Rapid Identification of Pathogens in Positive Blood Culture of Patients with Sepsis: Review and Meta-Analysis of the Performance of the Sepsityper Kit

Sepsis is one of the leading causes of deaths, and rapid identification (ID) of blood stream infection is mandatory to perform adequate antibiotic therapy. The advent of MALDI-TOF Mass Spectrometry for the rapid ID of pathogens was a major breakthrough in microbiology. Recently, this method was combined with extraction methods for pathogens directly from positive blood cultures. This review summarizes the results obtained so far with the commercial Sepsityper sample preparation kit, which is now approved for in vitro diagnostic use. Summarizing data from 21 reports, the Sepsityper kit allowed a reliable ID on the species level of 80% of 3320 positive blood culture bottles. Gram negative bacteria resulted consistently in higher ID rates (90%) compared to Gram positive bacteria (76%) or yeast (66%). No relevant misidentifications on the genus level were reported at a log(score)cut-off of 1.6. The Sepsityper kit is a simple and reproducible method which extends the MALDI-TOF technology to positive blood culture specimens and shortens the time to result by several hours or even days. In combination with antibiotic stewardship programs, this rapid ID allows a much faster optimization of antibiotic therapy in patients with sepsis compared to conventional workflows

Bosnia and Herzegovina - Meeting Copenhagen economic criteria for accession to the EU

Delegation of the European Commission based in Sarajevo, Bosnia and Herzegovina (BH) granted the consortium represented by ECORYS a contract for EU support to the Economic Policy Research Unit, a subdivision of the Economic Policy Planning Unit of the Council of Ministers of Bosnia and Herzegovina. As part of this project activities a subproject was designed trying to assess the position of BH against the benchmarks of the Copenhagen economic criteria and to identify policy measures for meeting the criteria. The issues of particular relevance to the project included: presentation of the Copenhagen economic criteria, analysis of the existing situation in the country, strategic and policy documents addressing the subject, identification of gaps to be filled in order to achieve the benchmark, and policy recommendations. In July, 2006 ECORYS appointed the Center for Social and Economic Research (CASE), an international, non-profit research and advisory institution, to research on the subject. The research project team comprised experts: Messrs. Rafa³ Antczak (team leader), Wojciech Paczyñski, and Ranko Markuš, Mmes. Ma³gorzata Antczak and Karina Kostrzewa, assisted by Mr. Erol Mujanovic. The report was based on available national account and microeconomic data, strategic and policy documents of the BH governmental bodies, relevant reports by international organisations, EU institutions, academic and research centres and opinions of key stakeholders. The analytical research on the economic developments in BH by international financial institutions, especially the IMF and World Bank, as well as domestic bodies, especially the Economic Policy Research Unit, was extensively exploited in the research. However, the primary focus of the research was on structural and institutional aspects facilitating or impeding functioning of a market economy in the BH and country's capacity to cope with competitive pressure and market forces within the EU. Therefore, the report focuses on background analysis of economic factors influencing the functioning of market economy and the capacity to withstand the competition in the EU market. The research consists of four main parts. In Part 1, the Copenhagen economic criteria are presented in a comparative perspective of the recent experiences of the new member states and acceding countries to allow diagnosing of the most important gaps to be filled by BH. Part 2 analyses macroeconomic developments in BH, presenting them in a comparative perspective relative to EU candidate countries. The special focus is on two fields where BH faces particularly difficult challenges: labour market and foreign trade. Also, the three scenarios of BH catching-up with the EU are presented. Privatisation process which is one of the most important institutional and structural features of every transition economy and especially relevant from the perspective of meeting the Copenhagen criteria is analysed in Part 3. Part 4 comprises analysis of microeconomic developments in BH with the elements of the financial analysis of enterprises, both state and private. The financial analysis of enterprises concentrates on current situation and identification of trends in microeconomic developments to identify comparative advantages, assess productivity, and to position the BH enterprise sector towards the potential competition on the EU markets. Finally, Part 5 includes policy recommendations for decision makers both from the BH government and the EC. The research is supplemented by the Annexes providing background pieces of information on the analysed topics. The project team established contacts with representatives of international organizations, the BH governmental bodies, and research community in BH to collect pieces of information and consult on research topics. However, the authors of the researchers bear the sole responsibility for the pieces of information and opinions presented in the report.Bosnia and Herzegovina, Copenhagen criteria, EU accession, European integration, competitiveness

