Defining an extended-spectrum β-lactamase

ABSTRACTThe term ‘extended-spectrum β-lactamase’ (ESBL), initially ‘extended-broad-spectrum β-lactamase’, was first coined for derivatives of TEM and SHV enzymes able to hydrolyse oxyimino-cephalosporins. These all belonged to β-lactamase functional group 2be. Subsequently, the term has been stretched to include: (i) enzymes with spectra similar to those of TEM and SHV mutants but derived from other sources, e.g., the CTX-M and VEB types; (ii) TEM and SHV mutants with borderline ESBL activity, e.g., TEM-12; and (iii) various β-lactamases conferring wider resistance than their parent types but not meeting the definition for group 2be, e.g., OXA derivatives and mutant AmpC types with increased activity against cefepime. It seems best—and pragmatic—that the term ‘ESBL’ retains its broad modern usage, but that should always be accompanied by mention of the enzyme's family as, e.g., in ‘TEM ESBL’ or ‘OXA ESBL’, not as a sole moniker

Major role of pKpQIL-like plasmids in the early dissemination of KPC-type carbapenemases in the UK

Objectives: KPC-producing Enterobacteriaceae were first seen in the UK in 2003 and have been increasingly reported since 2010, largely owing to an ongoing outbreak in North-West England. We examined the role of clonal spread and plasmid transmission in their emergence. Methods: Isolates comprised KPC-positive Klebsiella pneumoniae (n=33), Escherichia coli (n=7) and Enterobacter spp. (n=4) referred to the national reference laboratory between 2008 and 2010 from 17 UK centres, including three in North-West England. Isolates were typed by MLST. Plasmids were transferred by electroporation and characterised by PCR or sequencing. PCR screening assays were developed to distinguish plasmid pKpQIL variants. Results: The K. pneumoniae isolates included 10 STs, of which three belonged to clonal group (CG) 258. CG258 (n=19) isolates were detected in 13 centres but accounted for only 7/19 (36.8%) of those from North-West England. Most KPC-producers (37/44, 84.1%), including 16/19 CG258 K. pneumoniae carried blaKPC on IncFIIK2 plasmids. Sequencing of a subset of these plasmids (n=11) revealed similarities with published pKpQIL. One variant, pKpQIL-UK - identified in K. pneumoniae CG258 (n=5) and ST468 (n=1) isolates from distinct centres - had only a few nucleotide changes from classical pKpQIL, whereas pKpQIL-D1 (n=1) and pKpQIL-D2 (n=4), from isolates of various species in the North-West, harboured large variations reflecting replacement of the partitioning and replication functions and potentially thereby facilitating spread. PCR revealed that 36/37 (97.3%) IncFIIK2-type plasmids in KPC-positive isolates had pKpQIL markers. Conclusions: pKpQIL-like plasmids played a major role in the early dissemination of KPC enzymes in the UK

Antimicrobial Resources for Disinfection of Potable Water Systems for Future Spacecraft

As human exploration adventures beyond low earth orbit, life support systems will require more innovation and research to become self-sustaining and durable. One major concern about future space travel is the ability to store and decontaminate water for consumption and hygiene. This project explores materials and technologies for possible use in future water systems without requiring point-of-use (POU) filtering or chemical additives such as iodine or silver that require multiple doses to remain effective. This experimentation tested the efficacy of a variety of antimicrobial materials against biofilm formation in a high shear CDC Biofilm Reactor (CBR) and some materials in a low shear Drip Flow Reactor (DFR) which(also utilizes ultra violet light emitting diodes (UVLEDs) as an antimicrobial resource. Most materials were tested in the CBR using the ASTM E 2562-07 1method involving the Pseudomonas aeruginosa and coupon samples that vary in their antimicrobial coatings and surface layer topographies. In a controlled environmental chamber (CEC), the CBR underwent a batch phase, continuous flow phase (CFP), and a harvest before analysis. The DFR portion of this experimentation was performed in order to assess the antimicrobial capabilities of ultraviolet-A LEDs (UV-A) in potable water systems. The ASTM E 2647-08 was modified in order to incorporate UV-A LEDs and to operate as a closed, re-circulating system. The modified DFR apparatus that was utilized contains 4 separate channels each of which contain 2 UV-A LEDs (1 chamber is masked off to serve as a control) and each channel is equipped with its own reservoir and peristaltic pump head. The 10 DFR runs discussed in this report include 4 initial experimental runs that contained blank microscope slides to test the UVA LEDs alone, 2 that incorporated solid silver coupons, 2 that utilized titanium dioxide (Ti02) coupons as a photocatalyst, and 2 runs that utilized silver coated acrylic slides. Both the CBR and DFR experiments were analyzed for microbial content via heterotrophic plate counts (HPC) and acridine orange direct counts (AODC). Ofthe materials used in the CBR, only two materials performed as anti~icrobials under high shear conditions (a reduction of 5 or more logs) showing a>7 log reduction in viable microbes

