Identification of a new allelic variant of the Acinetobacter baumannii cephalosporinase, ADC-7 beta-lactamase: defining a unique family of class C enzymes

Acinetobacter spp. are emerging as opportunistic hospital pathogens that demonstrate resistance to many classes of antibiotics. In a metropolitan hospital in Cleveland, a clinical isolate of Acinetobacter baumannii that tested resistant to cefepime and ceftazidime (MIC = 32 microg/ml) was identified. Herein, we sought to determine the molecular basis for the extended-spectrum-cephalosporin resistance. Using analytical isoelectric focusing, a beta-lactamase with a pI of > or = 9.2 was detected. PCR amplification with specific A. baumannii cephalosporinase primers yielded a 1,152-bp product which, when sequenced, identified a novel 383-amino-acid class C enzyme. Expressed in Escherichia coli DH10B, this beta-lactamase demonstrated greater resistance against ceftazidime and cefotaxime than cefepime (4.0 microg/ml versus 0.06 microg/ml). The kinetic characteristics of this beta-lactamase were similar to other cephalosporinases found in Acinetobacter spp. In addition, this cephalosporinase was inhibited by meropenem, imipenem, ertapenem, and sulopenem (K(i) < 40 microM). The amino acid compositions of this novel enzyme and other class C beta-lactamases thus far described for A. baumannii, Acinetobacter genomic species 3, and Oligella urethralis in Europe and South Africa suggest that this cephalosporinase defines a unique family of class C enzymes. We propose a uniform designation for this family of cephalosporinases (Acinetobacter-derived cephalosporinases [ADC]) found in Acinetobacter spp. and identify this enzyme as ADC-7 beta-lactamase. The coalescence of Acinetobacter ampC beta-lactamases into a single common ancestor and the substantial phylogenetic distance separating them from other ampC genes support the logical value of developing a system of nomenclature for these Acinetobacter cephalosporinase genes.     

New comparative genomics approach reveals a conserved health span signature across species

Environmental and genetic interventions extend health span in a range of organisms by triggering changes in different specific but complementary pathways. We investigated the gene expression changes that occur across species when health span is extended via different interventions. To perform this comparison using heterogeneous datasets from different measurement platforms and organisms, we developed a novel non-parametric methodology that can detect statistical significance of overlaps in ranked lists of genes, and estimate the number of genes with a common expression profile. By comparing genetic and environmental interventions that consistently lead to increased health span in invertebrates and vertebrates we built a conserved health span signature and described how such a signature depends on tissue type. Furthermore, we examined the relationship between calorie restriction and resveratrol administration and for the first time, identified common gene and pathway changes in calorie restriction and resveratrol in both invertebrates and mammals. Our approach can thus be used to explore and better define the relationships between highly complex biological phenomena, in this case those that affect the health and longevity.     

In vitro antienterococcal activity explains associations between exposures to antimicrobial agents and risk of colonization by multiresistant enterococci

We compared ceftriaxone and piperacillin-tazobactam at doses ranging from 0.1 to 2 times the human equivalent daily dose (HEDD), to determine their impact on gastrointestinal colonization by ampicillin- and vancomycin-resistant Enterococcus faecium C68 in a mouse model. Ceftriaxone failed to promote colonization at doses up to 0.25 times the HEDD, whereas piperacillin-tazobactam promoted colonization at doses up to 0.5 times the HEDD. Ceftriaxone promoted colonization at doses at least 0.5 times the HEDD, whereas piperacillin-tazobactam inhibited colonization at doses at least 0.75 times the HEDD. Both piperacillin-tazobactam and ceftriaxone inhibited colonization by an enterococcal strain devoid of low-affinity penicillin-binding protein-5 (significantly increasing its susceptibility to these agents), at doses that promoted colonization by E. faecium C68. These results support a model in which the impact that different beta -lactam agents have on colonization by VRE is related to the level of the beta -lactam agent's intrinsic antienterococcal activity against the colonizing strain.     

A CTSA agenda to advance methods for comparative effectiveness research

Clinical research needs to be more useful to patients, clinicians, and other decision makers. To meet this need, more research should focus on patient-centered outcomes, compare viable alternatives, and be responsive to individual patients' preferences, needs, pathobiology, settings, and values. These features, which make comparative effectiveness research (CER) fundamentally patient-centered, challenge researchers to adopt or develop methods that improve the timeliness, relevance, and practical application of clinical studies. In this paper, we describe 10 priority areas that address 3 critical needs for research on patient-centered outcomes (PCOR): (1) developing and testing trustworthy methods to identify and prioritize important questions for research; (2) improving the design, conduct, and analysis of clinical research studies; and (3) linking the process and outcomes of actual practice to priorities for research on patient-centered outcomes. We argue that the National Institutes of Health, through its clinical and translational research program, should accelerate the development and refinement of methods for CER by linking a program of methods research to the broader portfolio of large, prospective clinical and health system studies it supports. Insights generated by this work should be of enormous value to PCORI and to the broad range of organizations that will be funding and implementing CER.     

Viral meningitis in child care center staff and parents: an outbreak of echovirus 30 infections.

