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Emergent resistance-associated mutations at first- or second-line HIV-1 virologic failure with second-generation InSTIs in two- and three-drug regimens: the Virostar-1 study. 在两药和三药治疗方案中使用第二代 InSTIs 导致一线或二线 HIV-1 病毒学治疗失败时出现的耐药性相关突变:Virostar-1 研究。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-22 DOI: 10.1093/jac/dkae377
Anne-Geneviève Marcelin, Cathia Soulie, Marc Wirden, Guillaume Barriere, François Durand, Charlotte Charpentier, Diane Descamps, Vincent Calvez

Background: Second-generation integrase strand transfer inhibitors (InSTIs) have a high barrier to resistance and potent antiretroviral activity. They are recommended as first- or second-line (FL and SL) options in two- and three-drug regimens (2DR and 3DR) in international treatment guidelines. However, there are limited real-world data on emerging resistance at the time of virological failure (VF) with these regimens.

Objectives: The Virostar-1 study objective is to analyse the emergence of resistance-associated mutations (RAMs) over 3 years with DTG-based 2DRs and DTG- or bictegravir (BIC)-based 3DRs in people living with HIV (PLWH) experiencing a VF (FL or SL).

Methods: Retrospective analysis of genotypic resistance detected at the time of a FL or SL VF with BIC/FTC/TAF, DTG/ABC/3TC, DTG/3TC and DTG/RPV between 2019 and 2022 was conducted from a French multicentre database. VF was defined as two consecutive HIV-1 plasma viral loads > 50 c/mL. Sanger assays were performed at VF within standard clinical care. Resistance mutations were reported using the ANRS algorithm. Selection biases prevent group comparisons.

Results: During the period, N = 5986 PLWH were followed either in FL or SL. The VF rate was overall low: BIC/FTC/TAF, 6.8%; DTG/ABC/3TC, 7.5%; DTG/3TC, 5.1%; and DTG/RPV, 2.1%. Some emergent InSTI or NRTI RAMs were detected with BIC/FTC/TAF 4%, DTG/ABC/3TC 8.5%, DTG/3TC 18% and 39% emergent NNRTI RAMs with DTG/RPV. However, a complete absence of dual resistance against NRTIs and InSTIs was observed.

Conclusions: We detected rare emergent InSTI RAMs and few emergent NRTI RAMs in PLWH failing DTG- or BIC-based regimens in FL or SL. The observed rates of emergent RAMs at VF were 4% with BIC/FTC/TAF, 8.5% with DTG/ABC/3TC, 18% with DTG/3TC and 39% with DTG/RPV.

背景:第二代整合酶链转移抑制剂(InSTIs)具有较高的耐药屏障和强大的抗逆转录病毒活性。国际治疗指南推荐在两药和三药治疗方案(2DR 和 3DR)中将其作为一线或二线(FL 和 SL)选择。然而,在使用这些方案出现病毒学失败(VF)时,有关新出现耐药性的实际数据却很有限:Virostar-1研究的目的是分析以DTG为基础的2DR和以DTG或比特拉韦(BIC)为基础的3DR在经历VF(FL或SL)的艾滋病病毒感染者(PLWH)中的3年耐药性相关突变(RAM)的出现情况:法国多中心数据库对2019年至2022年期间使用BIC/FTC/TAF、DTG/ABC/3TC、DTG/3TC和DTG/RPV治疗FL或SL VF时检测到的基因型耐药性进行了回顾性分析。VF定义为连续两次HIV-1血浆病毒载量>50 c/mL。在标准临床治疗范围内的 VF 期进行 Sanger 分析。耐药性突变采用 ANRS 算法进行报告。由于存在选择偏差,因此无法进行分组比较:在此期间,共有 5986 名 PLWH 接受了 FL 或 SL 的随访。VF率总体较低:BIC/FTC/TAF,6.8%;DTG/ABC/3TC,7.5%;DTG/3TC,5.1%;DTG/RPV,2.1%。在 BIC/FTC/TAF 4%、DTG/ABC/3TC 8.5%、DTG/3TC 18%、DTG/RPV 39% 和 NNRTI RAM 中发现了一些新出现的 InSTI 或 NRTI RAM。然而,我们观察到完全不存在对 NRTIs 和 InSTIs 的双重耐药性:我们在 FL 或 SL 地区使用 DTG 或 BIC 方案失败的 PLWH 中发现了罕见的 InSTI RAMs 和少数 NRTI RAMs。在 VF 期观察到的突发 RAM 发生率为:BIC/FTC/TAF 4%,DTG/ABC/3TC 8.5%,DTG/3TC 18%,DTG/RPV 39%。
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引用次数: 0
Identifying AWaRe indicators for appropriate antibiotic use: a narrative review. 确定合理使用抗生素的 AWaRe 指标:叙述性综述。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-18 DOI: 10.1093/jac/dkae370
Elisa Funiciello, Giulia Lorenzetti, Aislinn Cook, Jan Goelen, Catrin E Moore, Stephen M Campbell, Brian Godman, Deborah Tong, Benedikt Huttner, Pem Chuki, Michael Sharland

Introduction: Quality indicators (QIs) are widely used tools for antibiotic stewardship programmes. The Access, Watch, Reserve (AWaRe) system has been developed by the WHO to classify antibiotics based on their spectrum of activity and potential selection of antibiotic resistance. This review aimed to identify existing indicators for optimal antibiotic use to inform the development of future AWaRe QIs.

Methods: A literature search was performed in PubMed. We included articles describing QIs for hospital and primary healthcare antibiotic use. We extracted information about (i) the type of infection; (ii) setting; (iii) target for quality assessment; and (iv) methodology used for the development. We then identified the indicators that reflected the guidance provided in the AWaRe system.

