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Comment on: Impact of adequate empirical combination therapy on mortality in septic shock due to Pseudomonas aeruginosa bloodstream infections: a multicentre retrospective cohort study. 评论充分的经验性综合疗法对铜绿假单胞菌血流感染所致脓毒性休克死亡率的影响:一项多中心回顾性队列研究。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-09 DOI: 10.1093/jac/dkae366
Caglayan Merve Ayaz, Özge Turhan
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引用次数: 0
A loading dose of clofazimine to rapidly achieve steady-state-like concentrations in patients with nontuberculous mycobacterial disease. 非结核分枝杆菌疾病患者服用氯法齐明的负荷剂量,可迅速达到类似稳态的浓度。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-08 DOI: 10.1093/jac/dkae309
Ralf Stemkens, Arthur Lemson, Simon E Koele, Elin M Svensson, Lindsey H M Te Brake, Reinout van Crevel, Martin J Boeree, Wouter Hoefsloot, Jakko van Ingen, Rob E Aarnoutse

Objectives: Clofazimine is a promising drug for the treatment of nontuberculous mycobacterial (NTM) diseases. Accumulation of clofazimine to reach steady-state plasma concentrations takes months. A loading dose may reduce the time to steady-state-like concentrations. We evaluated the pharmacokinetics (PK), safety and tolerability of a loading dose regimen in patients with NTM disease.

Methods: Adult participants received a 4-week loading dose regimen of 300 mg clofazimine once daily, followed by a maintenance dose of 100 mg once daily (combined with other antimycobacterial drugs). Blood samples for PK analysis were collected on three occasions. A population PK model for clofazimine was developed and simulations were performed to assess the time to reach steady-state-like (target) concentrations for different dosing regimens.

Results: Twelve participants were included. The geometric mean peak and trough clofazimine concentrations after the 4-week loading phase were 0.87 and 0.50 mg/L, respectively. Adverse events were common, but mostly mild and none led to discontinuation of clofazimine. Our loading dose regimen reduced the predicted median time to target concentrations by 1.5 months compared to no loading dose (3.8 versus 5.3 months). Further time benefit was predicted with a 6-week loading dose regimen (1.4 versus 5.3 months).

Conclusion: A 4-week loading dose regimen of 300 mg once daily reduced the time to target clofazimine concentrations and was safe and well-tolerated. Extending the loading phase to 6 weeks could further decrease the time to target concentrations. Using a loading dose of clofazimine is a feasible strategy to optimize treatment of NTM disease.

Clinical trials registration: NCT05294146.

目的:氯法齐明是一种治疗非结核分枝杆菌疾病的有效药物。氯法齐明需要数月才能累积到稳态血浆浓度。负荷剂量可缩短达到类似稳态浓度的时间。我们评估了NTM疾病患者负荷剂量方案的药代动力学(PK)、安全性和耐受性:成年参与者接受为期 4 周的负荷剂量治疗,每天一次,每次 300 毫克氯法齐明,然后每天一次,每次 100 毫克的维持剂量(与其他抗霉菌药物联合使用)。共采集了三次用于 PK 分析的血液样本。建立了氯法齐明的群体PK模型,并进行了模拟,以评估不同给药方案达到类似稳态(目标)浓度的时间:结果:共纳入了 12 名参与者。在为期4周的负荷阶段后,氯法嗪明的几何平均峰值浓度为0.87毫克/升,谷值浓度为0.50毫克/升。不良反应很常见,但大多较轻,没有任何不良反应导致患者停用氯法齐明。与无负荷剂量相比,我们的负荷剂量方案将达到目标浓度的预测中位时间缩短了 1.5 个月(3.8 个月对 5.3 个月)。预计6周负荷剂量方案可进一步缩短时间(1.4个月对5.3个月):结论:每天一次、每次300毫克的4周负荷剂量方案缩短了氯唑明达到目标浓度的时间,并且安全、耐受性良好。将负荷阶段延长至 6 周可进一步缩短达到目标浓度的时间。使用氯唑明负荷剂量是优化NTM疾病治疗的可行策略:临床试验注册:NCT05294146。
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引用次数: 0
Point-of-care tests to manage acute respiratory tract infections in primary care: a systematic review and qualitative synthesis of healthcare professional and patient views. 基层医疗机构管理急性呼吸道感染的床旁检测:对医护人员和患者观点的系统回顾和定性综述。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-08 DOI: 10.1093/jac/dkae349
Melanie E Hoste, Aleksandra J Borek, Marta Santillo, Nia Roberts, Sarah Tonkin-Crine, Sibyl Anthierens

Objectives: To review the evidence on healthcare professionals' (HCPs) and patients' views of the use of point-of-care tests (POCTs) in the management of acute respiratory tract infections (RTIs) in primary care settings.

Methods: We conducted a systematic review of studies up to 28 April 2023. We included studies that included qualitative methods and results; focused on HCPs' and/or patients' views/experiences of POCTs for acute RTIs; and were conducted in primary care settings. We conducted a thematic synthesis to identify how their views on POCTs and interventions can support test use (PROSPERO registration: CRD42019150347).

