Grazing-incidence coherent x-ray imaging in true reflection geometry

NASA Astrophysics Data System (ADS)

Sun, Tao; Jiang, Zhang; Strzalka, Joseph; Wang, Jin

2012-02-01

The development of the 3^rd and 4^th generation synchrotrons has stimulated extensive research activities in x-ray imaging techniques. Among all, coherent diffractive imaging (CDI) shows great promise, as its resolution is only limited by the wavelength of the source. Most of the CDI work reported thus far used transmission geometry, which however is not suitable for samples on opaque substrates or in which only the surfaces are the regions of interest. Even though two groups have performed CDI experiments (using laser or x-ray) in reflection geometry and succeeded in reconstructing the planar image of the surface, the theoretical underpinnings and analysis approaches of their techniques are essentially identical to transmission CDI. Most importantly, they couldn't obtain the structural information along sample thickness direction. Here, we introduce a reflection CDI technique that works at grazing-incidence geometry. By visualizing Au nanostructures fabricated on Si substrate, we demonstrate that this innovative imaging technique is capable of obtaining both 2D and 3D information of surfaces or buried structures in the samples. In the meanwhile, we will also explain the grazing-incidence-scattering based-algorithm developed for 3D phase retrieval.

Three-dimensional coherent X-ray diffractive imaging of whole frozen-hydrated cells

PubMed Central

Rodriguez, Jose A.; Xu, Rui; Chen, Chien-Chun; Huang, Zhifeng; Jiang, Huaidong; Chen, Allan L.; Raines, Kevin S.; Pryor Jr, Alan; Nam, Daewoong; Wiegart, Lutz; Song, Changyong; Madsen, Anders; Chushkin, Yuriy; Zontone, Federico; Bradley, Peter J.; Miao, Jianwei

2015-01-01

A structural understanding of whole cells in three dimensions at high spatial resolution remains a significant challenge and, in the case of X-rays, has been limited by radiation damage. By alleviating this limitation, cryogenic coherent diffractive imaging (cryo-CDI) can in principle be used to bridge the important resolution gap between optical and electron microscopy in bio-imaging. Here, the first experimental demonstration of cryo-CDI for quantitative three-dimensional imaging of whole frozen-hydrated cells using 8 keV X-rays is reported. As a proof of principle, a tilt series of 72 diffraction patterns was collected from a frozen-hydrated Neospora caninum cell and the three-dimensional mass density of the cell was reconstructed and quantified based on its natural contrast. This three-dimensional reconstruction reveals the surface and internal morphology of the cell, including its complex polarized sub-cellular structure. It is believed that this work represents an experimental milestone towards routine quantitative three-dimensional imaging of whole cells in their natural state with spatial resolutions in the tens of nanometres. PMID:26306199

Three-dimensional coherent X-ray diffractive imaging of whole frozen-hydrated cells

DOE PAGES

Rodriguez, Jose A.; Xu, Rui; Chen, Chien -Chun; ...

2015-09-01

Here, a structural understanding of whole cells in three dimensions at high spatial resolution remains a significant challenge and, in the case of X-rays, has been limited by radiation damage. By alleviating this limitation, cryogenic coherent diffractive imaging (cryo-CDI) can in principle be used to bridge the important resolution gap between optical and electron microscopy in bio-imaging. Here, the first experimental demonstration of cryo-CDI for quantitative three-dimensional imaging of whole frozen-hydrated cells using 8 Kev X-rays is reported. As a proof of principle, a tilt series of 72 diffraction patterns was collected from a frozen-hydrated Neospora caninum cell and themore » three-dimensional mass density of the cell was reconstructed and quantified based on its natural contrast. This three-dimensional reconstruction reveals the surface and internal morphology of the cell, including its complex polarized sub-cellular structure. Finally, it is believed that this work represents an experimental milestone towards routine quantitative three-dimensional imaging of whole cells in their natural state with spatial resolutions in the tens of nanometres.« less

Three-dimensional coherent X-ray diffractive imaging of whole frozen-hydrated cells.

PubMed

Rodriguez, Jose A; Xu, Rui; Chen, Chien-Chun; Huang, Zhifeng; Jiang, Huaidong; Chen, Allan L; Raines, Kevin S; Pryor, Alan; Nam, Daewoong; Wiegart, Lutz; Song, Changyong; Madsen, Anders; Chushkin, Yuriy; Zontone, Federico; Bradley, Peter J; Miao, Jianwei

2015-09-01

A structural understanding of whole cells in three dimensions at high spatial resolution remains a significant challenge and, in the case of X-rays, has been limited by radiation damage. By alleviating this limitation, cryogenic coherent diffractive imaging (cryo-CDI) can in principle be used to bridge the important resolution gap between optical and electron microscopy in bio-imaging. Here, the first experimental demonstration of cryo-CDI for quantitative three-dimensional imaging of whole frozen-hydrated cells using 8 keV X-rays is reported. As a proof of principle, a tilt series of 72 diffraction patterns was collected from a frozen-hydrated Neospora caninum cell and the three-dimensional mass density of the cell was reconstructed and quantified based on its natural contrast. This three-dimensional reconstruction reveals the surface and internal morphology of the cell, including its complex polarized sub-cellular structure. It is believed that this work represents an experimental milestone towards routine quantitative three-dimensional imaging of whole cells in their natural state with spatial resolutions in the tens of nanometres.

High-dynamic-range coherent diffractive imaging: ptychography using the mixed-mode pixel array detector

PubMed Central

Giewekemeyer, Klaus; Philipp, Hugh T.; Wilke, Robin N.; Aquila, Andrew; Osterhoff, Markus; Tate, Mark W.; Shanks, Katherine S.; Zozulya, Alexey V.; Salditt, Tim; Gruner, Sol M.; Mancuso, Adrian P.

2014-01-01

Coherent (X-ray) diffractive imaging (CDI) is an increasingly popular form of X-ray microscopy, mainly due to its potential to produce high-resolution images and the lack of an objective lens between the sample and its corresponding imaging detector. One challenge, however, is that very high dynamic range diffraction data must be collected to produce both quantitative and high-resolution images. In this work, hard X-ray ptychographic coherent diffractive imaging has been performed at the P10 beamline of the PETRA III synchrotron to demonstrate the potential of a very wide dynamic range imaging X-ray detector (the Mixed-Mode Pixel Array Detector, or MM-PAD). The detector is capable of single photon detection, detecting fluxes exceeding 1 × 108 8-keV photons pixel−1 s−1, and framing at 1 kHz. A ptychographic reconstruction was performed using a peak focal intensity on the order of 1 × 1010 photons µm−2 s−1 within an area of approximately 325 nm × 603 nm. This was done without need of a beam stop and with a very modest attenuation, while ‘still’ images of the empty beam far-field intensity were recorded without any attenuation. The treatment of the detector frames and CDI methodology for reconstruction of non-sensitive detector regions, partially also extending the active detector area, are described. PMID:25178008

High-dynamic-range coherent diffractive imaging: ptychography using the mixed-mode pixel array detector.

PubMed

Giewekemeyer, Klaus; Philipp, Hugh T; Wilke, Robin N; Aquila, Andrew; Osterhoff, Markus; Tate, Mark W; Shanks, Katherine S; Zozulya, Alexey V; Salditt, Tim; Gruner, Sol M; Mancuso, Adrian P

2014-09-01

Coherent (X-ray) diffractive imaging (CDI) is an increasingly popular form of X-ray microscopy, mainly due to its potential to produce high-resolution images and the lack of an objective lens between the sample and its corresponding imaging detector. One challenge, however, is that very high dynamic range diffraction data must be collected to produce both quantitative and high-resolution images. In this work, hard X-ray ptychographic coherent diffractive imaging has been performed at the P10 beamline of the PETRA III synchrotron to demonstrate the potential of a very wide dynamic range imaging X-ray detector (the Mixed-Mode Pixel Array Detector, or MM-PAD). The detector is capable of single photon detection, detecting fluxes exceeding 1 × 10(8) 8-keV photons pixel(-1) s(-1), and framing at 1 kHz. A ptychographic reconstruction was performed using a peak focal intensity on the order of 1 × 10(10) photons µm(-2) s(-1) within an area of approximately 325 nm × 603 nm. This was done without need of a beam stop and with a very modest attenuation, while `still' images of the empty beam far-field intensity were recorded without any attenuation. The treatment of the detector frames and CDI methodology for reconstruction of non-sensitive detector regions, partially also extending the active detector area, are described.

In situ observation of dynamic electrodeposition processes by soft x-ray fluorescence microspectroscopy and keyhole coherent diffractive imaging

NASA Astrophysics Data System (ADS)

Bozzini, Benedetto; Kourousias, George; Gianoncelli, Alessandra

2017-03-01

This paper describes two novel in situ microspectroscopic approaches to the dynamic study of electrodeposition processes: x-ray fluorescence (XRF) mapping with submicrometric space resolution and keyhole coherent diffractive imaging (kCDI) with nanometric lateral resolution. As a case study, we consider the pulse-plating of nanocomposites with polypyrrole matrix and Mn x Co y O z dispersoids, a prospective cathode material for zinc-air batteries. This study is centred on the detailed measurement of the elemental distributions developing in two representative subsequent growth steps, based on the combination of in situ identical-location XRF microspectroscopy—accompanied by soft-x ray absorption microscopy—and kCDI. XRF discloses space and time distributions of the two electrodeposited metals and kCDI on the one hand allows nanometric resolution and on the other hand provides complementary absorption as well as phase contrast modes. The joint information derived from these two microspectroscopies allows measurement of otherwise inaccessible observables that are a prerequisite for electrodeposition modelling and control accounting for dynamic localization processes.

Cryogenic coherent X-ray diffraction imaging of biological samples at SACLA: a correlative approach with cryo-electron and light microscopy.

