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In vitro activity of delafloxacin against clinical levofloxacin-resistant Helicobacter pylori isolates. 德拉氧氟沙星对耐左氧氟沙星的临床幽门螺旋杆菌分离物的体外活性。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae269
Victor Luzarraga, Julie Cremniter, Chloé Plouzeau, Anthony Michaud, Lauranne Broutin, Christophe Burucoa, Maxime Pichon

Background: Increasing antibiotic resistance in Helicobacter pylori necessitates research on new active molecules. In 2017, delafloxacin, a new fluoroquinolone with chemical properties of activity under acidic conditions, was approved for treatment of community-acquired bacterial pneumonia and acute bacterial skin and soft-tissue infections. Mutations in gyrA are responsible for fluoroquinolone resistance, but certain clinical isolates of H. pylori appear to display a dual phenotype: resistance to levofloxacin associated with very low delafloxacin MICs.

Objectives: To estimate epidemiological cut-off (ECOFF) values and to identify mutations in the gyrA gene, specific to FQ resistance, without increasing the MICs of delafloxacin.

Methods: Clinical strains (n = 231) were collected in the bacteriology laboratory of Poitiers University Hospital over a 2 year period to determine the ECOFF of delafloxacin. Retrospectively, 101 clinical strains with an levofloxacin-resistant phenotype (MIC > 1 mg/L) were selected from 2018 to 2022 for delafloxacin MIC determination and QRDR (gyrA) sequencing.

Results: The estimated ECOFF of delafloxacin was ≤0.125 mg/L. No H. pylori isolate showed a levofloxacin-sensitive phenotype with a delafloxacin MIC of >0.125 mg/L. Among the levofloxacin-resistant H. pylori isolates, 53.5% had delafloxacin MICs of ≤0.125 mg/L. The N87I mutation was associated with dual levofloxacin/delafloxacin resistance (P < 0.001) in contrast to the N87K and D91N mutations (P > 0.05). Mutations D91G and D91Y were not associated with a delafloxacin resistance phenotype (P > 0.05).

Conclusions: Delafloxacin seems to be a therapeutic alternative for levofloxacin-resistant strains with greater in vitro activity. However, further clinical/biological investigations are required to determine its efficacy in H. pylori eradication.

背景:幽门螺旋杆菌对抗生素的耐药性不断增加,因此有必要研究新的活性分子。2017 年,具有酸性条件下活性化学特性的新型氟喹诺酮药物德拉氧氟沙星获批用于治疗社区获得性细菌性肺炎以及急性细菌性皮肤和软组织感染。gyrA的突变是导致氟喹诺酮耐药性的原因,但某些临床分离的幽门螺杆菌似乎显示出双重表型:对左氧氟沙星耐药,但对地氟沙星的MIC很低:目的:估算流行病学临界值(ECOFF),并在不增加地氟沙星MIC的情况下,确定gyrA基因中特异于FQ耐药性的突变:普瓦捷大学医院细菌学实验室在两年内收集了临床菌株(n = 231),以确定德拉氧沙星的ECOFF。回顾性地选择了2018年至2022年期间101株具有左氧氟沙星耐药表型(MIC > 1 mg/L)的临床菌株,进行了地拉沙星MIC测定和QRDR(gyrA)测序:估计的德拉氧氟沙星ECOFF≤0.125 mg/L。没有幽门螺杆菌分离株显示对左氧氟沙星敏感的表型,其对地氟沙星的 MIC >0.125 mg/L。在对左氧氟沙星耐药的幽门螺杆菌分离株中,53.5%的幽门螺杆菌对地氟沙星的耐药浓度≤0.125 mg/L。N87I 突变与左氧氟沙星/地氟沙星双重耐药性有关(P 0.05)。D91G和D91Y突变与地拉沙星耐药表型无关(P > 0.05):结论:对于左氧氟沙星耐药菌株,地拉沙星似乎是一种治疗替代品,其体外活性更高。然而,要确定其在根除幽门螺杆菌方面的疗效,还需要进一步的临床/生物学研究。
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引用次数: 0
Role of volume and inoculum in MIC assessment: a study with meropenem and Klebsiella pneumoniae. 容量和接种量在 MIC 评估中的作用:一项关于美罗培南和肺炎克雷伯菌的研究。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae283
Kamilla N Alieva, Maria V Golikova, Stephen H Zinner

Objectives: Pharmacodynamic parameters evaluated under conditions that simulate an infection site volume and microbial load might reveal hidden risks of resistance selection and subsequent treatment failure. The study aimed to investigate the predictive potential of MICs determined at various conditions on the antimicrobial effect and emergence of resistance.