Results: We included 33 studies, developing 9 categories each for HCP and patient data. We identified 38 factors affecting POCT use: 28 from HCPs and 10 from patients. Factors exist outside and within consultations, and post-consultations, illustrating that some cannot be addressed by HCPs alone. Fourteen interventions were identified that could address factors and support POCT use, with 7 interventions appearing to address the most factors. Some interventions were beyond the scope of HCPs and patients and needed to be addressed at system and organizational levels. Both groups had mixed views on the use of POCTs and highlighted implementation challenges.

Discussion: This review highlights numerous factors affecting POCT use in primary care. Policy-makers planning to implement POCTs are likely to achieve more by providing multi-faceted interventions that target factors outside, within, and post-consultation. Some interventions may need to be already established before POCT introduction. Whilst evidence beyond general practice is limited, similar factors suggest that similar context-tailored interventions would be appropriate.

目的综述医护人员(HCPs)和患者对在基层医疗机构使用床旁检测(POCTs)治疗急性呼吸道感染(RTIs)的看法:我们对截至 2023 年 4 月 28 日的研究进行了系统回顾。我们纳入了包含定性方法和结果的研究;这些研究关注的是初级保健人员和/或患者对急性 RTI POCT 的看法/体验;这些研究是在初级保健环境中进行的。我们进行了专题综述,以确定他们对 POCT 和干预措施的看法如何支持检测的使用(PROSPERO 注册:CRD42019150347):我们纳入了 33 项研究,为 HCP 和患者数据各制定了 9 个类别。我们确定了 38 个影响 POCT 使用的因素:其中 28 项来自 HCP,10 项来自患者。这些因素既存在于会诊之外,也存在于会诊之内和会诊之后,说明有些因素仅靠医疗保健人员是无法解决的。已确定 14 项干预措施可解决各种因素并支持 POCT 的使用,其中 7 项干预措施似乎可解决最多的因素。有些干预措施超出了保健医生和患者的能力范围,需要在系统和组织层面加以解决。两组人员对使用 POCT 的看法不一,并强调了实施方面的挑战:本综述强调了影响 POCT 在初级保健中使用的诸多因素。计划实施 POCT 的政策制定者可能会通过提供针对诊疗外、诊疗内和诊疗后因素的多方面干预措施来取得更大的成果。有些干预措施可能需要在引入 POCT 之前就已确立。虽然全科医生以外的证据有限,但类似的因素表明,根据具体情况采取类似的干预措施也是合适的。
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引用次数: 0
Concentrations of ceftazidime and avibactam in bile fluid-a prospective phase IIb study. 胆汁中头孢他啶和阿维菌素的浓度--一项前瞻性 IIb 期研究。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-07 DOI: 10.1093/jac/dkae361
Andrea Witowski, Lars Palmowski, Iris K Minichmayr, Markus Zeitlinger, Christoph Dorn, Constantin Lier, Michael Adamzik, Hartmuth Nowak, Tim Rahmel

Background: The rise in carbapenem-resistant bacteria and the limited number of effective antibiotics pose a major health-care threat. The combination of ceftazidime (CAZ) and avibactam (AVI) represents an approved treatment option for carbapenem-resistant intra-abdominal infections. However, data on the pharmacokinetic profile of AVI in the hepatobiliary compartment is lacking.

Objectives: To provide clinical in vivo data on the concentration of AVI in bile fluid as a surrogate for hepatobiliary excretion.

Methods: A single dose of 2000/500 mg CAZ/AVI was administered prolonged over 2 h to 10 patients prior to abdominal surgery, with bile samples available in nine patients in this phase IIb study (DRKS-ID: DRKS00023533). Antibiotic concentrations in plasma (0-8 h), bile (after resection) and pharmacodynamic parameters were determined.

Results: The mean concentration across individuals in bile was 33.5 mg/L (±20.5 mg/L) for CAZ and 7.1 mg/L (±3.5 mg/L) for AVI, resulting in bile/plasma ratios of 0.58 (±0.26) and 0.61 (±0.18). The Cmax in plasma was 87.2 mg/L (±25.0 mg/L) for CAZ and 18.6 mg/L (±6.29 mg/L) for AVI, with AUC0-∞ values of 351 h·mg/L (±104 h·mg/L) and 72.1 h·mg/L (±32.1 h·mg/L), respectively. Plasma concentrations of both CAZ and AVI remained more than 50% of the dosing interval above the minimum inhibitory concentrations (T>MIC > 50%; MICCAZ = 8 mg/L, MICAVI = 1 mg/L) in all patients. No antibiotic-associated side effects were reported during the 30-day follow-up.

Conclusions: The concentrations of CAZ and AVI in bile suggest their potential as a valuable therapeutic option for multi-resistant biliary infections.