PubMed

Takayama, Yuki; Yonekura, Koji

2016-03-01

Coherent X-ray diffraction imaging at cryogenic temperature (cryo-CXDI) allows the analysis of internal structures of unstained, non-crystalline, whole biological samples in micrometre to sub-micrometre dimensions. Targets include cells and cell organelles. This approach involves preparing frozen-hydrated samples under controlled humidity, transferring the samples to a cryo-stage inside a vacuum chamber of a diffractometer, and then exposing the samples to coherent X-rays. Since 2012, cryo-coherent diffraction imaging (CDI) experiments have been carried out with the X-ray free-electron laser (XFEL) at the SPring-8 Ångstrom Compact free-electron LAser (SACLA) facility in Japan. Complementary use of cryo-electron microscopy and/or light microscopy is highly beneficial for both pre-checking samples and studying the integrity or nature of the sample. This article reports the authors' experience in cryo-XFEL-CDI of biological cells and organelles at SACLA, and describes an attempt towards reliable and higher-resolution reconstructions, including signal enhancement with strong scatterers and Patterson-search phasing.

Novel Fourier-domain constraint for fast phase retrieval in coherent diffraction imaging.

PubMed

Latychevskaia, Tatiana; Longchamp, Jean-Nicolas; Fink, Hans-Werner

2011-09-26

Coherent diffraction imaging (CDI) for visualizing objects at atomic resolution has been realized as a promising tool for imaging single molecules. Drawbacks of CDI are associated with the difficulty of the numerical phase retrieval from experimental diffraction patterns; a fact which stimulated search for better numerical methods and alternative experimental techniques. Common phase retrieval methods are based on iterative procedures which propagate the complex-valued wave between object and detector plane. Constraints in both, the object and the detector plane are applied. While the constraint in the detector plane employed in most phase retrieval methods requires the amplitude of the complex wave to be equal to the squared root of the measured intensity, we propose a novel Fourier-domain constraint, based on an analogy to holography. Our method allows achieving a low-resolution reconstruction already in the first step followed by a high-resolution reconstruction after further steps. In comparison to conventional schemes this Fourier-domain constraint results in a fast and reliable convergence of the iterative reconstruction process. © 2011 Optical Society of America

Imaging of Biological Tissues by Visible Light CDI

NASA Astrophysics Data System (ADS)

Karpov, Dmitry; Dos Santos Rolo, Tomy; Rich, Hannah; Fohtung, Edwin

Recent advances in the use of synchrotron and X-ray free electron laser (XFEL) based coherent diffraction imaging (CDI) with application to material sciences and medicine proved the technique to be efficient in recovering information about the samples encoded in the phase domain. The current state-of-the-art algorithms of reconstruction are transferable to optical frequencies, which makes laser sources a reasonable milestone both in technique development and applications. Here we present first results from table-top laser CDI system for imaging of biological tissues and reconstruction algorithms development and discuss approaches that are complimenting the data quality improvement that is applicable to visible light frequencies due to it's properties. We demonstrate applicability of the developed methodology to a wide class of soft bio-matter and condensed matter systems. This project is funded by DOD-AFOSR under Award No FA9550-14-1-0363 and the LANSCE Professorship at LANL.

Free-electron-laser coherent diffraction images of individual drug-carrying liposome particles in solution.

PubMed

Huang, Chi-Feng; Liang, Keng S; Hsu, Tsui-Ling; Lee, Tsung-Tse; Chen, Yi-Yun; Yang, Shun-Min; Chen, Hsiang-Hsin; Huang, Shih-Hsin; Chang, Wei-Hau; Lee, Ting-Kuo; Chen, Peilin; Peng, Kuei-En; Chen, Chien-Chun; Shi, Cheng-Zhi; Hu, Yu-Fang; Margaritondo, Giorgio; Ishikawa, Tetsuya; Wong, Chi-Huey; Hwu, Y

2018-02-08

Using the excellent performances of a SACLA (RIKEN/HARIMA, Japan) X-ray free electron laser (X-FEL), coherent diffraction imaging (CDI) was used to detect individual liposome particles in water, with or without inserted doxorubicin nanorods. This was possible because of the electron density differences between the carrier, the liposome, and the drug. The result is important since liposome nanocarriers at present dominate drug delivery systems. In spite of the low cross-section of the original ingredients, the diffracted intensity of drug-free liposomes was sufficient for spatial reconstruction yielding quantitative structural information. For particles containing doxorubicin, the structural parameters of the nanorods could be extracted from CDI. Furthermore, the measurement of the electron density of the solution enclosed in each liposome provides direct evidence of the incorporation of ammonium sulphate into the nanorods. Overall, ours is an important test for extending the X-FEL analysis of individual nanoparticles to low cross-sectional systems in solution, and also for its potential use to optimize the manufacturing of drug nanocarriers.

Information recovery in propagation-based imaging with decoherence effects

NASA Astrophysics Data System (ADS)

Froese, Heinrich; Lötgering, Lars; Wilhein, Thomas

2017-05-01

During the past decades the optical imaging community witnessed a rapid emergence of novel imaging modalities such as coherent diffraction imaging (CDI), propagation-based imaging and ptychography. These methods have been demonstrated to recover complex-valued scalar wave fields from redundant data without the need for refractive or diffractive optical elements. This renders these techniques suitable for imaging experiments with EUV and x-ray radiation, where the use of lenses is complicated by fabrication, photon efficiency and cost. However, decoherence effects can have detrimental effects on the reconstruction quality of the numerical algorithms involved. Here we demonstrate propagation-based optical phase retrieval from multiple near-field intensities with decoherence effects such as partially coherent illumination, detector point spread, binning and position uncertainties of the detector. Methods for overcoming these systematic experimental errors - based on the decomposition of the data into mutually incoherent modes - are proposed and numerically tested. We believe that the results presented here open up novel algorithmic methods to accelerate detector readout rates and enable subpixel resolution in propagation-based phase retrieval. Further the techniques are straightforward to be extended to methods such as CDI, ptychography and holography.

Noise models for low counting rate coherent diffraction imaging.

PubMed

Godard, Pierre; Allain, Marc; Chamard, Virginie; Rodenburg, John

2012-11-05

Coherent diffraction imaging (CDI) is a lens-less microscopy method that extracts the complex-valued exit field from intensity measurements alone. It is of particular importance for microscopy imaging with diffraction set-ups where high quality lenses are not available. The inversion scheme allowing the phase retrieval is based on the use of an iterative algorithm. In this work, we address the question of the choice of the iterative process in the case of data corrupted by photon or electron shot noise. Several noise models are presented and further used within two inversion strategies, the ordered subset and the scaled gradient. Based on analytical and numerical analysis together with Monte-Carlo studies, we show that any physical interpretations drawn from a CDI iterative technique require a detailed understanding of the relationship between the noise model and the used inversion method. We observe that iterative algorithms often assume implicitly a noise model. For low counting rates, each noise model behaves differently. Moreover, the used optimization strategy introduces its own artefacts. Based on this analysis, we develop a hybrid strategy which works efficiently in the absence of an informed initial guess. Our work emphasises issues which should be considered carefully when inverting experimental data.

Toward Imaging of Small Objects with XUV Radiation

NASA Astrophysics Data System (ADS)

Sayrac, Muhammed; Kolomenski, Alexandre A.; Boran, Yakup; Schuessler, Hans

The coherent diffraction imaging (CDI) technique has the potential to capture high resolution images of nano- or micron-sized structures when using XUV radiation obtained by high harmonic radiation (HHG) process. When a small object is exposed to XUV radiation, a diffraction pattern of the object is created. The advances in the coherent HHG enable obtaining photon flux sufficient for XUV imaging. The diffractive imaging technique from coherent table top XUV beams have made possible nanometer-scale resolution imaging by replacing the imaging optics with a computer reconstruction algorithm. In this study, we present our initial work on diffractive imaging using a tabletop XUV source. The initial investigation of imaging of a micron-sized mesh with an optimized HHG source is demonstrated. This work was supported in part by the Robert A. Welch Foundation Grant No. A1546 and the Qatar Foundation under the grant NPRP 8-735-1-154. M. Sayrac acknowledges support from the Ministry of National Education of the Republic of Turkey.

Quantitative Evaluation of Hard X-ray Damage to Biological Samples using EUV Ptychography

NASA Astrophysics Data System (ADS)

Baksh, Peter; Odstrcil, Michal; Parsons, Aaron; Bailey, Jo; Deinhardt, Katrin; Chad, John E.; Brocklesby, William S.; Frey, Jeremy G.

2017-06-01

Coherent diffractive imaging (CDI) has become a standard method on a variety of synchrotron beam lines. The high brilliance short wavelength radiation from these sources can be used to reconstruct attenuation and relative phase of a sample with nanometre resolution via CDI methods. However, the interaction between the sample and high energy ionising radiation can cause degradation to sample structure. We demonstrate, using a laboratory based high harmonic generation (HHG) based extreme ultraviolet (EUV) source, imaging a sample of hippocampal neurons using the ptychography method. The significant increase in contrast of the sample in the EUV light allows identification of damage induced from exposure to 7.3 keV photons, without causing any damage to the sample itself.

Coherent diffractive imaging of time-evolving samples with improved temporal resolution

DOE PAGES

Ulvestad, A.; Tripathi, A.; Hruszkewycz, S. O.; ...

2016-05-19

Bragg coherent x-ray diffractive imaging is a powerful technique for investigating dynamic nanoscale processes in nanoparticles immersed in reactive, realistic environments. Its temporal resolution is limited, however, by the oversampling requirements of three-dimensional phase retrieval. Here, we show that incorporating the entire measurement time series, which is typically a continuous physical process, into phase retrieval allows the oversampling requirement at each time step to be reduced, leading to a subsequent improvement in the temporal resolution by a factor of 2-20 times. The increased time resolution will allow imaging of faster dynamics and of radiation-dose-sensitive samples. Furthermore, this approach, which wemore » call "chrono CDI," may find use in improving the time resolution in other imaging techniques.« less

Continuous motion scan ptychography: Characterization for increased speed in coherent x-ray imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng, Junjing; Nashed, Youssef S. G.; Chen, Si

Ptychography is a coherent diffraction imaging (CDI) method for extended objects in which diffraction patterns are acquired sequentially from overlapping coherent illumination spots. The object’s complex transmission function can be reconstructed from those diffraction patterns at a spatial resolution limited only by the scattering strength of the object and the detector geometry. Most experiments to date have positioned the illumination spots on the sample using a move-settle-measure sequence in which the move and settle steps can take longer to complete than the measure step. We describe here the use of a continuous “fly-scan” mode for ptychographic data collection in whichmore » the sample is moved continuously, so that the experiment resembles one of integrating the diffraction patterns from multiple probe positions. This allows one to use multiple probe mode reconstruction methods to obtain an image of the object and also of the illumination function. We show in simulations, and in x-ray imaging experiments, some of the characteristics of fly-scan ptychography, including a factor of 25 reduction in the data acquisition time. This approach will become increasingly important as brighter x-ray sources are developed, such as diffraction limited storage rings.« less

Continuous motion scan ptychography: Characterization for increased speed in coherent x-ray imaging

DOE PAGES

Deng, Junjing; Nashed, Youssef S. G.; Chen, Si; ...

