Azithromycin

阿奇霉素
  • 文章类型: Journal Article
    本研究旨在检查血液培养中发现的副伤寒沙门氏菌的频率,并评估沙门氏菌分离株对不同抗生素的抗生素敏感性模式。此外,该研究旨在评估伤寒沙门氏菌引起的肠道热趋势的范式转变(S.伤寒)至副伤寒沙门氏菌(S.副伤寒)。
    回顾性研究。
    该研究招募了12岁及以上被诊断患有肠热(血培养阳性)并入住PeelameduSamanaiduGovindasamyNaidu(PSG)医院的患者。
    该研究分析了2010年至2022年间从医院106例肠热患者收集的沙门氏菌分离株的人口统计学和抗生素敏感性。评估了沙门氏菌分离株对多种抗生素的敏感性。
    有106名参与者,其中95人(89.62%)有与伤寒沙门氏菌有关的肠热,从2010年到2022年,只有11例(10.38%)与副伤寒沙门氏菌A相关的肠道热,该研究发现沙门氏菌引起的肠道热患病率普遍下降。但是在2014年至2022年之间,与伤寒沙门氏菌相关的肠道热的发病率迅速增加。阿奇霉素(100%,n=106)和头孢曲松(99%,n=105)对沙门氏菌分离株非常有效,而萘啶酸被3个分离株(4.72%,n=3)。
    该研究发现,与甲型副伤寒相比,伤寒沙门氏菌的发病率更高,男性对肠热的易感性更高。
    没有声明。
    UNASSIGNED: This study aims to examine the frequency of Salmonella Paratyphi found in blood cultures and evaluate the antibiotic susceptibility pattern of Salmonella isolates to different antibiotics. Additionally, the study aims to assess the paradigm shift in the trend of enteric fever caused by Salmonella Typhi (S. Typhi) to Salmonella Paratyphi(S. Paratyphi) .
    UNASSIGNED: Retrospective study.
    UNASSIGNED: The study enrolled patients aged 12 years and above diagnosed with enteric fever (positive blood culture) and admitted to Peelamedu Samanaidu Govindasamy Naidu (PSG) Hospital.
    UNASSIGNED: The study analyzed demographic and antibiotic susceptibility profiles of Salmonella isolates collected from 106 enteric fever patients in the hospital between 2010 and 2022. The susceptibility profiles of Salmonella isolates to multiple antibiotics were assessed.
    UNASSIGNED: There were 106 participants, and 95 (89.62%) of them had enteric fever linked to Salmonella Typhi, while only 11 (10.38%) had enteric fever linked to Salmonella Paratyphi A. From 2010 to 2022, the study discovered a general decline in the prevalence of enteric fever caused by Salmonella species. But between 2014 and 2022, the incidence of enteric fever linked to S. Typhi rapidly increased. Azithromycin (100% , n = 106) and ceftriaxone (99% , n = 105) were highly effective against the Salmonella isolates, whereas nalidixic acid was resisted by 3 isolates (4.72%, n = 3).
    UNASSIGNED: The study observed a higher incidence of Salmonella Typhi in comparison to Paratyphi A and a greater susceptibility of males to enteric fever.
    UNASSIGNED: None declared.
