全球产KPC肺炎克雷伯菌的KPC分布与序列分型分析

目的分析全球产肺炎克雷伯菌碳青霉烯酶(KPC)的肺炎克雷伯菌的序列分型数据,探讨KPC-2、KPC-3与主要流行克隆之间的关系。方法从NCBI中下载全球肺炎克雷伯菌的基因组,分析KPC的分布情况。对产KPC肺炎克雷伯菌基因组进行多位点序列分析,确定其序列分型(sequence type, ST)。分析KPC在不同克隆菌株中的分布情况,以及在主要流行克隆ST11、ST258及ST512中KPC变异体KPC-2和KPC-3的流行率差异。结果全球肺炎克雷伯菌的基因组中产KPC 1 943株,有KPC变异体14种,以KPC-2(959/1 943,49.4%)和KPC-3(952/1 943,49.0%)为主;有115种ST型,以ST258(996/1 943,51.3%)、ST11(285/1 943,14.7%)和ST512(259/1 943,13.3%)为主。959株KPC-2菌株分布在87种ST中,以ST258(413/959,43.1%)和ST11(274/959,28.6%)为主;952株KPC-3菌株分布在45种ST中,以ST258(570/952,59.9%)和ST512 (259/952,27.2%)为主。KPC-2在ST11菌株中的流行率(274/285,96.1%)显著高于在ST258中的流行率(414/996,41.6%),差异有统计学意义(χ~2=43.819,P=0.000);KPC-3在ST512中的流行率(259/259,100%)显著高于在ST258中的流行率(570/996,57.2%),差异有统计学意义(χ~2=206.645,P=0.000)。结论从全球范围来看,KPC的流行以KPC-2和KPC-3为主,KPC-2的流行克隆菌株以ST11和ST258为主,KPC-3的流行克隆菌株以ST258和ST512为主,加强该类细菌的监测对于预防院内感染控制具有重要作用。     

Mechanisms of resistance and clinical relevance of resistance to β-lactams, glycopeptides, and fluoroquinolones

The widespread use of antibiotics has resulted in a growing problem of antimicrobial resistance in the community and hospital settings. Antimicrobial classes for which resistance has become a major problem include the β-lactams, the glycopeptides, and the fluoroquinolones. In gram-positive bacteria, β-lactam resistance most commonly results from expression of intrinsic low-affinity penicillin-binding proteins. In gram-negative bacteria, expression of acquired β-lactamases presents a particular challenge owing to some natural spectra that include virtually all β-lactam classes. Glycopeptide resistance has been largely restricted to nosocomial Enterococcus faecium strains, the spread of which is promoted by ineffective infection control mechanisms for fecal organisms and the widespread use of colonization-promoting antimicrobials (especially cephalosporins and antianaerobic antibiotics). Fluoroquinolone resistance in community-associated strains of Escherichia coli, many of which also express β-lactamases that confer cephalosporin resistance, is increasingly prevalent. Economic and regulatory forces have served to discourage large pharmaceutical companies from developing new antibiotics, suggesting that the antibiotics currently on the market may be all that will be available for the coming decade. As such, it is critical that we devise, test, and implement antimicrobial stewardship strategies that are effective at constraining and, ideally, reducing resistance in human pathogenic bacteria.     

Identification of Extended-Spectrum-β-Lactamase-Positive Klebsiella pneumoniae Urinary Tract Isolates Harboring KPC and CTX-M β-Lactamases in Nonhospitalized Patients

Forty-seven extended-spectrum-β-lactamase-positive Klebsiella pneumoniae urinary tract isolates from nonhospitalized patients were identified, and 79% harbored KPC and/or CTX-M β-lactamases. Approximately 90% of the isolates were resistant to trimethoprim-sulfamethoxazole and levofloxacin, and 40% were resistant to a carbapenem, while 92% were susceptible to polymyxin B, 87% were susceptible to tigecycline, and 79% were susceptible to fosfomycin. Increased use of broader-spectrum antibiotics may help to prevent their dissemination and reduce the risk of progression to invasive disease.     

KPC型β-内酰胺酶研究进展

KPC型β-内酰胺酶属于Ambler分类的A类、Bush分类的2f亚群，其特点是水解除头霉素类以外的几乎所有β-内酰胺类抗生素，包括青霉素类、头孢菌素类、单酰胺类和碳青霉烯类。其活性可被克拉维酸所抑制。由于产KPC酶菌株可能仅对碳青霉烯类灵敏度减低，尚达不到完全耐药的水平；产KPC菌株应用ESBLs确证试验检测可能阳性，很容易错误地鉴定为ESBLs菌株；以及产KPC菌株接种效应的存在，显著影响亚胺培南的MIC，这些因素都给实验室检测带来很多困难。尽管产KPC酶菌株较少且仅分布于少数国家，但其水解底物谱的广泛性和质粒介导的可传播性，必将给临床抗感染治疗带来威胁。因此，应引起临床医师和实验室的高度重视。     

KPC型碳青霉烯酶研究进展

碳青霉烯类抗生素包括亚胺培南、美罗培南和厄他培南等是治疗肠杆菌科细菌尤其是产超广谱β内酰胺酶(ESBLs)及AmpC酶等多重耐药菌株引起感染的最有效的抗菌药物[1].然而,随着碳青霉烯类抗生素耐药肠杆菌科细菌(carbapenem-resistant Enterobacteriaceae,CRE)的出现及不断增多,该类药物的临床应用受到严峻的挑战.     

