Consequences of revised CLSI and EUCAST guidelines for antibiotic susceptibility patterns of ESBL- and AmpC β-lactamase-producing clinical Enterobacteriaceae isolates

Objectives This study aimed to: (i) analyse the antibiotic susceptibility testing (AST) profiles of extended spectrum β-lactamase (ESBL)- and AmpC β-lactamase-producing clinical Enterobacteriaceae isolates applying EUCAST 2013 AST guidelines; and (ii) evaluate discrepancies in AST profiles according to EUCAST 2010 guidelines, EUCAST 2013 guidelines, CLSI 2009 guidelines and CLSI 2013 guidelines. Methods The 195 ESBL- and/or AmpC β-lactamase-producing Enterobacteriaceae isolates used in this study were systematically characterized by disc diffusion AST interpreted according to the 2013 guidelines of EUCAST and CLSI, the EUCAST 2010 guidelines and the CLSI 2009 guidelines. Results Individual cephalosporin AST patterns according to EUCAST 2013 guidelines were described for individual ESBL and AmpC β-lactamase genotypes. Significant differences in the susceptibility rates of important cephalosporins such as cefepime, ceftazidime and cefotaxime applying EUCAST 2013 and CLSI 2013 AST guidelines were demonstrated for ESBL- and AmpC β-lactamase-producing isolates. Conclusions The confirmation of ESBL and/or AmpC β-lactamase production can support the selection of an adequate antibiotic drug therapy. Despite a harmonized CLSI and EUCAST ‘report as found' strategy for cephalosporins and ESBL-producing isolates, AST interpretation according to the CLSI 2013 and EUCAST 2013 guidelines shows significant differences in susceptibility rates for mainstay cephalosporins such as cefepime, ceftazidime and cefotaxime. Thus, further harmonization of clinical breakpoints is warrante

Effects of clinical breakpoint changes in CLSI guidelines 2010/2011 and EUCAST guidelines 2011 on antibiotic susceptibility test reporting of Gram-negative bacilli

Objectives The aim of this study was to analyse the effects of clinical breakpoint changes in CLSI 2010 and 2011 guidelines and EUCAST 2011 guidelines on antibiotic susceptibility testing (AST) reports. Methods In total, 3713 non-duplicate clinical isolates of Enterobacteriaceae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter baumannii were analysed. Inhibition zone diameters were determined for β-lactams, carbapenems, fluoroquinolones, aminoglycosides and trimethoprim/sulfamethoxazole. CLSI 2009-11 and EUCAST 2011 clinical breakpoints were applied. Results Changes in resistance as defined per the guidelines affected individual species and drug classes differently. The cefepime resistance rate in Escherichia coli and Enterobacter cloacae increased from 2.1% and 1.3% to 8.2% and 6.9%, respectively, applying CLSI 2009-11 versus EUCAST 2011 guidelines. Ertapenem resistance rates in E. cloacae increased from 2.6% with CLSI 2009 to 7.2% for CLSI 2010 and 2011, and to 10.1% when applying EUCAST 2011. Cefepime and meropenem resistance rates in P. aeruginosa increased from 12.2% and 20.6% to 19.8% and 27.7%, respectively, comparing CLSI 2009-11 with EUCAST 2011. Tobramycin and gentamicin resistance rates in A. baumannii increased from 15.9% and 25.4% to 34.9% and 44.4% applying CLSI 2009-11 versus EUCAST 2011. Conclusions Higher resistance rates reported due to breakpoint changes in CLSI and EUCAST guidelines will result in increasing numbers of Gram-negative bacilli reported as multidrug resistant. AST reports classifying amoxicillin/clavulanic acid, cefepime or carbapenem resistance will lead clinicians to use alternative agents. Upon implementation of the EUCAST guidelines, laboratories should be aware of the implications of modified drug susceptibility testing reports on antibiotic prescription policie

Comparison of European Committee on Antimicrobial Susceptibility Testing (EUCAST) and CLSI screening parameters for the detection of extended-spectrum β-lactamase production in clinical Enterobacteriaceae isolates