Detection of fragments arising from >10 GeV electron-nucleus collisions

Much is understood about the interaction of both high energy electrons with nucleons and lower energy electrons with nucleons and nuclei. Although a number of experiments involving high energy inelastic scattering of electrons from quarks bound in nuclei have been performed, many interpretations of the data are still discussed. A project called PEGASYS was conceived at PEP to further investigate this physics. Unfortunately, the termination of PEP operations curtailed this experiment and much of the physics remains unexplored. In this paper we present some details of one proposed part of this project (tagged nuclear structure functions) and some considerations made in designing a detector suitable for observing very low momentum nuclear fragements around a cold-cluster gas target

Prevention and control of multi-drug-resistant Gram-negative bacteria: recommendations from a Joint Working Party

Multi-drug-resistant (MDR) Gram-negative bacterial infections have become prevalent in some European countries. Moreover, increased use of broad-spectrum antimicrobial agents selects organisms with resistance and, by increasing their numbers, increases their chance of spread. This report describes measures that are clinically effective for preventing transmission when used by healthcare workers in acute and primary healthcare premises. Methods for systematic review 1946–2014 were in accordance with SIGN 501 and the Cochrane Collaboration;2 critical appraisal was applied using AGREEII.3 Accepted guidelines were used as part of the evidence base and to support expert consensus. Questions for review were derived from the Working Party Group, which included patient representatives in accordance with the Patient Intervention Comparison Outcome (PICO) process. Recommendations are made in the following areas: screening, diagnosis and infection control precautions including hand hygiene, single-room accommodation, and environmental screening and cleaning. Recommendations for specific organisms are given where there are species differences. Antibiotic stewardship is covered in a separate publication

Design of the CART data system for the US Department of Energy's ARM Program

The Department of Energy (DOE) has initiated a major atmospheric research effort to reduce the uncertainties found in general circulation and other models due to the effects of clouds and radiation. The objective of the Atmospheric Radiation Measurement Program (ARM) is to provide an experimental testbed for the study of important atmospheric effects, particularly cloud and radiative processes, and testing parameterizations of the processes for use in atmospheric models. This experimental testbed, known as the Clouds and Radiation Testbed (CART), will include a complex data system, the CART Data Environment (CDE). The major functions of the CDE will be to: acquire environments from instruments and external data sources; perform quality assessments of the data streams; create data streams of known quality to be used as model input compared to model output; execute the models and capture their predictions; and make data streams associated with model tests available to ARM investigators in near real-time. The CDE will also be expected to capture ancillary information ( meta-data'') associated with the data streams, provide data management facilities for design of ARM experiments, and provide for archival data storage. The first section of this paper presents background information on CART. Next the process for the functional design of the system is described, the functional requirements summarized, and the conceptual architecture of the CDE is presented. Finally, the status of the CDE design activities is summarized, and major technical challenges are discussed

Mental health in paediatric and adult myositis-related diseases : current state of research, interventions, and future steps from the MIHRA Psychological Impact Scientific Working Group

Psychological and emotional well-being are critical aspects of overall health for individuals with chronic rheumatologic conditions. Mental health-related literature, however, predominantly focuses on systemic lupus erythematosus or rheumatoid arthritis, with limited emphasis on idiopathic inflammatory myopathies (IIMs). High proportions of those with juvenile myositis report psychological distress at levels warranting mental health referral. Adults with dermatomyositis diagnosed with depression or anxiety do not receive adequate mental health care. Mental health symptoms in those with IIMs are associated with worse health-related quality of life, medication adherence, and disease outcomes. Despite demonstrated high rates of mental health burden, access to mental health care remains severely lacking. Data related to mental health burden is limited by small sample size, limited generalisability, variable methods of assessment, and inconsistent diagnosis codes to define mental health conditions. Additional research is needed to validate current screening tools in myositis populations. Other relevant measurable factors include disease severity, non-health- and health-related trauma exposure, loneliness, isolation, loss of control, sleep difficulties, fatigue, pain, self-esteem, body image, sexual health, and health inequities. Studiesare needed investigating the efficacy of therapeutic and pharmacologic interventions among patients with myositis who experience depression and anxiety. Currently, knowledge and resources are limited around mental health burden and potential intervention for those living with IIMs. The Myositis International Health & Research Collaborative Alliance (MIHRA) Psychological Impact Scientific Working Group offers a preliminary road map to characterise and prioritise the work ahead to understand baseline mental health burden and compare avenues for intervention

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results