Methods: We assessed meropenem MICs (microdilution: 0.2 mL, 5 × 105 cfu/mL; macrodilution: 2 mL, 5 × 105 cfu/mL), MICHVs (220 mL, 5 × 105 cfu/mL), MICHIs (0.2 mL, 5 × 107 cfu/mL) and MICHVIs (220 mL, 5 × 107 cfu/mL) for five Klebsiella pneumoniae strains and analysed these values alongside the results of experiments in a dynamic in vitro model. A clinically relevant meropenem dosing regimen was simulated and the starting bacterial inocula were 106 and 108 cfu/mL.

Results: The effectiveness of meropenem agreed with MICHVs for the 106 cfu/mL inoculum and with MICHIs or MICHVIs for the 108 cfu/mL inoculum. Strains characterized as resistant according to these values grew during meropenem exposure, and resistant mutants were selected.

Conclusions: Our results suggest that MICHV-based parameters may be suitable for predicting antibacterial effects and the risk of resistance development when the inoculum is 106 cfu/mL, while MICHI- or MICHVI-based parameters are suitable for these purposes when the inoculum is 108 cfu/mL. Also, the correlation between resistance selection and the MICHI-based parameter was as high as one that corresponds with a mutant prevention concentration (MPC)-based parameter; this suggests that the MPC can be replaced by the more easily determined alternative parameter MICHI.

目的:在模拟感染部位体积和微生物负荷的条件下评估药效学参数,可能会揭示耐药性选择和随后治疗失败的隐藏风险。本研究旨在探讨在不同条件下测定的 MICs 对抗菌效果和耐药性产生的预测潜力:我们评估了五株肺炎克雷伯氏菌的美罗培南 MICs(微量稀释:0.2 mL,5 × 105 cfu/mL;大量稀释:2 mL,5 × 105 cfu/mL)、MICHVs(220 mL,5 × 105 cfu/mL)、MICHIs(0.2 mL,5 × 107 cfu/mL)和 MICHVIs(220 mL,5 × 107 cfu/mL),并将这些值与动态体外模型中的实验结果一起进行了分析。模拟了与临床相关的美罗培南给药方案,起始细菌接种量分别为 106 和 108 cfu/mL:结果:对于 106 cfu/mL 的接种体,美罗培南的有效性与 MICHVs 一致;对于 108 cfu/mL 的接种体,美罗培南的有效性与 MICHIs 或 MICHVIs 一致。根据这些值确定为耐药的菌株在美罗培南暴露期间生长,并筛选出耐药突变体:我们的研究结果表明,当接种量为 106 cfu/mL 时,基于 MICHV 的参数可能适用于预测抗菌效果和耐药性产生的风险,而当接种量为 108 cfu/mL 时,基于 MICHI 或 MICHVI 的参数适用于上述目的。此外,抗性选择与基于 MICHI 的参数之间的相关性与基于突变预防浓度(MPC)的参数之间的相关性一样高;这表明,可以用更容易确定的替代参数 MICHI 来取代 MPC。
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引用次数: 0
Antibiotic use by clinical presentation across all healthcare providers in rural Burkina Faso: a healthcare visit exit survey. 布基纳法索农村地区所有医疗服务提供者按临床表现使用抗生素的情况:医疗服务就诊出口调查。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae252
Daniel Valia, Brecht Ingelbeen, Guétawendé Job Wilfried Nassa, Bérenger Kaboré, François Kiemdé, Toussaint Rouamba, Adélaïde Compaoré, Juste Stéphane Kouanda, Annie Robert, Hector Rodriguez-Villalobos, Marianne A B Van Der Sande, Halidou Tinto

Background: To guide antibiotic stewardship interventions, understanding for what indications antibiotics are used is essential.

Methods: In rural Burkina Faso, we measured antibiotic dispensing across all healthcare providers. From October 2021 to February 2022, we surveyed patients in Nanoro district, Burkina Faso, following visits to health centres (3), pharmacies (2), informal medicine vendors (5) and inpatients in health centres. We estimated prevalence of antibiotic use and the proportion of Watch group antibiotics by provider type and by clinical presentation, assessing compliance with WHO's AWaRe Antibiotic Book. We estimated per capita antibiotic use by multiplying prevalence of antibiotic use, mean DDD per adult treatment course, and the rate of healthcare visits per 1000 inhabitants per day, estimated from a prior household survey.