背景:耐碳青霉烯类细菌的增加和有效抗生素的有限数量对医疗保健构成了重大威胁。头孢他啶(CAZ)和阿维巴坦(AVI)的联合用药已被批准用于治疗耐碳青霉烯类药物的腹腔感染。然而,目前尚缺乏 AVI 在肝胆区的药代动力学特征数据:目的:提供AVI在胆汁液中的浓度作为肝胆排泄替代物的临床活体数据:在这项 IIb 期研究(DRKS-ID:DRKS00023533)中,有 9 名患者获得了胆汁样本。研究测定了血浆(0-8 小时)、胆汁(切除术后)中的抗生素浓度和药效学参数:CAZ和AVI在胆汁中的平均浓度分别为33.5毫克/升(±20.5毫克/升)和7.1毫克/升(±3.5毫克/升),胆汁/血浆比分别为0.58(±0.26)和0.61(±0.18)。CAZ在血浆中的最大浓度为87.2毫克/升(±25.0毫克/升),AVI为18.6毫克/升(±6.29毫克/升),AUC0-∞值分别为351小时-毫克/升(±104小时-毫克/升)和72.1小时-毫克/升(±32.1小时-毫克/升)。所有患者的CAZ和AVI血浆浓度在给药间隔期内均高于最低抑制浓度的50%以上(T>MIC > 50%;MICCAZ = 8 mg/L,MICAVI = 1 mg/L)。在30天的随访过程中,没有出现与抗生素相关的副作用:结论:CAZ和AVI在胆汁中的浓度表明,它们有可能成为治疗多重耐药性胆道感染的重要选择。
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引用次数: 0
Target-site cefiderocol pharmacokinetics in soft tissues of healthy volunteers. 健康志愿者软组织中的目标部位头孢哌酮药代动力学。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-07 DOI: 10.1093/jac/dkae359
Maria Sanz-Codina, Wisse van Os, Anh Duc Pham, Anselm Jorda, Michael Wölf-Duchek, Felix Bergmann, Edith Lackner, Constantin Lier, J G Coen van Hasselt, Iris K Minichmayr, Christoph Dorn, Markus Zeitlinger, Valentin Al Jalali

Background: Cefiderocol may potentially be used to treat skin and soft tissue infections (SSTIs). However, the pharmacokinetics of cefiderocol in human soft tissues have not yet been determined. The objective of the present PK study was to investigate whether target-site concentrations of cefiderocol are sufficiently high for the treatment of SSTIs.

Methods: In this pharmacokinetic study, a single intravenous dose of 2 g cefiderocol was administered to eight healthy male volunteers. Drug concentrations were determined in plasma, muscle and subcutis over 8 h. Free plasma concentrations were calculated using the plasma protein binding determined with ultrafiltration. Free tissue concentrations were obtained using microdialysis. Penetration ratios were calculated as AUC0-8h_free_tissue/AUC0-8h_free_plasma. A population pharmacokinetic model was developed, and the probability of target attainment (PTA) was determined using Monte Carlo simulations.

Results: Cefiderocol showed good tissue penetration, with mean penetration ratios ± standard deviation of 0.99 ± 0.33 and 0.92 ± 0.30 for subcutis and muscle, respectively. Cefiderocol pharmacokinetics in plasma were best described with a two-compartment model, and tissue concentrations were described by scaling the tissue concentrations to concentrations in the peripheral compartment of the plasma model. For a thrice-daily regimen with 2 g doses intravenously infused over 3 h, PTA was ≥90% for MIC values up to 4 mg/L, both based on free plasma and soft tissue pharmacokinetics.

Conclusions: This study indicates that a dose of 2 g cefiderocol achieves concentrations in plasma considered sufficient for treating relevant bacterial species. Assuming a comparable PK/PD target for soft tissues, sufficiently high concentrations would also be achieved in soft tissues.