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  • 文章类型: Journal Article
    背景:宿主对肺炎支原体的不当免疫反应会产生过度的炎症,导致肺通气功能(PVF)受损。阿奇霉素加吸入特布他林已用于治疗肺功能受损儿童的肺炎支原体肺炎(MPP),但之前的随机对照试验(RCTs)显示疗效和安全性不一致.本研究旨在首先对该综合疗法进行系统评价。
    方法:本研究在国际前瞻性系统评价注册中心(PROSPEROCRD42023452139)注册。进行了符合PRISMA的系统评价和荟萃分析。截至6月,全面检索了6个英文数据库和4个中文数据库,2023年。选择阿奇霉素序贯疗法加吸入特布他林的RCTs。修订后的Cochrane风险偏倚工具(RoB2)用于评估所有研究的方法学质量,使用Stata15.0进行meta分析,并进行计划亚组和敏感性分析.通过漏斗图和Harbord检验评估出版偏倚。使用建议分级评估证据的确定性,评估,发展和评价建议。
    结果:最终纳入20个随机对照试验中的1,938名儿科患者。荟萃分析结果显示,联合治疗能够显著提高总有效率(RR=1.20,95CI1.15~1.25),一秒用力呼气量(SMD=1.14,95CIs,0.98至1.29),一秒用力呼气量/用力肺活量之比(SMD=2.16,95CIs,1.46to2.86),最大呼气流量(SMD=1.17,95CIs,0.91至1.43)。与阿奇霉素单独治疗相比,联合治疗的不良反应风险增加了23%。但没有发现显著差异。Harbord回归分析显示无发表偏倚(P=0.148)。证据的总体质量从中等到非常低。
    结论:首次系统评价和荟萃分析提示阿奇霉素序贯疗法联合吸入特布他林对MPP患儿是安全且有益的。此外,联合治疗代表PVF的显著改善。由于缺乏高质量的证据,我们的结果应该在未来得到足够有力的随机对照试验的证实.
    BACKGROUND: An improper host immune response to Mycoplasma pneumoniae generates excessive inflammation, which leads to the impairment of pulmonary ventilation function (PVF). Azithromycin plus inhaled terbutaline has been used in the treatment of Mycoplasma pneumoniae pneumonia (MPP) in children with impaired pulmonary function, but previous randomized controlled trials (RCTs) showed inconsistent efficacy and safety. This study is aimed to firstly provide a systematic review of the combined therapy.
    METHODS: This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO CRD42023452139). A PRISMA-compliant systematic review and meta-analysis was performed. Six English and four Chinese databases were comprehensively searched up to June, 2023. RCTs of azithromycin sequential therapy plus inhaled terbutaline were selected. The revised Cochrane risk of bias tool for randomized trials (RoB2) was used to evaluate the methodological quality of all studies, and meta-analysis was performed using Stata 15.0 with planned subgroup and sensitivity analyses. Publication bias was evaluated by a funnel plot and the Harbord\' test. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation recommendations.
    RESULTS: A total of 1,938 pediatric patients from 20 RCTs were eventually included. The results of meta-analysis showed that combined therapy was able to significantly increase total effectiveness rate (RR = 1.20, 95%CI 1.15 to 1.25), forced expiratory volume in one second (SMD = 1.14, 95%CIs, 0.98 to 1.29), the ratio of forced expiratory volume in one second/forced vital capacity (SMD = 2.16, 95%CIs, 1.46 to 2.86), peak expiratory flow (SMD = 1.17, 95%CIs, 0.91 to 1.43). The combined therapy was associated with a 23% increased risk of adverse reactions compared to azithromycin therapy alone, but no significant differences were found. Harbord regression showed no publication bias (P = 0.148). The overall quality of the evidence ranged from moderate to very low.
    CONCLUSIONS: This first systematic review and meta-analysis suggested that azithromycin sequential therapy plus inhaled terbutaline was safe and beneficial for children with MPP. In addition, the combined therapy represented significant improvement of PVF. Due to lack of high-quality evidence, our results should be confirmed by adequately powered RCTs in the future.