Results: Outpatient antibiotic use was more frequent after health centre visits (54.8%, of which 16.5% Watch, n = 1249) than after visits to pharmacies (26.2%, 16.3% Watch, n = 328) and informal medicine vendors (26.9%, 50.0% Watch, n = 349). The frequency of antibiotic use was highest for bronchitis (79.9% antibiotic use, of which 12.6% Watch), malaria (31.9%, 23.1% Watch), gastroenteritis (76.0%, 31.7% Watch), rhinopharyngitis (40.4%, 8.3% Watch) and undifferentiated fever (77.0%, 44.8% Watch). Compliance with WHO AWaRe guidance could have averted at least 68.4% of all Watch antibiotic use in outpatients at health centres. Community-wide, 2.9 DDD (95% CI 1.9-3.9) were used per 1000 adult inhabitants per day.

Conclusions: Most Watch antibiotic use at community level or primary care deviated from WHO guidance. Antibiotic stewardship should focus on key clinical presentations and include primary care and self-medication.

背景:为指导抗生素管理干预措施,了解抗生素的使用适应症至关重要:为了指导抗生素管理干预措施,了解抗生素的使用适应症至关重要:在布基纳法索农村地区,我们测量了所有医疗服务提供者的抗生素配药情况。从 2021 年 10 月到 2022 年 2 月,我们对布基纳法索纳诺罗地区的患者进行了调查,调查对象包括医疗中心(3 人)、药房(2 人)、非正规药贩(5 人)和医疗中心的住院患者。我们按医疗机构类型和临床表现估算了抗生素的使用率和观察组抗生素的比例,并评估了是否符合世界卫生组织的《AWaRe 抗生素手册》。我们将抗生素使用率、每个成人疗程的平均DDD和根据之前的家庭调查估算出的每1000名居民每天的医疗就诊率相乘,从而估算出人均抗生素使用量:在医疗中心就诊后(54.8%,其中16.5%为观察期,n=1249),门诊抗生素使用频率高于在药店(26.2%,16.3%为观察期,n=328)和非正规药贩(26.9%,50.0%为观察期,n=349)就诊后。抗生素使用频率最高的疾病是支气管炎(79.9%使用抗生素,其中 12.6% Watch)、疟疾(31.9%,23.1% Watch)、肠胃炎(76.0%,31.7% Watch)、鼻咽炎(40.4%,8.3% Watch)和未分型发热(77.0%,44.8% Watch)。如果遵守世界卫生组织的 AWaRe 指南,医疗中心的门诊病人至少可以避免 68.4% 的观察期抗生素使用。在整个社区,每 1000 名成年居民每天使用 2.9 滴滴涕(95% CI 1.9-3.9):结论:社区或基层医疗机构的大部分抗生素使用情况都偏离了世界卫生组织的指导原则。抗生素管理应关注主要的临床表现,包括初级保健和自我用药。
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引用次数: 0
Advances in the clinical treatment of multidrug-resistant pathogens using polymyxins. 使用多粘菌素临床治疗耐多药病原体的进展。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae344
Yizhen Huang, Mingrui Liao, Xuzhi Hu, Honghua Hu, Haoning Gong

Objectives: Polymyxins are a vital class of antibiotics used to combat multidrug-resistant Gram-negative bacteria. However, their use is limited due to potential nephrotoxicity and the availability of alternative antibiotics. This review aims to examine the properties of polymyxins and the clinical advances in their use for treating infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB).

Methods: This review analyses literature on polymyxin properties and various clinical approaches, including intravenous drip infusion, nebulized or dry powder inhalation, and ointment application. Treatment efficacy in terms of bacterial eradication, cure rate and mortality rate are reviewed and evaluated.

Results: Polymyxins have been reintroduced to treat critical infections due to the increasing prevalence of CR-GNB. Clinical trials and studies have confirmed that polymyxins can effectively treat CR-GNB infections when the formulation and administration are appropriate, with acceptable levels of nephrotoxicity.

Conclusions: In the future, the development of polymyxin formulations will aim to improve their clinical effectiveness while reducing toxicity and side effects and preventing the emergence of polymyxin-resistant strains. Enhanced efficacy and minimized potential side effects can be achieved by developing new polymyxin-delivery systems that provide a smart and controlled release or customized patient administration.

