Ceftaroline fosamil for the treatment of Gram-positive endocarditis: CAPTURE study experience

Background

The clinical experience of ceftaroline fosamil (CPT-F) therapy for Gram-positive infective endocarditis is reported from CAPTURE, a retrospective study conducted in the USA.

清热合剂对上呼吸道感染常见致病菌的体外抑菌试验

目的观察清热合剂对上呼吸道感染常见致病菌的体外抑菌活性。方法上呼吸道感染常见致病菌163株中不产超广谱β-内酰胺酶(ESBLs)革兰阴性菌74株(大肠埃希菌33株,肺炎克雷伯菌24株,铜绿假单胞菌17株);产ESBLs革兰阴性菌10株(大肠埃希菌6株,肺炎克雷伯菌4株);革兰阳性菌79株[耐甲氧西林金黄色葡萄球菌(MRSA)11株、甲氧西林敏感金黄色葡萄球菌(MSSA)46株,肺炎链球菌22株]。采用琼脂稀释法对清热合剂进行定量抑菌试验,配制含有不同药物浓度的琼脂平板,在平板上接种待测菌株菌悬液,孵育后观察含药平板,记录最低抑菌浓度(MIC)。结果清热合剂对大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌等革兰阴性菌的MIC90分别为88、176、22 g/L,其对产ESBLs与不产ESBLs革兰阴性菌的抑菌效果一致;不同浓度药物对铜绿假单胞菌的累积抑菌率均最高。清热合剂对MSSA、MRSA和肺炎链球菌等革兰阳性菌的MIC90分别为11、11、22 g/L,MRSA的MIC90与MSSA相同,但MIC50略高于MSSA;不同浓度药物对MSSA和MRSA的累积抑菌率均高于肺炎链球菌,对MSSA与MRSA的累积抑菌率相近。结论清热合剂对上呼吸道感染常见的致病菌除肺炎克雷伯菌之外均有一定的抑菌作用,对革兰阳性菌的抑菌效果明显优于革兰阴性菌。     

2012—2015年1380株肝移植术后感染病原菌的分布及耐药性分析

目的了解江苏省人民医院肝移植术后感染病原菌的分布及耐药性,为临床合理用药提供参考。方法对2012年1月—2015年1月江苏省人民医院肝移植术后感染病原菌的分布及耐药性进行统计分析。结果共分离出病原菌1 380株,主要来源于痰液标本。病原菌分布以革兰阴性菌为主,占69.57%,革兰阳性菌和真菌分别占20.07%、10.36%;其中革兰阴性菌以鲍曼不动杆菌、肺炎克雷伯菌为主,革兰阳性菌以溶血葡萄球菌为主;革兰阴性菌对美罗培南、阿米卡星、亚胺培南较为敏感,耐药率均低于30%,对头孢曲松、氨曲南等的耐药率均较高;革兰阳性菌对万古霉素、利奈唑胺、替考拉宁较为敏感,耐药率均低于20%,对氨苄西林、诺氟沙星等耐药率均较高。结论肝移植术后感染病原菌的构成主要是鲍曼不动杆菌、肺炎克雷伯菌和溶血葡萄球菌,临床选择抗菌药物时建议选用病原菌表现较低耐药性的美罗培南、阿米卡星、万古霉素、利奈唑胺等药物。     