What is the impact,prevalence, disability,and quality of life of pediatric headache?

Pediatric headache is a common health problem in children, with a significant headache reported in more than 75% by the age of 15 years. Pediatric migraine occurs in up to 10.6% of children between the ages of 5 and 15 years and in up to 28% of adolescents between the ages of 15 and 19 years. Given this high frequency, the impact of this disease on the lives of these children and their parents can be quite significant. This impact can be assessed with disease-specific disability and impairment as well as disease non-specific effects on quality of life. The goal of evaluation should be recognition of this impact, whereas the goal of management should be effective treatment that minimizes the impact of this disorder in the short term and for the life of the patient.     

Diversity,Epidemiology, and Genetics of Class D β-Lactamases

Class D β-lactamase-mediated resistance to β-lactams has been increasingly reported during the last decade. Those enzymes also known as oxacillinases or OXAs are widely distributed among Gram negatives. Genes encoding class D β-lactamases are known to be intrinsic in many Gram-negative rods, including Acinetobacter baumannii and Pseudomonas aeruginosa, but play a minor role in natural resistance phenotypes. The OXAs (ca. 150 variants reported so far) are characterized by an important genetic diversity and a great heterogeneity in terms of β-lactam hydrolysis spectrum. The acquired OXAs possess either a narrow spectrum or an expanded spectrum of hydrolysis, including carbapenems in several instances. Acquired class D β-lactamase genes are mostly associated to class 1 integron or to insertion sequences.Class D β-lactamases, also known as oxacillinases or OXA-type β-lactamases (OXAs), are active-serine-site enzymes like Ambler class A and class C β-lactamases, differing from class A and C enzymes in amino acid structure, whereas class B β-lactamases are metalloenzymes with a Zn²⁺ ion(s) in the active site (4, 71, 78). Even though class D includes mostly enzymes with higher hydrolysis rates for cloxacillin and oxacillin than for benzylpenicillin (hence the name oxacillinases), not all class D β-lactamases have this characteristic. Most of the class D enzymes belong to group 2d of the Bush functional classification scheme for β-lactamases (23). Among the four β-lactamase molecular classes, class D β-lactamases are the most diverse enzymes (107). This diversity is observed at both the genetic and biochemical levels, with enzymes possessing either a narrow or expanded spectrum of hydrolysis. In addition, several class D β-lactamases have an expanded spectrum of activity resulting from point mutations.Although many class D β-lactamase genes are embedded into class 1 integrons, recent reports indicated that other specific genetic structures, including insertion sequences and transposons, may be associated with class D β-lactamase genes. Numerous class D β-lactamase genes have been identified as a source of acquired resistance in gram-negative bacteria, but recent studies have shown that class D β-lactamases are also naturally produced in clinically significant pathogens and environmental species (107).This review focuses on the diversity and substrate profiles of class D β-lactamases, their sources, and the genetics of acquisition of the corresponding genes. All the class D β-lactamases for which a sequence is available in the GenBank databases are listed in Table ​Table11.

TABLE 1.

Features of oxacillinases

Do Performance Measures of Strength,Balance, and Mobility Predict Quality of Life and Community Reintegration After Stroke?

Objective

To investigate the extent to which physical performance measures of strength, balance, and mobility taken at discharge from inpatient stroke rehabilitation can predict health-related quality of life (HRQoL) and community reintegration after 6 months.

Relativity analysis of middle and old people hypertension and hyperglycemia,diabetes

Background：Hypertension，diabetesaremainriskfactorsofcardiovasculardiseases．Manydatashows：hypertensionmorbidityrateofdiabetespatientsisapparentlyhigherthanthatofnon－diabetespeople．Inforeigncountry，hypertensionmorbidityrateofdiabetespatientsreaches４０％～８０％．Inourcountry，surveyof２２０thousandpeoplein１９９４showedthathypertensionmorbidityrateofdiabetespatientsis５５．４％．insulinresistanceiscommonpathogeneticfoundationofhypertensionandtype２diabetes．Inpreviousreports，therewasli…     

Bactericidal Activity,Absence of Serum Effect,and Time-Kill Kinetics of Ceftazidime-Avibactam against β-Lactamase-Producing Enterobacteriaceae and Pseudomonas aeruginosa