Hadron-Hadron Interactions from Nf=2+1+1N_f=2+1+1 Lattice QCD: isospin-1 KKKK scattering length

We present results for the interaction of two kaons at maximal isospin. The calculation is based on $N_f=2+1+1$ flavour gauge configurations generated by the European Twisted Mass Collaboration with pion masses ranging from about $230$ to $450\,\textrm{MeV}$ at three values of the lattice spacing. The elastic scattering length $a_0^{I=1}$ is calculated at several values of the bare strange and light quark masses. We find $M_K a_0 = -0.385(16)_{\textrm{stat}} (^{+0}_{-12})_{m_s}(^{+0}_{-5})_{Z_P}(4)_{r_f}$ as the result of a combined extrapolation to the continuum and to the physical point, where the first error is statistical, and the three following are systematical. This translates to $a_0 = -0.154(6)_{\textrm{stat}}(^{+0}_{-5})_{m_s} (^{+0}_{-2})_{Z_P}(2)_{r_f}\,\textrm{fm}$.Comment: 28 pages, 18 tables, 14 figure

Meson-meson scattering lengths at maximum isospin from lattice QCD

We summarize our lattice QCD determinations of the pion-pion, pion-kaon and kaon-kaon s-wave scattering lengths at maximal isospin with a particular focus on the extrapolation to the physical point and the usage of next-to-leading order chiral perturbation theory to do so. We employ data at three values of the lattice spacing and pion masses ranging from around 230 MeV to around 450 MeV, applying Luescher's finite volume method to compute the scattering lengths. We find that leading order chiral perturbation theory is surprisingly close to our data even in the kaon-kaon case for our entire range of pion masses.Comment: 10 pages, 8 figures, Presented at the 9th International Workshop on Chiral Dynamics, Sept. 17-21, 2018, Duke University, Durham, NC, USA , submitted to PoS, (C18-09-17.6). Funding acknowledgements added in v2 replacement, comma added in abstract. In v3 replacement, corrected typo in equation 6.2 which was referring to the pion-kaon reduced mass instead of the pion mas

Hadron-Hadron Interactions from Nf=2+1+1N_f=2+1+1 Lattice QCD: I=3/2I=3/2 πK\pi K Scattering Length

In this paper we report on results for the s-wave scattering length of the $\pi$-$K$ system in the $I=3/2$ channel from $N_f=2+1+1$ Lattice QCD. The calculation is based on gauge configurations generated by the European Twisted Mass Collaboration with pion masses ranging from about $230$ to $450\,\text{MeV}$ at three values of the lattice spacing. Our main result reads $M_{\pi}\,a_0^{3/2,\text{phys}} = -0.059(2)$. Using chiral perturbation theory we are also able to estimate $M_{\pi}\,a_0^{1/2,\text{phys}} = 0.163(3)$. The error includes statistical and systematic uncertainties, and for the latter in particular errors from the chiral and continuum extrapolations.Comment: 30 pages, 6 figures, 15 table

The η′\eta^\prime meson at the physical point with Nf=2N_f=2 Wilson twisted mass fermions

We present results for the eta prime meson and the topological susceptibility in two flavour lattice QCD. The results are obtained using Wilson twisted mass fermions at maximal twist with pion masses ranging from 340 MeV down to the physical point. A comparison to literature values is performed giving a handle on discretisation effects.Comment: Lattice 2017 proceeding contributio

Detection of Methicillin Resistance in Staphylococcus aureus From Agar Cultures and Directly From Positive Blood Cultures Using MALDI-TOF Mass Spectrometry-Based Direct-on-Target Microdroplet Growth Assay

