组肺结核患儿的细胞因子反应：CoV2+（肺结核和 SARS-CoV2 血清阳性）和 CoV2-（肺结核和 SARS-CoV2 血清阴性）。每组 30 名儿童，分别在基线、第 3 个月和第 6 个月测量细胞因子水平：结果：与CoV2-儿童相比，CoV2+儿童的细胞因子（包括IFN-γ、IL-2、TNFα、IL-1α和IL-6）水平在基线时明显升高，而IL-1β和IL-18的水平则有所降低。第3个月和第6个月时，观察到各组间细胞因子水平无明显差异。此外，在治疗过程中，两组儿童的细胞因子水平普遍下降。在CoV2+组，大多数细胞因子与基线和第3个月时的SARS-CoV2 IgG尖峰蛋白水平呈正相关：本研究是首次对结核病流行国家的 SARS-CoV2 血清阳性和血清阴性结核病患儿的全身炎症反应进行描述的研究之一。研究结果加深了我们对儿童肺结核和 SARS-CoV2 血清阳性的免疫发病机制的了解，并为未来的治疗策略提供了参考。

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引用次数: 0

Trends of common laboratory biomarkers after SARS-CoV-2 infection 感染 SARS-CoV-2 后常见实验室生物标志物的变化趋势

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-10-17 DOI: 10.1016/j.jinf.2024.106318

Background

Most studies that explore the long-term effects of COVID-19 are based on subjectively reported symptoms, while laboratory-measured biomarkers are mainly examined in studies of relatively small cohorts. This study investigates the long-term effects of SARS-CoV-2 infection on common laboratory biomarkers.

Methods

We utilized a retrospective cohort of SARS-CoV-2 infected individuals and rigorously matched controls based on demographic and clinical characteristics, examining 63 common laboratory biomarkers. Additional lab-specific cohorts were matched with an additional criterion of baseline biomarker values. Differences in biomarkers over a 12-month follow-up were analyzed using standardized mean difference-in-differences.

Results

The general cohort included 361,061 matched pairs, with 26M laboratory results. The effects on most biomarkers lasted 1–4 months and were consistent with anticipated changes after acute viral infections. Some biomarkers presented prolonged effects, consistent across the general and lab-specific cohorts. One group of such findings included a 7–8 month decrease in WBC counts, mainly driven by decreased counts of neutrophils, monocytes, and basophils. Potassium levels were decreased for 3–5 months. Vaccinated individuals’ data suggested potentially smaller effects on WBCs, but cohort sizes limited this analysis.

Conclusions

This study explores SARS-CoV-2 infection effects on common laboratory biomarkers, characterizing the direction and duration of these effects on the largest infected cohort to date. The effects of most biomarkers resolve in the first months following infection. The most notable longer-lasting effects involved the immune system. Further research is required to characterize the magnitude of these effects among specific individuals.

背景：大多数探讨 COVID-19 长期影响的研究都是基于主观报告的症状，而实验室测量的生物标志物主要是在相对较小的队列研究中进行的。本研究调查了 SARS-CoV-2 感染对常见实验室生物标志物的长期影响：方法：我们利用 SARS-CoV-2 感染者的回顾性队列以及根据人口统计学和临床特征严格匹配的对照组，检测了 63 种常见的实验室生物标志物。其他实验室特异性队列以生物标志物基线值为额外标准进行匹配。在 12 个月的随访过程中，生物标志物的差异采用标准化平均差异进行分析：一般队列包括 361,061 对匹配对，共 2600 万个实验室结果。对大多数生物标志物的影响持续了 1-4 个月，与急性病毒感染后的预期变化一致。有些生物标志物的影响持续时间较长，这在一般组群和特定实验室组群中是一致的。其中一组研究结果包括白细胞计数持续 7-8 个月下降，主要原因是中性粒细胞、单核细胞和嗜碱性粒细胞计数减少。钾含量下降持续了 3-5 个月。接种疫苗者的数据表明，白细胞受到的影响可能较小，但队列规模限制了这一分析：本研究探讨了 SARS-CoV-2 感染对常见实验室生物标志物的影响，确定了这些影响在迄今为止最大的感染人群中的方向和持续时间。大多数生物标志物的影响在感染后的头几个月就会消失。最显著、持续时间较长的影响涉及免疫系统。要确定这些影响在特定个体中的程度，还需要进一步的研究。

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引用次数: 0

Evaluating the effect of BCG vaccination for non-specific protection from infection in senior citizens during the COVID-19 pandemic: A randomised clinical trial 评估在 COVID-19 大流行期间接种卡介苗对老年人非特异性感染保护的效果：随机临床试验。

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-10-17 DOI: 10.1016/j.jinf.2024.106319

Objectives

The Bacillus Calmette-Guérin (BCG) vaccine may induce non-specific protection against unrelated infections. We tested the effect of BCG on the risk of infections among Danish senior citizens.