Objectives To compare the performance of European Committee on Antimicrobial Susceptibility Testing (EUCAST) and CLSI breakpoints following their revision in 2010, for the detection of extended-spectrum β-lactamase (ESBL) production in Enterobacteriaceae. Methods 236 well-characterized clinical isolates (including 118 ESBL producers) were investigated by antibiotic disc testing with cefpodoxime, ceftriaxone, cefepime, cefotaxime EUCAST (5 μg/disc), ceftazidime EUCAST (10 μg/disc), cefotaxime CLSI (30 μg/disc) and ceftazidime CLSI (30 μg/disc) with the Kirby-Bauer method. Additionally, synergy phenomena were recorded between amoxicillin/clavulanic acid discs (20/10 μg/disc) and cefepime (30 μg/disc), EUCAST cefotaxime (5 μg/disc), EUCAST ceftazidime (10 μg/disc), CLSI cefotaxime (30 μg/disc) and CLSI ceftazidime [30 μg/disc; disc approximation method (DAM)]. Results Overall sensitivity of the cefotaxime EUCAST non-susceptible breakpoint equalled sensitivity of the cefotaxime CLSI ESBL screening breakpoint (99.2%). With the ceftazidime EUCAST non-susceptible breakpoint, 27/118 ESBL-producing isolates were not detected, whereas the ceftazidime CLSI ESBL screening breakpoint missed 41/118 ESBL-producing isolates. For cefpodoxime the resistant EUCAST breakpoint showed higher sensitivity for ESBL detection compared with the CLSI ESBL screening breakpoint/disc content (100% versus 98.3%, respectively). Sensitivities of ceftazidime and cefotaxime DAM with CLSI or EUCAST disc contents were comparable (sensitivities ranging from 84.7% to 89.8%). DAM with cefepime displayed the highest overall sensitivity (96.6%). In AmpC-producing isolates, synergy of amoxicillin/clavulanic acid with cefepime showed sensitivity and specificity for ESBL detection of 100% and 97.4%, respectively. Conclusions EUCAST non-susceptible breakpoints for ceftazidime and cefpodoxime detect more ESBL-producing Enterobacteriaceae isolates compared with corresponding CLSI ESBL screening breakpoints. Implementation of the cefepime DAM can facilitate ESBL screening, especially in strains producing an AmpC β-lactamase since the test shows high sensitivity and specificit

Evaluation of the AID ESBL line probe assay for rapid detection of extended-spectrum β-lactamase (ESBL) and KPC carbapenemase genes in Enterobacteriaceae

Objectives This study aimed at evaluating the AID ESBL line probe assay for the detection of extended-spectrum β-lactamase (ESBL) and KPC carbapenemase genes in Enterobacteriaceae. Methods The AID ESBL line probe assay was verified for accuracy of its probes using PCR products from clinical ESBL Enterobacteriaceae strains harbouring TEM, SHV and CTX-M ESBL genes and KPC genes and mutant fusion PCR products generated from Enterobacteriaceae strains containing wild-type (wt) TEM and wt SHV. Sensitivity and specificity was determined testing a set of 424 clinical Enterobacteriaceae strains (including 170 strains negative for TEM, SHV, CTX-M and KPC to evaluate the possibility of false positive signals). Results The line probe assay was shown to detect with 100% accuracy ESBL genes for which oligonucleotide probes are present in the assay. Testing a set of 424 clinical Enterobacteriaceae strains showed 100% sensitivity and specificity for the detection and differentiation of TEM, SHV and CTX-M ESBL genes present in that group. In addition, the line probe assay detected KPC genes accurately. Conclusions The AID ESBL line probe assay is an accurate and easy-to-use test for the detection of ESBL and KPC genes, which can readily be implemented in the diagnostic laborator