OBJECTIVE: A report of five cases of viral meningitis among adults with children enrolled in a child care center prompted an investigation of risk factors for viral transmission from children to adult household members. METHODS: To determine recent echovirus 30 (E30) infections, the authors conducted a serologic survey. To determine risk factors for infection among adult household members, they conducted a retrospective cohort study using written questionnaires. RESULTS: Recent E30 infections were found in 84% of children tested, 57% of adult household members tested, and 47% of staff members tested. Infected adults were more likely than infected children to have clinical meningitis. Among adult household members, changing diapers was a risk factor for recent infection. Women who changed > or = 90 diapers per month had a higher infection rate than women who changed fewer diapers; in contrast, men who changed > or = 90 diapers per month had a lower infection rate than men who changed fewer diapers. Handwashing was protective: there was a negative correlation between handwashing after diaper changes and E30 infection among adults with infected children in diapers. CONCLUSIONS: Because child care centers can be a source of enteroviral infections among adult household members, adults with viral meningitis should be questioned about their children's day care or preschool attendance. The importance of handwashing should be stressed to adults with children in day care.     

Effectiveness of Helicobacter pylori therapies in a clinical practice setting.

BACKGROUND: Whether eradication rates for Helicobacter pylori treatment regimens obtained in controlled clinical trials (efficacy) can also be obtained in clinical practice (effectiveness) is unknown because no such trials have been reported in the United States. OBJECTIVES: To determine the eradication rates of H pylori in a community practice setting and the effects of practice variation in the choice of treatment regimen on patient outcome (H pylori infection cure) and cost. METHODS: Between February 1 and December 30, 1996, 38 community-based gastroenterologists in the Portland, Ore, metropolitan area enrolled a total of 250 patients infected with H pylori, as determined by endoscopic or noninvasive methods. Various therapeutic regimens aimed at eradicating H pylori were used by the gastroenterologists, and a posttreatment urea breath test was used to determine H pylori infection cure. Compliance and incidental effects were also measured and decision analysis was used to estimate the cost of treatment. RESULTS: The regimens used varied considerably. Patients receiving a 2- or 3-times-a-day treatment regimen were significantly more compliant (P=.01) than those receiving a 4-times-a-day regimen. Proton pump inhibitor-based triple-therapy regimens were significantly more effective than all other treatment regimens combined (87% vs 70%; P = .001) in eradicating H pylori. These proton pump inhibitor-based triple-therapy regimens were also more cost-effective by decision analysis for a hypothetical cohort of patients with duodenal ulcer disease. CONCLUSIONS: The considerable variation in the choice of treatment regimens affects the clinical and economic outcomes of patients undergoing therapy for H pylori infection. Whether these data reflect the outcome in other communities is unknown but should be determined. It will be necessary to determine if the dissemination of these data results in a reduction of practice variation and improvement in clinical and economic outcomes of patients being treated for H pylori infection in clinical practice.     

真菌培养对真菌性皮肤病的诊断和治疗的作用

1 临床资料我院门诊收治患者49(男25,女24)例,病程1 wk～15 a,包括体癣11例、股癣6例、手足癣21例、真菌性龟头炎2例、甲癣9例. 真菌培养时常规消毒取材部位,用取材刀取皮屑于玻片上,取沙氏培养基试管,将接种环烧红,在试管中的培养基上轻沾,用接种环粘取少量皮屑放在培养基上,轻轻用接种环压之,放入27℃电热恒温培养箱,培养7～14 d,用接种环取少许菌落于玻片,镜下观察菌株形态.     

ORIGINAL ARTICLE: Sparing of the hippocampus and limbic circuit during whole brain radiation therapy: A dosimetric study using helical tomotherapy

Introduction: The study aims to assess the feasibility of dosimetrically sparing the limbic circuit during whole brain radiation therapy (WBRT) and prophylactic cranial irradiation (PCI). Methods and Materials: We contoured the brain/brainstem on fused MRI and CT as the target volume (PTV) in 11 patients, excluding the hippocampus and the rest of the limbic circuit, which were considered organs at risk (OARs). PCI and WBRT helical tomotherapy plans were prepared for each patient with a 1.0-cm field width, pitch = 0.285, initial modulation factor = 2.5. We attempted to spare the hippocampus and the rest of the limbic circuit while treating the rest of the brain to 30 Gy in 15 fractions (PCI) or 35 Gy in 14 fractions (WBRT) with V₁₀₀ ≥ 95%. The quality of the plans was assessed by calculating mean dose and equivalent uniform dose (EUD) for OARs and the % volume of the PTV receiving the prescribed dose, V₁₀₀. Results: In the PCI plans, mean doses/EUD were: hippocampus 12.5 Gy/14.23 Gy, rest of limbic circuit 17.0 Gy/19.02 Gy. In the WBRT plans, mean doses/EUD were: hippocampus 14.3 Gy/16.07 Gy, rest of limbic circuit 17.9 Gy/20.74 Gy. The mean V₁₀₀ for the rest of the brain (PTV) were 94.7% (PCI) and 95.1% (WBRT). Mean PCI and WBRT treatment times were essentially identical (mean 15.23 min, range 14.27–17.5). Conclusions: It is dosimetrically feasible to spare the hippocampus and the rest of the limbic circuit using helical tomotherapy while treating the rest of the brain to full dose.