Methods

Single-blinded randomised controlled trial including 1676 volunteers >65 years. Participants were randomised 1:1 to BCG or placebo and followed for 12 months. The primary outcome was acute infection leading to medical contact. Secondary outcomes were verified SARS-CoV-2 infection, self-reported respiratory symptoms, and all-cause hospitalisation. Data was analysed using Cox regression models, estimating hazard ratios (HR) with 95% confidence intervals (CI).

Results

The incidence of acute infection was 52.1 and 58.2 per 100 person-years for BCG and placebo, respectively (HR=0.89, 95% CI=0.78–1.02). There was no effect of BCG on SARS-CoV-2 infections (0.97, 0.75–1.26) or all-cause hospitalisations (1.10, 0.80–1.50), but BCG was associated with more respiratory symptoms (1.21, 1.10–1.33). BCG reduced the incidence of acute infections among participants <75 years (0.82, 0.70–0.95) but not among those >75 years (1.14, 0.88–1.47). In participants, who were COVID-19 vaccinated before enrolment, BCG was associated with lower incidence of acute infections (0.65, 0.50–0.85).

Conclusion

BCG did not reduce risk of acute infections among Danish seniors overall, but the effect was modified by age group and COVID-19 vaccination.

Trial registration

ClinicalTrials.gov (NCT04542330) and EU Clinical Trials Register (EudraCT number 2020-003904-15). Full trial protocol is available at ClinicalTrials.gov.

Summary

In a randomised clinical trial among Danish senior citizens, BCG vaccination did not reduce the overall risk of acute infection, but BCG was associated with reduced risk in participants <75 years and participants who received COVID-19 vaccines prior to enrolment.

目的：卡介苗（Bacillus Calmette-Guérin，BCG）可诱导非特异性保护，预防无关感染。我们测试了卡介苗对丹麦老年人感染风险的影响：单盲随机对照试验，包括 1,676 名年龄大于 65 岁的志愿者。参与者按 1:1 的比例随机接受卡介苗或安慰剂治疗，并随访 12 个月。主要结果是急性感染导致医疗接触。次要结果是经证实的 SARS-CoV-2 感染、自我报告的呼吸道症状和全因住院。数据采用 Cox 回归模型进行分析，估算出危险比（HR）和 95% 的置信区间（CI）：卡介苗和安慰剂的急性感染发病率分别为每100人年52.1例和58.2例（HR=0.89，95% CI=0.78-1.02）。卡介苗对 SARS-CoV-2 感染（0.97，0.75-1.26）或全因住院（1.10，0.80-1.50）没有影响，但卡介苗与更多呼吸道症状（1.21，1.10-1.33）相关。卡介苗降低了 75 岁参与者的急性感染发病率（1.14，0.88-1.47）。在入组前接种过 COVID-19 疫苗的参与者中，卡介苗与较低的急性感染发病率相关（0.65，0.50-0.85）：卡介苗总体上并未降低丹麦老年人的急性感染风险，但其效果因年龄组和接种 COVID-19 疫苗而异：试验注册：ClinicalTrials.gov（NCT04542330）和欧盟临床试验注册（EudraCT 编号 2020-003904-15）。摘要：在一项针对丹麦老年人的随机临床试验中，卡介苗接种并未降低急性感染的总体风险，但卡介苗接种可降低参与者的风险。