目的:多粘菌素是一类重要的抗生素,用于抗击具有多重耐药性的革兰氏阴性菌。然而,由于其潜在的肾毒性和替代抗生素的存在,多粘菌素的使用受到了限制。本综述旨在研究多粘菌素的特性及其用于治疗耐碳青霉烯革兰阴性菌(CR-GNB)感染的临床进展:本综述分析了有关多粘菌素特性和各种临床方法的文献,包括静脉滴注、雾化或干粉吸入以及软膏涂抹。结果:结果:由于 CR-GNB 的发病率越来越高,多粘菌素被重新用于治疗重症感染。临床试验和研究证实,多粘菌素在配方和用药适当的情况下可有效治疗 CR-GNB 感染,且肾毒性水平可接受:结论:今后,多粘菌素制剂的开发将致力于提高其临床疗效,同时降低毒性和副作用,并防止出现对多粘菌素耐药的菌株。通过开发新型多粘菌素给药系统,实现智能控释或为患者量身定制给药方案,可提高疗效并将潜在副作用降至最低。
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引用次数: 0
Infective endocarditis caused by penicillin-resistant viridans group streptococci: a series of nine cases from a Spanish cohort. 耐青霉素病毒性链球菌引起的感染性心内膜炎:西班牙队列中的九个系列病例。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae345
Francesc Escrihuela-Vidal, Núria Fernández-Hidalgo, Patricia Muñoz, Miguel Villamarín, Nicolás Jiménez García, Encarnación Moral Escudero, Francisco Javier Martínez Marcos, Guillermo Cuervo, Lucía Boix-Palop, Dámaris Berbel, Jordi Carratalà, Jose M Miró

Background: Infective endocarditis (IE) caused by viridans and gallolyticus group streptococci (VGS-GGS) resistant to penicillin (PEN-R; minimum inhibitory concentration ≥4 mg/L) is rare but poses therapeutic challenges.

Objectives: To describe the characteristics of patients with IE caused by PEN-R VGS-GGS, focusing on antimicrobial management.

Methods: Retrospective analysis of a prospective cohort of definite IE caused by PEN-R VGS-GGS between 2008 and 2023 in 40 Spanish hospitals. We describe clinical characteristics, management and outcome of the cases, and compare them to IE caused by VGS-GGS with susceptibility or susceptibility with increased exposure to penicillin (PEN-I).

Results: We identified nine cases of PEN-R VGS-GGS IE in a cohort of 1563 streptococcal IE (0.58%). All isolates belonged to S. mitis group. Three cases died during hospitalization and no relapse occurred at 3 months of follow-up. Compared to cases with susceptibility or PEN-I, PEN-R showed a higher rate of mitral location (78% versus 51%), surgical indication (67% versus 51%), and in-hospital mortality (33% versus 12%). Most cases (86%) showed resistance to third-generation cephalosporins. The preferred antibiotic regimen was beta-lactam-based: ceftriaxone plus gentamicin, penicillin plus gentamicin, ceftriaxone plus levofloxacin, and ceftaroline plus daptomycin. Two cases received a combination of vancomycin plus gentamicin. Levofloxacin was used in two cases in combination with ceftriaxone or daptomycin. All patients that received cardiac surgery were cured at the end of follow-up.

Conclusions: IE caused by PEN-R VGS-GGS was rare and only affected mitis group streptococci. Antibiotic combination including a beta-lactam seems to be effective in its management.

背景:由对青霉素(PEN-R;最小抑菌浓度≥4 mg/L)耐药的病毒和溶胆链球菌(VGS-GGS)引起的感染性心内膜炎(IE)非常罕见,但给治疗带来了挑战:描述由 PEN-R VGS-GGS 引起的 IE 患者的特征,重点关注抗菌药物管理:方法:对西班牙 40 家医院 2008 年至 2023 年期间由 PEN-R VGS-GGS 引起的明确 IE 的前瞻性队列进行回顾性分析。我们描述了这些病例的临床特征、管理和结果,并将其与对青霉素(PEN-I)敏感的 VGS-GGS 引起的 IE 或对青霉素(PEN-I)暴露增加的 VGS-GGS 引起的 IE 进行了比较:在 1563 例链球菌 IE(0.58%)中,我们发现了 9 例 PEN-R VGS-GGS IE。所有分离株都属于肝炎链球菌。其中 3 例在住院期间死亡,随访 3 个月未见复发。与易感病例或 PEN-I 型病例相比,PEN-R 型病例的二尖瓣位置(78% 对 51%)、手术指征(67% 对 51%)和院内死亡率(33% 对 12%)均较高。大多数病例(86%)对第三代头孢菌素产生了耐药性。首选的抗生素方案以β-内酰胺类为主:头孢曲松加庆大霉素、青霉素加庆大霉素、头孢曲松加左氧氟沙星、头孢他啶加达托霉素。两个病例使用了万古霉素加庆大霉素的组合疗法。有两个病例使用了左氧氟沙星与头孢曲松或达托霉素的联合疗法。所有接受心脏手术的患者在随访结束时均已治愈:结论:由PEN-R VGS-GGS引起的IE很少见,而且只影响米氏链球菌。结论:PEN-R VGS-GGS引起的IE非常罕见,且只感染米氏链球菌,包括β-内酰胺类在内的抗生素组合似乎对治疗有效。
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引用次数: 0
Combination therapy with IV fosfomycin for adult patients with serious Gram-negative infections: a review of the literature. 对患有严重革兰氏阴性菌感染的成年患者采用静脉注射磷霉素的联合疗法:文献综述。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae253
David A Butler, Nimish Patel, J Nicholas O'Donnell, Thomas P Lodise