2015-02-23

Ptychography is a coherent diffraction imaging (CDI) method for extended objects in which diffraction patterns are acquired sequentially from overlapping coherent illumination spots. The object’s complex transmission function can be reconstructed from those diffraction patterns at a spatial resolution limited only by the scattering strength of the object and the detector geometry. Most experiments to date have positioned the illumination spots on the sample using a move-settle-measure sequence in which the move and settle steps can take longer to complete than the measure step. We describe here the use of a continuous “fly-scan” mode for ptychographic data collection in whichmore » the sample is moved continuously, so that the experiment resembles one of integrating the diffraction patterns from multiple probe positions. This allows one to use multiple probe mode reconstruction methods to obtain an image of the object and also of the illumination function. We show in simulations, and in x-ray imaging experiments, some of the characteristics of fly-scan ptychography, including a factor of 25 reduction in the data acquisition time. This approach will become increasingly important as brighter x-ray sources are developed, such as diffraction limited storage rings.« less

Continuous motion scan ptychography: characterization for increased speed in coherent x-ray imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng, Junjing; Nashed, Youssef S. G.; Chen, Si

2015-01-01

Ptychography is a coherent diffraction imaging (CDI) method for extended objects in which diffraction patterns are acquired sequentially from overlapping coherent illumination spots. The object's complex transmission function can be reconstructed from those diffraction patterns at a spatial resolution limited only by the scattering strength of the object and the detector geometry. Most experiments to date have positioned the illumination spots on the sample using a move-settle-measure sequence in which the move and settle steps can take longer to complete than the measure step. We describe here the use of a continuous "fly-scan" mode for ptychographic data collection in whichmore » the sample is moved continuously, so that the experiment resembles one of integrating the diffraction patterns from multiple probe positions. This allows one to use multiple probe mode reconstruction methods to obtain an image of the object and also of the illumination function. We show in simulations, and in x-ray imaging experiments, some of the characteristics of fly-scan ptychography, including a factor of 25 reduction in the data acquisition time. This approach will become increasingly important as brighter x-ray sources are developed, such as diffraction limited storage rings.« less

Continuous motion scan ptychography: characterization for increased speed in coherent x-ray imaging.

PubMed

Deng, Junjing; Nashed, Youssef S G; Chen, Si; Phillips, Nicholas W; Peterka, Tom; Ross, Rob; Vogt, Stefan; Jacobsen, Chris; Vine, David J

2015-03-09

Ptychography is a coherent diffraction imaging (CDI) method for extended objects in which diffraction patterns are acquired sequentially from overlapping coherent illumination spots. The object's complex transmission function can be reconstructed from those diffraction patterns at a spatial resolution limited only by the scattering strength of the object and the detector geometry. Most experiments to date have positioned the illumination spots on the sample using a move-settle-measure sequence in which the move and settle steps can take longer to complete than the measure step. We describe here the use of a continuous "fly-scan" mode for ptychographic data collection in which the sample is moved continuously, so that the experiment resembles one of integrating the diffraction patterns from multiple probe positions. This allows one to use multiple probe mode reconstruction methods to obtain an image of the object and also of the illumination function. We show in simulations, and in x-ray imaging experiments, some of the characteristics of fly-scan ptychography, including a factor of 25 reduction in the data acquisition time. This approach will become increasingly important as brighter x-ray sources are developed, such as diffraction limited storage rings.

X-ray coherent diffraction imaging of cellulose fibrils in situ.

PubMed

Lal, Jyotsana; Harder, Ross; Makowski, Lee

2011-01-01

Cellulose is the most abundant renewable source of organic molecules on earth[1]. As fossil fuel reserves become depleted, the use of cellulose as a feed stock for fuels and chemicals is being aggressively explored. Cellulose is a linear polymer of glucose that packs tightly into crystalline fibrils that make up a substantial proportion of plant cell walls. Extraction of the cellulose chains from these fibrils in a chemically benign process has proven to be a substantial challenge [2]. Monitoring the deconstruction of the fibrils in response to physical and chemical treatments would expedite the development of efficient processing methods. As a step towards achieving that goal, we here describe Bragg-coherent diffraction imaging (CDI) as an approach to producing images of cellulose fibrils in situ within vascular bundles from maize.

Ultra-broadband ptychography with self-consistent coherence estimation from a high harmonic source

NASA Astrophysics Data System (ADS)

Odstrčil, M.; Baksh, P.; Kim, H.; Boden, S. A.; Brocklesby, W. S.; Frey, J. G.

2015-09-01

With the aim of improving imaging using table-top extreme ultraviolet sources, we demonstrate coherent diffraction imaging (CDI) with relative bandwidth of 20%. The coherence properties of the illumination probe are identified using the same imaging setup. The presented methods allows for the use of fewer monochromating optics, obtaining higher flux at the sample and thus reach higher resolution or shorter exposure time. This is important in the case of ptychography when a large number of diffraction patterns need to be collected. Our microscopy setup was tested on a reconstruction of an extended sample to show the quality of the reconstruction. We show that high harmonic generation based EUV tabletop microscope can provide reconstruction of samples with a large field of view and high resolution without additional prior knowledge about the sample or illumination.

Invited Article: Coherent imaging using seeded free-electron laser pulses with variable polarization: First results and research opportunities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Capotondi, F.; Pedersoli, E.; Mahne, N.

2013-05-15

FERMI-Elettra, the first vacuum ultraviolet and soft X-ray free-electron laser (FEL) using by default a 'seeded' scheme, became operational in 2011 and has been opened to users since December 2012. The parameters of the seeded FERMI FEL pulses and, in particular, the superior control of emitted radiation in terms of spectral purity and stability meet the stringent requirements for single-shot and resonant coherent diffraction imaging (CDI) experiments. The advantages of the intense seeded FERMI pulses with variable polarization have been demonstrated with the first experiments performed using the multipurpose experimental station operated at the diffraction and projection imaging (DiProI) beamline.more » The results reported here were obtained with fixed non-periodic targets during the commissioning period in 2012 using 20-32 nm wavelength range. They demonstrate that the performance of the FERMI FEL source and the experimental station meets the requirements of CDI, holography, and resonant magnetic scattering in both multi- and single-shot modes. Moreover, we present the first magnetic scattering experiments employing the fully circularly polarized FERMI pulses. The ongoing developments aim at pushing the lateral resolution by using shorter wavelengths provided by double-stage cascaded FERMI FEL-2 and probing ultrafast dynamic processes using different pump-probe schemes, including jitter-free seed laser pump or FEL-pump/FEL-probe with two color FEL pulses generated by the same electron bunch.« less

Ptychographic imaging with partially coherent plasma EUV sources

NASA Astrophysics Data System (ADS)

Bußmann, Jan; Odstrčil, Michal; Teramoto, Yusuke; Juschkin, Larissa

2017-12-01

We report on high-resolution lens-less imaging experiments based on ptychographic scanning coherent diffractive imaging (CDI) method employing compact plasma sources developed for extreme ultraviolet (EUV) lithography applications. Two kinds of discharge sources were used in our experiments: a hollow-cathode-triggered pinch plasma source operated with oxygen and for the first time a laser-assisted discharge EUV source with a liquid tin target. Ptychographic reconstructions of different samples were achieved by applying constraint relaxation to the algorithm. Our ptychography algorithms can handle low spatial coherence and broadband illumination as well as compensate for the residual background due to plasma radiation in the visible spectral range. Image resolution down to 100 nm is demonstrated even for sparse objects, and it is limited presently by the sample structure contrast and the available coherent photon flux. We could extract material properties by the reconstruction of the complex exit-wave field, gaining additional information compared to electron microscopy or CDI with longer-wavelength high harmonic laser sources. Our results show that compact plasma-based EUV light sources of only partial spatial and temporal coherence can be effectively used for lens-less imaging applications. The reported methods may be applied in combination with reflectometry and scatterometry for high-resolution EUV metrology.

Pediatric Central Diabetes Insipidus: Brain Malformations Are Common and Few Patients Have Idiopathic Disease.

PubMed

Werny, David; Elfers, Clinton; Perez, Francisco A; Pihoker, Catherine; Roth, Christian L

2015-08-01

Pediatric cohorts of central diabetes insipidus (CDI) have shown varying prevalences for the different causes of CDI, including idiopathic. The objective of the study was to determine the causes of CDI at a pediatric tertiary care center and to characterize their clinical outcomes. All patients with CDI at Seattle Children's Hospital were identified and retrospectively analyzed. From 2000 to 2013, 147 patients with CDI were encountered (mean age 7 y at diagnosis, mean follow-up 6.2 y). The different causes of CDI were grouped, and age of diagnosis, anterior pituitary hormone deficiencies (APHDs), and presence of the posterior pituitary bright spot (PPBS) were analyzed. Patients with idiopathic CDI had infundibular thickening measured using a systematic method. Brain malformations caused 24% of CDI cases, and 12.2% were idiopathic. Four of 22 patients with initially idiopathic CDI were diagnosed with an underlying condition, none occurring later than 2.5 years from diagnosis. APHDs were as common in the brain malformation group as they were in the tumor/infiltrative group (72% vs 85%; P = .09). The PPBS was present in at least 13% of patients and in 19% of those with brain malformations. Patients with idiopathic CDI and stalk thickening on the initial magnetic resonance imaging were more likely to have an underlying diagnosis (40% vs 0%; P = .03). Brain malformations were a more common cause of pediatric CDI than previously reported. These patients have a high rate of APHDs, and many have persistence of the PPBS. Idiopathic CDI is an uncommon diagnosis, and none of our patients were diagnosed with Langerhans cell histiocytosis or germinoma for more than 3 years from CDI diagnosis. Providers can consider less frequent magnetic resonance imaging after this time point. A systematic method of infundibular measurement on the initial magnetic resonance imaging may predict an underlying germinoma or Langerhans cell histiocytosis.