{"title":"Evaluating the effect of BCG vaccination for non-specific protection from infection in senior citizens during the COVID-19 pandemic: A randomised clinical trial","authors":"","doi":"10.1016/j.jinf.2024.106319","DOIUrl":"10.1016/j.jinf.2024.106319","url":null,"abstract":"<div><h3>Objectives</h3><div>The Bacillus Calmette-Guérin (BCG) vaccine may induce non-specific protection against unrelated infections. We tested the effect of BCG on the risk of infections among Danish senior citizens.</div></div><div><h3>Methods</h3><div>Single-blinded randomised controlled trial including 1676 volunteers >65 years. Participants were randomised 1:1 to BCG or placebo and followed for 12 months. The primary outcome was acute infection leading to medical contact. Secondary outcomes were verified SARS-CoV-2 infection, self-reported respiratory symptoms, and all-cause hospitalisation. Data was analysed using Cox regression models, estimating hazard ratios (HR) with 95% confidence intervals (CI).</div></div><div><h3>Results</h3><div>The incidence of acute infection was 52.1 and 58.2 per 100 person-years for BCG and placebo, respectively (HR=0.89, 95% CI=0.78–1.02). There was no effect of BCG on SARS-CoV-2 infections (0.97, 0.75–1.26) or all-cause hospitalisations (1.10, 0.80–1.50), but BCG was associated with more respiratory symptoms (1.21, 1.10–1.33). BCG reduced the incidence of acute infections among participants <75 years (0.82, 0.70–0.95) but not among those >75 years (1.14, 0.88–1.47). In participants, who were COVID-19 vaccinated before enrolment, BCG was associated with lower incidence of acute infections (0.65, 0.50–0.85).</div></div><div><h3>Conclusion</h3><div>BCG did not reduce risk of acute infections among Danish seniors overall, but the effect was modified by age group and COVID-19 vaccination.</div></div><div><h3>Trial registration</h3><div>ClinicalTrials.gov (NCT04542330) and EU Clinical Trials Register (EudraCT number 2020-003904-15). Full trial protocol is available at ClinicalTrials.gov.</div></div><div><h3>Summary</h3><div>In a randomised clinical trial among Danish senior citizens, BCG vaccination did not reduce the overall risk of acute infection, but BCG was associated with reduced risk in participants <75 years and participants who received COVID-19 vaccines prior to enrolment.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessment of neutralizing antibody response as a correlate of protection against symptomatic SARS-CoV-2 infections after administration of two doses of the CoronaVac inactivated COVID-19 vaccine: A phase III randomized controlled trial 评估中和抗体反应作为接种两剂 CoronaVac COVID-19 灭活疫苗后对无症状 SARS-CoV-2 感染的保护作用的相关因素：III期随机对照试验。

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-10-16 DOI: 10.1016/j.jinf.2024.106315

Background

The emergence of variants of concerns of SARS-CoV-2 highlights the need for comprehensively elucidating the correlates of protection for different COVID-19 vaccine types. Inactivated COVID-19 vaccines are currently amongst the most widely administered vaccines globally. However, investigations into the correlates of protection for inactivated COVID-19 vaccines are relatively rare.

Methods

Data from a phase III double-blind, randomized, placebo-controlled clinical trial (NCT0445659) that evaluated the efficacy and safety of the CoronaVac vaccine in healthcare professionals were utilized in this secondary analysis. Additionally, the correlation between neutralizing antibody levels measured by micro-cytopathic effect (CPE) neutralization assay and the occurrence of laboratory-confirmed infections was assessed using neutralizing antibodies measured in blood samples collected on day 28 after receiving two doses of the vaccine. Finally, the protective threshold required to provide 50% protection against symptomatic illness and virus infections was estimated.

Results

The risk of infection was negatively correlated with the levels of post-vaccination neutralizing antibodies measured on day 28 after the second dose. A neutralization titer of 30 (95% CI: 2–56) was predicted to provide 50% efficacy against symptomatic infection, whilst a titer of 42 (95% CI: 24–62) was predicted to provide 50% efficacy against total infection. Lastly, a neutralization titer of 247 (95% CI: 139–506) or higher was required to achieve 80% or higher protection against symptomatic infections.

Conclusions

The results highlight the value of neutralizing antibody response as a correlate of protection, which can be used to inform future vaccine development and implementation. Further studies of immune correlates of protection for other vaccines are warranted.