Treatment of patients with serious infections due to resistant Gram-negative bacteria remains highly problematic and has prompted clinicians to use existing antimicrobial agents in innovative ways. One approach gaining increased therapeutic use is combination therapy with IV fosfomycin. This article reviews the preclinical pharmacokinetic/pharmacodynamic (PK/PD) infection model and clinical data surrounding the use of combination therapy with IV fosfomycin for the treatment of serious infections caused by resistant Gram-negative bacteria. Data from dynamic in vitro and animal infection model studies of highly resistant Enterobacterales and non-lactose fermenters are positive and suggest IV fosfomycin in combination with a β-lactam, polymyxin or aminoglycoside produces a synergistic effect that rivals or surpasses that of other aminoglycoside- or polymyxin-containing regimens. Clinical studies performed to date primarily have involved patients with pneumonia and/or bacteraemia due to Klebsiella pneumoniae, Pseudomonas aeruginosa or Acinetobacter baumannii. Overall, the observed success rates with fosfomycin combination regimens were consistent with those reported for other combination regimens commonly used to treat these patients. In studies in which direct treatment comparisons can be derived, the results suggest that patients who received fosfomycin combination therapy had similar or improved outcomes compared with other therapies and combinations, especially when it was used in combination with a β-lactam that (1) targets PBP-3 and (2) has exceptional stability in the presence of β-lactamases. Collectively, the data indicate that combination therapy with IV fosfomycin should be considered as a potential alternative to aminoglycoside or polymyxin combinations for patients with antibiotic-resistant Gram-negative infections when benefits outweigh risks.

治疗因耐药革兰氏阴性菌导致严重感染的患者仍然是个大问题,这促使临床医生以创新的方式使用现有的抗菌药物。静脉滴注磷霉素联合疗法是一种治疗效果越来越好的方法。本文回顾了临床前药代动力学/药效学(PK/PD)感染模型,以及有关使用静脉注射磷霉素联合疗法治疗耐药革兰氏阴性菌引起的严重感染的临床数据。对高度耐药的肠杆菌和非乳糖发酵菌进行的动态体外和动物感染模型研究数据是积极的,表明静脉注射磷霉素与β-内酰胺类、多粘菌素或氨基糖苷类药物联用可产生协同效应,其效果可与其他含氨基糖苷类或多粘菌素的治疗方案相媲美或更胜一筹。迄今为止进行的临床研究主要涉及肺炎克雷伯菌、铜绿假单胞菌或鲍曼不动杆菌引起的肺炎和/或菌血症患者。总体而言,所观察到的磷霉素联合疗法的成功率与其他常用于治疗这类患者的联合疗法的成功率一致。在可以进行直接治疗比较的研究中,结果表明,与其他疗法和联合疗法相比,接受磷霉素联合疗法的患者获得了相似或更好的治疗效果,尤其是当磷霉素与(1)靶向 PBP-3,(2)在β-内酰胺酶存在的情况下具有超强稳定性的β-内酰胺类药物联合使用时。总之,这些数据表明,对于耐抗生素革兰氏阴性菌感染患者,在利大于弊的情况下,应考虑将静脉注射磷霉素联合疗法作为氨基糖苷类或多粘菌素联合疗法的潜在替代方案。
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引用次数: 0
Characterization of a multiresistance optrA- and lsa(E)-harbouring unconventional circularizable structure in Streptococcus suis. 猪链球菌中具有多重抗性的 optrA 和 lsa(E)-harbouring 非常规可循环结构的特征。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae250
Qin Yang, Luxin Li, Guanzheng Zhao, Qingpo Cui, Xiaowei Gong, Luyu Ying, Tingting Yang, Mengjiao Fu, Zhangqi Shen

Objectives: To identify novel genetic elements facilitating the horizontal transfer of the oxazolidinone/phenicol resistance gene optrA and the pleuromutilin-lincosamide-streptogramin A resistance gene lsa(E) in Streptococcus suis.