Emerging opportunities in structural biology with X-ray free-electron lasers

PubMed Central

Schlichting, Ilme; Miao, Jianwei

2012-01-01

X-ray free-electron lasers (X-FELs) produce X-ray pulses with extremely brilliant peak intensity and ultrashort pulse duration. It has been proposed that radiation damage can be “outrun” by using an ultra intense and short X-FEL pulse that passes a biological sample before the onset of significant radiation damage. The concept of “diffraction-before-destruction” has been demonstrated recently at the Linac Coherent Light Source, the first operational hard X-ray FEL, for protein nanocrystals and giant virus particles. The continuous diffraction patterns from single particles allow solving the classical “phase problem” by the oversampling method with iterative algorithms. If enough data are collected from many identical copies of a (biological) particle, its three-dimensional structure can be reconstructed. We review the current status and future prospects of serial femtosecond crystallography (SFX) and single-particle coherent diffraction imaging (CDI) with X-FELs. PMID:22922042

Color Doppler imaging of retinal diseases.

PubMed

Dimitrova, Galina; Kato, Satoshi

2010-01-01

Color Doppler imaging (CDI) is a widely used method for evaluating ocular circulation that has been used in a number of studies on retinal diseases. CDI assesses blood velocity parameters by using ultrasound waves. In ophthalmology, these assessments are mainly performed on the retrobulbar blood vessels: the ophthalmic, the central retinal, and the short posterior ciliary arteries. In this review, we discuss CDI use for the assessment of retinal diseases classified into the following: vascular diseases, degenerations, dystrophies, and detachment. The retinal vascular diseases that have been investigated by CDI include diabetic retinopathy, retinal vein occlusions, retinal artery occlusions, ocular ischemic conditions, and retinopathy of prematurity. Degenerations and dystrophies included in this review are age-related macular degeneration, myopia, and retinitis pigmentosa. CDI has been used for the differential diagnosis of retinal detachment, as well as the evaluation of retrobulbar circulation in this condition. CDI is valuable for research and is a potentially useful diagnostic tool in the clinical setting.

Evaluation of partial coherence correction in X-ray ptychography

DOE PAGES

Burdet, Nicolas; Shi, Xiaowen; Parks, Daniel; ...

2015-02-23

Coherent X-ray Diffraction Imaging (CDI) and X-ray ptychography both heavily rely on the high degree of spatial coherence of the X-ray illumination for sufficient experimental data quality for reconstruction convergence. Nevertheless, the majority of the available synchrotron undulator sources have a limited degree of partial coherence, leading to reduced data quality and a lower speckle contrast in the coherent diffraction patterns. It is still an open question whether experimentalists should compromise the coherence properties of an X-ray source in exchange for a higher flux density at a sample, especially when some materials of scientific interest are relatively weak scatterers. Amore » previous study has suggested that in CDI, the best strategy for the study of strong phase objects is to maintain a high degree of coherence of the illuminating X-rays because of the broadening of solution space resulting from the strong phase structures. In this article, we demonstrate the first systematic analysis of the effectiveness of partial coherence correction in ptychography as a function of the coherence properties, degree of complexity of illumination (degree of phase diversity of the probe) and sample phase complexity. We have also performed analysis of how well ptychographic algorithms refine X-ray probe and complex coherence functions when those variables are unknown at the start of reconstructions, for noise-free simulated data, in the case of both real-valued and highly-complex objects.« less

Noise distribution and denoising of current density images

PubMed Central

Beheshti, Mohammadali; Foomany, Farbod H.; Magtibay, Karl; Jaffray, David A.; Krishnan, Sridhar; Nanthakumar, Kumaraswamy; Umapathy, Karthikeyan

2015-01-01

Abstract. Current density imaging (CDI) is a magnetic resonance (MR) imaging technique that could be used to study current pathways inside the tissue. The current distribution is measured indirectly as phase changes. The inherent noise in the MR imaging technique degrades the accuracy of phase measurements leading to imprecise current variations. The outcome can be affected significantly, especially at a low signal-to-noise ratio (SNR). We have shown the residual noise distribution of the phase to be Gaussian-like and the noise in CDI images approximated as a Gaussian. This finding matches experimental results. We further investigated this finding by performing comparative analysis with denoising techniques, using two CDI datasets with two different currents (20 and 45 mA). We found that the block-matching and three-dimensional (BM3D) technique outperforms other techniques when applied on current density (J). The minimum gain in noise power by BM3D applied to J compared with the next best technique in the analysis was found to be around 2 dB per pixel. We characterize the noise profile in CDI images and provide insights on the performance of different denoising techniques when applied at two different stages of current density reconstruction. PMID:26158100

[Etiological diagnosis of central diabetes insipidus: about 41 cases].

PubMed

Chaker, Fatma; Chihaoui, Melika; Yazidi, Meriem; Slimane, Hedia

2016-01-01

The occurrence of polyuria-polydipsia syndrome with hypotonic urine requires careful diagnostic strategy. This study aims to evaluate diagnostic modalities for central diabetes insipidus. We conducted a retrospective study of 41 cases with central diabetes insipidus (CDI). Data were collected at the Department of Endocrinology, University Hospital La Rabta, Tunis, from 1990 to 2013. We identified the circumstances for detecting CDI, the abnormalities in anterior pituitary assessment and pituitary imaging. CDI occurred in the postoperative period in 20 patients. The average urine 24-hour volume was significantly higher in patients with CDI outside a surgical setting. Water deprivation test was successful in all patients who benefited from it. Outside of neurosurgery, infiltration causes were found in 6 patients and tumor causes were found in 6 patients. CDI was associated with empty sella turcica in 1 case and idiopathic sella turcica in 3 patients. Hypothalamic-pituitary magnetic resonance imaging and anterior pituitary balance sheet are systematic outside pituitary surgery setting and obvious primary polydipsia.

CENTRAL DIABETES INSIPIDUS: CLINICAL CHARACTERISTICS AND LONG-TERM COURSE IN A LARGE COHORT OF ADULTS.

PubMed

Masri-Iraqi, Hiba; Hirsch, Dania; Herzberg, Dana; Lifshitz, Avner; Tsvetov, Gloria; Benbassat, Carlos; Shimon, Ilan

2017-05-01

Central diabetes insipidus (CDI) is a rare heterogeneous condition with various underlying causes. This study sought to increase the still-limited data on the clinical characteristics and long-term course in adults diagnosed with CDI. Data on demographics, presentation, imaging findings, affected pituitary axes, treatment, and complications were collected retrospectively from the files of 70 adult patients with CDI followed at a referral endocrine clinic. Forty women and 30 men were included. Mean age was 46.8 ± 15 years at the time of this study and 29.3 ± 20 years at CDI diagnosis. Twenty-eight patients were diagnosed in childhood. Forty patients (57%) acquired CDI following surgery. Main sellar pathologies were: craniopharyngioma, 17 patients (11 diagnosed in childhood); Langerhans histiocytosis, 10 patients (5 diagnosed in childhood); 7 patients (all diagnosed as adults) had a growth hormone-secreting adenoma; 12 patients (17%; 6 diagnosed in childhood) had idiopathic CDI. At least one anterior pituitary axis was affected in 73% of the cohort: 59% had growth hormone deficiency, 56% hypogonadism, 55% central hypothyroidism, 44% adrenocorticotropic hormone-cortisol deficiency. Patients with postoperative/trauma CDI (n = 44) tended to have multiple anterior pituitary axes deficits compared to the nonsurgical group of patients. All patients were treated with vasopressin preparations, mostly nasal spray. Hyponatremia developed in 32 patients, more in women, and was severe (<125 mEq/L) in 10 patients. Hypernatremia (>150 mEq/L) was noticed in 5 patients. Overall, the calculated complication rate was 22 in 1,250 treatment-years. Most adult patients with CDI have anterior pituitary dysfunction. Stability is usually achieved with long-term treatment. Women were more susceptible to desmopressin complications, albeit with an overall relatively low complication rate. ACTH = adrenocorticotropic hormone CDI = central diabetes insipidus GH = growth hormone MRI = magnetic resonance imaging.

Electric current density imaging of tablet dissolution.

PubMed

Mikac, Ursa; Demsar, Alojz; Sersa, Igor; Demsar, Franci

2002-01-01

The Electric current density imaging technique (CDI) was used to monitor the dissolution of and ion migration from tablets of different acids in agar-agar gel. Conventional MRI cannot monitor these processes, since it can only show changes in the size of the tablet during the dissolving process. CDI traces the dissolved ions thanks to changes in conductivity.

Optical design and simulation of a new coherence beamline at NSLS-II

NASA Astrophysics Data System (ADS)

Williams, Garth J.; Chubar, Oleg; Berman, Lonny; Chu, Yong S.; Robinson, Ian K.

2017-08-01

We will discuss the optical design for a proposed beamline at NSLS-II, a late-third generation storage ring source, designed to exploit the spatial coherence of the X-rays to extract high-resolution spatial information from ordered and disordered materials through Coherent Diffractive Imaging, executed in the Bragg- and forward-scattering geometries. This technique offers a powerful tool to image sub-10 nm spatial features and, within ordered materials, sub-Angstrom mapping of deformation fields. Driven by the opportunity to apply CDI to a wide range of samples, with sizes ranging from sub-micron to tens-of-microns, two optical designs have been proposed and simulated under a wide variety of optical configurations using the software package Synchrotron Radiation Workshop. The designs, their goals, and the results of the simulation, including NSLS-II ring and undulator source parameters, of the beamline performance as a function of its variable optical components is described.