Results: A total of 773 indicators for antibiotic use were identified. The management of health services and/or workers, the consumption of antibiotics, and antibiotic prescribing/dispensing were the principal targets for quality assessment. There was a similar distribution of indicators across primary and secondary care. For infection-specific indicators, about 50% focused on respiratory tract infections. Only a few QIs included information on review treatment or microbiological investigations. Although only 8 (1%) indicators directly cited the AWaRe system in the wording of the indicators, 445 (57.6%) indicators reflected the guidance provided in the AWaRe book.

Conclusions: A high number of indicators for appropriate antibiotic use have been developed. However, few are currently based directly on the WHO AWaRe system. There is a clear need to develop globally applicable AWaRe based indicators that can be integrated into antibiotic stewardship programmes.

导言:质量指标(QIs)是抗生素管理计划中广泛使用的工具。世界卫生组织开发了 "获取、观察、储备"(AWaRe)系统,根据抗生素的活性范围和抗生素耐药性的潜在选择对抗生素进行分类。本综述旨在确定最佳抗生素使用的现有指标,为未来 AWaRe QIs 的开发提供参考:方法:在 PubMed 上进行文献检索。我们收录了描述医院和基层医疗机构抗生素使用 QIs 的文章。我们提取了以下信息:(i) 感染类型;(ii) 环境;(iii) 质量评估目标;(iv) 制定方法。然后,我们确定了反映 AWaRe 系统所提供指导的指标:结果:共确定了 773 项抗生素使用指标。医疗服务和/或工作人员的管理、抗生素的使用以及抗生素的处方/配药是质量评估的主要目标。指标在初级和二级医疗机构的分布情况相似。在感染特异性指标方面,约 50%侧重于呼吸道感染。只有少数质量指标包括复查治疗或微生物学检查的信息。虽然只有 8 项(1%)指标在指标措辞中直接引用了 AWaRe 系统,但有 445 项(57.6%)指标反映了 AWaRe 书籍中提供的指导:结论:已经制定了大量抗生素合理使用指标。然而,目前直接基于世界卫生组织 AWaRe 系统的指标很少。显然有必要制定全球适用的基于 AWaRe 的指标,并将其纳入抗生素监管计划。
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引用次数: 0
Quantitative performance of humanized serum and epithelial lining fluid exposures of tigecycline and levofloxacin against a challenge set of Klebsiella pneumoniae and Pseudomonas aeruginosa in a standardized neutropenic murine pneumonia model. 在标准化中性鼠肺炎模型中,人源化血清和上皮内衬液暴露替加环素和左氧氟沙星对一组肺炎克雷伯菌和铜绿假单胞菌挑战的定量表现。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-18 DOI: 10.1093/jac/dkae333
Andrew J Fratoni, Alissa M Padgett, Erin M Duffy, David P Nicolau

Background: Lack of uniformity in infection models complicates preclinical development. The COMBINE protocol has standardized the murine neutropenic pneumonia model. Herein we provide benchmark efficacy data of humanized exposures of tigecycline and levofloxacin in plasma and epithelial lining fluid (ELF) against a collection of Klebsiella pneumoniae and Pseudomonas aeruginosa.

Methods: Following the COMBINE protocol, plasma and ELF human-simulated regimens (HSRs) of tigecycline 100 mg followed by 50 mg q12h and levofloxacin 750 mg once daily were developed and confirmed in the murine neutropenic pneumonia model. Tigecycline HSRs were tested against seven K. pneumoniae isolates. Levofloxacin HSRs were assessed against 10 K. pneumoniae and 9 P. aeruginosa. The change in cfu/lung over 24 h for each treatment was calculated. Each isolate was tested in duplicate against both the plasma and ELF HSRs on separate experiment days.

Results: Tigecycline 1.8 and 3 mg/kg q12h achieved humanized exposures of serum and ELF, respectively. Levofloxacin 120 and 90 mg/kg q8h led to fAUC exposures in plasma and ELF similar to in humans. Both tigecycline regimens were ineffective across the MIC range. Levofloxacin regimens achieved multilog kill against susceptible isolates, and no appreciable cfu/lung reductions in isolates with an MIC of ≥32 mg/L. Differences in cfu/lung were evident between the levofloxacin plasma and ELF HSRs against isolates with MICs of 4 and 8 mg/L.

Conclusions: Administering HSRs of tigecycline and levofloxacin based on both serum/plasma and ELF in the COMBINE pneumonia model resulted in cfu/lung values reasonably aligned with MIC. These data serve as translational benchmarks for future investigations with novel compounds.

背景:感染模型缺乏统一性使临床前开发变得复杂。COMBINE 方案规范了小鼠中性肺炎模型。在此,我们提供了血浆和上皮内衬液(ELF)中替加环素和左氧氟沙星人源化暴露对肺炎克雷伯菌和铜绿假单胞菌的基准疗效数据:按照 COMBINE 方案,开发了替加环素 100 毫克、50 毫克 q12h 和左氧氟沙星 750 毫克每日一次的血浆和上皮内衬液人体模拟方案(HSR),并在小鼠中性粒细胞减少性肺炎模型中进行了确认。针对七种肺炎克氏菌分离物测试了替加环素 HSR。左氧氟沙星 HSR 针对 10 个肺炎克氏菌和 9 个铜绿假单胞菌进行了评估。计算每种处理 24 小时内 cfu/肺的变化。在不同的实验日,针对血浆和 ELF HSR 对每种分离物进行重复测试:结果:替加环素 1.8 和 3 mg/kg q12h 分别达到了血清和 ELF 的人源化暴露。左氧氟沙星120毫克和90毫克/千克 q8小时后,血浆和ELF中的fAUC暴露量与人体相似。两种替加环素治疗方案在MIC范围内均无效。左氧氟沙星治疗方案对易感分离株有多倍杀灭作用,对MIC≥32 mg/L的分离株的cfu/lung没有明显降低。左氧氟沙星血浆 HSR 和 ELF HSR 对 MIC 值为 4 毫克/升和 8 毫克/升的分离株的 cfu/lung 降幅差异明显:结论:在 COMBINE 肺炎模型中使用基于血清/血浆和 ELF 的替加环素和左氧氟沙星 HSR,其 cfu/lung 值与 MIC 值相当一致。这些数据可作为今后研究新型化合物的转化基准。
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引用次数: 0
Ceftriaxone-resistant Neisseria gonorrhoeae detected in England, 2015-24: an observational analysis. 2015-24 年英格兰发现的耐头孢曲松淋病奈瑟菌:观察分析。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-17 DOI: 10.1093/jac/dkae369
Helen Fifer, Michel Doumith, Luciana Rubinstein, Laura Mitchell, Mark Wallis, Selena Singh, Gurmit Jagjit Singh, Michael Rayment, John Evans-Jones, Alison Blume, Olamide Dosekun, Kenny Poon, Achyuta Nori, Michaela Day, Rachel Pitt-Kendall, Suzy Sun, Prarthana Narayanan, Emma Callan, Anna Vickers, Jack Minshull, Kirsty F Bennet, James E C Johnson, John Saunders, Sarah Alexander, Hamish Mohammed, Neil Woodford, Katy Sinka, Michelle Cole