早期联合测定炎症因子对不同病原菌血流感染的鉴别诊断价值

目的 探讨早期联合测定外周血降钙素原(PCT)、C反应蛋白(CRP)和内毒素对不同病原菌血流感染的脓毒症鉴别诊断的临床价值.方法 回顾性分析2012年1月至2013年12月首都医科大学附属世纪坛医院ICU血培养阳性的脓毒症患者152例,根据血培养结果分革兰阴性杆菌与革兰阳性球菌及真菌血流感染组,分别观察患者入科后第1天的外周血PCT、CRP、内毒素和三者联合后的水平在早期诊断的价值.结果 (1)共收集血流感染病例152例,革兰阴性菌共93例(61.18％),以肺炎克雷伯氏菌、鲍曼不动杆菌、大肠埃希氏菌、洋葱伯克霍尔德菌、铜绿假单胞菌为主;革兰阳性菌43例(28.29％),金黄色葡萄球菌13例(8.55％);真菌16例(10.53％).(2)对三组患者的炎症指标进行比较,革兰阴性菌组内毒素阳性60例(64.52％),革兰阳性菌及真菌组均未检测到内毒素阳性值.革兰阴性菌PCT为7.760 (3.365,28.585) ng/mL,革兰阳性菌为0.705 (0.265,3.225) ng/mL,真菌为1.245 (0.543,1.998) ng/mL,三组间差异具有统计学意义;CRP在革兰阴性菌为(126.01±66.53) mg/L,革兰阳性菌(77.58±54.21) mg/L,真菌(140.14±71.21) mg/L,血流感染真菌组升高更为明显.(3)比较各细菌组的受试者工作特征曲线(ROC曲线)的诊断效应,区分革兰阳性菌组和真菌组的ROC曲线显示,AUCPCT+CRP=0.791,PCT截点为0.92 ng/mL,CRP截点为68.00 mg/L,敏感性为50％,特异性为95.5％;区分革兰阴性菌组和真菌组的ROC曲线显示:AUCPCT+CRP+LPS=0.947,PCT截点为2.16ng/mL,CRP截点为94.10 mg/L时,内毒素阳性为截点,敏感性为82.8％,特异性为100％;区分革兰阴性菌组和革兰阳性菌组的ROC曲线显示AUCPCT+CRP+LPS=90.2％,PCT截点为2.68 ng/mL,CRP截点为106.5 mg/L,内毒素阳性为截点,敏感性为74.2％,特异性为97.7％.结论 重症监护病房的血流感染仍以革兰阴性菌为主,早期联合外周血PCT、CRP、内毒素检测,与单一炎症因子相比,可明显提高对不同病原菌血流感染脓毒症患者早期诊断的敏感性和特异性.     

Determination of Tedizolid susceptibility interpretive criteria for gram-positive pathogens according to clinical and laboratory standards institute guidelines

For effective antibacterial therapy, physicians require qualitative test results using susceptibility breakpoints provided by clinical microbiology laboratories. This article summarizes the key components used to establish the Clinical Laboratory Standards Institute (CLSI) breakpoints for tedizolid. First, in vitro studies using recent surveillance and clinical trial isolates ascertained minimal inhibitory concentration (MIC) distributions against pertinent organisms, including staphylococci, streptococci, and enterococci. Studies in animal models of infection determined rates of antibacterial efficacy and survival following administration of tedizolid phosphate at doses equivalent to those in humans. Pharmacokinetic and pharmacodynamic analyses examined the relationship between plasma concentrations and MICs against the target organism. Finally, clinical trials assessed clinical and microbiologic outcomes by MIC. All these data were evaluated and combined to obtain the ratified CLSI susceptibility criteria for tedizolid of ≤0.5 μg/mL for Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, and Enterococcus faecalis and ≤0.25 μg/mL for Streptococcus anginosus group.     

C-di-GMP turnover influences motility and biofilm formation in Bacillus amyloliquefaciens PG12

Bis-(3′→5′) cyclic dimeric guanosine monophosphate (c-di-GMP) is defined as a highly versatile secondary messenger in bacteria, coordinating diverse aspects of bacterial growth and behavior, including motility and biofilm formation. Bacillus amyloliquefaciens PG12 is an effective biocontrol agent against apple ring rot caused by Botryosphaeria dothidea. In this study, we characterized the core regulators of c-di-GMP turnover in B. amyloliquefaciens PG12. Using bioinformatic analysis, heterologous expression and biochemical characterization of knockout and overexpression derivatives, we identified and characterized two active diguanylate cyclases (which catalyze c-di-GMP biosynthesis), YhcK and YtrP and one active c-di-GMP phosphodiesterase (which degrades c-di-GMP), YuxH. Furthermore, we showed that elevating c-di-GMP levels up to a certain threshold inhibited the swimming motility of B. amyloliquefaciens PG12. Although yhcK, ytrP and yuxH knockout mutants did not display defects in biofilm formation, significant increases in c-di-GMP levels induced by YtrP or YuxH overexpression stimulated biofilm formation in B. amyloliquefaciens PG12. Our results indicate that B. amyloliquefaciens possesses a functional c-di-GMP signaling system that influences the bacterium's motility and ability to form biofilms. Since motility and biofilm formation influence the efficacy of biological control agent, our work provides a basis for engineering a more effective strain of B. amyloliquefaciens PG12.     