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  • 文章类型: Journal Article
    存在的阿奇霉素的光降解是在紫外线照射下使用H2O2在水中进行的。在这项研究中考虑的反应变量是H2O2溶液的量和阿奇霉素的初始浓度,以评估光降解过程的性能。在搅拌20分钟期间,在黑暗中未观察到阿奇霉素降解。研究表明,在紫外线照射下,使用H2O2作为氧化剂可以有效地光降解阿奇霉素。辐照溶液的pH值显着改变了阿奇霉素的降解。在酸性pH下降解较低,并且随着pH变为碱性而显示出增加的趋势。随着H2O2的量增加(浓度增加),阿奇霉素的降解增加。随着反应溶液中阿奇霉素的浓度升高,阿奇霉素的降解降低。使用含有3mLH2O2的1.0ppmAZT溶液在1小时内实现了AZT的最高降解。获得的实验数据很好地拟合了零级反应动力学。发现这项研究的结果非常出色。与文献中报道的相比,它们在1小时内显示出100%的降解,使用纳米材料进行光催化和使用光辐射和/或H2O2进行光解。发现UV/H2O2系统对阿奇霉素的光降解非常有效,该系统可用于降解工业废水中存在的其他有机污染物。
    The photodegradation of azithromycin present was carried out in water using H2O2 under UV irradiation. The reaction variables considered in this study were the amount of H2O2 solution and the initial concentration of azithromycin to evaluate the performance of the photodegradation process. The azithromycin degradation was not observed in the dark during stirring for 20 min. The study showed an efficient photodegradation of azithromycin using H2O2 as an oxidant in the presence of UV irradiation. The azithromycin degradation was altered significantly by the pH of the irradiated solution. The degradation was low at an acidic pH and showed an increasing trend as the pH changed to basic. The azithromycin degradation increased with a higher amount (higher concentration) of H2O2. The degradation of azithromycin decreased with a higher concentration of azithromycin in the reacting solution. The highest degradation of AZT was achieved in 1 h using a 1.0 ppm AZT solution containing 3 mL of H2O2. The experimental data obtained were well-fitted to zero-order reaction kinetics. The results of this study were found quite excellent. They showed 100% degradation in 1 h when compared with those reported in the literature, both with photocatalysis using nanomaterials and photolysis using light irradiation and/or H2O2. The UV/H2O2 system was found to be quite efficient for the photodegradation of azithromycin, and this system can be applied to degrade other organic pollutants present in industrial wastewater.
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  • 文章类型: Case Reports
    阿奇霉素可导致严重的胆汁淤积性肝病。我们描述了2例继发于药物性胆汁淤积性肝损伤的顽固性瘙痒,对有症状的药物治疗没有反应,需要并对治疗性血浆置换(TPE)反应良好。首先是一名60岁男性,已知患有稳定的慢性淋巴细胞白血病(CLL)和良性前列腺增生,第二个是一名46岁的女性,已知患有原发性胆汁性肝硬化(PBC),在六周和两周时出现,分别,轻度COVID-19肺炎后。在COVID-19肺炎期间,他们的非处方药(OCT)阿奇霉素使用史呈阳性。他们有两周的严重瘙痒史,与睡眠剥夺和生活质量受损有关。肝功能检查显示胆汁淤积性肝损伤。包括胆汁酸螯合剂和抗组胺药在内的多种治疗方法仍然难以治疗瘙痒。在三个疗程的TPE后观察到患者症状的快速和持久的缓解。我们的病例突出表明,在最近的COVID-19大流行期间,医学上顽固性胆汁淤积性瘙痒是抗生素滥用的不良反应。TPE后观察到持续的症状改善。
    Azithromycin can result in severe cholestatic liver disease. We describe two cases of intractable pruritus secondary to drug-induced cholestatic liver injury, unresponsive to symptomatic medical therapy, necessitating and responding well to therapeutic plasma exchange (TPE). The first is a case of a 60-year-old male known to have stable chronic lymphocytic leukemia (CLL) and benign prostatic hyperplasia, and the second is a 46-year-old female known to have primary biliary cirrhosis (PBC) who presented at six weeks and two weeks, respectively, post-mild-COVID-19 pneumonia. Their drug histories were positive for over-the-counter (OCT) azithromycin use during the COVID-19 pneumonia period. They presented with a two-week history of severe itching, associated with sleep deprivation and impaired quality of life. Liver function tests revealed a cholestatic pattern of liver injury. Pruritus remained refractory to multiple lines of treatment including bile acid sequestrants and antihistamines. Rapid and long-lasting relief of the patient\'s symptoms was observed after three sessions of TPE. Our cases highlight medically recalcitrant cholestatic pruritus as an adverse effect of antibiotic misuse during the recent COVID-19 pandemic. Sustained symptomatic improvements were seen after TPE.