Objectives: Since June 2022, there has been a rise in the number of ceftriaxone-resistant Neisseria gonorrhoeae cases detected in England (n = 15), of which a third were XDR. We describe the demographic and clinical details of the recent cases and investigate the phenotypic and molecular characteristics of the isolates. For a comprehensive overview, we also reviewed 16 ceftriaxone-resistant cases previously identified in England since December 2015 and performed a global genomic comparison of all publicly available ceftriaxone-resistant N. gonorrhoeae strains with mosaic penA alleles.

Methods: All N. gonorrhoeae isolates resistant to ceftriaxone (MIC > 0.125 mg/L) were whole-genome sequenced and compared with 142 global sequences of ceftriaxone-resistant N. gonorrhoeae. Demographic, behavioural and clinical data were collected.

Results: All cases were heterosexual, and most infections were associated with travel from the Asia-Pacific region. However, some had not travelled outside England within the previous few months. There were no ceftriaxone genital treatment failures, but three of five pharyngeal infections and the only rectal infection failed treatment. The isolates represented 13 different MLST STs, and most had the mosaic penA-60.001 allele. The global genomes clustered into eight major phylogroups, with regional associations. All XDR isolates belonged to the same phylogroup, represented by MLST ST16406.

Conclusions: Most cases of ceftriaxone-resistant N. gonorrhoeae detected in England were associated with travel from the Asia-Pacific region. All genital infections were successfully treated with ceftriaxone, but there were extragenital treatment failures. Ceftriaxone resistance continues to be associated with the penA-60.001 allele within multiple genetic backgrounds and with widespread dissemination in the Asia-Pacific region.

目标:自 2022 年 6 月以来,英格兰发现的耐头孢曲松淋病奈瑟菌病例数量有所增加(n = 15),其中三分之一为 XDR。我们描述了近期病例的人口统计学和临床细节,并调查了分离物的表型和分子特征。为了全面了解情况,我们还回顾了自2015年12月以来在英格兰发现的16例耐药头孢曲松病例,并对所有公开发表的耐头孢曲松淋球菌菌株进行了全球基因组比较,这些菌株均具有嵌合penA等位基因:对所有对头孢曲松耐药(MIC > 0.125 mg/L)的淋球菌分离株进行全基因组测序,并与全球142株头孢曲松耐药淋球菌序列进行比较。收集了人口统计学、行为学和临床数据:结果:所有病例均为异性恋者,大多数感染与来自亚太地区的旅行有关。不过,有些病例在过去几个月中没有出过英国。没有头孢曲松生殖器治疗失败的病例,但五例咽部感染中的三例和唯一的直肠感染治疗失败。这些分离株代表了 13 种不同的 MLST ST,其中大多数具有镶嵌的 penA-60.001 等位基因。全球基因组分为八大系统群,并具有区域关联性。所有 XDR 分离物都属于同一系统群,以 MLST ST16406 为代表:英国发现的大多数耐头孢曲松淋球菌病例都与来自亚太地区的旅行有关。所有生殖器感染病例都成功接受了头孢曲松治疗,但也有生殖器外治疗失败的病例。头孢曲松耐药性仍然与多种遗传背景中的penA-60.001等位基因有关,并在亚太地区广泛传播。
{"title":"Ceftriaxone-resistant Neisseria gonorrhoeae detected in England, 2015-24: an observational analysis.","authors":"Helen Fifer, Michel Doumith, Luciana Rubinstein, Laura Mitchell, Mark Wallis, Selena Singh, Gurmit Jagjit Singh, Michael Rayment, John Evans-Jones, Alison Blume, Olamide Dosekun, Kenny Poon, Achyuta Nori, Michaela Day, Rachel Pitt-Kendall, Suzy Sun, Prarthana Narayanan, Emma Callan, Anna Vickers, Jack Minshull, Kirsty F Bennet, James E C Johnson, John Saunders, Sarah Alexander, Hamish Mohammed, Neil Woodford, Katy Sinka, Michelle Cole","doi":"10.1093/jac/dkae369","DOIUrl":"https://doi.org/10.1093/jac/dkae369","url":null,"abstract":"<p><strong>Objectives: </strong>Since June 2022, there has been a rise in the number of ceftriaxone-resistant Neisseria gonorrhoeae cases detected in England (n = 15), of which a third were XDR. We describe the demographic and clinical details of the recent cases and investigate the phenotypic and molecular characteristics of the isolates. For a comprehensive overview, we also reviewed 16 ceftriaxone-resistant cases previously identified in England since December 2015 and performed a global genomic comparison of all publicly available ceftriaxone-resistant N. gonorrhoeae strains with mosaic penA alleles.</p><p><strong>Methods: </strong>All N. gonorrhoeae isolates resistant to ceftriaxone (MIC > 0.125 mg/L) were whole-genome sequenced and compared with 142 global sequences of ceftriaxone-resistant N. gonorrhoeae. Demographic, behavioural and clinical data were collected.</p><p><strong>Results: </strong>All cases were heterosexual, and most infections were associated with travel from the Asia-Pacific region. However, some had not travelled outside England within the previous few months. There were no ceftriaxone genital treatment failures, but three of five pharyngeal infections and the only rectal infection failed treatment. The isolates represented 13 different MLST STs, and most had the mosaic penA-60.001 allele. The global genomes clustered into eight major phylogroups, with regional associations. All XDR isolates belonged to the same phylogroup, represented by MLST ST16406.</p><p><strong>Conclusions: </strong>Most cases of ceftriaxone-resistant N. gonorrhoeae detected in England were associated with travel from the Asia-Pacific region. All genital infections were successfully treated with ceftriaxone, but there were extragenital treatment failures. Ceftriaxone resistance continues to be associated with the penA-60.001 allele within multiple genetic backgrounds and with widespread dissemination in the Asia-Pacific region.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466114","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
Population pharmacokinetics/pharmacodynamics of minocycline plus rifampicin in patients with complicated skin and skin structure infections caused by MRSA. 米诺环素联合利福平在 MRSA 引起的复杂皮肤和皮肤结构感染患者中的群体药代动力学/药效学。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-16 DOI: 10.1093/jac/dkae363
Sonia Luque Pardos, William Hope, Antigone Kotsaki, Shampa Das, Evangelos J Giamarellos-Bourboulis, Theano Kontopoulouk, Karolina Akinosoglou, Miriam O'Hare, Marie L G Attwood, Karen E Bowker, Alan R Noel, Andrew M Lovering, Mark A J Bayliss, Rebecca N Evans, Alasdair P MacGowan