背景：令人担忧的 SARS-CoV-2 变异株的出现凸显了全面阐明不同 COVID-19 疫苗类型的保护相关性的必要性。COVID-19 灭活疫苗是目前全球接种最广泛的疫苗之一。然而，对 COVID-19 灭活疫苗保护相关性的调查却相对较少：本二次分析采用了一项 III 期双盲、随机、安慰剂对照临床试验（NCT0445659）的数据，该试验评估了 CoronaVac 疫苗对医护人员的有效性和安全性。此外，还利用接种两剂疫苗后第 28 天采集的血样中测得的中和抗体，评估了微小细胞病理效应 (CPE) 中和测定法测得的中和抗体水平与实验室确诊感染发生率之间的相关性。最后，还估算了对无症状疾病和病毒感染提供 50%保护所需的保护阈值：结果：感染风险与接种第二剂疫苗后第 28 天测得的接种后中和抗体水平呈负相关。预测中和滴度为 30（95% CI：2-56）时，对无症状感染的有效率为 50%，而滴度为 42（95% CI：24-62）时，对全部感染的有效率为 50%。最后，中和滴度达到247（95% CI：139-506）或更高，才能对无症状感染产生80%或更高的保护作用：结论：研究结果凸显了中和抗体反应作为保护相关因素的价值，可为未来疫苗的开发和实施提供参考。有必要进一步研究其他疫苗的免疫保护相关性。

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引用次数: 0

Mechanisms and implications of IgG4 responses to SARS-CoV-2 and other repeatedly administered vaccines IgG4 对 SARS-CoV-2 和其他重复接种疫苗的反应机制和影响。

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-10-16 DOI: 10.1016/j.jinf.2024.106317

Vaccine-induced immunoglobulin G (IgG) profiles can vary with respect to the predominant subclasses that characterize the response. Among IgG subclasses, IgG4 is reported to have anti-inflammatory properties, but can also exhibit reduced capacity for virus neutralization and activation of Fc-dependent effector functions. Here, we review evidence that IgG4 subclass responses can be disproportionately increased in response to some types of vaccines targeting an array of diseases, including pertussis, HIV, malaria, and COVID-19. The basis for enhanced IgG4 induction by vaccines is poorly understood but may be associated with platform- or dose regimen–specific differences in antigen exposure and/or cytokine stimulation. The clinical implications of vaccine-induced IgG4 responses remain uncertain, though collective evidence suggests that proportional increases in IgG4 might reduce vaccine antigen-specific immunity. Additional work is needed to determine underlying mechanisms and to elucidate what role IgG4 may play in modifications of vaccine-induced immunity to disease.

疫苗诱导的免疫球蛋白 G (IgG) 可因反应的主要亚类而有所不同。据报道，在 IgG 亚类中，IgG4 具有抗炎特性，但也会表现出中和病毒和激活 Fc 依赖性效应器功能的能力下降。在此，我们回顾了一些证据，这些证据表明，在接种某些类型的疫苗时，IgG4 亚类的反应会不成比例地增加，这些疫苗针对的疾病包括百日咳、艾滋病、疟疾和 COVID-19。疫苗诱导 IgG4 增高的原因尚不清楚，但可能与抗原暴露和/或细胞因子刺激的平台或剂量方案特异性差异有关。疫苗诱导的 IgG4 反应对临床的影响仍不确定，但有综合证据表明，IgG4 的比例增加可能会降低疫苗抗原特异性免疫力。还需要做更多的工作来确定潜在的机制，并阐明 IgG4 在改变疫苗诱导的疾病免疫中可能扮演的角色。

引用次数: 0

Global practice variation of suppressive antimicrobial treatment for prosthetic joint infections: A cross-sectional survey study 假体关节感染抑制性抗菌治疗的全球实践差异：一项横断面调查研究。

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-10-15 DOI: 10.1016/j.jinf.2024.106316

Objectives

To identify global differences in the use of suppressive antimicrobial therapy (SAT) in the management of prosthetic joint infection (PJI).

Methods

An online survey was designed to investigate clinician’s approach to SAT for PJI, including indications, preferred antimicrobial drugs, dosing, treatment duration and follow-up. The survey was distributed to members of four international (bone and joint) infection societies and study groups.