背景:头孢羟氨苄可用于治疗皮肤和软组织感染(SSTI)。然而,头孢羟氨苄在人体软组织中的药代动力学尚未确定。本药效学研究的目的是探讨头孢羟氨苄的靶位浓度是否足以治疗SSTI:在这项药代动力学研究中,8 名健康男性志愿者单次静脉注射了 2 克头孢羟氨苄。游离血浆浓度通过超滤测定的血浆蛋白结合力计算得出。游离组织浓度通过微透析法获得。渗透率按 AUC0-8h_free_tissue/AUC0-8h_free_plasma 计算。建立了群体药代动力学模型,并通过蒙特卡罗模拟确定了达到目标的概率(PTA):结果:头孢羟氨苄显示出良好的组织渗透性,皮下和肌肉的平均渗透率(± 标准差)分别为 0.99 ± 0.33 和 0.92 ± 0.30。血浆中头孢羟氨苄的药代动力学用两室模型进行了最佳描述,而组织浓度则是通过将组织浓度与血浆模型中外周室的浓度进行缩比来描述的。根据游离血浆和软组织药代动力学,在每天三次、每次 2 克剂量、分 3 小时静脉注射的治疗方案中,当 MIC 值高达 4 毫克/升时,PTA ≥90%:这项研究表明,2 克头孢羟氨苄的血浆浓度足以治疗相关的细菌种类。假设软组织的 PK/PD 目标相当,那么在软组织中也能达到足够高的浓度。
{"title":"Target-site cefiderocol pharmacokinetics in soft tissues of healthy volunteers.","authors":"Maria Sanz-Codina, Wisse van Os, Anh Duc Pham, Anselm Jorda, Michael Wölf-Duchek, Felix Bergmann, Edith Lackner, Constantin Lier, J G Coen van Hasselt, Iris K Minichmayr, Christoph Dorn, Markus Zeitlinger, Valentin Al Jalali","doi":"10.1093/jac/dkae359","DOIUrl":"https://doi.org/10.1093/jac/dkae359","url":null,"abstract":"<p><strong>Background: </strong>Cefiderocol may potentially be used to treat skin and soft tissue infections (SSTIs). However, the pharmacokinetics of cefiderocol in human soft tissues have not yet been determined. The objective of the present PK study was to investigate whether target-site concentrations of cefiderocol are sufficiently high for the treatment of SSTIs.</p><p><strong>Methods: </strong>In this pharmacokinetic study, a single intravenous dose of 2 g cefiderocol was administered to eight healthy male volunteers. Drug concentrations were determined in plasma, muscle and subcutis over 8 h. Free plasma concentrations were calculated using the plasma protein binding determined with ultrafiltration. Free tissue concentrations were obtained using microdialysis. Penetration ratios were calculated as AUC0-8h_free_tissue/AUC0-8h_free_plasma. A population pharmacokinetic model was developed, and the probability of target attainment (PTA) was determined using Monte Carlo simulations.</p><p><strong>Results: </strong>Cefiderocol showed good tissue penetration, with mean penetration ratios ± standard deviation of 0.99 ± 0.33 and 0.92 ± 0.30 for subcutis and muscle, respectively. Cefiderocol pharmacokinetics in plasma were best described with a two-compartment model, and tissue concentrations were described by scaling the tissue concentrations to concentrations in the peripheral compartment of the plasma model. For a thrice-daily regimen with 2 g doses intravenously infused over 3 h, PTA was ≥90% for MIC values up to 4 mg/L, both based on free plasma and soft tissue pharmacokinetics.</p><p><strong>Conclusions: </strong>This study indicates that a dose of 2 g cefiderocol achieves concentrations in plasma considered sufficient for treating relevant bacterial species. Assuming a comparable PK/PD target for soft tissues, sufficiently high concentrations would also be achieved in soft tissues.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Real-world effectiveness of early anti-SARS therapy in severely immunocompromised COVID-19 outpatients during the SARS-CoV-2 omicron variant era: a propensity score-adjusted retrospective cohort study. SARS-CoV-2 omicron变异体时代严重免疫力低下的COVID-19门诊患者早期抗SARS治疗的实际效果:倾向得分调整的回顾性队列研究。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-07 DOI: 10.1093/jac/dkae351
Héctor Pinargote-Celorio, Óscar Moreno-Pérez, Pilar González-De-La-Aleja, Jara Llenas-García, Pedro María Martínez Pérez-Crespo, Juan-Carlos Rodríguez-Díaz, Belén Martínez-López, Nicolás Merchante Gutiérrez, José-Manuel Ramos-Rincón, Esperanza Merino

Background: The effectiveness of the early treatment for antiviral agents in SARS-CoV-2 infection is closely related to patient comorbidities. Data on effectiveness in immunocompromised patients are limited, with reports involving highly heterogeneous and not well-defined populations. We aimed to assess the effectiveness of treatment in reducing hospitalizations in a real-world cohort of severely immunocompromised COVID-19 outpatients.

Patients and methods: We conducted a multicentre, retrospective, observational cohort study of immunocompromised outpatients attended in infectious diseases departments from 1 January to 31 December 2022. Propensity score matching (PSM) multivariable logistic regression models were used to estimate the adjusted odds ratio [(aOR, 95% confidence interval (CI)] for the association between antiviral prescription and outcome (COVID-19-related hospitalization up to Day 90).

Results: We identified 746 immunocompromised outpatients with confirmed SARS-CoV-2 infection. After eligibility criteria and PSM, a total of 410 patients were analysed: 205 receiving treatment (remdesivir, sotrovimab or nirmatrelvir/ritonavir) and 205 matched controls. Fifty-two patients required at least one COVID-19-related hospitalization 8 (3.9%) versus 44 (21.5%) in the antiviral and matched control cohorts, respectively. There were 13 deaths at 90 days, of which only 4 were COVID-19-related and none in the antiviral treatment group. After adjustment for residual confounders, the use of early therapy was associated with a protective effect on the risk of hospitalization [aOR 0.13 (0.05-0.29)], as was the use of biological immunomodulators [aOR 0.27 (0.10-0.74)], whereas chronic obstructive pulmonary disease [aOR 4.65 (1.09-19.69)] and anti-CD20 use [aOR 2.76 (1.31-5.81)] increased the odds.