Methods: The complete genomes of S. suis HB18 and two transconjugants were obtained using both the Illumina and Nanopore platforms. MICs were determined by broth microdilution. Inverse PCR was performed to identify circular forms of the novel unconventional circularizable structure (UCS), genomic island (GI) and integrative and conjugative element (ICE). Conjugation experiments assessed the transferability of optrA and lsa(E) genes in S. suis.

Results: S. suis HB18 carried a multiresistance gene cluster optrA-lsa(E)-lnu(B)-aphA-aadE-spw. This gene cluster, flanked by intact and truncated erm(B) in the same orientation, resided on a novel ICESsuHB18. Inverse PCR revealed the existence of a novel UCS, named UCS-optrA + lsa(E), which could excise the gene cluster optrA-lsa(E)-lnu(B)-aphA-aadE-spw and one copy of erm(B) from ICESsuHB18. Two transconjugants with different characteristics were obtained. In transconjugant T-JH-GI, UCS-optrA + lsa(E) excised from ICESsuHB18 inserted into the erm(B)-positive GI, designated GISsuHB18, generating the novel GISsuHB18-1. Meanwhile, in T-JH-ICE, genetic rearrangement events occurred in ICESsuHB18 and GISsuHB18, forming the novel ICESsuHB18-1.

Conclusions: This is the first report demonstrating the functionally active UCS-optrA + lsa(E) excising from ICESsuHB18 and inserting into the erm(B)-positive GISsuHB18 during the conjugation process. The location of optrA and lsa(E) on a multiresistance UCS enhances its persistence and dissemination.

目的鉴定猪链球菌中促进恶唑烷酮/苯酚抗性基因 optrA 和胸腺嘧啶-林可霉素-链霉亲和素 A 抗性基因 lsa(E) 水平转移的新型遗传因子:方法:利用 Illumina 和 Nanopore 平台获得了猪链球菌 HB18 和两个转座子的完整基因组。通过肉汤微稀释法测定 MIC。反向 PCR 鉴定了新型非常规可循环结构 (UCS)、基因组岛 (GI) 和整合与共轭元件 (ICE) 的循环形式。共轭实验评估了鼠疫杆菌中 optrA 和 lsa(E) 基因的可转移性:结果:S. suis HB18携带一个多抗性基因簇 optrA-lsa(E)-lnu(B)-aphA-aadE-spw。该基因簇位于一个新的 ICESsuHB18 上,其两侧是同方向的完整erm(B)和截短erm(B)。反向 PCR 发现了一种新的 UCS,命名为 UCS-optrA + lsa(E),它可以从 ICESsuHB18 上切除 optrA-lsa(E)-lnu(B)-aphA-aadE-spw 基因簇和一个 erm(B) 拷贝。获得了两个具有不同特征的转结合体。在转杂子 T-JH-GI 中,从 ICESsuHB18 中切除的 UCS-optrA + lsa(E) 插入到erm(B)阳性的 GI 中,命名为 GISsuHB18,产生了新的 GISsuHB18-1。同时,在 T-JH-ICE 中,ICESsuHB18 和 GISsuHB18 发生了基因重排事件,形成了新型 ICESsuHB18-1:这是首次报道功能活跃的 UCS-optrA + lsa(E) 在共轭过程中从 ICESsuHB18 中切除并插入到 erm(B) 阳性的 GISsuHB18 中。optrA 和 lsa(E) 位于多抗性 UCS 上,增强了其持久性和传播性。
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引用次数: 0
Evaluation of three commercial lateral flow immunoassays for the detection of KPC, VIM, NDM, IMP and OXA-48-like carbapenemases. 评估用于检测 KPC、VIM、NDM、IMP 和 OXA-48 类碳青霉烯酶的三种商用侧流免疫分析法。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae262
Sara Cuffari, Noemi Aiezza, Alberto Antonelli, Tommaso Giani, Gian Maria Rossolini
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引用次数: 0
A pharmacometric multistate model for predicting long-term treatment outcomes of patients with pulmonary TB. 预测肺结核患者长期治疗效果的药物计量多态模型。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae256
Yu-Jou Lin, Yuanxi Zou, Mats O Karlsson, Elin M Svensson

Background: Studying long-term treatment outcomes of TB is time-consuming and impractical. Early and reliable biomarkers reflecting treatment response and capable of predicting long-term outcomes are urgently needed.