Background: The population pharmacokinetics/pharmacodynamics (PK/PD) of minocycline, rifampicin and linezolid in patients with complicated skin and soft tissue infections (cSSTIs) caused by MRSA are described.

Methods: Samples were collected in a Phase 4 study of oral minocycline plus rifampicin versus linezolid showing minocycline plus rifampicin to be non-inferior to linezolid. Antibiotics were assayed by HPLC or LC-MS, and a population PK model was developed using Pmetrics. The association between PK/PD indices and patient outcomes was explored.

Results: A three-compartment model (with an absorption compartment) with first-order input and elimination best described the data for the three drugs. No covariates were included in the final model. The population median values (95% credibility limits) of the clearance and volume of distribution were 7.412 L/h (5.121-8.361) and 14.155 L (6.799-33.901) for minocycline, 5.683 L/h (3.703-7.726) and 7.736 L (6.031-8.948) for rifampicin, and 1.970 L/h (1.326-2.499) and 20.169 L (12.857-32.629) for linezolid, respectively. Maximum a posteriori probability-Bayesian estimation plots of observed versus predicted had a slope of 0.999 r20.967 for minocycline, slope 0.998 r20.769 for rifampicin and slope 0.998 r20.895 for linezolid. PK/PD indices were not related to clinical outcome. Taking a translational minocycline fAUC24h/MIC target of >0.5 for minocycline in the presence of rifampicin, 96% (49/51) of patients reached the target.

Conclusions: Population PK models of minocycline, rifampicin and linezolid were developed in patients with MRSA cSSTI and almost all patients reached the predefined PD index targets. As a result, neither AUC, MIC nor the AUC/MIC ratio could be related to clinical outcome.

背景:描述了米诺环素、利福平和利奈唑胺在MRSA引起的复杂皮肤和软组织感染(cSSTI)患者中的群体药代动力学/药效学(PK/PD):在口服米诺环素加利福平与利奈唑胺的第 4 期研究中收集了样本,结果显示米诺环素加利福平与利奈唑胺的疗效相当。抗生素通过 HPLC 或 LC-MS 进行检测,并使用 Pmetrics 建立了群体 PK 模型。探讨了 PK/PD 指数与患者预后之间的关联:结果:采用一阶输入和消除的三室模型(含一个吸收室)对三种药物的数据进行了最佳描述。最终模型中未包含协变量。米诺环素的清除率和分布容积的人群中位值(95% 可信限)分别为 7.412 L/h (5.121-8.361) 和 14.155 L (6.799-33.901) 。901),利福平为 5.683 L/h(3.703-7.726)和 7.736 L(6.031-8.948),利奈唑胺为 1.970 L/h(1.326-2.499)和 20.169 L(12.857-32.629)。米诺环素的观察值与预测值的最大后验概率-贝叶斯估计图的斜率为 0.999 r20.967,利福平的斜率为 0.998 r20.769,利奈唑胺的斜率为 0.998 r20.895。PK/PD 指数与临床结果无关。在利福平存在的情况下,米诺环素的转化米诺环素fAUC24h/MIC目标值>0.5,96%(49/51)的患者达到了目标值:在MRSA cSSTI患者中建立了米诺环素、利福平和利奈唑胺的人群PK模型,几乎所有患者都达到了预定义的PD指数目标。因此,AUC、MIC或AUC/MIC比值均与临床结果无关。
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引用次数: 0
Antibiotic biocompatibility assay and anti-biofilm strategies for Pseudomonas aeruginosa infection in bioengineered artificial skin substitutes. 针对生物工程人工皮肤替代品中铜绿假单胞菌感染的抗生素生物相容性检测和抗生物膜策略。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-16 DOI: 10.1093/jac/dkae365
María I Quiñones-Vico, Marta Andrades-Amate, Ana Fernández-González, Ana Ubago-Rodríguez, Kirsten Moll, Anna Norrby-Teglund, Mattias Svensson, José Gutiérrez-Fernández, Salvador Arias-Santiago

Objectives: Bioengineered artificial skin substitutes (BASS) are an advanced therapy for treating extensively burned patients. Pseudomonas aeruginosa (P. aeruginosa) infections represent a major challenge in these patients as formation of biofilms impede wound healing and perpetuate a chronic inflammatory state. Here we assessed antibiotics (alone or in combination) with respect to cytotoxicity, as well as antimicrobial efficacy in P. aeruginosa biofilm formed on infection of BASS.