Developing a vaccine against Zika

The race to develop a vaccine against Zika began in February 2016, when the unusual clustering of cases of microcephaly and other neurological disorders associated with Zika virus infection led to the declaration of a public health emergency of international concern. When the World Health Organization held its first consultation in March, 14 active vaccine projects had already been announced.1 Today, WHO’s pipeline tracker counts about 30 active projects, pursued by developers from endemic and non-endemic countries, private and public sector.2 Such a jump start in vaccine development is rare, and several candidates have already progressed to clinical development. This pace is facilitated by our collective experience in developing vaccines against flaviviruses, the availability of novel vaccine technologies that greatly facilitate manufacturing of vaccines appropriate for trials in humans, and generous funding from some governments to support both basic research and product development

Hadron formation in high energy photonuclear reactions

We present a new method to account for coherence length effects in a semi-classical transport model. This allows us to describe photo- and electroproduction at large nuclei (A>12) and high energies using a realistic coupled channel description of the final state interactions that goes beyond simple Glauber theory. We show that the purely absorptive treatment of the final state interactions can lead to wrong estimates of color transparency and formation time effects in particle production. As an example, we discuss exclusive rho^0 photoproduction on Pb at a photon energy of 7 GeV as well as K^+ production in the photon energy range 1-7 GeV.Comment: 14 pages, 6 figures, version published in Phys. Rev.

Pion emission in 2H, 12C, 27Al, gamma pi+ reactions at threshold

The first data from MAX-lab in Lund, Sweden on pion production in photonuclear reactions at threshold energies, is presented. The decrease of the total yield of pi+ in gamma + 12C, 27Al reactions below 200 MeV as well as differential, dsigma/dOmega, cross sections follow essentially predictions from an intranuclear cascade model with an attractive potential for pion-nucleus interaction in its simplest form. Double differential, d2sigma/dOmegadT, cross sections at 176 MeV show, however, deviations from the model, which call for refinements of nuclear and Coulomb potentials and possibly also for coherent pion production mechanisms.Comment: 19 pages, 7 figure

Photoproduction of mesons in nuclei at GeV energies

In a transport model that combines initial state interactions of the photon with final state interactions of the produced particles we present a calculation of inclusive photoproduction of mesons in nuclei in the energy range from 1 to 7 GeV. We give predictions for the photoproduction cross sections of pions, etas, kaons, antikaons, and $\pi^+\pi^-$ invariant mass spectra in ^{12}C and ^{208}Pb. The effects of nuclear shadowing and final state interaction of the produced particles are discussed in detail.Comment: Text added in summary in general reliability of the method, references updated. Phys. Rev. C (2000) in pres

Pion-Production in Heavy-Ion Collisions at SIS energies

We investigate the production of pions in heavy-ion collisions in the energy range of $1$ - $2$ GeV/A. The dynamics of the nucleus-nucleus collisions is described by a set of coupled transport equations of the Boltzmann-Uehling-Uhlenbeck type for baryons and mesons. Besides the $N(938)$ and the $\Delta(1232)$ we also take into account nucleon resonances up to masses of $1.9 GeV/c^2$ as well as $\pi$-, $\eta$- and $\rho$-mesons. We study in detail the influence of the higher baryonic resonances and the $2\pi$-production channels ($NN\to NN \pi\pi$) on the pion spectra in comparison to $\pi^-$ data from $Ar + KCl$ collisions at $1.8$ GeV/A and $\pi^0$-data for $Au+Au$ at 1.0 GeV/A. We, furthermore, present a detailed comparison of differential pion angular distributions with the BEVALAC data for Ar + KCl at 1.8 GeV/A. The general agreement obtained indicates that the overall reactions dynamics is well described by our novel transport approach.Comment: 31 pages, 18 figures (inlcuded), to appear in Z. Phys.

Quasifree eta photoproduction from nuclei and medium modifications of resonances

We investigate the sensitivity of the differential cross section, recoil nucleon polarization and the photon asymmetry to changes in the elementary amplitude, medium modifications of the resonance $(S_{11},D_{13})$ masses, as well as nuclear target effects. All calculations are performed within a relativistic plane wave impulse approximation formalism resulting in analytical expressions for all observables. The spin observables are shown to be unique tools to study subtle effects that are not accessible by only looking at the unpolarized differential cross section.Comment: 27 pages, 8 figures, Revtex, To be published in Phys. Rev.