Conclusions: Early antiviral treatment was associated with a reduced risk of COVID-19-related hospitalization in ambulatory severely immunocompromised COVID-19 patients.

背景:SARS-CoV-2 感染早期抗病毒药物治疗的效果与患者的合并症密切相关。有关免疫力低下患者疗效的数据十分有限,报告涉及的人群高度不均且定义不清。我们的目的是评估治疗对减少严重免疫力低下的 COVID-19 门诊患者住院率的有效性:我们对 2022 年 1 月 1 日至 12 月 31 日期间在传染病科就诊的免疫力低下门诊患者进行了一项多中心、回顾性、观察性队列研究。研究采用倾向得分匹配(PSM)多变量逻辑回归模型来估算抗病毒药物处方与治疗结果(COVID-19相关住院至第90天)之间的调整赔率[(aOR,95%置信区间(CI)]:我们确定了 746 名确诊感染 SARS-CoV-2 的免疫力低下的门诊患者。根据资格标准和 PSM,共对 410 名患者进行了分析:205 名接受治疗(雷米地韦、索罗维单抗或尼马瑞韦/利托那韦),205 名为匹配对照。52名患者需要至少一次与COVID-19相关的住院治疗,抗病毒治疗组和匹配对照组分别为8人(3.9%)和44人(21.5%)。90 天内有 13 人死亡,其中只有 4 人与 COVID-19 相关,抗病毒治疗组无一人死亡。对残余混杂因素进行调整后,早期治疗对住院风险有保护作用[aOR 0.13 (0.05-0.29)],使用生物免疫调节剂也有保护作用[aOR 0.27 (0.10-0.74)],而慢性阻塞性肺病[aOR 4.65 (1.09-19.69)]和抗CD20[aOR 2.76 (1.31-5.81)]会增加住院风险:结论:早期抗病毒治疗可降低COVID-19相关住院风险。
{"title":"Real-world effectiveness of early anti-SARS therapy in severely immunocompromised COVID-19 outpatients during the SARS-CoV-2 omicron variant era: a propensity score-adjusted retrospective cohort study.","authors":"Héctor Pinargote-Celorio, Óscar Moreno-Pérez, Pilar González-De-La-Aleja, Jara Llenas-García, Pedro María Martínez Pérez-Crespo, Juan-Carlos Rodríguez-Díaz, Belén Martínez-López, Nicolás Merchante Gutiérrez, José-Manuel Ramos-Rincón, Esperanza Merino","doi":"10.1093/jac/dkae351","DOIUrl":"https://doi.org/10.1093/jac/dkae351","url":null,"abstract":"<p><strong>Background: </strong>The effectiveness of the early treatment for antiviral agents in SARS-CoV-2 infection is closely related to patient comorbidities. Data on effectiveness in immunocompromised patients are limited, with reports involving highly heterogeneous and not well-defined populations. We aimed to assess the effectiveness of treatment in reducing hospitalizations in a real-world cohort of severely immunocompromised COVID-19 outpatients.</p><p><strong>Patients and methods: </strong>We conducted a multicentre, retrospective, observational cohort study of immunocompromised outpatients attended in infectious diseases departments from 1 January to 31 December 2022. Propensity score matching (PSM) multivariable logistic regression models were used to estimate the adjusted odds ratio [(aOR, 95% confidence interval (CI)] for the association between antiviral prescription and outcome (COVID-19-related hospitalization up to Day 90).</p><p><strong>Results: </strong>We identified 746 immunocompromised outpatients with confirmed SARS-CoV-2 infection. After eligibility criteria and PSM, a total of 410 patients were analysed: 205 receiving treatment (remdesivir, sotrovimab or nirmatrelvir/ritonavir) and 205 matched controls. Fifty-two patients required at least one COVID-19-related hospitalization 8 (3.9%) versus 44 (21.5%) in the antiviral and matched control cohorts, respectively. There were 13 deaths at 90 days, of which only 4 were COVID-19-related and none in the antiviral treatment group. After adjustment for residual confounders, the use of early therapy was associated with a protective effect on the risk of hospitalization [aOR 0.13 (0.05-0.29)], as was the use of biological immunomodulators [aOR 0.27 (0.10-0.74)], whereas chronic obstructive pulmonary disease [aOR 4.65 (1.09-19.69)] and anti-CD20 use [aOR 2.76 (1.31-5.81)] increased the odds.</p><p><strong>Conclusions: </strong>Early antiviral treatment was associated with a reduced risk of COVID-19-related hospitalization in ambulatory severely immunocompromised COVID-19 patients.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Suboptimal response to combination therapy with tixagevimab/cilgavimab and remdesivir for persistent SARS-CoV-2 infections in immunocompromised patients-authors' response. 免疫功能低下患者持续感染 SARS-CoV-2 后,对替卡西单抗/西格维单抗和雷米替韦联合疗法的反应不理想--作者的回应。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-07 DOI: 10.1093/jac/dkae357
Tzong-Yow Wu, Pao-Yu Chen, Jann-Tay Wang, Wang-Da Liu, Yee-Chun Chen, Shan-Chwen Chang
{"title":"Suboptimal response to combination therapy with tixagevimab/cilgavimab and remdesivir for persistent SARS-CoV-2 infections in immunocompromised patients-authors' response.","authors":"Tzong-Yow Wu, Pao-Yu Chen, Jann-Tay Wang, Wang-Da Liu, Yee-Chun Chen, Shan-Chwen Chang","doi":"10.1093/jac/dkae357","DOIUrl":"10.1093/jac/dkae357","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The two-component sensor factor envZ influences antibiotic resistance and virulence in the evolutionary dynamics of multidrug-resistant Salmonella enteritidis causing multisite invasive infections. 双组分传感因子 envZ 在引起多部位侵袭性感染的耐多药肠炎沙门氏菌的进化动态中影响抗生素耐药性和毒力。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-04 DOI: 10.1093/jac/dkae355
Lifei Yu, Xinhong Han, Wang Zhang, Ying Fu, Shaoxue Yang, Shenghai Wu, Jie Jin, Siying Li, Yan Chen, Yan Jiang, Yunsong Yu