Methods: Cell viability, structure and functionality were evaluated using microscopy and trans-epidermal water loss analyses, respectively. BASS were established and infected for 24 h to allow P. aeruginosa biofilm formation, after which two antimicrobial approaches, treatment and prevention, were tested. In the latter, antibiotics were added to BASS before infection. The antimicrobial effect was determined using real-time calorimetry.

Results: In dose-response experiments, 1.25 mg/mL amikacin, 0.02 mg/mL ciprofloxacin, 0.051 mg/mL colistin, 1 mg/mL meropenem and colistin in combination with either amikacin, ciprofloxacin and meropenem did not affect BASS' viability, structure and functionality. All antibiotics, except colistin, showed effective antimicrobial activity at these non-cytotoxic concentrations. For concentrations below the highest non-cytotoxic ones, successive treatments resulted in higher bacterial metabolic rates. Only the combinations managed to eradicate the infection with repeated treatments. With respect to prevention of infection, all antibiotics at the highest non-cytotoxic concentrations and the combinations were effective. This preventive capacity was maintained for at least 5 days.

Conclusion: The findings highlight the potential for developing BASS with antimicrobial properties that can prevent infections during wound healing in burn patients.

目的:生物工程人工皮肤替代物(BASS)是治疗大面积烧伤患者的一种先进疗法。铜绿假单胞菌(P. aeruginosa)感染是这些患者面临的一大挑战,因为生物膜的形成会阻碍伤口愈合并使慢性炎症状态持续存在。在此,我们评估了抗生素(单独使用或联合使用)的细胞毒性以及在 BASS 感染后形成的铜绿假单胞菌生物膜中的抗菌效果:方法:分别使用显微镜和经表皮失水分析评估细胞活力、结构和功能。建立并感染 BASS 24 小时,使铜绿假单胞菌形成生物膜,然后测试治疗和预防两种抗菌方法。后者是在感染前向 BASS 中添加抗生素。结果:结果:在剂量反应实验中,1.25 毫克/毫升阿米卡星、0.02 毫克/毫升环丙沙星、0.051 毫克/毫升可乐定、1 毫克/毫升美罗培南以及可乐定与阿米卡星、环丙沙星和美罗培南的组合均不影响 BASS 的活力、结构和功能。在这些无细胞毒性浓度下,除秋水仙素外,所有抗生素都显示出有效的抗菌活性。在低于最高无细胞毒性浓度的情况下,连续处理会导致细菌代谢率升高。只有复方制剂能够通过反复治疗根除感染。在预防感染方面,无细胞毒性浓度最高的所有抗生素和组合抗生素都有效。这种预防能力至少可维持 5 天:研究结果表明,开发具有抗菌特性的 BASS 有助于预防烧伤患者伤口愈合期间的感染。
{"title":"Antibiotic biocompatibility assay and anti-biofilm strategies for Pseudomonas aeruginosa infection in bioengineered artificial skin substitutes.","authors":"María I Quiñones-Vico, Marta Andrades-Amate, Ana Fernández-González, Ana Ubago-Rodríguez, Kirsten Moll, Anna Norrby-Teglund, Mattias Svensson, José Gutiérrez-Fernández, Salvador Arias-Santiago","doi":"10.1093/jac/dkae365","DOIUrl":"https://doi.org/10.1093/jac/dkae365","url":null,"abstract":"<p><strong>Objectives: </strong>Bioengineered artificial skin substitutes (BASS) are an advanced therapy for treating extensively burned patients. Pseudomonas aeruginosa (P. aeruginosa) infections represent a major challenge in these patients as formation of biofilms impede wound healing and perpetuate a chronic inflammatory state. Here we assessed antibiotics (alone or in combination) with respect to cytotoxicity, as well as antimicrobial efficacy in P. aeruginosa biofilm formed on infection of BASS.</p><p><strong>Methods: </strong>Cell viability, structure and functionality were evaluated using microscopy and trans-epidermal water loss analyses, respectively. BASS were established and infected for 24 h to allow P. aeruginosa biofilm formation, after which two antimicrobial approaches, treatment and prevention, were tested. In the latter, antibiotics were added to BASS before infection. The antimicrobial effect was determined using real-time calorimetry.</p><p><strong>Results: </strong>In dose-response experiments, 1.25 mg/mL amikacin, 0.02 mg/mL ciprofloxacin, 0.051 mg/mL colistin, 1 mg/mL meropenem and colistin in combination with either amikacin, ciprofloxacin and meropenem did not affect BASS' viability, structure and functionality. All antibiotics, except colistin, showed effective antimicrobial activity at these non-cytotoxic concentrations. For concentrations below the highest non-cytotoxic ones, successive treatments resulted in higher bacterial metabolic rates. Only the combinations managed to eradicate the infection with repeated treatments. With respect to prevention of infection, all antibiotics at the highest non-cytotoxic concentrations and the combinations were effective. This preventive capacity was maintained for at least 5 days.</p><p><strong>Conclusion: </strong>The findings highlight the potential for developing BASS with antimicrobial properties that can prevent infections during wound healing in burn patients.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466113","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
Impact of discontinuing routine fluoroquinolone prophylaxis in neutropenic allogeneic haematopoietic stem cell transplant recipients: an observational study. 中性粒细胞异基因造血干细胞移植受者停止常规氟喹诺酮预防措施的影响:一项观察性研究。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-14 DOI: 10.1093/jac/dkae360
Anat Stern, Israel Henig, Maya Cohen, Ivan Gur, Oryan Henig, Tsila Zuckerman, Mical Paul

Background: Uncertainty exists as to the role of fluoroquinolone (FQ) prophylaxis for patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) in the era of rising antibiotic resistance.