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  • 文章类型: Journal Article
    背景:布地奈德,能够降低血管通透性,抑制粘液分泌,减轻水肿和痉挛,在中国被广泛用于合并传染病的治疗。这项研究评估了布地奈德作为阿奇霉素辅助治疗中国小儿支原体肺炎的疗效和安全性。旨在为其临床应用奠定坚实的理论基础。
    方法:我们在5个英文数据库和4个中文数据库中对合格研究进行了全面搜索,涵盖出版物,直至2023年10月31日。使用标准软件(StataCorporation,学院站,TX)。这项研究是按照系统评价和荟萃分析的首选报告项目中概述的指南进行的。
    结果:本研究共涉及24项随机对照试验,包括2034名患者。我们的发现表明,布地奈德与阿奇霉素联合治疗小儿支原体肺炎可获得更好的治疗效果(静脉:比值比[OR],0.156,P<.001;顺序:OR,0.163,P=.001;口服:OR,0.139,P<.001),改善肺功能(1秒用力呼气量:加权平均差[WMD],-0.28,P=.001;最大呼气流量:大规模杀伤性武器,-0.554,P=.002;强迫肺活量:大规模杀伤性武器,-0.321,P<.001),肺部炎症减少(IL-6:WMD,4.760,P=0.002;C反应蛋白:WMD,5.520,P<.001;TNF-α:WMD,9.124,P<.001),减少发烧的持续时间,更快的咳嗽和啰音的解决,所有这些都没有增加不良事件的发生。
    结论:布地奈德和阿奇霉素的联合使用显示出更高的治疗效果,促进改善肺功能,缩短症状持续时间,有效减轻C反应蛋白等炎症因子的过度表达,TNF-α,和IL-6,均未增加小儿支原体肺炎的不良反应。
    BACKGROUND: Budesonide, capable of reducing vascular permeability, suppressing mucus secretion, and alleviating edema and spasms, is widely used in China for combined infectious disease treatment. This study assesses budesonide\'s efficacy and safety as an adjunct to azithromycin in pediatric Mycoplasma pneumonia management in China, aiming to establish a strong theoretical foundation for its clinical application.
    METHODS: We conducted a comprehensive search for qualifying studies across 5 English databases and 4 Chinese databases, covering publications until October 31, 2023. Endpoint analyses were performed using standard software (Stata Corporation, College Station, TX). This study was conducted in compliance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
    RESULTS: A total of 24 randomized controlled trials were involved in the current study, including 2034 patients. Our findings indicate that the combination of budesonide with azithromycin for the treatment of pediatric Mycoplasma pneumonia delivers superior therapeutic efficacy (Intravenous: odds ratio [OR], 0.156, P < .001; Sequential: OR, 0.163, P = .001; Oral: OR, 0.139, P < .001), improved pulmonary function (Forced expiratory volume in 1 second: weighted mean differences [WMD], -0.28, P = .001; Peak expiratory flow: WMD, -0.554, P = .002; Forced vital capacity: WMD, -0.321, P < .001), diminished lung inflammation (IL-6: WMD, 4.760, P = .002; c-reactive protein: WMD, 5.520, P < .001; TNF-α: WMD, 9.124, P < .001), reduced duration of fever, faster resolution of cough and rales, all without increasing the occurrence of adverse events.
    CONCLUSIONS: The combination of budesonide and azithromycin demonstrates enhanced therapeutic effectiveness, promotes improved pulmonary function, shortens the duration of symptoms, and effectively mitigates the overexpression of inflammatory factors like c-reactive protein, TNF-α, and IL-6, all without an associated increase in adverse reactions in pediatric mycoplasma pneumonia.