Complex EUV imaging reflectometry: spatially resolved 3D composition determination and dopant profiling with a tabletop 13nm source

NASA Astrophysics Data System (ADS)

Porter, Christina L.; Tanksalvala, Michael; Gerrity, Michael; Miley, Galen P.; Esashi, Yuka; Horiguchi, Naoto; Zhang, Xiaoshi; Bevis, Charles S.; Karl, Robert; Johnsen, Peter; Adams, Daniel E.; Kapteyn, Henry C.; Murnane, Margaret M.

2018-03-01

With increasingly 3D devices becoming the norm, there is a growing need in the semiconductor industry and in materials science for high spatial resolution, non-destructive metrology techniques capable of determining depth-dependent composition information on devices. We present a solution to this problem using ptychographic coherent diffractive imaging (CDI) implemented using a commercially available, tabletop 13 nm source. We present the design, simulations, and preliminary results from our new complex EUV imaging reflectometer, which uses coherent 13 nm light produced by tabletop high harmonic generation. This tool is capable of determining spatially-resolved composition vs. depth profiles for samples by recording ptychographic images at multiple incidence angles. By harnessing phase measurements, we can locally and nondestructively determine quantities such as device and thin film layer thicknesses, surface roughness, interface quality, and dopant concentration profiles. Using this advanced imaging reflectometer, we can quantitatively characterize materials-sciencerelevant and industry-relevant nanostructures for a wide variety of applications, spanning from defect and overlay metrology to the development and optimization of nano-enhanced thermoelectric or spintronic devices.

An economic evaluation of Clostridium difficile infection management in an Italian hospital environment.

PubMed

Magalini, S; Pepe, G; Panunzi, S; Spada, P L; De Gaetano, A; Gui, D

2012-12-01

Clostridium difficile infection (CDI) accounts for the majority of nosocomial cases of diarrhea, and with recent upsurge of multidrug-resistant strains, morbidity and mortality have increased. Data on clinical impact of CDI come mostly from Anglo-Saxon countries, while in Italy only two studies address the issue and no economic data exist on costs of CDI in the in hospital setting. A retrospective cross-sectional study with pharmacoeconomic analysis was performed on the CDI series of the Policlinico Gemelli of Rome, a major 1400 bed Hospital. The clinical charts of 133 patients in a 26 month period were reviewed. All costs of the involved resources were calculated and statistical analysis was carried out with means and standard deviations, and categorical variables as number and percentages. The results show the significant sanitary costs of CDI in an Italian hospital setting. The cost analysis of the various elements (exams, imaging studies, therapies, etc.) shows that none independently influences the high cost burden of CDI, but that it is the simple length of hospital stay that represents the most important factor. Prevention of CDI is the most cost-effective approach. The major break-through in cost reduction of CDI would be a therapeutical intervention or procedure that shortens hospital length of stay.

The value of color Doppler imaging and intralesional steroid injection in pediatric orbital capillary hemangioma.

PubMed

Ke, Yifeng; Hao, Rui; He, Yanjin; Tam, Eric S; Li, Xiaorong

2014-05-01

To evaluate color Doppler imaging (CDI) as the primary imaging modality in the diagnosis of pediatric orbital capillary hemangioma. This is a retrospective study of 36 consecutive cases of orbital capillary hemangiomas between January 2006 and July 2011. Data on demographic details, clinical findings, gray-scale ultrasonography, CDI characteristics, treatment, and follow-up period were reviewed. The mean age of onset was 7 weeks. Twenty-nine (81%) lesions presented as eyelid masses, whereas seven (19%) presented as exophthalmos. Nineteen (53%) tumors were located on the upper eyelid, seven (19%) on the lower eyelid, six (17%) in the medial canthus, and one on both upper and lower eyelids. Ultrasonography depicted a heterogeneous, well-defined, irregular tumor with a low or moderate echogenicity. All lesions presented with abundant color blood flow on CDI. The intralesional blood flow had a mean peak systolic velocity of 37.5 ± 24.5 cm/second, and a mean resistance index of 0.69 ± 0.16, representing a shift in the pulse Doppler toward high velocity and high resistance. After a single intratumoral injection of betamethasone, 18 cases (50%) resolved. Additionally, 15 (42%) and four (11%) cases resolved after two injections and three injections, respectively. Only three (8%) masses persisted after three injections within the follow-up period. The blood flow characteristics of CDI play a vital role in the differentiation of orbital capillary hemangiomas from other orbital lesions. The availability and lack of adverse effects of CDI enable its utilization in the early clinical diagnosis of pediatric orbital capillary hemangioma. Copyright © 2014. Published by Elsevier B.V.

Structural and superionic properties of Ag+-rich ternary phases within the AgI-MI2 systems

NASA Astrophysics Data System (ADS)

Hull, S.; Keen, D. A.; Berastegui, P.

2002-12-01

The effects of temperature on the crystal structure and ionic conductivity of the compounds Ag2CdI4, Ag2ZnI4 and Ag3SnI5 have been investigated by powder diffraction and impedance spectroscopy techniques. varepsilon-Ag2CdI4 adopts a tetragonal crystal structure under ambient conditions and abrupt increases in the ionic conductivity are observed at 407(2), 447(3) and 532(4) K, consistent with the sequence of transitions varepsilon-Ag2CdI 4 rightarrow beta-Ag2CdI 4 + beta-AgI + CdI2 rightarrow alpha-AgI + CdI2 rightarrow alpha-Ag2CdI4. Hexagonal beta-Ag2CdI4 is metastable at ambient temperature. The ambient-temperature beta phase of Ag2ZnI4 is orthorhombic and the structures of beta-Ag2CdI4 and beta-Ag2ZnI4 can, respectively, be considered as ordered derivatives of the wurtzite (beta) and zincblende (gamma) phases of AgI. On heating Ag2ZnI4, there is a 12-fold increase in ionic conductivity at 481(1) K and a further eightfold increase at 542(3) K. These changes result from decomposition of beta-Ag2ZnI4 into alpha-AgI + ZnI2, followed by the appearance of superionic alpha-Ag2ZnI4 at the higher temperature. The hexagonal crystal structure of alpha-Ag2ZnI4 is a dynamically disordered counterpart to the beta modification. Ag3SnI5 is only stable at temperatures in excess of 370(3) K and possesses a relatively high ionic conductivity (sigma approx 0.19Omega-1 cm-1 at 420 K) due to dynamic disorder of the Ag+ and Sn2+ within a cubic close packed I- sublattice. The implications of these findings for the wider issue of high ionic conductivity in AgI-MI2 compounds is discussed, with reference to recently published studies of Ag4PbI6 and Ag2HgI4 and new data for the temperature dependence of the ionic conductivity of the latter compound.

Growth and properties of wide bandgap (MgSe)n(ZnxCd1-xSe)m short-period superlattices

NASA Astrophysics Data System (ADS)

Garcia, Thor A.; Tamargo, Maria C.

2017-12-01

We report the molecular beam epitaxy (MBE) growth and properties of (MgSe)n(ZnxCd1-x Se)m short-period superlattices(SPSLs) for potential application in II-VI devices grown on InP substrates. SPSL structures up to 1 μm thick with effective bandgaps ranging from 2.6 eV to above 3.42 eV are grown and characterized, extending the typical range possible for the ZnxCdyMg1-x-ySe random alloy beyond 3.2 eV. Additionally, ZnxCd1-xSe single and multiple quantum well structures using the SPSL barriers are also grown and investigated. The structures are characterized utilizing reflection high-energy electron diffraction, X-ray reflectance, X-ray diffraction and photoluminescence. We observed layer-by-layer growth and smoother interfaces in the QWs grown with SPSL when compared to the ZnxCdyMg1-x-ySe random alloy. The results indicate that this materials platform is a good candidate to replace the random alloy in wide bandgap device applications.

Infrared laser transillumination CT imaging system using parallel fiber arrays and optical switches for finger joint imaging

NASA Astrophysics Data System (ADS)

Sasaki, Yoshiaki; Emori, Ryota; Inage, Hiroki; Goto, Masaki; Takahashi, Ryo; Yuasa, Tetsuya; Taniguchi, Hiroshi; Devaraj, Balasigamani; Akatsuka, Takao

2004-05-01

The heterodyne detection technique, on which the coherent detection imaging (CDI) method founds, can discriminate and select very weak, highly directional forward scattered, and coherence retaining photons that emerge from scattering media in spite of their complex and highly scattering nature. That property enables us to reconstruct tomographic images using the same reconstruction technique as that of X-Ray CT, i.e., the filtered backprojection method. Our group had so far developed a transillumination laser CT imaging method based on the CDI method in the visible and near-infrared regions and reconstruction from projections, and reported a variety of tomographic images both in vitro and in vivo of biological objects to demonstrate the effectiveness to biomedical use. Since the previous system was not optimized, it took several hours to obtain a single image. For a practical use, we developed a prototype CDI-based imaging system using parallel fiber array and optical switches to reduce the measurement time significantly. Here, we describe a prototype transillumination laser CT imaging system using fiber-optic based on optical heterodyne detection for early diagnosis of rheumatoid arthritis (RA), by demonstrating the tomographic imaging of acrylic phantom as well as the fundamental imaging properties. We expect that further refinements of the fiber-optic-based laser CT imaging system could lead to a novel and practical diagnostic tool for rheumatoid arthritis and other joint- and bone-related diseases in human finger.

Management of diabetes insipidus and adipsia in the child.

PubMed

Di Iorgi, Natascia; Morana, Giovanni; Napoli, Flavia; Allegri, Anna Elsa Maria; Rossi, Andrea; Maghnie, Mohamad

2015-06-01

Central diabetes insipidus (CDI) is a complex and heterogeneous clinical syndrome affecting the hypothalamic-neurohypophyseal network and water balance. A recent national surveillance in Denmark showed a prevalence rate of twenty-three CDI patients per 100,000 inhabitants in five years. The differential diagnosis between several presenting conditions with polyuria and polydipsia is puzzling, and the etiological diagnosis of CDI remains a challenge before the identification of an underlying cause. For clinical practice, a timely diagnosis for initiating specific treatment in order to avoid central nervous system damage, additional pituitary defects and the risk of dissemination of germ cell tumor is advisable. Proper etiological diagnosis can be achieved via a series of steps that start with careful clinical observation of several signs and endocrine symptoms and then progress to more sophisticated imaging tools. This review summarizes the best practice and approach for the diagnosis and treatment of patients with CDI. Copyright © 2015 Elsevier Ltd. All rights reserved.