Objectives: We aimed to evaluate rates of bloodstream infections (BSI), resistance patterns and outcomes of patients after discontinuing routine FQ prophylaxis administration.

Methods: All adult recipients of first HSCT from 2017 to 2020 were retrospectively included and classified according to time of HSCT as FQ group (HSCT January 2017-December 2018) or no FQ group (January 2019-December 2020). The primary outcome was Gram-negative (GN) BSI from day -7 to 30 days post-HSCT. The independent association between the study period and BSI was assessed using survival analysis, and adjusting for confounders.

Results: We included 254 patients, 130 (51%) and 124 (49%) in the FQ and no FQ groups, respectively. Compared to the FQ group, no FQ had significantly more GN BSI (21% versus 33%, P = 0.027) and the median time to first GN BSI was significantly shorter [4 (IQR 1-8) days versus 6 (1-10) days, P = 0.009]. Following adjustment, FQ prophylaxis remained associated with lower hazard for GN BSI (hazard ratio 0.57, 95% CI 0.34-0.93). Eighty-two GN BSI episodes had FQ susceptibility testing. More GN BSI episodes were FQ resistant in the FQ group (68.9% versus 41.6%, P = 0.021). No significant difference was found for 30-day mortality, time to first febrile neutropenia and time to first broad-spectrum antibiotics between the groups (P was not significant).

Conclusions: FQ prophylaxis is associated with fewer GN BSI in the early post-HSCT period even in high FQ resistance settings, with FQ resistance rates reaching >60% following prophylaxis.

背景:在抗生素耐药性不断上升的时代,氟喹诺酮类药物(FQ)对异基因造血干细胞移植(HSCT)患者的预防作用尚不确定:我们旨在评估血流感染(BSI)率、耐药性模式以及停止常规FQ预防性用药后患者的预后:回顾性纳入2017年至2020年首次接受造血干细胞移植的所有成人受者,并根据造血干细胞移植时间分为FQ组(2017年1月至2018年12月接受造血干细胞移植)或无FQ组(2019年1月至2020年12月)。主要结果是造血干细胞移植后第-7天至30天的革兰氏阴性(GN)BSI。研究期间与 BSI 之间的独立关联采用生存分析法进行评估,并对混杂因素进行调整:我们共纳入了 254 例患者,其中 FQ 组和无 FQ 组分别有 130 例(51%)和 124 例(49%)。与 FQ 组相比,无 FQ 组发生 GN BSI 的比例明显更高(21% 对 33%,P = 0.027),发生首次 GN BSI 的中位时间明显更短 [4 (IQR 1-8) 天对 6 (1-10) 天,P = 0.009]。经调整后,FQ 预防仍与较低的 GN BSI 危险相关(危险比 0.57,95% CI 0.34-0.93)。有82例GN BSI进行了FQ药敏试验。FQ 组中耐 FQ 的 GN BSI 例数更多(68.9% 对 41.6%,P = 0.021)。在30天死亡率、首次发热性中性粒细胞减少时间和首次使用广谱抗生素时间方面,两组间无明显差异(P不显著):结论:即使在FQ耐药率较高的情况下,FQ预防也能减少HSCT术后早期的GN BSI,预防后FQ耐药率>60%。
{"title":"Impact of discontinuing routine fluoroquinolone prophylaxis in neutropenic allogeneic haematopoietic stem cell transplant recipients: an observational study.","authors":"Anat Stern, Israel Henig, Maya Cohen, Ivan Gur, Oryan Henig, Tsila Zuckerman, Mical Paul","doi":"10.1093/jac/dkae360","DOIUrl":"https://doi.org/10.1093/jac/dkae360","url":null,"abstract":"<p><strong>Background: </strong>Uncertainty exists as to the role of fluoroquinolone (FQ) prophylaxis for patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) in the era of rising antibiotic resistance.</p><p><strong>Objectives: </strong>We aimed to evaluate rates of bloodstream infections (BSI), resistance patterns and outcomes of patients after discontinuing routine FQ prophylaxis administration.</p><p><strong>Methods: </strong>All adult recipients of first HSCT from 2017 to 2020 were retrospectively included and classified according to time of HSCT as FQ group (HSCT January 2017-December 2018) or no FQ group (January 2019-December 2020). The primary outcome was Gram-negative (GN) BSI from day -7 to 30 days post-HSCT. The independent association between the study period and BSI was assessed using survival analysis, and adjusting for confounders.</p><p><strong>Results: </strong>We included 254 patients, 130 (51%) and 124 (49%) in the FQ and no FQ groups, respectively. Compared to the FQ group, no FQ had significantly more GN BSI (21% versus 33%, P = 0.027) and the median time to first GN BSI was significantly shorter [4 (IQR 1-8) days versus 6 (1-10) days, P = 0.009]. Following adjustment, FQ prophylaxis remained associated with lower hazard for GN BSI (hazard ratio 0.57, 95% CI 0.34-0.93). Eighty-two GN BSI episodes had FQ susceptibility testing. More GN BSI episodes were FQ resistant in the FQ group (68.9% versus 41.6%, P = 0.021). No significant difference was found for 30-day mortality, time to first febrile neutropenia and time to first broad-spectrum antibiotics between the groups (P was not significant).</p><p><strong>Conclusions: </strong>FQ prophylaxis is associated with fewer GN BSI in the early post-HSCT period even in high FQ resistance settings, with FQ resistance rates reaching >60% following prophylaxis.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466017","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
Overall status of carbapenem resistance among clinical isolates of Acinetobacter baumannii: a systematic review and meta-analysis. 鲍曼不动杆菌临床分离株对碳青霉烯类耐药性的总体状况:系统综述和荟萃分析。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-11 DOI: 10.1093/jac/dkae358
Ali Ghahramani, Mohammad Mahdi Naghadian Moghaddam, Joben Kianparsa, Mohammad Hossein Ahmadi

Background: Resistance to carbapenems, the first-line treatment for infections caused by Acinetobacter baumannii, is increasing throughout the world. The aim of the present study was to determine the global status of resistance to carbapenems in clinical isolates of this pathogen, worldwide.