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  • 文章类型: Journal Article
    取决于所施加的热氧化条件,阿奇霉素(AZM)的化学稳定性可能受到损害。本报告阐述了在不同温度条件(20-80°C)下这一过程的证据。暴露于紫外线辐射的时间(在257nm下照射1-3小时),通过使用热活化的钼酸铈(Ce2(MoO4)3)/多壁碳纳米管(MWCNT)基复合电极进行的电化学测量,以及空气饱和度(在1.2Lmin-1和15kPa下与大气空气的1-3小时饱和度)。在120°C的热处理导致Ce2(MoO4)3中的协同水消除,从而改善了其对抗生素氧化的电催化作用,而MWCNT对于降低电荷转移电阻和促进信号放大是必不可少的。理论实验数据显示,使用在CH3OH/H2O(10:90%,v/v)。在这些条件下记录高度灵敏(230nM检测极限)和精确(RSD<4.0%)的测量。结果还表明,AZM随着温度的升高而降低其半衰期,暴露于紫外线辐射的时间,和空气饱和度增加。这一事实加强了对基于AZM的药物的连续质量控制的需求,使用更接近运输和储存过程中观察到的条件,减少对消费者健康的影响。
    The chemical stability of azithromycin (AZM) may be compromised depending on the imposed thermo-oxidative conditions. This report addresses evidence of this process under varying conditions of temperature (20-80 °C), exposure time to UV radiation (1-3 h irradiation at 257 nm), and air saturation (1-3 h saturation with atmospheric air at 1.2 L min-1 and 15 kPa) through electrochemical measurements performed with a thermoactivated cerium molybdate (Ce2(MoO4)3)/multi-walled carbon nanotubes (MWCNT)-based composite electrode. Thermal treatment at 120 °C led to coordinated water elimination in Ce2(MoO4)3, improving its electrocatalytic effect on antibiotic oxidation, while MWCNT were essential to reduce the charge-transfer resistance and promote signal amplification. Theoretical-experimental data revealed remarkable reactivity for the irreversible oxidation of AZM on the working sensor using phosphate buffer (pH = 8) prepared in CH3OH/H2O (10:90%, v/v). Highly sensitive (230 nM detection limit) and precise (RSD < 4.0%) measurements were recorded under these conditions. The results also showed that AZM reduces its half-life as the temperature, exposure time to UV radiation, and air saturation increase. This fact reinforces the need for continuous quality control of AZM-based pharmaceuticals, using conditions closer to those observed during their transport and storage, reducing impacts on consumers\' health.
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  • 文章类型: Journal Article
    用于治疗COVID-19的抗病毒疗法可能与显著的心律失常潜力有关。在本研究中,使用离体兔心脏的Langendorff模型评估了这些疗法的潜在心脏毒性副作用.对51颗雌性兔子的心脏进行了逆行灌注,采用Langendorff设置。在心内膜和心外膜放置了八根导管以进行电生理研究,从而获得90%复极化时的周期长度依赖性动作电位持续时间(APD90),QT间期和复极化色散。生成基线数据后,将心脏分为四组:在第1组(HXC)中,心脏用1µM羟氯喹治疗。此后,另外输注3µM羟氯喹。第2组(HXC+AZI)灌注3µM羟氯喹,然后灌注150µM阿奇霉素。在第3组(LOP)中,心脏灌注3µM洛匹那韦,然后灌注5µM和10µM洛匹那韦。第4组(REM)灌注1µMremdesivir,然后灌注5µM和10µMremdesivir。基于羟氯喹和阿奇霉素的疗法具有由动作电位延长和分散度增加介导的显着心律失常潜力。洛匹那韦和remdesivir在电生理方面的总体变化明显不明显。根据remdesivir报告的心动过缓事件,它显著降低了室性逃逸心律的发生率。
    Antiviral therapies for treatment of COVID-19 may be associated with significant proarrhythmic potential. In the present study, the potential cardiotoxic side effects of these therapies were evaluated using a Langendorff model of the isolated rabbit heart. 51 hearts of female rabbits were retrogradely perfused, employing a Langendorff-setup. Eight catheters were placed endo- and epicardially to perform an electrophysiology study, thus obtaining cycle length-dependent action potential duration at 90% of repolarization (APD90), QT intervals and dispersion of repolarization. After generating baseline data, the hearts were assigned to four groups: In group 1 (HXC), hearts were treated with 1 µM hydroxychloroquine. Thereafter, 3 µM hydroxychloroquine were infused additionally. Group 2 (HXC + AZI) was perfused with 3 µM hydroxychloroquine followed by 150 µM azithromycin. In group 3 (LOP) the hearts were perfused with 3 µM lopinavir followed by 5 µM and 10 µM lopinavir. Group 4 (REM) was perfused with 1 µM remdesivir followed by 5 µM and 10 µM remdesivir. Hydroxychloroquine- and azithromycin-based therapies have a significant proarrhythmic potential mediated by action potential prolongation and an increase in dispersion. Lopinavir and remdesivir showed overall significantly less pronounced changes in electrophysiology. In accordance with the reported bradycardic events under remdesivir, it significantly reduced the rate of the ventricular escape rhythm.