Objectives: To assess the impact of mutations in the two-component sensor envZ on antibiotic resistance and virulence in the evolutionary dynamics of MDR Salmonella enteritidis (S. enteritidis).

Methods: Five S. enteritidis isolates obtained from a patient with multisite invasive infections were analysed. Analysis of antibiotic resistance genes, virulence genes and SNP was performed through WGS. RNA sequencing, quantitative RT-PCR, virulence testing in a Galleria mellonella (G. mellonella) infection model and in vitro cell experiments were used to examine the effects of envZ mutations.

Results: WGS revealed identical resistance and virulence genes on an IncFIB(S)/IncFII(S)/IncX1 fusion plasmid in all strains. The faecal strains harboured envZ mutations, reducing outer membrane protein ompD and ompF transcriptional level. Virulence testing demonstrated elevated virulence in envZ mutant strains. In vitro experiments revealed increased adhesion, invasion and phagocytosis resistance in envZ mutants, along with reduced biofilm formation and growth rates.

Conclusions: These findings highlight novel genetic locations on envZ influencing antibiotic resistance and virulence in clinical S. enteritidis strains. envZ mutations impact antibiotic resistance by down-regulating ompD and ompF expression and enhance virulence, contributing to multisite infections with increased fitness costs.

目的评估双组分传感器 envZ 的突变对 MDR 肠炎沙门氏菌(S. enteritidis)进化动态中抗生素耐药性和毒力的影响:方法:分析了从一名多部位侵袭性感染患者体内分离出的五株肠炎沙门氏菌。通过 WGS 对抗生素耐药基因、毒力基因和 SNP 进行了分析。利用 RNA 测序、定量 RT-PCR、Galleria mellonella(G. mellonella)感染模型毒力测试和体外细胞实验来研究 envZ 突变的影响:结果:WGS 发现所有菌株中的 IncFIB(S)/IncFII(S)/IncX1 融合质粒上都有相同的抗性和毒力基因。粪便菌株携带 envZ 突变,降低了外膜蛋白 ompD 和 ompF 的转录水平。毒力测试表明,envZ 突变菌株的毒力增强。体外实验显示,envZ 突变株的粘附性、侵袭性和抗吞噬性增强,生物膜形成和生长速度降低:这些发现突显了 envZ 上影响临床肠炎球菌菌株抗生素耐药性和毒力的新基因位置。
{"title":"The two-component sensor factor envZ influences antibiotic resistance and virulence in the evolutionary dynamics of multidrug-resistant Salmonella enteritidis causing multisite invasive infections.","authors":"Lifei Yu, Xinhong Han, Wang Zhang, Ying Fu, Shaoxue Yang, Shenghai Wu, Jie Jin, Siying Li, Yan Chen, Yan Jiang, Yunsong Yu","doi":"10.1093/jac/dkae355","DOIUrl":"https://doi.org/10.1093/jac/dkae355","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the impact of mutations in the two-component sensor envZ on antibiotic resistance and virulence in the evolutionary dynamics of MDR Salmonella enteritidis (S. enteritidis).</p><p><strong>Methods: </strong>Five S. enteritidis isolates obtained from a patient with multisite invasive infections were analysed. Analysis of antibiotic resistance genes, virulence genes and SNP was performed through WGS. RNA sequencing, quantitative RT-PCR, virulence testing in a Galleria mellonella (G. mellonella) infection model and in vitro cell experiments were used to examine the effects of envZ mutations.</p><p><strong>Results: </strong>WGS revealed identical resistance and virulence genes on an IncFIB(S)/IncFII(S)/IncX1 fusion plasmid in all strains. The faecal strains harboured envZ mutations, reducing outer membrane protein ompD and ompF transcriptional level. Virulence testing demonstrated elevated virulence in envZ mutant strains. In vitro experiments revealed increased adhesion, invasion and phagocytosis resistance in envZ mutants, along with reduced biofilm formation and growth rates.</p><p><strong>Conclusions: </strong>These findings highlight novel genetic locations on envZ influencing antibiotic resistance and virulence in clinical S. enteritidis strains. envZ mutations impact antibiotic resistance by down-regulating ompD and ompF expression and enhance virulence, contributing to multisite infections with increased fitness costs.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The efficacy of antimicrobial solutions against multispecies bacterial biofilm with or without negative pressure wound therapy in an in vitro wound model. 在体外伤口模型中,采用或不采用负压伤口疗法的抗菌溶液对多菌种细菌生物膜的疗效。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-03 DOI: 10.1093/jac/dkae338
Shamaila Tahir, Farhana Parvin, Matthew Wang, Anand K Deva, Karen Vickery, Honghua Hu