Methods: Electronic databases were searched using the appropriate keywords, including: 'Acinetobacter' 'baumannii', 'Acinetobacter baumannii' and 'A. baumannii', 'resistance', 'antibiotic resistance', 'antibiotic susceptibility', 'antimicrobial resistance', 'antimicrobial susceptibility', 'carbapenem', 'carbapenems', 'imipenem', 'meropenem' and 'doripenem'. Finally, following some exclusions, 177 studies from various countries were included in this study. The data were then subjected to a meta-analysis.

Results: The average resistance rate of A. baumannii to imipenem, meropenem and doripenem was 44.7%, 59.4% and 72.7%, respectively. A high level of heterogeneity (I2 > 50%, P value < 0.05) was detected in the studies representing resistance to imipenem, meropenem and doripenem in A. baumannii isolates. Begg's and Egger's tests did not indicate publication bias (P value > 0.05).

Conclusions: The findings of the current study indicate that the overall resistance to carbapenems in clinical isolates of A. baumannii is relatively high and prevalent throughout the world. Moreover, time trend analysis showed that the resistance has increased from the year 2000 to 2023. This emphasizes the importance of conducting routine antimicrobial susceptibility testing before selecting a course of treatment, as well as monitoring and controlling antibiotic resistance patterns in A. baumannii strains, and seeking novel treatment options to lessen the emergence and spread of resistant strains and to reduce the treatment failure.

背景:碳青霉烯类是治疗鲍曼不动杆菌感染的一线药物,其耐药性在全球范围内不断增加。本研究旨在确定全球范围内该病原体临床分离株对碳青霉烯类抗生素的耐药性状况:方法:使用适当的关键词搜索电子数据库,包括鲍曼不动杆菌"、"鲍曼不动杆菌 "和 "鲍曼不动杆菌"、"耐药性"、"抗生素耐药性"、"抗生素敏感性"、"抗菌药耐药性"、"抗菌药敏感性"、"碳青霉烯类"、"碳青霉烯类"、"亚胺培南"、"美罗培南 "和 "多尼培南"。最后,经过一些排除,来自不同国家的 177 项研究被纳入本研究。然后对数据进行了荟萃分析:结果:鲍曼菌对亚胺培南、美罗培南和多瑞培南的平均耐药率分别为 44.7%、59.4% 和 72.7%。异质性较高(I2>50%,P值0.05):目前的研究结果表明,鲍曼不动杆菌临床分离株对碳青霉烯类药物的总体耐药性相对较高,并且在全球范围内普遍存在。此外,时间趋势分析表明,从 2000 年到 2023 年,耐药性有所增加。这强调了在选择治疗方案前进行常规抗菌药物敏感性检测、监测和控制鲍曼不动杆菌菌株的抗生素耐药模式以及寻求新的治疗方案以减少耐药菌株的出现和传播并减少治疗失败的重要性。
{"title":"Overall status of carbapenem resistance among clinical isolates of Acinetobacter baumannii: a systematic review and meta-analysis.","authors":"Ali Ghahramani, Mohammad Mahdi Naghadian Moghaddam, Joben Kianparsa, Mohammad Hossein Ahmadi","doi":"10.1093/jac/dkae358","DOIUrl":"10.1093/jac/dkae358","url":null,"abstract":"<p><strong>Background: </strong>Resistance to carbapenems, the first-line treatment for infections caused by Acinetobacter baumannii, is increasing throughout the world. The aim of the present study was to determine the global status of resistance to carbapenems in clinical isolates of this pathogen, worldwide.</p><p><strong>Methods: </strong>Electronic databases were searched using the appropriate keywords, including: 'Acinetobacter' 'baumannii', 'Acinetobacter baumannii' and 'A. baumannii', 'resistance', 'antibiotic resistance', 'antibiotic susceptibility', 'antimicrobial resistance', 'antimicrobial susceptibility', 'carbapenem', 'carbapenems', 'imipenem', 'meropenem' and 'doripenem'. Finally, following some exclusions, 177 studies from various countries were included in this study. The data were then subjected to a meta-analysis.</p><p><strong>Results: </strong>The average resistance rate of A. baumannii to imipenem, meropenem and doripenem was 44.7%, 59.4% and 72.7%, respectively. A high level of heterogeneity (I2 > 50%, P value < 0.05) was detected in the studies representing resistance to imipenem, meropenem and doripenem in A. baumannii isolates. Begg's and Egger's tests did not indicate publication bias (P value > 0.05).</p><p><strong>Conclusions: </strong>The findings of the current study indicate that the overall resistance to carbapenems in clinical isolates of A. baumannii is relatively high and prevalent throughout the world. Moreover, time trend analysis showed that the resistance has increased from the year 2000 to 2023. This emphasizes the importance of conducting routine antimicrobial susceptibility testing before selecting a course of treatment, as well as monitoring and controlling antibiotic resistance patterns in A. baumannii strains, and seeking novel treatment options to lessen the emergence and spread of resistant strains and to reduce the treatment failure.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400355","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
Correction to: Real-world data on long-acting intramuscular maintenance therapy with cabotegravir and rilpivirine mirror Phase 3 results. 更正:卡博替拉韦和利匹韦林长效肌肉注射维持疗法的真实世界数据反映了第 3 阶段的结果。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-10 DOI: 10.1093/jac/dkae372
{"title":"Correction to: Real-world data on long-acting intramuscular maintenance therapy with cabotegravir and rilpivirine mirror Phase 3 results.","authors":"","doi":"10.1093/jac/dkae372","DOIUrl":"10.1093/jac/dkae372","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466115","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
Systematic review on oral antibacterial relay therapy for acute staphylococcal prosthetic joint infections treated with debridement, antibiotics and implant retention (DAIR). 对采用清创、抗生素和植入物保留(DAIR)治疗急性葡萄球菌假体关节感染的口服抗菌中继疗法进行系统回顾。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-09 DOI: 10.1093/jac/dkae347
Benoit Gachet, Agnès Dechartres, Eric Senneville, Olivier Robineau