Results

Respondents comprised 330 physicians (204 infectious diseases specialists, 110 orthopedic surgeons, 23 clinical microbiologists) from 43 different countries (Europe, n = 134, 41%; Oceania n = 112, 34%; North America, n = 51, 16%; other, n = 33, 10%; total response rate 20%). After debridement, antibiotics and implant retention (DAIR) or one-stage revision, SAT would be initiated often or almost always by 38% of respondents from North America, but only in 6% from Europe and 7% from Oceania. First choices of SAT for staphylococcal PJI were oral cephalosporins (39%) and tetracyclines (31%) in North America; tetracyclines (27%) and anti-staphylococcal penicillins (22%) in Europe; and anti-staphylococcal penicillins (55%) in Oceania. There was no global or regional preferred SAT regimen for Gram-negative PJI. Of all respondents, dosage of SAT was never lowered (n = 126, 38%), lowered for specific antibiotics (n = 125, 38%) or lowered for all antibiotics (n = 79, 24%). SAT was prescribed for a lifelong duration (n = 43, 13%), a fixed duration (range 6 months–3 years) (n = 104, 32%) or for an undetermined duration (n = 154, 47%).

Conclusions

Approach to SAT in PJI is highly regional, with no consensus regarding the indication, selection, dose, or duration of SAT between physicians worldwide. This reflects the paucity of data and need for high quality studies to define the optimal use of SAT in the treatment of patients with PJI.

目的确定全球在使用抑制性抗菌疗法（SAT）治疗人工关节感染（PJI）方面的差异：方法：设计了一项在线调查，以调查临床医生对 PJI 采用抑制性抗菌疗法的方法，包括适应症、首选抗菌药物、剂量、疗程和随访。调查对象为四个国际（骨与关节）感染学会和研究小组的成员：受访者包括来自 43 个不同国家的 330 名医生（204 名传染病专家、110 名骨科外科医生、23 名临床微生物学家）（欧洲 134 人，占 41%；大洋洲 112 人，占 34%；北美 51 人，占 16%；其他 33 人，占 10%；总回复率 20%）。在清创、抗生素和种植体保留（DAIR）或一期翻修后，38% 的北美受访者会经常或几乎总是启动 SAT，但只有 6% 的欧洲受访者和 7% 的大洋洲受访者会这样做。在北美洲，治疗葡萄球菌 PJI 的首选 SAT 是口服头孢菌素（39%）和四环素（31%）；在欧洲，首选四环素（27%）和抗葡萄球菌青霉素（22%）；在大洋洲，首选抗葡萄球菌青霉素（55%）。全球或各地区都没有针对革兰氏阴性 PJI 的首选 SAT 方案。在所有受访者中，从未降低过 SAT 的剂量（126 人，38%）、降低了特定抗生素的剂量（125 人，38%）或降低了所有抗生素的剂量（79 人，24%）。SAT 的处方持续时间为终身（43 人，占 13%）、固定持续时间（6 个月至 3 年不等）（104 人，占 32%）或未确定持续时间（154 人，占 47%）：结论：PJI 中的 SAT 治疗方法具有很强的区域性，世界各地的医生对 SAT 的适应症、选择、剂量或持续时间没有达成共识。这反映了数据的匮乏，需要进行高质量的研究，以确定在治疗 PJI 患者时 SAT 的最佳使用方法。

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引用次数: 0

Duration of antimicrobial treatment for uncomplicated streptococcal bacteraemia: Another example of shorter is better 无并发症链球菌菌血症的抗菌治疗时间：时间越短越好的另一个例子

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-10-13 DOI: 10.1016/j.jinf.2024.106313

Objectives

Duration of treatment for uncomplicated streptococcal bacteraemia is unknown. The study aims to assess clinical outcomes of patients with uncomplicated streptococcal bacteraemia receiving a short course (5–10 days) of antimicrobial treatment compared to those receiving the traditional, longer duration (11–18 days).

Methods

This retrospective study was conducted at the Lausanne University Hospital, Switzerland and included episodes of uncomplicated streptococcal bacteraemia among adult patients from 2015 to 2023. Clinical failure was defined as mortality, recurrence of bacteraemia by the same streptococcal species and development in bone and joint infection within 120 days.