An image is worth a thousand words: why nouns tend to dominate verbs in early word learning.

PubMed

McDonough, Colleen; Song, Lulu; Hirsh-Pasek, Kathy; Golinkoff, Roberta Michnick; Lannon, Robert

2011-03-01

Nouns are generally easier to learn than verbs (e.g., Bornstein, 2005; Bornstein et al., 2004; Gentner, 1982; Maguire, Hirsh-Pasek, & Golinkoff, 2006). Yet, verbs appear in children's earliest vocabularies, creating a seeming paradox. This paper examines one hypothesis about the difference between noun and verb acquisition. Perhaps the advantage nouns have is not a function of grammatical form class but rather related to a word's imageability. Here, word imageability ratings and form class (nouns and verbs) were correlated with age of acquisition according to the MacArthur-Bates Communicative Development Inventory (CDI) (Fenson et al., 1994). CDI age of acquisition was negatively correlated with words' imageability ratings. Further, a word's imageability contributes to the variance of the word's age of acquisition above and beyond form class, suggesting that at the beginning of word learning, imageability might be a driving factor.

Evaluation of Correlation between Pretest Probability for Clostridium difficile Infection and Clostridium difficile Enzyme Immunoassay Results

PubMed Central

Reske, Kimberly A.; Hink, Tiffany; Dubberke, Erik R.

2016-01-01

ABSTRACT The objective of this study was to evaluate the clinical characteristics and outcomes of hospitalized patients tested for Clostridium difficile and determine the correlation between pretest probability for C. difficile infection (CDI) and assay results. Patients with testing ordered for C. difficile were enrolled and assigned a high, medium, or low pretest probability of CDI based on clinical evaluation, laboratory, and imaging results. Stool was tested for C. difficile by toxin enzyme immunoassay (EIA) and toxigenic culture (TC). Chi-square analyses and the log rank test were utilized. Among the 111 patients enrolled, stool samples from nine were TC positive and four were EIA positive. Sixty-one (55%) patients had clinically significant diarrhea, 19 (17%) patients did not, and clinically significant diarrhea could not be determined for 31 (28%) patients. Seventy-two (65%) patients were assessed as having a low pretest probability of having CDI, 34 (31%) as having a medium probability, and 5 (5%) as having a high probability. None of the patients with low pretest probabilities had a positive EIA, but four were TC positive. None of the seven patients with a positive TC but a negative index EIA developed CDI within 30 days after the index test or died within 90 days after the index toxin EIA date. Pretest probability for CDI should be considered prior to ordering C. difficile testing and must be taken into account when interpreting test results. CDI is a clinical diagnosis supported by laboratory data, and the detection of toxigenic C. difficile in stool does not necessarily confirm the diagnosis of CDI. PMID:27927930

Deformation twinning of a silver nanocrystal under high pressure. Supplementary materials

DOE PAGES

Huang, X. J.; Yang, W. G.; Harder, R.; ...

2015-10-20

Within a high-pressure environment, crystal deformation is controlled by complex processes such as dislocation motion, twinning, and phase transitions, which change materials’ microscopic morphology and alter their properties. Likewise, understanding a crystal’s response to external stress provides a unique opportunity for rational tailoring of its functionalities. It is very challenging to track the strain evolution and physical deformation from a single nanoscale crystal under high-pressure stress. Here, we report an in situ three-dimensional mapping of morphology and strain evolutions in a single-crystal silver nanocube within a high-pressure environment using the Bragg Coherent Diffractive Imaging (CDI) method. We also observed amore » continuous lattice distortion, followed by a deformation twining process at a constant pressure. The ability to visualize stress-introduced deformation of nanocrystals with high spatial resolution and prominent strain sensitivity provides an important route for interpreting and engineering novel properties of nanomaterials.« less

Evaluation of Correlation between Pretest Probability for Clostridium difficile Infection and Clostridium difficile Enzyme Immunoassay Results.

PubMed

Kwon, Jennie H; Reske, Kimberly A; Hink, Tiffany; Burnham, C A; Dubberke, Erik R

2017-02-01

The objective of this study was to evaluate the clinical characteristics and outcomes of hospitalized patients tested for Clostridium difficile and determine the correlation between pretest probability for C. difficile infection (CDI) and assay results. Patients with testing ordered for C. difficile were enrolled and assigned a high, medium, or low pretest probability of CDI based on clinical evaluation, laboratory, and imaging results. Stool was tested for C. difficile by toxin enzyme immunoassay (EIA) and toxigenic culture (TC). Chi-square analyses and the log rank test were utilized. Among the 111 patients enrolled, stool samples from nine were TC positive and four were EIA positive. Sixty-one (55%) patients had clinically significant diarrhea, 19 (17%) patients did not, and clinically significant diarrhea could not be determined for 31 (28%) patients. Seventy-two (65%) patients were assessed as having a low pretest probability of having CDI, 34 (31%) as having a medium probability, and 5 (5%) as having a high probability. None of the patients with low pretest probabilities had a positive EIA, but four were TC positive. None of the seven patients with a positive TC but a negative index EIA developed CDI within 30 days after the index test or died within 90 days after the index toxin EIA date. Pretest probability for CDI should be considered prior to ordering C. difficile testing and must be taken into account when interpreting test results. CDI is a clinical diagnosis supported by laboratory data, and the detection of toxigenic C. difficile in stool does not necessarily confirm the diagnosis of CDI. Copyright © 2017 American Society for Microbiology.

Etiological and clinical characteristics of central diabetes insipidus in children: a single center experience.

PubMed

Hunter, Janel D; Calikoglu, Ali S

2016-01-01

Central diabetes insipidus (CDI) results from a number of conditions affecting the hypothalamic-neurohypophyseal system to cause vasopressin deficiency. Diagnosis of CDI is challenging, and clinical data and guidelines for management are lacking. We aim to characterize clinical and radiological characteristics of a cohort of pediatric patients with CDI. A chart review of 35 patients with CDI followed at North Carolina Children's Hospital from 2000 to 2015 was undertaken. The frequencies of specific etiologies of CDI and characteristic magnetic resonance imaging (MRI) findings were determined. The presence of additional hormone deficiencies at diagnosis and later in the disease course was ascertained. Patient characteristics and management strategies were evaluated. The cohort included 14 female and 21 male patients with a median age of 4.7 years (range, less than 1 month to 16 years) at diagnosis. Median duration of follow-up was 5 years (range, 2 months to 16 years). The cause of CDI was intracranial mass in 13 patients (37.2 %), septo-optic dysplasia in 9 patients (25.7 %), holoprosencephaly in 5 patients (14.2 %), Langerhans cell histiocytosis in 3 patients (8.6 %), isolated pituitary hypoplasia in 2 patients (5.7 %), and encephalocele in 1 patient (2.9 %). Patients were symptomatic for a mean of 6.3 months (range, less than 1 month to 36 months) prior to diagnosis of CDI. Growth hormone (GH), thyrotropin (TSH), adrenocorticotropic hormone (ACTH), and gonadotropin deficiencies were present at diagnosis in 34, 23, 23, and 6 % of patients, respectively. GH, TSH, ACTH, and gonadotropin deficiencies were diagnosed during follow-up in 23, 40, 37, and 14 % of patients, respectively. In patients with structural CNS abnormalities, development of additional hormone deficiencies occurred anywhere from 2 months to 13 years after the time of initial presentation. All patients in our cohort had an underlying organic etiology for CDI, with intracranial masses and CNS malformations being most common. Therefore, MRI of the brain is indicated in all pediatric patients with CDI. Other pituitary hormone deficiencies should be investigated at diagnosis as well as during follow-up.

Evaluation of the Effects of Acupuncture on Blood Flow in Humans with Ultrasound Color Doppler Imaging

PubMed Central

Takayama, Shin; Watanabe, Masashi; Kusuyama, Hiroko; Nagase, Satoru; Seki, Takashi; Nakazawa, Toru; Yaegashi, Nobuo

2012-01-01

Color Doppler imaging (CDI) can be used to noninvasively create images of human blood vessels and quantitatively evaluate blood flow in real-time. The purpose of this study was to assess the effects of acupuncture on the blood flow of the peripheral, mesenteric, and retrobulbar arteries by CDI. Statistical significance was defined as P values less than 0.05. Blood flow in the radial and brachial arteries was significantly lower during needle stimulation on LR3 than before in healthy volunteers, but was significantly higher after needle stimulation than before. LR3 stimulation also resulted in a significant decrease in the vascular resistance of the short posterior ciliary artery and no significant change of blood flow through the superior mesenteric artery (SMA) during acupuncture. In contrast, ST36 stimulation resulted in a significant increase in blood flow through the SMA and no significant change in the vascular resistance of the retrobulbar arteries. Additionally, acupuncture at previously determined acupoints in patients with open-angle glaucoma led to a significant reduction in the vascular resistance of the central retinal artery and short posterior ciliary artery. Our results suggest that acupuncture can affect blood flow of the peripheral, mesenteric, and retrobulbar arteries, and CDI can be useful to evaluate hemodynamic changes by acupuncture. PMID:22778772

The clinical pattern of diabetes Insipidus in a large university hospital in the Middle East.

PubMed

Babiker, Amir M I; Al Jurayyan, Nasir A M; Al Jurayyan, Rushaid N A; Al Gadi, Iman; Drop, Stenvert L S

2015-04-01

Diabetes insipidus is a rare but serious endocrine disorder. Paediatric patients were evaluated for polyuria at King Khalid University Hospital, Riyadh, Saudi Arabia, over a decade (2000-13). Relevant clinical examination and/or a triad of high serum osmolality, hypernatremia and low urine osmolality due to increased urine output confirmed the diagnosis. Water deprivation test was required in some cases with non-classic presentations. Appropriate brain imaging was performed whenever central diabetes insipidus (CDI) was suspected. Twenty-eight patients, 15 males (53.6%) and 13 females (46.4%), aged 0-17 years (mean: 6 years) were included. The calculated period prevalence was 7 in 10,000. In our cohort, 60.7% (17 of 28 patients) had CDI, 21.4% (6 of 28) were diagnosed with nephrogenic diabetes insipidus (NDI) and 17.9% (5 of 30) had psychogenic polydipsia. CDI was due to variable aetiology. Though CDI was the commonest, NDI was not a rare encounter in our community, possibly because of high consanguineous marriages. © The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Nephrotic syndrome complicated by idiopathic central diabetes insipidus.