Update on linezolid: the first oxazolidinone antibiotic

Linezolid is the first of an entirely new class of antibiotics, the oxazolidinones, in decades. It has a spectrum of activity against virtually all important Gram-positive pathogens. The unique mechanism of action of linezolid makes cross-resistance with other antimicrobial agents unlikely. Linezolid has both intravenous and oral formulations and the latter is 100% bioavailable. Since its first approval and marketing in March 2000 in the US, linezolid has gained approval for use in many other countries for the treatment of community-acquired and nosocomial pneumonia, complicated and uncomplicated skin and soft-tissue infections, and infections caused by methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, including cases with concurrent bacteraemia. Several earlier comprehensive reviews summarised the chemistry, mechanism of action, pharmacokinetics, clinical efficacy and safety profile of linezolid. The present review provides an update on the latest data regarding the antimicrobial activity of linezolid versus other commonly used agents, the clinical and health-economic outcomes of linezolid versus vancomycin and teicoplanin, and safety issues.     

Genetics of Fungi Pathogenic for Man

Abstract

Great strides have been made in research on fungi pathogenic to man and animal during the last three decades, but little progress has been made in the genetics of these microorganisms. The principal reason for such a delay in genetic research is that mechanisms for genetic recombination were not known to exist in most of the pathogens.¹ It was not until the early part of the last decade that the parasexual cycle in Aspergillus fumigatus² and heterothallism in several ringworm fungi were discovered.^3-8 The reports of heterothallism in dermatophytes stimulated medical mycologists to search for the perfect state in systemic pathogens. Within the last 5 years, heterothallism has been discovered in Blastomyces dermatitidis, Histo-plasma capsulatum, and Geotrichum candidum.^9-11 Although for the last 10 years steady progress has been made employing these fungi as genetic tools, our knowledge of the genetics of human pathogenic fungi is fragmentary compared with what is known about the saprophytes and plant pathogens. This review is restricted to the results of recent genetic studies on true fungi pathogenic to man and animals. Although pathogenic fungi, by broad definition, might include those producing poisonous effects upon ingestion and those which cause disease only rarely and under special circumstances, this review is devoted only to those fungi generally recognized as pathogens for man. An understanding of the basic principles of mycology and genetics is assumed.     

Development of DNA polymerase IIIC inhibitors for the treatment of Gram-positive bacterial infections

Gram-positive (Gm⁺) bacteria express three distinct DNA polymerase-exonucleases. One of these, Gm⁺ DNA polymerase IIIC (DNA pol IIIC), is a highly conserved enzyme with little homology to mammalian DNA polymerase α and Gram-negative (Gm^–) DNA polymerases. DNA pol IIIC has been shown to be essential in the replicative DNA synthesis of Gm⁺ bacteria and, as such, represents an attractive, hitherto unexploited target for antimicrobial drug development. This article briefly reviews claims for DNA pol IIIC inhibitors for the treatment of bacterial infections, registered during the period 1996 – 2004. Biological data are sparse in these patents and few claims are backed up with in vivo animal model data. Although DNA pol IIIC has clearly been validated as a bona fide target for antimicrobial drug development, the effectiveness of such an agent in the clinic, particularly against resistant strains of Gm⁺ bacteria, remains to be determined.     

Pathogenesis and prevention of immune reconstitution disease during antiretroviral therapy

A long-held doctrine is that bactericidal antibiotics are required for infections in neutropenic patients. We evaluated the available published evidence regarding the role of linezolid, a bacteriostatic antibiotic, in neutropenic patients with Gram-positive infection. We retrieved two prospective comparative studies (one of them a double-blind, randomized, controlled trial), a prospective cohort study, two retrospective studies and eight case reports that focused on the use of linezolid for Gram-positive bacterial infections in neutropenic patients. Linezolid was administered to 438 neutropenic patients, mainly on a compassionate-use basis, as other antibiotics failed to cure the infection or were associated with significant adverse events. The clinical cure rate ranged between 57 and 87.3% in the intention-to-treat population of the prospective studies. In total, 56 out of 438 (12.7%) neutropenic patients that received linezolid died during therapy. In the only randomized controlled trial that compared linezolid with vancomycin in the treatment of Gram-positive infections in neutropenic patients, mortality was 5.6 versus 7.6%, respectively (p = 0.4). In conclusion, the available evidence suggests that linezolid may be successful in a significant proportion of neutropenic patients with infection, despite the fact that it is a bacteriostatic agent. Such data seem to justify further studies regarding the role of linezolid in this patient population.