Results

During the study period, 336 episodes of uncomplicated streptococcal bacteraemia were included. The median duration of antimicrobial treatment was 10 days (interquartile range: 7–14); 184 (55%) and 152 (45%) episodes received a short (5–10 days) and long (11–18 days) duration of antimicrobial treatment, respectively. Forty-three (13%) episodes had clinical failure; 120-day mortality was 11% (36 episodes); recurrence of bacteraemia by the same streptococcal species was observed in 8 episodes (2%). No difference in clinical failure was observed between episodes receiving short and long courses of antimicrobial treatment (10% versus 16%; P 0.143). The Cox multivariable regression model found that a Charlson comorbidity index >4 (aHR 4.87, 95% CI 3.08–7.71), and septic shock (1.67, 1.04–2.67) were associated with clinical failure; a short course of antimicrobial treatment was not associated with clinical failure (0.90, 0.57–1.12).

Conclusions

This study has shown that a short duration of antimicrobial treatment for cases of streptococcal bacteraemia is effective and safe.

目的：无并发症链球菌菌血症的治疗时间尚不清楚。本研究旨在评估接受短疗程（5-10 天）抗菌药物治疗的无并发症链球菌菌血症患者与接受传统长疗程（11-18 天）抗菌药物治疗的患者的临床疗效。临床失败定义为死亡、同一链球菌菌血症复发以及在120天内出现骨关节感染。抗菌治疗的中位持续时间为 10 天（四分位数间距：7-14 天）；分别有 184 例（55%）和 152 例（45%）患者接受了短期（5-10 天）和长期（11-18 天）抗菌治疗。43例（13%）临床治疗失败；120天死亡率为11%（36例）；8例（2%）再次发生同一链球菌菌血症。接受短疗程和长疗程抗菌治疗的病例在临床失败率上没有差异（10% 对 16%；P 0.143）。Cox多变量回归模型发现，Charlson合并症指数>4（aHR 4.87，95% CI 3.08-7.71）和脓毒性休克（1.67，1.04-2.67）与临床失败有关；抗菌治疗疗程短与临床失败无关（0.90，0.57-1.12）。

{"title":"Duration of antimicrobial treatment for uncomplicated streptococcal bacteraemia: Another example of shorter is better","authors":"","doi":"10.1016/j.jinf.2024.106313","DOIUrl":"10.1016/j.jinf.2024.106313","url":null,"abstract":"<div><h3>Objectives</h3><div>Duration of treatment for uncomplicated streptococcal bacteraemia is unknown. The study aims to assess clinical outcomes of patients with uncomplicated streptococcal bacteraemia receiving a short course (5–10 days) of antimicrobial treatment compared to those receiving the traditional, longer duration (11–18 days).</div></div><div><h3>Methods</h3><div>This retrospective study was conducted at the Lausanne University Hospital, Switzerland and included episodes of uncomplicated streptococcal bacteraemia among adult patients from 2015 to 2023. Clinical failure was defined as mortality, recurrence of bacteraemia by the same streptococcal species and development in bone and joint infection within 120 days.</div></div><div><h3>Results</h3><div>During the study period, 336 episodes of uncomplicated streptococcal bacteraemia were included. The median duration of antimicrobial treatment was 10 days (interquartile range: 7–14); 184 (55%) and 152 (45%) episodes received a short (5–10 days) and long (11–18 days) duration of antimicrobial treatment, respectively. Forty-three (13%) episodes had clinical failure; 120-day mortality was 11% (36 episodes); recurrence of bacteraemia by the same streptococcal species was observed in 8 episodes (2%). No difference in clinical failure was observed between episodes receiving short and long courses of antimicrobial treatment (10% versus 16%; <em>P</em> 0.143). The Cox multivariable regression model found that a Charlson comorbidity index >4 (aHR 4.87, 95% CI 3.08–7.71), and septic shock (1.67, 1.04–2.67) were associated with clinical failure; a short course of antimicrobial treatment was not associated with clinical failure (0.90, 0.57–1.12).</div></div><div><h3>Conclusions</h3><div>This study has shown that a short duration of antimicrobial treatment for cases of streptococcal bacteraemia is effective and safe.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pandrug-resistant Klebsiella pneumoniae isolated from Ukrainian war victims are hypervirulent 从乌克兰战争受害者体内分离出的耐潘生菌肺炎克雷伯氏菌具有高病毒性。

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection

Pub Date : 2024-10-11 DOI: 10.1016/j.jinf.2024.106312

Objectives

Carbapenem- and colistin-resistant Klebsiella pneumoniae were isolated from war victims treated in hospitals in Ukraine. The question was whether these pandrug-resistant K. pneumoniae are pathogenic and capable of causing disease in a broader context.