Background: The management of acute prosthetic joint infections (PJIs) often involves a debridement, antibiotics and implant retention (DAIR) strategy.

Objective: Our objective was to conduct a systematic review and a network meta-analysis (NMA) to assess the comparative effectiveness of available oral antimicrobial regimens for the treatment of acute staphylococcal PJIs treated with DAIR.

Methods: We conducted a systematic review searching articles from databases creation until 31 December 2023. We included articles on acute staphylococcal PJIs managed with DAIR with an oral antibiotic regimen relaying the initial management. The primary outcome was the remission rate.

Results: Out of the 2421 studies screened, six studies completed the systematic review criteria: one randomized controlled trial and five observational studies. There was heterogeneity in patients' populations, duration and posology of treatments, definition of outcome and length of follow-up. Studies revealed 10 antibiotic regimens and most data focusing on five combinations recommended by the IDSA's guidelines: rifampicin associated to fluoroquinolone, clindamycin, cycline, linezolid or trimethoprim-sulfamethoxazole. Treatment comparisons were often secondary, without adjustment for confounding factors, resulting in a high risk of bias. Owing to inconsistencies a complete analysis, including an NMA was not possible.

Conclusion: The available data highlight five companions to rifampicin, however, there is insufficient evidence to compare them. The literature does not provide a basis for rationalizing alternatives when rifampicin cannot be used.

背景:急性人工关节感染(PJI)的治疗通常采用清创、抗生素和植入物保留(DAIR)策略:我们的目的是进行一项系统性综述和一项网络荟萃分析(NMA),以评估现有口服抗菌药方案对采用 DAIR 治疗急性葡萄球菌 PJI 的比较效果:我们对 2023 年 12 月 31 日前创建的数据库中的文章进行了系统性检索。方法:我们对截至 2023 年 12 月 31 日创建的数据库中的文章进行了系统性检索,纳入了使用 DAIR 治疗急性金黄色葡萄球菌 PJI 的文章,这些文章采用口服抗生素治疗方案进行初始治疗。主要结果是缓解率:在筛选出的 2421 项研究中,有 6 项研究符合系统综述标准:1 项随机对照试验和 5 项观察性研究。这些研究在患者人群、治疗持续时间和姿势、疗效定义和随访时间等方面存在异质性。研究揭示了 10 种抗生素治疗方案,大多数数据集中于 IDSA 指南推荐的五种组合:利福平联合氟喹诺酮、克林霉素、环素、利奈唑胺或三甲双胍-磺胺甲噁唑。治疗方法的比较往往是次要的,没有对混杂因素进行调整,因此存在较高的偏倚风险。由于存在不一致之处,因此无法进行包括 NMA 在内的完整分析:现有数据强调了利福平的五种辅助治疗方法,但没有足够的证据对它们进行比较。在无法使用利福平的情况下,文献并未提供合理使用替代药物的依据。
{"title":"Systematic review on oral antibacterial relay therapy for acute staphylococcal prosthetic joint infections treated with debridement, antibiotics and implant retention (DAIR).","authors":"Benoit Gachet, Agnès Dechartres, Eric Senneville, Olivier Robineau","doi":"10.1093/jac/dkae347","DOIUrl":"https://doi.org/10.1093/jac/dkae347","url":null,"abstract":"<p><strong>Background: </strong>The management of acute prosthetic joint infections (PJIs) often involves a debridement, antibiotics and implant retention (DAIR) strategy.</p><p><strong>Objective: </strong>Our objective was to conduct a systematic review and a network meta-analysis (NMA) to assess the comparative effectiveness of available oral antimicrobial regimens for the treatment of acute staphylococcal PJIs treated with DAIR.</p><p><strong>Methods: </strong>We conducted a systematic review searching articles from databases creation until 31 December 2023. We included articles on acute staphylococcal PJIs managed with DAIR with an oral antibiotic regimen relaying the initial management. The primary outcome was the remission rate.</p><p><strong>Results: </strong>Out of the 2421 studies screened, six studies completed the systematic review criteria: one randomized controlled trial and five observational studies. There was heterogeneity in patients' populations, duration and posology of treatments, definition of outcome and length of follow-up. Studies revealed 10 antibiotic regimens and most data focusing on five combinations recommended by the IDSA's guidelines: rifampicin associated to fluoroquinolone, clindamycin, cycline, linezolid or trimethoprim-sulfamethoxazole. Treatment comparisons were often secondary, without adjustment for confounding factors, resulting in a high risk of bias. Owing to inconsistencies a complete analysis, including an NMA was not possible.</p><p><strong>Conclusion: </strong>The available data highlight five companions to rifampicin, however, there is insufficient evidence to compare them. The literature does not provide a basis for rationalizing alternatives when rifampicin cannot be used.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390764","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
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Journal of Antimicrobial Chemotherapy
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