Avibactam, a non-β-lactam β-lactamase inhibitor with activity against extended-spectrum β-lactamases (ESBLs), KPC, AmpC, and some OXA enzymes, extends the antibacterial activity of ceftazidime against most ceftazidime-resistant organisms producing these enzymes. In this study, the bactericidal activity of ceftazidime-avibactam against 18 Pseudomonas aeruginosa isolates and 15 Enterobacteriaceae isolates, including wild-type isolates and ESBL, KPC, and/or AmpC producers, was evaluated. Ceftazidime-avibactam MICs (0.016 to 32 μg/ml) were lower than those for ceftazidime alone (0.06 to ≥256 μg/ml) against all isolates except for 2 P. aeruginosa isolates (1 bla_VIM-positive isolate and 1 bla_OXA-23-positive isolate). The minimum bactericidal concentration/MIC ratios of ceftazidime-avibactam were ≤4 for all isolates, indicating bactericidal activity. Human serum and human serum albumin had a minimal effect on ceftazidime-avibactam MICs. Ceftazidime-avibactam time-kill kinetics were evaluated at low MIC multiples and showed time-dependent reductions in the number of CFU/ml from 0 to 6 h for all strains tested. A ≥3-log₁₀ decrease in the number of CFU/ml was observed at 6 h for all Enterobacteriaceae, and a 2-log₁₀ reduction in the number of CFU/ml was observed at 6 h for 3 of the 6 P. aeruginosa isolates. Regrowth was noted at 24 h for some of the isolates tested in time-kill assays. These data demonstrate the potent bactericidal activity of ceftazidime-avibactam and support the continued clinical development of ceftazidime-avibactam as a new treatment option for infections caused by Enterobacteriaceae and P. aeruginosa, including isolates resistant to ceftazidime by mechanisms dependent on avibactam-sensitive β-lactamases.     

Efficacy,tolerability, and safety of cannabinoids for chemotherapy-induced nausea and vomiting—a systematic review of systematic reviews

Background

There is growing public and legislative body support for the medical use of cannabis products, for example, for chemotherapy-induced nausea and vomiting (CINV), in Germany.

Methods

A comprehensive literature search until November 2015 was conducted in MEDLINE, DARE and Cochrane libraries for systematic reviews of randomized controlled trials (RCTs) comparing herbal or pharmaceutical cannabinoids (CB) versus placebo or conventional antiemetics for CINV. Outcomes were reduction of CINV for efficacy, drop-out rates due to adverse events for tolerability, and serious adverse events for safety. The methodology quality of the systematic reviews was evaluated by the tool assessment of multiple systematic reviews (AMSTAR).

Results

Six systematic reviews of RCTs included the pharmaceutical CBs dronabinol, levonantradol, and nabilone or whole plant extract (e.g., nabiximol) compared with placebo or conventional antiemetics. There was moderate quality evidence on the efficacy of CBs compared to placebo and conventional antiemetics for CINV. There was moderate quality evidence that pharmaceutical CBs were less tolerated and less safe than placebo and conventional antiemetics in CINV. One RCT examining whole plant extract was included into the systematic reviews. No RCT was found comparing CBs with neurokinine?1 receptor antagonists.

Conclusions

With safe and effective antiemetics available, CBs cannot be recommended as first- or second-line therapy for CINV. Some guidelines recommend pharmaceutical CBs as third-line treatment in the management of breakthrough nausea and vomiting. Due to the lack of RCT data and safety concerns, herbal cannabis cannot be recommended for CINV.

     

Does experience of the 'occult' predict use of complementary medicine? Experience of, and beliefs about, both complementary medicine and ways of telling the future

This study looked at the relationship between ratings of the perceived effectiveness of 24 methods for telling the future, 39 complementary therapies (CM) and 12 specific attitude statements about science and medicine. A total of 159 participants took part. The results showed that the participants were deeply sceptical of the effectiveness of the methods for telling the future which factored into meaningful and interpretable factors. Participants were much more positive about particular, but not all, specialties of complementary medicine (CM). These also factored into a meaningful factor structure. Finally, the 12 attitude to science/medicine statements revealed four factors: scepticism of medicine; the importance of psychological factors; patient protection; and the importance of scientific evaluation. Regressional analysis showed that belief in the total effectiveness of different ways of predicting the future was best predicted by beliefs in the effectiveness of the CM therapies. Although interest in the occult was associated with interest in CM, participants were able to distinguish between the two, and displayed scepticism about the effectiveness of methods of predicting the future and some CM therapies.     

Hospices in partnership? Public health,end of life,and the responsibility of hospices

Public health approaches to palliative care must appreciate that health professionals are part of communities, and the importance of partnerships should not be ignored – despite the inherent challenges. The true partners in a public health approach towards the end of life are of course, dying people, their families and friends, and members of the communities within which they are living and dying. However, we ignore important partnerships with nurses, doctors, and other healthcare professionals at our peril. This paper situates hospices within the broader community and uses vignette's to highlight approaches to community engagement and the challenges of partnership.