Current and prospective treatments for multidrug-resistant gram-positive infections

Introduction: Staphylococcus aureus and Enterococcus spp. are two of the most common organisms causing nosocomial infections today; and are consistently associated with high mortality rates (approximately 20 and 44%, respectively). Resistance among these pathogens to first line agents such as methicillin and vancomycin continues to rise while isolates with reduced susceptibility to newer agents including linezolid and daptomycin continue to emerge, representing a serious concern for clinicians.

Areas covered: Mechanisms of action and resistance as well as in vitro and clinical experience in the treatment of resistant staphylococci and enterococci with currently available agents are discussed. Additionally, novel combination regimens showing enhanced efficacy and available data pertaining to prospective therapies including solithromycin, tedizolid, dalbavancin and oritavancin will be covered.

Expert opinion: With an increase in organisms displaying reduced susceptibility to vancomycin and the associated treatment failures, the significance of alternative therapies such as daptomycin, linezolid, ceftaroline, and prospective anti-gram-positive agents is on the rise. As our understanding of antimicrobial pharmacokinetic-pharmacodynamics principles continues to evolve, the selection of highly effective agents and optimization of dosages may lead to improved patient outcomes and delay the development of resistance.     

2014—2018年耐碳青霉烯类肺炎克雷伯菌分离及耐药率分析#br#

目的 通过对耐碳青霉烯类肺炎克雷伯菌(carbapenem-resistant Klebsiella pneumoniae, CRKP)和非耐碳青霉烯类肺炎克雷伯菌的分离结果和耐药性分析，为临床提供合理治疗方案。方法 回顾性对比分析2014年1月—2018年12月分离出的284株CRKP和2272株非CRKP的标本来源、病区分布和耐药性。数据分析采用Whonet5.6统计软件，使用 SPSS 20.0软件进行差异显著性分析，耐药率比较采用χ2检验。结果 2014—2018年5年CRKP分离率分别为0、0.6%、0.2%、3.2%和26.5%，平均分离率为11.1%；病区分布主要为重症监护病房(ICU)、干部保健病房、神经内科、呼吸内科、肿瘤外科，构成比分别为33.8%、26.1%、8.8%、7.0%和4.9%。ICU的CRKP分离率明显高于非ICU(χ2=101.514, P<0.05)，二者比较差异具有显著性。CRKP标本来源主要是痰液，构成比达到48.6%。CRKP出现多重耐药，CRKP对常用的革兰阴性抗菌药物头孢菌素类、氟喹诺酮类、碳青霉烯类耐药率均超过95%，对氨基糖苷类的耐药率也超过90%；而非CRKP耐药率较低，对所有11种抗菌药物耐药率<28.6%，非CRKP对11种抗菌药物的耐药率均低于CRKP，且差异有显著性(P<0.05)。结论 CRKP分离率和耐药率较高，CRKP的耐药率明显高于非CRKP，检验科应及时报告CRKP的分离和耐药情况，加强抗菌药物的管理，强化消毒、隔离等感染控制措施。     

Role of insulin resistance indices in predicting new‐onset diabetes after kidney transplantation

New‐onset diabetes mellitus (NODAT) is a serious complication following renal transplantation. In this cohort study, we studied 118 nondiabetic renal transplant recipients to examine whether indices of insulin resistance and secretion calculated before transplantation and at 3 months post‐transplantation are associated with the development of NODAT within 1 year. We also analysed the long‐term impact of early diagnosed NODAT. Insulin indices were calculated using homeostasis model assessment (HOMA) and McAuley's Index. NODAT was diagnosed using fasting plasma glucose. Median follow‐up was 11 years. The cumulative incidence of NODAT at 1 year was 37%. By logistic regression, recipient age (per year) was the only significant pretransplant predictor of NODAT (OR 1.04, CI 1.009–1.072), while age (OR 1.04, CI 1.005–1.084) and impaired fasting glucose (OR 2.97, CI 1.009–8.733) were significant predictors at 3 months. Pretransplant and 3‐month insulin resistance and secretion indices did not predict NODAT. All‐cause mortality was significantly higher in recipients developing NODAT within 1 year compared with those remaining nondiabetic (44% vs. 22%, log‐rank P = 0.008). By Cox's regression analysis, age (HR 1.075, CI 1.042–1.110), 1‐year creatinine (HR 1.007, CI 1.004–1.010) and NODAT within 3 months (HR 2.4, CI 1.2–4.9) were independent predictors of death. In conclusion, NODAT developing early after renal transplantation was associated with poor long‐term patient survival. Insulin indices calculated pretransplantation using HOMA and McAuley's Index did not predict NODAT.     

A Randomized Controlled Trial of the Clinical Utility of Genotypic Resistance Testing in Patients with Limited Prior Exposure to Antiretroviral Drugs

Abstract

Purpose: To assess the clinical utility of genotypic resistance testing among HIV-1-infected patients with limited prior exposure to antiretroviral drugs. Method: Patients experiencing virological failure were randomly allocated to either centralized genotypic resistance testing or to no testing and were followed for a minimum of 1 year. Results: 55 patients were recruited from 14 centers in the United Kingdom. There were no demonstrable differences between the groups in terms of virological or immunological response. For patients allocated to resistance testing, there was an increased tendency to recycle previously used drugs. Conclusion: The study did not demonstrate a benefit of genotypic resistance testing in this population, although statistical power was low. However, testing did alter prescribing behavior, and clinical effects may become manifest in the longer term.     