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  • 文章类型: Journal Article
    静止原脱发的特征是通常在压力事件后过度脱落。铁蛋白已在临床实践中用作非贫血性铁缺乏症的生物标志物。在COVID19大流行期间,据报道,端粒脱落是covid后表现的一部分。由于铁蛋白也是covid感染病例中炎症的生物标志物,这项研究的目的是评估铁蛋白的价值与后covid端程脱落的情况下,100名患者从covid19恢复4-12周纳入研究,获得了详细的药物和实验室病史,并测量了血清铁蛋白水平。静止期脱发患者的平均血清铁蛋白水平显着低于对照组(分别为68.52±126和137±137.597ug/L)。有止动素流出的患者使用的阿奇霉素和伊维菌素明显较多,维生素C明显较少,D,乳铁蛋白和锌比对照组,虽然血清铁蛋白较低,它仍然高于诊断非贫血性缺铁症的临界值,我们建议在这些病例中它不是一个好的生物标志物.我们的次要结果显示,在活动性感染期间使用的膳食补充剂,如维生素C,D,乳铁蛋白和锌可能具有预防后covid脱发的价值,而阿奇霉素和伊维菌素可能对止动素产生长期负面影响。
    Telogen effluvium is characterized by excessive hair shedding usually following a stressful event. Ferritin has been used in clinical practice as a biomarker of nonanemic iron deficiency in cases of telogen effluvium. During the years of the COVID19 pandemic, telogen effluvium was reported as a part of post covid manifestations. As ferritin was also a biomarker for inflammation in cases with covid infection, this study was designed to evaluate the value of ferritin in cases with postcovid telogen effluvium one hundred patients recovering from covid 19 for 4-12 weeks were included in the study, detailed drug and laboratory history was obtained and serum ferritin level was measured. the mean serum level of ferritin among telogen effluvium patients was significantly lower than controls (68.52 ± 126 and 137 ± 137.597 ug/L respectively). Patients with telogen effluvium used significantly more azithromycin and ivermectin and significantly less vitamin C, D, lactoferrin and zinc than the controls Although serum ferritin is lower among telogen effluvium patients, it was still higher than the cutoff value for diagnosing nonanemic iron deficiency, we suggest that it will not be a good biomarkers in these cases. Our secondary outcomes showed that dietary supplements used during active infection such as vitamin C, D, lactoferrin and zinc might have a preventive value on postcovid hair loss, while azithromycin and ivermectin could have a negative long term effect on telogen effluvium.