Objectives: To develop a pharmacometric multistate model to evaluate the link between potential predictors and long-term outcomes.

Methods: Data were obtained from two Phase II clinical trials (TMC207-C208 and TMC207-C209) with bedaquiline on top of a multidrug background regimen. Patients were typically followed throughout a 24 week investigational treatment period plus a 96 week follow-up period. A five-state multistate model (active TB, converted, recurrent TB, dropout, and death) was developed to describe observed transitions. Evaluated predictors included patient characteristics, baseline TB disease severity and on-treatment biomarkers.

Results: A fast bacterial clearance in the first 2 weeks and low TB bacterial burden at baseline increased probability to achieve conversion, whereas patients with XDR-TB were less likely to reach conversion. Higher estimated mycobacterial load at the end of 24 week treatment increased the probability of recurrence. At 120 weeks, the model predicted 55% (95% prediction interval, 50%-60%), 6.5% (4.2%-9.0%) and 7.5% (5.2%-10%) of patients in converted, recurrent TB and death states, respectively. Simulations predicted a substantial increase of recurrence after 24 weeks in patients with slow bacterial clearance regardless of baseline bacterial burden.

Conclusions: The developed multistate model successfully described TB treatment outcomes. The multistate modelling framework enables prediction of several outcomes simultaneously, and allows mechanistically sound investigation of novel promising predictors. This may help support future biomarker evaluation, clinical trial design and analysis.

背景:研究结核病的长期治疗效果既耗时又不切实际。迫切需要能反映治疗反应并能预测长期疗效的早期可靠生物标志物:方法:从两个二期临床试验中获取数据,并对其进行分析:数据来自两项II期临床试验(TMC207-C208和TMC207-C209),在多药背景方案基础上使用贝达喹啉。通常对患者进行为期 24 周的研究治疗和 96 周的随访。我们建立了一个五态多态模型(活动性肺结核、转化、复发性肺结核、辍学和死亡)来描述观察到的转归。评估的预测因素包括患者特征、基线结核病严重程度和治疗中的生物标志物:结果:前两周细菌清除快、基线肺结核细菌负荷低的患者实现转阴的几率增加,而XDR-TB患者实现转阴的几率较低。在 24 周治疗结束时,估计的结核菌载量越高,复发的可能性就越大。120 周时,模型预测转阴、结核复发和死亡患者的比例分别为 55%(95% 预测区间,50%-60%)、6.5%(4.2%-9.0%)和 7.5%(5.2%-10%)。模拟预测,无论基线细菌负荷如何,细菌清除缓慢的患者在 24 周后的复发率会大幅上升:结论:所开发的多态模型成功地描述了结核病的治疗结果。多态建模框架能同时预测多种结果,并能从机理上研究新的有前途的预测因子。这将有助于支持未来的生物标志物评估、临床试验设计和分析。
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引用次数: 0
Long-acting injectable antiretrovirals for HIV treatment in the ICONA cohort: physicians' and nurses' points of view. ICONA 队列中用于艾滋病治疗的长效注射抗逆转录病毒药物:医生和护士的观点。
IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-10-01 DOI: 10.1093/jac/dkae273
A Cingolani, A Tavelli, S De Benedittis, I Mastrorosa, C Muccini, T Bini, A Carraro, M Compagno, M Mazzitelli, M Guastavigna, M Cernuschi, C Torti, A Antinori, A d'Arminio Monforte

Background: Implementation level of long-acting injectable agents cabotegravir/rilpivirine (LAI CAB/RPV) for human immunodeficiency virus (HIV) treatment in Italy is still not known. The aim of this study is to identify the status of implementation of LAI CAB-RPV and its barriers.

Materials and methods: A cross-sectional online survey was conducted among infectious diseases (ID) physicians and nurses belonging to the ICONA network in Italy. Three validate 4-items measures were used: Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM) and Feasibility of Intervention Measure (FIM).

