New antimicrobial agents for the treatment of Gram-positive bacterial infections.

Since the 1970s, resistance to antimicrobial agents has become an escalating problem. In the last 25 years, treatment of infections caused by Gram-positive bacteria has been more problematical than ever, with infections being caused by multidrug-resistant organisms, particularly methicillin-resistant staphylococci, penicillin- and erythromycin-resistant pneumococci, and vancomycin-resistant enterococci. There is a continuing effort in the pharmaceutical industry to develop new antimicrobial agents for the treatment of resistant infections. Linezolid, quinupristin-dalfopristin, daptomycin, tigecyline, new glycopeptides and ceftobiprole are the main agents recently introduced or under clinical development. This review summarises their major properties, the results of recent studies with these agents, and future treatment possibilities.     

达托霉素临床应用专家意见

全球范围内，革兰阴性杆菌是威胁患者安全的主要耐药菌，但革兰阳性球菌感染导致的治疗失败同样是临床难题。随着耐药革兰阳性球菌对糖肽类药物不敏感以及最低抑菌浓度不断高漂移，体外检测敏感而临床治疗失败的病例不断增多，临床上迫切需要有效的、新型抗菌药物用于救治革兰阳性球菌感染患者。达托霉素是一种新型环脂肽类抗生素，具有全新抗菌靶点和快速杀菌活性，可穿透生物膜，因其不导致菌体溶解，从而避免细菌内容物炎症介质释放引发的严重炎症反应，在治疗菌血症、感染性心内膜炎、复杂皮肤软组织感染等方面具有良好的临床应用价值。为合理应用达托霉素有效救治患者，中国研究型医院学会感染性疾病循证与转化专业委员会组织国内专家撰写达托霉素临床应用专家意见，以期为广大临床工作者提供借鉴。     

达托霉素血浆浓度的UPLC-MS/MS法测定及其在重症患者体内药代动力学

建立测定血浆和置换液中达托霉素的高通量UPLC-MS/MS方法,采用Kinetex C₁₈色谱柱(50 mm×2.1 mm,1.7 μm),柱温45 ℃,流动相为含0.1%甲酸水溶液-乙腈,流速0.4 mL/min,电喷雾离子化正离子扫描模式下,达托霉素m/z 810.9→159.1;内标来曲唑m/z 286.2→217.2,分析时长2.5 min。达托霉素在血浆(1~200 μg/mL)和置换液(0.005~20 μg/mL)中均呈现良好的线性关系,日内及日间精密度、准确度、稳定性等均符合生物样品测定要求。静脉滴注6 mg/kg达托霉素在接受持续肾脏替代治疗(CRRT)治疗的感染性休克患者体内的c_max和AUC_0-24明显低于健康受试者,下降比例分别为50%和60%,未达到预期的杀菌效果。这可能与感染性休克患者毛细血管通透性增加联合间隙水肿,从而使药物的分布容积增加有关,此外,肾脏替代治疗模式可体外滤过约16%的达托霉素,导致剂量不足和感染治疗不彻底。研究结果推荐在接受CRRT治疗的感染性休克患者中使用达托霉素应适当增加剂量,且须对该类患者进行达托霉素治疗药物浓度监测。     

Infective endocarditis associated with acute leukemia: Report of two cases

There have been few reports regarding infective endocarditis (IE) in patients with leukemia. In the first case, a 15‐year‐old girl with Down syndrome was diagnosed with acute lymphoblastic leukemia. On admission, methicillin‐sensitive Staphylococcus aureus (MSSA) was detected on blood culture. Echocardiography was performed because MSSA was detected repeatedly even after treatment. Vegetation in all of the atria and ventricles met the Duke criteria defining IE. She died of multiple organ failure 21 days after diagnosis. In the second case, an 11‐year‐old boy with acute myeloid leukemia underwent peripheral blood stem cell transplantation (PBSCT). He had fever 68 days after PBSCT, and methicillin‐resistant S. aureus (MRSA) was detected on blood culture. Echocardiography showed vegetation in the right atrium and ventricle. Daptomycin was administered for 7 weeks, and recurrence was not observed. IE should be considered when S. aureus bacteremia is documented even in patients with leukemia.     

Morbidity,mortality, and management of methicillin-resistant S. aureus bacteremia in the USA: update on antibacterial choices and understanding

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with significant healthcare costs, morbidity, and mortality in the United States. Complications of MRSA bacteremia include infective endocarditis, osteomyelitis, and sepsis, all of which are difficult to treat. Time to effective therapy and antibacterial choice greatly affect patient outcomes. Vancomycin and daptomycin remain first-line therapies; however, reports of vancomycin-associated treatment failure and reduced daptomycin susceptibility highlight the need to define alternative strategies for MRSA bacteremia treatment. In addition, several patient- and pathogen-specific factors influence the outcomes of MRSA bacteremia. It is, therefore, critical to explore the interaction between host- and pathogen-specific factors and its effect on MRSA bacteremia pathogenesis and mortality. This review discusses the factors that drive the development of MRSA bacteremia and examines alternative treatment strategies.     

Maximizing positive outcomes for patients with staphylococcal infections

Maximizing positive outcomes for serious Gram-positive infections, such as those caused by Staphylococcus species, requires an aggressive treatment approach. Although specific approaches will depend upon many factors, the underlying common strategy should recognize the positive contribution of minimizing complications and inpatient treatment duration and the efficient use of healthcare resources, while also focusing on rapid resolution of infection and safety and tolerability. To advance the standard of care for patients, we need to utilize therapies that enable such a range of factors to be improved. Treatment guidelines are useful to establish evidence-based standards of care, but they are updated infrequently and there is currently no pan-European consensus for the treatment of staphylococcal infections. With the benefit of the clinical experience that has been acquired for the most recently licensed antibiotics, together with an appreciation of the appropriate usage of older agents, there are good prospects for achieving positive outcomes earlier and in a greater range of patients with staphylococcal infections, and treatment guidelines should be updated regularly to reflect this.     

A simplified three-times weekly daptomycin dosing regimen for chronic hemodialysis patients

Evaluation of: Salama NN, Segal JH, Churchwell MD et al. Intradialytic administration of daptomycin in end stage renal disease patients on hemodialysis. Clin. J. Am. Soc. Nephrol. 4, 1190–1194 (2009).

Approximately 2.3 million patients worldwide are undergoing chronic renal replacement therapy. In that population, acute infections substantially contribute to the excessive morbidity and mortality. The risk for invasive methicillin-resistant Staphylococcus aureus infections in this population is approximately 100-fold higher than in the general population, therefore dialysis patients currently account for up to approximately 15% of all invasive methicillin-resistant Staphylococcus aureus infections. A simplified three-times weekly dosing regimen for hemodialysis patients now allows for practical, hassle-free and effective treatment with daptomycin, which is licensed for the treatment of complicated skin and soft tissue infections, including resistant strains of Staphylococcus aureus and life-threatening Gram-positive infections, vancomycin-resistant enterococcal infections and right-sided endocarditis.