PubMed

Konomoto, Takao; Tanaka, Etsuko; Imamura, Hideaki; Orita, Mayuko; Sawada, Hirotake; Nunoi, Hiroyuki

2014-05-01

There is ongoing discussion regarding the mechanisms underlying edema formation in nephrotic syndrome (NS). Many studies published in the last decade reported that primary renal sodium retention was a major factor in edema formation. However, many of the factors influencing edema formation in NS remain unclear, including the role of arginine vasopressin (AVP). We report a 12-year-old boy with steroid-dependent NS complicated by idiopathic central diabetes insipidus (CDI). He did not develop edema during his first relapse of NS after developing CDI, despite having hypoalbuminemia. He had polydipsia, polyuria, low urine osmolality, and a low serum arginine AVP level. His fractional excretion of sodium was only slightly low. Endocrinological testing and magnetic resonance imaging revealed idiopathic CDI. After starting desmopressin therapy, he developed edema when his NS relapsed. This is the first known reported case of NS in a patient with CDI. The findings suggest that appropriate AVP secretion in response to an increase in serum osmolality caused by renal sodium retention is necessary for excess extracellular fluid accumulation in NS. Further investigation is needed to more fully understand the role of AVP in edema formation in NS.

Utilization of Health Services Among Adults With Recurrent Clostridium difficile Infection: A 12-Year Population-Based Study

PubMed Central

Kuntz, Jennifer L.; Baker, Jennifer M.; Kipnis, Patricia; Li, Sherian Xu; Liu, Vincent; Xie, Yang; Marcella, Stephen; Escobar, Gabriel J.

2017-01-01

BACKGROUND Considerable efforts have been dedicated to developing strategies to prevent and treat recurrent Clostridium difficile infection (rCDI); however, evidence of the impact of rCDI on patient healthcare utilization and outcomes is limited. OBJECTIVE To compare healthcare utilization and 1-year mortality among adults who had rCDI, nonrecurrent CDI, or no CDI. METHODS We performed a nested case-control study among adult Kaiser Foundation Health Plan members from September 1, 2001, through December 31, 2013. We identified CDI through the presence of a positive laboratory test result and divided patients into 3 groups: patients with rCDI, defined as CDI in the 14–57 days after initial CDI; patients with nonrecurrent CDI; and patients who never had CDI. We conducted 3 matched comparisons: (1) rCDI vs no CDI; (2) rCDI vs nonrecurrent CDI; (3) nonrecurrent CDI vs no CDI. We followed patients for 1 year and compared healthcare utilization between groups, after matching patients on age, sex, and comorbidity. RESULTS We found that patients with rCDI consistently have substantially higher levels of healthcare utilization in various settings and greater 1-year mortality risk than both patients who had nonrecurrent CDI and patients who never had CDI. CONCLUSIONS Patients who develop an initial CDI are generally characterized by excess underlying, severe illness and utilization. However, patients with rCDI experience even greater adverse consequences of their disease than patients who do not experience rCDI. Our results further support the need for continued emphasis on identifying and using novel approaches to prevent and treat rCDI. PMID:27760583

Utilization of Health Services Among Adults With Recurrent Clostridium difficile Infection: A 12-Year Population-Based Study.

PubMed

Kuntz, Jennifer L; Baker, Jennifer M; Kipnis, Patricia; Li, Sherian Xu; Liu, Vincent; Xie, Yang; Marcella, Stephen; Escobar, Gabriel J

2017-01-01

BACKGROUND Considerable efforts have been dedicated to developing strategies to prevent and treat recurrent Clostridium difficile infection (rCDI); however, evidence of the impact of rCDI on patient healthcare utilization and outcomes is limited. OBJECTIVE To compare healthcare utilization and 1-year mortality among adults who had rCDI, nonrecurrent CDI, or no CDI. METHODS We performed a nested case-control study among adult Kaiser Foundation Health Plan members from September 1, 2001, through December 31, 2013. We identified CDI through the presence of a positive laboratory test result and divided patients into 3 groups: patients with rCDI, defined as CDI in the 14-57 days after initial CDI; patients with nonrecurrent CDI; and patients who never had CDI. We conducted 3 matched comparisons: (1) rCDI vs no CDI; (2) rCDI vs nonrecurrent CDI; (3) nonrecurrent CDI vs no CDI. We followed patients for 1 year and compared healthcare utilization between groups, after matching patients on age, sex, and comorbidity. RESULTS We found that patients with rCDI consistently have substantially higher levels of healthcare utilization in various settings and greater 1-year mortality risk than both patients who had nonrecurrent CDI and patients who never had CDI. CONCLUSIONS Patients who develop an initial CDI are generally characterized by excess underlying, severe illness and utilization. However, patients with rCDI experience even greater adverse consequences of their disease than patients who do not experience rCDI. Our results further support the need for continued emphasis on identifying and using novel approaches to prevent and treat rCDI. Infect Control Hosp Epidemiol. 2016;1-8.

Delivery of CdiA Nuclease Toxins into Target Cells during Contact-Dependent Growth Inhibition

PubMed Central

Webb, Julia S.; Nikolakakis, Kiel C.; Willett, Julia L. E.; Aoki, Stephanie K.

2013-01-01

Bacterial contact-dependent growth inhibition (CDI) is mediated by the CdiB/CdiA family of two-partner secretion proteins. CDI systems deploy a variety of distinct toxins, which are contained within the polymorphic C-terminal region (CdiA-CT) of CdiA proteins. Several CdiA-CTs are nucleases, suggesting that the toxins are transported into the target cell cytoplasm to interact with their substrates. To analyze CdiA transfer to target bacteria, we used the CDI system of uropathogenic Escherichia coli 536 (UPEC536) as a model. Antibodies recognizing the amino- and carboxyl-termini of CdiAUPEC536 were used to visualize transfer of CdiA from CDIUPEC536+ inhibitor cells to target cells using fluorescence microscopy. The results indicate that the entire CdiAUPEC536 protein is deposited onto the surface of target bacteria. CdiAUPEC536 transfer to bamA101 mutants is reduced, consistent with low expression of the CDI receptor BamA on these cells. Notably, our results indicate that the C-terminal CdiA-CT toxin region of CdiAUPEC536 is translocated into target cells, but the N-terminal region remains at the cell surface based on protease sensitivity. These results suggest that the CdiA-CT toxin domain is cleaved from CdiAUPEC536 prior to translocation. Delivery of a heterologous Dickeya dadantii CdiA-CT toxin, which has DNase activity, was also visualized. Following incubation with CDI+ inhibitor cells targets became anucleate, showing that the D.dadantii CdiA-CT was delivered intracellularly. Together, these results demonstrate that diverse CDI toxins are efficiently translocated across target cell envelopes. PMID:23469034

Carbodiimide for Covalent α-Amylase Immobilization onto Magnetic Nanoparticles

NASA Astrophysics Data System (ADS)

Milani, Zeinab Mortazavi; Jalal, Razieh; Goharshadi, Elaheh K.

Covalent cross-linking of enzymes to magnetite (Fe3O4) nanoparticles (MNPs) is one of the useful enzyme immobilization methods which provides repeated use of the catalyst, facilitates enzyme separation from the reaction mixture, and sometimes improves biocatalysts stability. The aim of this study was to immobilize α-amylase onto MNPs via covalent attachment using carbodiimide (CDI) molecules. MNPs were synthesized by the co-precipitation method. The size and the structure of the particles were characterized by X-ray diffraction and transmission electron microscopy. The effects of different operational conditions of direct α-amylase binding on MNPs in the presence of CDI were investigated by using the shaking method. Fourier transform infrared spectroscopy was used to confirm the success of immobilization. The optimum conditions and catalytic properties of immobilized α-amylase were also evaluated. The efficiency of immobilization and the residual activity of the immobilized α-amylase were dependent on the mass ratio of MNPs: CDI: α-amylase and the immobilization temperature. The optimum pH for the free and immobilized amylase was 6. The free and immobilized α-amylase showed maximum activity at 20∘C and 35∘C, respectively. The immobilized α-amylase was more thermostable than the free one. The retained activity for free α-amylase after 19 storage days was 57.7% whereas it was 100% for the immobilized α-amylase. In repeated batch experiments, the immobilized α-amylase retained a residual activity of 45% after 11 repeated uses. The Km and Vmax values for the immobilized enzyme were larger than those of the free enzyme. The immobilization of α-amylase on MNPs using CDI improves its stability and reusability.

Economic burden of primary compared with recurrent Clostridium difficile infection in hospitalized patients: a prospective cohort study.

PubMed

Shah, D N; Aitken, S L; Barragan, L F; Bozorgui, S; Goddu, S; Navarro, M E; Xie, Y; DuPont, H L; Garey, K W

2016-07-01

Few studies have investigated the additional healthcare costs of recurrent C. difficile infection (CDI). To quantify inpatient treatment costs for CDI and length of stay among hospitalized patients with primary CDI only, compared with CDI patients who experienced recurrent CDI. This was a prospective, observational cohort study of hospitalized adult patients with primary CDI followed for three months to assess for recurrent CDI episodes. Total and CDI-attributable hospital length of stay (LOS) and hospitalization costs were compared among patients who did or did not experience at least one recurrent CDI episode. In all, 540 hospitalized patients aged 62±17 years (42% males) with primary CDI were enrolled, of whom 95 patients (18%) experienced 101 recurrent CDI episodes. CDI-attributable median (interquartile range) LOS and costs (in US$) increased from 7 (4-13) days and $13,168 (7,525-24,456) for patients with primary CDI only versus 15 (8-25) days and $28,218 (15,050-47,030) for patients with recurrent CDI (P<0.0001, each). Total hospital median LOS and costs increased from 11 (6-22) days and $20,693 (11,287-41,386) for patients with primary CDI only versus 24 (11-48) days and $45,148 (20,693-82,772) for patients with recurrent CDI (P<0.0001, each). The median cost of pharmacological treatment while hospitalized was $60 (23-200) for patients with primary CDI only (N=445) and $140 (30-260) for patients with recurrent CDI (P=0.0013). This study demonstrated that patients with CDI experience a significant healthcare economic burden attributed to CDI. Economic costs and healthcare burden increased significantly for patients with recurrent CDI. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Attributable Healthcare Resource Utilization and Costs for Patients With Primary and Recurrent Clostridium difficile Infection in the United States.