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  • 文章类型: Journal Article
    生殖支原体感染的推荐一线治疗是阿奇霉素。然而,在全球范围内,生殖支原体对大环内酯的耐药率已增加到50%以上.2013年,澳大利亚引入了耐药性指导治疗(RGT)策略来管理生殖支原体感染。本研究评估了RGT方法与无RGT方法相比的成本效益(即,没有大环内酯抵抗谱测试)在女性中,男男性行为者(MSM),和在澳大利亚与女性发生性关系的男性(MSW)。我们构建了女性生殖支原体感染的动态传播模型,MSM,和澳大利亚的MSW,每个人都有10万人口。这些模型比较了十年来从医疗保健角度来看,RGT和无RGT方案之间获得的成本和质量调整寿命年(QALYs)。所有费用均以2022澳元(澳元)报告。在我们的模型中,RGT在女性和MSM中节省了成本,随着130万美元和1790万美元的净货币收益增量,分别。在MSW中,RGT方法不划算,每QALY的增量成本效益比为-106.96美元。在女性和MSM中,与没有RGT相比,RGT可以节省成本。支持将其作为这两个人口群体的国家管理战略。
    The recommended first-line treatment for Mycoplasma genitalium infections is azithromycin. However, the prevalence of macrolide resistance for M. genitalium has increased to more than 50% worldwide. In 2013, Australia introduced a resistance-guided therapy (RGT) strategy to manage M. genitalium infections. This study assesses the cost-effectiveness of the RGT approach compared to no RGT (i.e., without macrolide resistance profile test) in women, men who have sex with men (MSM), and men who have sex with women (MSW) in Australia. We constructed dynamic transmission models of M. genitalium infections in women, MSM, and MSW in Australia, each with a population of 100,000. These models compared the costs and quality-adjusted life-years (QALYs) gained between RGT and no RGT scenarios from a healthcare perspective over ten years. All costs are reported in 2022 Australian dollars (Australian $). In our model, RGT is cost saving in women and MSM, with the incremental net monetary benefit of $1.3 million and $17.9 million, respectively. In MSW, the RGT approach is not cost-effective, with an incremental cost-effectiveness ratio of -$106.96 per QALY gained. RGT is cost saving compared to no RGT for M. genitalium infections in women and MSM, supporting its adoption as the national management strategy for these two population groups.
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  • 文章类型: Journal Article
    由于抗菌素耐药性(AMR)基因的无法控制的传播,主要的抗生素组正失去效力。其中,编码β-内酰胺酶的β-内酰胺抗性基因由于其与可移动遗传元件的频繁关联而成为肠杆菌中最常见的抗性机制。在这种情况下,迫切需要新的方法来对抗移动AMR。当对一种抗生素的抗性的获得增加对另一种抗生素的敏感性并且可以被利用来选择性地消除AMR时,发生附带敏感性(CS)。然而,迄今为止描述的大多数CS网络都是由于染色体突变而出现的,无法用于解决移动AMR。这里,我们剖析了由获得普遍的抗生素抗性质粒引起的CS反应,以揭示β-内酰胺酶基因blaOXA-48的表达诱导CS对粘菌素和阿奇霉素的表达。我们接下来显示,其他临床相关的移动β-内酰胺酶在多个,系统发育无关的大肠杆菌菌株。最后,通过将实验与包含数千个抗生素敏感性测试的监测数据相结合,我们显示β-内酰胺酶诱导的CS在肠杆菌中普遍存在。这些结果表明,β-内酰胺酶的生理副作用可以在治疗上发挥作用。为合理设计特定疗法铺平道路,以阻断移动AMR或至少抵消其影响。
    Major antibiotic groups are losing effectiveness due to the uncontrollable spread of antimicrobial resistance (AMR) genes. Among these, β-lactam resistance genes -encoding β-lactamases- stand as the most common resistance mechanism in Enterobacterales due to their frequent association with mobile genetic elements. In this context, novel approaches that counter mobile AMR are urgently needed. Collateral sensitivity (CS) occurs when the acquisition of resistance to one antibiotic increases susceptibility to another antibiotic and can be exploited to eliminate AMR selectively. However, most CS networks described so far emerge as a consequence of chromosomal mutations and cannot be leveraged to tackle mobile AMR. Here, we dissect the CS response elicited by the acquisition of a prevalent antibiotic resistance plasmid to reveal that the expression of the β-lactamase gene blaOXA-48 induces CS to colistin and azithromycin. We next show that other clinically relevant mobile β-lactamases produce similar CS responses in multiple, phylogenetically unrelated E. coli strains. Finally, by combining experiments with surveillance data comprising thousands of antibiotic susceptibility tests, we show that β-lactamase-induced CS is pervasive within Enterobacterales. These results highlight that the physiological side-effects of β-lactamases can be leveraged therapeutically, paving the way for the rational design of specific therapies to block mobile AMR or at least counteract their effects.
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