Matrix-assisted laser desorption/ionization time-of-flight-mass spectrometry (MALDI-TOF MS)-based direct-on-target microdroplet growth assay (DOT-MGA) was recently described as a novel method of phenotypic antimicrobial susceptibility testing (AST). Here, we developed the application of MALDI-TOF MS-based DOT-MGA for Gram-positive bacteria including AST from agar cultures and directly from positive blood cultures (BCs) using the detection of methicillin resistance as example. Consecutively collected, a total of 14 methicillin-resistant Staphylococcus aureus (MRSA) and 14 methicillin-susceptible S. aureus (MSSA) clinical isolates were included. Furthermore, a collection of MRSA challenge strains comprising different SCCmec types, mec genes, and spa types was tested. Blood samples were spiked with MRSA and MSSA and positive BC broth processed by three different methods: serial dilution of BC broth, lysis/centrifugation, and differential centrifugation. Processed BC broth was directly used for rapid AST using DOT-MGA. Droplets of 6 μl with and without cefoxitin at the EUCAST breakpoint concentration were spotted in triplicates onto the surface of a MALDI target. Targets were incubated in a humidity chamber, followed by medium removal and on-target protein extraction with formic acid before adding matrix with an internal standard as a quality control (QC). Spectra were acquired and evaluated using MALDI Biotyper software. First, tests were considered as valid, if the growth control achieved an identification score of ≥1.7. For valid tests, same score criterion was used for resistant isolates when incubated with cefoxitin. An identification score <1.7 after incubation with cefoxitin defined susceptible isolates. On-target protein extraction using formic acid considerably improved detection of methicillin resistance in S. aureus and DOT-MGA showed feasible results for AST from agar cultures after 4 h incubation time. Comparing the different processing methods of positive BC broth, lysis/centrifugation method with a final dilution step 10–1 of the 0.5 McFarland suspension resulted in best test performance after 4 h incubation time. Overall, 96.4% test validity, 100% sensitivity, and 100% specificity were achieved for detection of methicillin resistance in clinical isolates. All strains of the MRSA challenge collection were successfully tested as methicillin-resistant. This first study on Gram-positive organisms showed feasibility and accuracy of MALDI-TOF MS-based DOT-MGA for rapid AST of S. aureus from agar cultures and directly from positive BCs

A Full MALDI-Based Approach to Detect Plasmid-Encoded KPC-Producing Klebsiella pneumoniae

KPC-producing Klebsiella pneumoniae represents a severe public health concern worldwide. The rapid detection of these isolates is of fundamental importance for the adoption of proper antibiotic treatment and infection control measures, and new applications of MALDI-TOF MS technology fit this purpose. In this study, we present a full MALDI-based approach to detect plasmid-encoded KPC-producing strains, accomplished by the automated detection of a KPC-specific peak (at 11,109 m/z) by a specific algorithm integrated into the MALDI Biotyper system (Bruker Daltonik), and the confirmation of carbapenemase activity by STAR-Carba imipenem hydrolysis assay. A total of 6209 K. pneumoniae isolates from Italy and Germany were investigated for the presence of the KPC-related peak, and a subset of them (n = 243) underwent confirmation of carbapenemase activity by STAR-Carba assay. The novel approach was further applied directly to positive blood culture bottles (n = 204), using the bacterial pellet obtained with Sepsityper kit (Bruker Daltonik). The novel approach enabled a reliable and very fast detection of KPC-producing K. pneumoniae strains, from colonies as well as directly from positive blood cultures. The automated peak detection enabled the instant detection of KPC-producing K. pneumoniae during the routine identification process, with excellent specificity (100%) and a good sensitivity (85.1%). The sensitivity is likely mainly related to the prevalence of the specific plasmid harboring clones among all the KPC-producing circulating strains. STAR-Carba carbapenemase confirmation showed 100% sensitivity and specificity, both from colonies and from positive blood cultures