Objectives: Biofilm is the major challenge in chronic wound management. Instilling a wound cleansing solution aids in wound bed cleaning and infectious pathogen elimination. Negative pressure wound therapy (NPWT) improves the wound-healing process. This study investigated the efficacy of two antimicrobials (Vashe Wound Cleanser and Prontosan Wound Irrigation Solution) against a multispecies bacterial biofilm with or without NPWT in an in vitro wound model.

Methods: A mixed multispecies biofilm containing Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pyogenes, and Acinetobacter baumannii was developed and verified by scanning electron microscopy and fluorescent in situ hybridization. The efficacy of Vashe and Prontosan against multispecies biofilm with or without NPWT was evaluated by colony-forming unit (cfu) of each species and total bacterial number, and visually confirmed by live/dead stain and confocal microscopy.

Results: Prontosan reduced biofilm cell numbers significantly: 6 instils over 24 h resulting in 3.86 ± 0.14 cfu log10 reduction without NPWT and 4.75 ± 0.13 cfu log10 reduction combined with NPWT (P < 0.01) and 12 instils over 48 h resulting in 5.24 ± 0.11 cfu log10 reduction without NPWT and biofilm eradication with NPWT (P < 0.001). NPWT alone or combined with Vashe failed to reduce multispecies biofilm numbers significantly over 24 or 48 h.

Conclusions: Prontosan significantly reduced biofilm cell numbers, with better efficacy over 48 than 24 h, emphasizing the necessity for persistent and robust treatment. NPWT enhanced the effectiveness of Prontosan instillation. However, NPWT alone or combined with Vashe showed limited efficacy and difficulty when combating the multispecies biofilm in vitro.

目的:生物膜是慢性伤口管理的主要挑战。灌注伤口清洁液有助于清洁伤口床和消除感染性病原体。伤口负压疗法(NPWT)可改善伤口愈合过程。本研究调查了两种抗菌剂(Vashe 伤口清洁剂和 Prontosan 伤口冲洗液)在体外伤口模型中使用或不使用 NPWT 对多菌种细菌生物膜的疗效:方法:开发了一种包含金黄色葡萄球菌、铜绿假单胞菌、化脓性链球菌和鲍曼不动杆菌的多菌种混合生物膜,并通过扫描电子显微镜和荧光原位杂交进行了验证。通过各菌种的菌落形成单位(cfu)和细菌总数来评估 Vashe 和 Prontosan 对有或无 NPWT 的多菌种生物膜的疗效,并通过活/死染色和共聚焦显微镜进行视觉确认:结果:Prontosan 能显著减少生物膜细胞数量:在不使用 NPWT 的情况下,24 小时内灌注 6 次可减少 3.86 ± 0.14 cfu log10,在使用 NPWT 的情况下,可减少 4.75 ± 0.13 cfu log10(P):Prontosan 能明显减少生物膜细胞数量,48 小时内的疗效优于 24 小时,强调了持续、稳健治疗的必要性。NPWT 增强了 Prontosan 灌注的效果。然而,在体外对抗多菌种生物膜时,NPWT 单独使用或与 Vashe 结合使用的疗效有限且困难重重。
{"title":"The efficacy of antimicrobial solutions against multispecies bacterial biofilm with or without negative pressure wound therapy in an in vitro wound model.","authors":"Shamaila Tahir, Farhana Parvin, Matthew Wang, Anand K Deva, Karen Vickery, Honghua Hu","doi":"10.1093/jac/dkae338","DOIUrl":"https://doi.org/10.1093/jac/dkae338","url":null,"abstract":"<p><strong>Objectives: </strong>Biofilm is the major challenge in chronic wound management. Instilling a wound cleansing solution aids in wound bed cleaning and infectious pathogen elimination. Negative pressure wound therapy (NPWT) improves the wound-healing process. This study investigated the efficacy of two antimicrobials (Vashe Wound Cleanser and Prontosan Wound Irrigation Solution) against a multispecies bacterial biofilm with or without NPWT in an in vitro wound model.</p><p><strong>Methods: </strong>A mixed multispecies biofilm containing Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pyogenes, and Acinetobacter baumannii was developed and verified by scanning electron microscopy and fluorescent in situ hybridization. The efficacy of Vashe and Prontosan against multispecies biofilm with or without NPWT was evaluated by colony-forming unit (cfu) of each species and total bacterial number, and visually confirmed by live/dead stain and confocal microscopy.</p><p><strong>Results: </strong>Prontosan reduced biofilm cell numbers significantly: 6 instils over 24 h resulting in 3.86 ± 0.14 cfu log10 reduction without NPWT and 4.75 ± 0.13 cfu log10 reduction combined with NPWT (P < 0.01) and 12 instils over 48 h resulting in 5.24 ± 0.11 cfu log10 reduction without NPWT and biofilm eradication with NPWT (P < 0.001). NPWT alone or combined with Vashe failed to reduce multispecies biofilm numbers significantly over 24 or 48 h.</p><p><strong>Conclusions: </strong>Prontosan significantly reduced biofilm cell numbers, with better efficacy over 48 than 24 h, emphasizing the necessity for persistent and robust treatment. NPWT enhanced the effectiveness of Prontosan instillation. However, NPWT alone or combined with Vashe showed limited efficacy and difficulty when combating the multispecies biofilm in vitro.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prediction of antimicrobial resistance in Klebsiella pneumoniae using genomic and metagenomic next-generation sequencing data. 利用基因组和元基因组新一代测序数据预测肺炎克雷伯氏菌的抗菌药耐药性。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae248
Xun Zhou, Ming Yang, Fangyuan Chen, Leilei Wang, Peng Han, Zhi Jiang, Siquan Shen, Guanhua Rao, Fan Yang