Application of Plasma Genotyping Technologies in Non–Small Cell Lung Cancer: A Practical Review

The rational treatment of metastatic NSCLC hinges on the timely detection of potentially targetable genomic alterations to guide therapy. Recent advances in highly sensitive genotyping technologies have allowed for development of novel plasma genotyping assays that are capable of noninvasively detecting targetable alterations in plasma cell-free DNA without reliance on traditional tissue genotyping. The rapid development of plasma genotyping has led to an explosion in the number of assay platforms available from both commercial and laboratory sources. The sheer number of such platforms has led to confusion among oncologists as to both the test characteristics and limitations of individual plasma genotyping assays and the clinical context in which these tests may be utilized either alone or in combination with traditional tissue genotyping. Reliable data from prospective validation against a tissue genotyping reference standard are available for only a limited number of platforms. Careful retrospective validation of alternative platforms utilizing paired tissue and plasma specimens collected under the auspices of clinical trials represent an alternative but reliable validation strategy. A consistent trend among these well-validated plasma genotyping assays has been the observation of high specificity and positive predictive value and more limited sensitivity. At present, validated assays can be considered actionable in instances in which a targetable genomic alteration is detected or an alternative nontargetable driver mutation is detected and can be used to infer the absence of one of the former.     

初诊多囊卵巢综合征患者血清betatrophin水平及其影响因素

目的 探讨初诊多囊卵巢综合症征（PCOS）患者血清betatrophin水平及其影响因素。方法 收集2016年8月至2017年3月就诊于安徽医科大学第一附属医院的初诊PCOS患者81例作为PCOS组，同期选择安徽医科大学第一附属医院体检中心就诊的30名月经周期规律的健康女性作为对照组。测量两组受试者基本临床及生化指标，采用酶联免疫吸附法测定空腹血清中betatrophin水平，比较两组上述指标变化；使用Pearson相关性分析betatrophin水平与代谢指标之间的关系，根据相关分析结果确定可能影响betatrophin的因素，进一步多元逐步回归分析betatrophin的独立因素。结果 PCOS组患者血清betatrophin水平（95.52±58.59） pg/mL高于对照组（148.57±110.91） pg/mL，差异有统计学意义（P<0.05），Pearson相关分析显示，PCOS组患者血清betatrophin水平与空腹血糖（FBG）、三酰甘油（TG）、体质指数（BMI）、腰臀比（WHR）呈正相关（P<0.01），与空腹胰岛素（FINS）、稳态模式胰岛素抵抗指数（HOMA-IR）无相关性（P>0.05）；多元逐步回归分析提示，TG是血清betatrophin的独立影响因素；NC组无上述相关性。结论 PCOS患者血清betatrophin水平水平高于健康人群，TG是其独立影响因素，betartophin可能与PCOS患者体内的糖、脂代谢紊乱有关。     

维生素D对非酒精性脂肪性肝病患者铁代谢的影响

目的 探讨非酒精性脂肪性肝病（NAFLD）患者血清维生素D水平对血清铁（SI）、铁蛋白（SF）及铁调素（Hepc）的影响及意义。方法 单纯性NAFLD患者186例根据血清25羟维生素D［3 25（OH）D3］水平分为维生素D缺乏组［25（OH）D3≤20 μg/L，115例，］和非缺乏组（71例），比较2组患者年龄、性别、体质指数（BMI）、血压、血脂、丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、γ-谷氨酰转肽酶（GGT）、空腹血糖（FPG）、空腹胰岛素（FINS）、稳态模型胰岛素抵抗指数（HOMA-IR）、SI、SF及Hepc水平；分析25（OH）D3与SI、SF、Hepc及HOMA-IR之间的相关性。结果 2组患者SI差异无统计学意义（P＞0.05），维生素D缺乏组BMI、FINS、SF、Hepc水平及HOMA-IR均高于非缺乏组（P＜0.05）。血清 25（OH）D3水平与 SF（r=-0.328）、Hepc（r=-0.314）及 HOMA-IR（r=-0.293）呈弱负相关（P＜ 0.05）。结论 维生素D水平下降增加了NAFDL患者体内铁负荷，加重了胰岛素抵抗。     

Management of the Urologic Sepsis Syndrome

In approximately one-third of patients with sepsis, the source of infection is the urinary tract. The management of sepsis has rapidly changed over the past two decades, and a review of urosepsis management is paramount. It is estimated that in 30% of patients with severe sepsis and septic shock, the underlying reason is a urinary tract infection (UTI). The prevalence of microbiologically proven urosepsis in urology departments has been reported as 1.5% (quarter of health care–associated UTIs). On a global level, it has been postulated that 5.4 million deaths occur due to sepsis. The main causes of urosepsis are indwelling urinary catheters and urologic interventions (stone treatment, prostate biopsies, and endoscopic urethral stricture treatment). Urosepsis-causative pathogens are primarily gram-negative bacteria; this is different from sepsis overall, which is dominated by gram-positive bacteria. Its been reported that the resistance rates of pathogens in urosepsis are >10% for almost all antibiotics. The main principles of management of urosepsis and sepsis are the same, including early goal-directed treatment and antibiotic administration within the first 45 min. Early goal-directed therapy was recently shown not to be superior to standard care; however, these results may not be applicable to settings in which standard care needs improvement. Selection of an appropriate antibiotic for the initial empirical treatment in urosepsis requires knowledge of previous interventions, antibiotic usage, and local resistance rates. Future research on the management of urosepsis should be directed toward identification of groups at risk of developing urosepsis, antibiotic selection, and value of biomarkers in treatment response (eg, lactate, procalcitonin).Patient summaryIn approximately one-third of patients with sepsis, the source of infection is the urinary tract. This review assessed causes and management of urosepsis and directions for future research.