Methods

Klebsiella pneumoniae clinical isolates (n = 37) were tested for antibiotic resistance and subjected to whole-genome sequencing (WGS). In addition, their pathogenicity was tested by serum resistance and two separate animal models.

Results

Isolates belonging to the sequence types (ST) 23, 147, 307, 395, and 512 were found to harbor resistance genes against carbapenems and cephalosporins. Nine isolates carried point mutations in pmrB and phoP genes associated with colistin resistance. All bacteria were equipped with multiple virulence genes, and the colistin-resistant isolates each carried 10 different genes. Colistin-resistant K. pneumoniae were more serum-resistant, more virulent against G. mellonella larvae, and displayed an increased survival in mice compared to colistin-susceptible bacteria. The iucA, peg-344, rmpA, rmpC, and rmpD genes were associated with increased virulence in animals.

Conclusions

Pandrug-resistant K. pneumoniae in Ukraine are hypervirulent and retain their pathogenicity, highlighting the need to prevent disseminated spread.

目的：从在乌克兰医院接受治疗的战争受害者体内分离出抗碳青霉烯类和抗大肠杆菌的肺炎克雷伯氏菌。问题是这些对潘生丁耐药的肺炎克雷伯菌是否具有致病性，是否能在更广泛的范围内致病：方法：对肺炎克雷伯菌临床分离株（n = 37）进行抗生素耐药性检测，并进行全基因组测序（WGS）。此外，还通过血清耐药性和两种不同的动物模型检测了它们的致病性：结果：发现属于序列类型（ST）23、147、307、395 和 512 的分离株携带对碳青霉烯类和头孢菌素的耐药基因。九个分离菌株的 pmrB 和 phoP 基因携带与可乐定耐药性相关的点突变。所有细菌都带有多种毒力基因，耐秋水仙素的分离株各带有 10 种不同的基因。与对秋水仙碱敏感的细菌相比，耐秋水仙碱的肺炎克氏菌对血清的抵抗力更强，对G. mellonella幼虫的毒力更强，在小鼠体内的存活率更高。iucA、peg-344、rmpA、rmpC 和 rmpD 基因与动物毒力增强有关：结论：乌克兰的耐潘生丁肺炎克氏菌具有很强的致病力，并能保持其致病性，因此需要防止其传播。

{"title":"Pandrug-resistant Klebsiella pneumoniae isolated from Ukrainian war victims are hypervirulent","authors":"","doi":"10.1016/j.jinf.2024.106312","DOIUrl":"10.1016/j.jinf.2024.106312","url":null,"abstract":"<div><h3>Objectives</h3><div>Carbapenem- and colistin-resistant <em>Klebsiella pneumoniae</em> were isolated from war victims treated in hospitals in Ukraine. The question was whether these pandrug-resistant <em>K. pneumoniae</em> are pathogenic and capable of causing disease in a broader context.</div></div><div><h3>Methods</h3><div><em>Klebsiella pneumoniae</em> clinical isolates (<em>n</em> = 37) were tested for antibiotic resistance and subjected to whole-genome sequencing (WGS). In addition, their pathogenicity was tested by serum resistance and two separate animal models.</div></div><div><h3>Results</h3><div>Isolates belonging to the sequence types (ST) 23, 147, 307, 395, and 512 were found to harbor resistance genes against carbapenems and cephalosporins. Nine isolates carried point mutations in <em>pmrB</em> and <em>phoP</em> genes associated with colistin resistance. All bacteria were equipped with multiple virulence genes, and the colistin-resistant isolates each carried 10 different genes. Colistin-resistant <em>K. pneumoniae</em> were more serum-resistant, more virulent against <em>G. mellonella</em> larvae, and displayed an increased survival in mice compared to colistin-susceptible bacteria. The <em>iucA</em>, <em>peg-344</em>, <em>rmpA</em>, <em>rmpC</em>, and <em>rmpD</em> genes were associated with increased virulence in animals.</div></div><div><h3>Conclusions</h3><div>Pandrug-resistant <em>K. pneumoniae</em> in Ukraine are hypervirulent and retain their pathogenicity, highlighting the need to prevent disseminated spread.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0