Objectives: Klebsiella pneumoniae is a significant pathogen with increasing resistance and high mortality rates. Conventional antibiotic susceptibility testing methods are time-consuming. Next-generation sequencing has shown promise for predicting antimicrobial resistance (AMR). This study aims to develop prediction models using whole-genome sequencing data and assess their feasibility with metagenomic next-generation sequencing data from clinical samples.

Methods: On the basis of 4170 K. pneumoniae genomes, the main genetic characteristics associated with AMR were identified using a LASSO regression model. Consequently, the prediction model was established, validated and optimized using clinical isolate read simulation sequences. To evaluate the efficacy of the model, clinical specimens were collected.

Results: Four predictive models for amikacin, ciprofloxacin, levofloxacin, and piperacillin/tazobactam, initially had positive predictive values (PPVs) of 92%, 98%, 99%, 94%, respectively, when they were originally constructed. When applied to clinical specimens, their PPVs were 96%, 96%, 95%, and 100%, respectively. Meanwhile, there were negative predictive values (NPVs) of 100% for ciprofloxacin and levofloxacin, and 'not applicable' (NA) for amikacin and piperacillin/tazobactam. Our method achieved antibacterial phenotype classification accuracy rates of 95.92% for amikacin, 96.15% for ciprofloxacin, 95.31% for levofloxacin and 100% for piperacillin/tazobactam. The sequence-based prediction antibiotic susceptibility testing (AST) reported results in an average time of 19.5 h, compared with the 67.9 h needed for culture-based AST, resulting in a significant reduction of 48.4 h.

Conclusions: These preliminary results demonstrated that the performance of prediction model for a clinically significant antimicrobial-species pair was comparable to that of phenotypic methods, thereby encouraging the expansion of sequence-based susceptibility prediction and its clinical validation and application.

目的:肺炎克雷伯氏菌是一种重要的病原体,其抗药性不断增强,死亡率很高。传统的抗生素药敏试验方法耗时较长。下一代测序技术在预测抗菌药耐药性(AMR)方面前景广阔。本研究旨在利用全基因组测序数据开发预测模型,并利用临床样本的元基因组下一代测序数据评估其可行性:方法:在 4170 个肺炎双球菌基因组的基础上,利用 LASSO 回归模型确定了与 AMR 相关的主要遗传特征。随后,利用临床分离样本读取模拟序列建立、验证并优化了预测模型。为评估模型的有效性,收集了临床标本:阿米卡星、环丙沙星、左氧氟沙星和哌拉西林/他唑巴坦的四个预测模型最初建立时的阳性预测值(PPV)分别为 90%、85%、84% 和 94%。当应用于临床样本时,其 PPV 值分别增至 96%、96%、95% 和 100%。同时,环丙沙星和左氧氟沙星的阴性预测值为 100%,而阿米卡星和哌拉西林/他唑巴坦的阴性预测值为 "不适用"。我们的方法对阿米卡星、环丙沙星、左氧氟沙星和哌拉西林/他唑巴坦的抗菌表型分类准确率分别为 96.08%、96.15%、95.31% 和 100%。基于序列的预测抗生素药敏试验(AST)报告结果的平均时间为 19.5 小时,与基于培养的 AST 所需的 67.9 小时相比,显著减少了 48.4 小时:这些初步结果表明,针对临床上重要的抗菌素种对的预测模型的性能与表型方法相当,因此鼓励扩大基于序列的药敏预测及其临床验证和应用。
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Journal of Antimicrobial Chemotherapy
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