Results: Out of 61 ICONA centres, 38 (62%) completed the survey: 57.9% were academic centres, 42.1% were hospital-based. In total, 104 respondents were ID physicians (57.4%), 77 were nurses (42.5%); 4.5% of all PWH followed at the 38 centres started LAI CAB/RPV at time of study. Centres taking care of >1000 PWH reported 95% application of procedures for LA implementation, higher than other centres (P = 0.009). Mean score of AIM was (16.0, standard deviation, SD, 3.3), of IAM (16.0, SD 3.0) and FIM (16.0, SD 2.9). A linear correlation was found between AIM and the number of people with HIV who started LAI CAB/RPV (25-50 versus <25, coefficient of correlation [b] 2.57, 95%CI 0.91-4.60, P = 0.004), academic versus hospital-based centres (b -1.59, 95%CI -2.76-0.110044, P = 0.007) and the absence of preliminary systematic assessment of staff (b -1.98, 95%CI -3.31-0.65, P = 0.004). Implementation barriers were not significantly different according to the number of PWH/centre.

Conclusions: LAI CAB/RPV implementation was low, with a great variability according to centre size. Tailored and centre-specific interventions to address barriers and to optimize the LA treatment implementation should be designed.

背景:长效注射剂卡博替拉韦/利匹韦林(LAI CAB/RPV)在意大利用于人类免疫缺陷病毒(HIV)治疗的实施水平尚不清楚。本研究旨在确定 LAI CAB-RPV 的实施状况及其障碍:对意大利 ICONA 网络的传染病(ID)医生和护士进行了横断面在线调查。采用了三个有效的 4 项测量方法:结果:在 61 个 ICONA 中心中,有 7 个中心的医生和护士接受了干预措施:在 61 个 ICONA 中心中,38 个(62%)完成了调查:57.9%为学术中心,42.1%为医院中心。共有104名受访者是内科医生(57.4%),77名是护士(42.5%);38家中心的所有PWH中有4.5%在调查时开始接受LAI CAB/RPV治疗。护理超过 1000 名残疾人的中心报告 LA 实施程序的应用率为 95%,高于其他中心(P = 0.009)。AIM 的平均得分为(16.0,标准差,SD,3.3),IAM 的平均得分为(16.0,标准差,3.0),FIM 的平均得分为(16.0,标准差,2.9)。AIM 与开始 LAI CAB/RPV 的 HIV 感染者人数呈线性相关(25-50 对结论):LAI CAB/RPV的实施率较低,不同中心的规模差异很大。应设计针对具体中心的定制干预措施,以消除障碍并优化 LA 治疗的实施。
{"title":"Long-acting injectable antiretrovirals for HIV treatment in the ICONA cohort: physicians' and nurses' points of view.","authors":"A Cingolani, A Tavelli, S De Benedittis, I Mastrorosa, C Muccini, T Bini, A Carraro, M Compagno, M Mazzitelli, M Guastavigna, M Cernuschi, C Torti, A Antinori, A d'Arminio Monforte","doi":"10.1093/jac/dkae273","DOIUrl":"10.1093/jac/dkae273","url":null,"abstract":"<p><strong>Background: </strong>Implementation level of long-acting injectable agents cabotegravir/rilpivirine (LAI CAB/RPV) for human immunodeficiency virus (HIV) treatment in Italy is still not known. The aim of this study is to identify the status of implementation of LAI CAB-RPV and its barriers.</p><p><strong>Materials and methods: </strong>A cross-sectional online survey was conducted among infectious diseases (ID) physicians and nurses belonging to the ICONA network in Italy. Three validate 4-items measures were used: Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM) and Feasibility of Intervention Measure (FIM).</p><p><strong>Results: </strong>Out of 61 ICONA centres, 38 (62%) completed the survey: 57.9% were academic centres, 42.1% were hospital-based. In total, 104 respondents were ID physicians (57.4%), 77 were nurses (42.5%); 4.5% of all PWH followed at the 38 centres started LAI CAB/RPV at time of study. Centres taking care of >1000 PWH reported 95% application of procedures for LA implementation, higher than other centres (P = 0.009). Mean score of AIM was (16.0, standard deviation, SD, 3.3), of IAM (16.0, SD 3.0) and FIM (16.0, SD 2.9). A linear correlation was found between AIM and the number of people with HIV who started LAI CAB/RPV (25-50 versus <25, coefficient of correlation [b] 2.57, 95%CI 0.91-4.60, P = 0.004), academic versus hospital-based centres (b -1.59, 95%CI -2.76-0.110044, P = 0.007) and the absence of preliminary systematic assessment of staff (b -1.98, 95%CI -3.31-0.65, P = 0.004). Implementation barriers were not significantly different according to the number of PWH/centre.</p><p><strong>Conclusions: </strong>LAI CAB/RPV implementation was low, with a great variability according to centre size. Tailored and centre-specific interventions to address barriers and to optimize the LA treatment implementation should be designed.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975705","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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