PubMed

Zhang, Dongmu; Prabhu, Vimalanand S; Marcella, Stephen W

2018-04-17

The economic burden of Clostridium difficile infection (CDI), the leading cause of nosocomial infectious diarrhea, is not well understood. The objective of this study was to estimate the healthcare resource utilization (HCRU) and costs attributable to primary CDI and recurrent CDI (rCDI). This is a database (MarketScan) study. Patients without CDI were matched 1:1 by propensity score to those with primary CDI but no recurrences to obtain HCRU and costs attributable to primary CDI. Patients with primary CDI but no recurrences were matched 1:1 by propensity score to those with primary CDI plus 1 recurrence in order to obtain HCRU and costs attributable to rCDI. Adjusted estimates for incremental cumulative hospitalized days and healthcare costs over a 6-month follow-up period were obtained by generalized linear models with a Poisson or gamma distribution and a log link. Bootstrapping was used to obtain 95% confidence intervals (CIs). A total of 55504 eligible CDI patients were identified. Approximately 25% of these CDI patients had rCDI. The cumulative hospitalized days attributable to primary CDI and rCDI over the 6-month follow-up period were 5.20 days (95% CI, 5.01-5.39) and 1.95 days (95% CI, 1.48-2.43), respectively. The healthcare costs attributable to primary CDI and rCDI over the 6-month follow-up period were $24205 (95% CI, $23436-$25013) and $10580 (95% CI, $8849-$12446), respectively. The HCRU and costs attributable to primary CDI and rCDI are quite substantial. It is necessary to reduce the burden of CDI, especially rCDI.

Attributable Healthcare Resource Utilization and Costs for Patients With Primary and Recurrent Clostridium difficile Infection in the United States

PubMed Central

Zhang, Dongmu; Prabhu, Vimalanand S; Marcella, Stephen W

2018-01-01

Abstract Background The economic burden of Clostridium difficile infection (CDI), the leading cause of nosocomial infectious diarrhea, is not well understood. The objective of this study was to estimate the healthcare resource utilization (HCRU) and costs attributable to primary CDI and recurrent CDI (rCDI). Methods This is a database (MarketScan) study. Patients without CDI were matched 1:1 by propensity score to those with primary CDI but no recurrences to obtain HCRU and costs attributable to primary CDI. Patients with primary CDI but no recurrences were matched 1:1 by propensity score to those with primary CDI plus 1 recurrence in order to obtain HCRU and costs attributable to rCDI. Adjusted estimates for incremental cumulative hospitalized days and healthcare costs over a 6-month follow-up period were obtained by generalized linear models with a Poisson or gamma distribution and a log link. Bootstrapping was used to obtain 95% confidence intervals (CIs). Results A total of 55504 eligible CDI patients were identified. Approximately 25% of these CDI patients had rCDI. The cumulative hospitalized days attributable to primary CDI and rCDI over the 6-month follow-up period were 5.20 days (95% CI, 5.01–5.39) and 1.95 days (95% CI, 1.48–2.43), respectively. The healthcare costs attributable to primary CDI and rCDI over the 6-month follow-up period were $24205 (95% CI, $23436–$25013) and $10580 (95% CI, $8849–$12446), respectively. Conclusions The HCRU and costs attributable to primary CDI and rCDI are quite substantial. It is necessary to reduce the burden of CDI, especially rCDI. PMID:29360950

A study of tablet dissolution by magnetic resonance electric current density imaging.

PubMed

Mikac, Ursa; Demsar, Alojz; Demsar, Franci; Sersa, Igor

2007-03-01

The electric current density imaging technique (CDI) was used to monitor the dissolution of ion releasing tablets (made of various carboxylic acids and of sodium chloride) by following conductivity changes in an agar-agar gel surrounding the tablet. Conductivity changes in the sample were used to calculate spatial and temporal changes of ionic concentrations in the sample. The experimental data for ion migration were compared to a mathematical model based on a solution of the diffusion equation with moving boundary conditions for the tablet geometry. Diffusion constants for different acids were determined by fitting the model to the experimental data. The experiments with dissolving tablets were used to demonstrate the potential of the CDI technique for measurement of ion concentration in the vicinity of ion releasing samples.

Assessment of Data Fusion Algorithms for Earth Observation Change Detection Processes.

PubMed

Molina, Iñigo; Martinez, Estibaliz; Morillo, Carmen; Velasco, Jesus; Jara, Alvaro

2016-09-30

In this work a parametric multi-sensor Bayesian data fusion approach and a Support Vector Machine (SVM) are used for a Change Detection problem. For this purpose two sets of SPOT5-PAN images have been used, which are in turn used for Change Detection Indices (CDIs) calculation. For minimizing radiometric differences, a methodology based on zonal "invariant features" is suggested. The choice of one or the other CDI for a change detection process is a subjective task as each CDI is probably more or less sensitive to certain types of changes. Likewise, this idea might be employed to create and improve a "change map", which can be accomplished by means of the CDI's informational content. For this purpose, information metrics such as the Shannon Entropy and "Specific Information" have been used to weight the changes and no-changes categories contained in a certain CDI and thus introduced in the Bayesian information fusion algorithm. Furthermore, the parameters of the probability density functions (pdf's) that best fit the involved categories have also been estimated. Conversely, these considerations are not necessary for mapping procedures based on the discriminant functions of a SVM. This work has confirmed the capabilities of probabilistic information fusion procedure under these circumstances.

Trends in Clostridium difficile infection and risk factors for hospital acquisition of Clostridium difficile among children with cancer.

PubMed

de Blank, Peter; Zaoutis, Theoklis; Fisher, Brian; Troxel, Andrea; Kim, Jason; Aplenc, Richard

2013-09-01

To study the trend of Clostridium difficile infection (CDI) and risk factors for hospital acquired CDI (HA-CDI) among children with cancer. We analyzed 33 095 first pediatric hospitalizations for malignancy among 43 pediatric hospitals between 1999 and 2011. The effect of demographics, disease characteristics, and weekly drug exposure (antibiotics, antacids, and chemotherapy) on HA-CDI was assessed with multivariate Cox regression. CDI was defined by the combination of International Classification of Diseases, 9th edition-Clinical Modification (ICD-9CM), CDI diagnostic assay billing code, and concurrent administration of a CDI-active antibiotic. HA-CDI was defined as CDI with assay occurring after the sixth hospital day. A total of 1736 admissions with CDI were identified, of which 380 were HA-CDI. CDI incidence increased from 1999-2006 (P = .01); however, CDI testing frequency and disease decreased from 2006-2010 (P < .05). Admissions with HA-CDI had longer lengths of stay compared with those without HA-CDI (35 days vs 12 days, P < .01) and greater risk of inpatient mortality (relative risk 2.3, P < .01). Increased risk of HA-CDI (hazard ratio [95% CI]) was seen after exposure to the following drugs: aminoglycoside (1.357 [1.053-1.749]), third generation cephalosporin (1.518 [1.177-1.959]), cefepime (2.383 [1.839-3.089]), and proton pump inhibiting agent (1.398 [1.096-1.784]) in the prior week, and chemotherapy (1.942 [1.491-2.529]) in the 8-14 days prior to HA-CDI onset. Histamine-2 receptor antagonist exposure in the prior week was associated with decreased risk of HA-CDI (0.730 [0.584-0.912]). Despite an apparent decrease in CDI incidence from 2006-2010, HA-CDI remains prevalent and morbid among children with cancer. Recent exposure to chemotherapy, proton pump inhibitor, and certain antibiotics were independent risk factors for HA-CDI. Copyright © 2013 Mosby, Inc. All rights reserved.

How to: Surveillance of Clostridium difficile infections.

PubMed

Krutova, M; Kinross, P; Barbut, F; Hajdu, A; Wilcox, M H; Kuijper, E J

2018-05-01

The increasing incidence of Clostridium difficile infections (CDI) in healthcare settings in Europe since 2003 has affected both patients and healthcare systems. The implementation of effective CDI surveillance is key to enable monitoring of the occurrence and spread of C. difficile in healthcare and the timely detection of outbreaks. The aim of this review is to provide a summary of key components of effective CDI surveillance and to provide some practical recommendations. We also summarize the recent and current national CDI surveillance activities, to illustrate strengths and weaknesses of CDI surveillance in Europe. For the definition of key components of CDI surveillance, we consulted the current European Society of Clinical Microbiology and Infectious Diseases (ESCMID) CDI-related guidance documents and the European Centre for Disease Prevention and Control (ECDC) protocol for CDI surveillance in acute care hospitals. To summarize the recent and current national CDI surveillance activities, we discussed international multicentre CDI surveillance studies performed in 2005-13. In 2017, we also performed a new survey of existing CDI surveillance systems in 33 European countries. Key components for CDI surveillance are appropriate case definitions of CDI, standardized CDI diagnostics, agreement on CDI case origin definition, and the presentation of CDI rates with well-defined numerators and denominators. Incorporation of microbiological data is required to provide information on prevailing PCR ribotypes and antimicrobial susceptibility to first-line CDI treatment drugs. In 2017, 20 European countries had a national CDI surveillance system and 21 countries participated in ECDC-coordinated CDI surveillance. Since 2014, the number of centres with capacity for C. difficile typing has increased to 35 reference or central laboratories in 26 European countries. Incidence rates of CDI, obtained from a standardized CDI surveillance system, can be used as an important quality indicator of healthcare at hospital as well as country level. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

The rise of Clostridium difficile infection in lung transplant recipients in the modern era.

PubMed

Lee, Janet T; Hertz, Marshall I; Dunitz, Jordan M; Kelly, Rosemary F; D'Cunha, Jonathan; Whitson, Bryan A; Shumway, Sara J

2013-01-01

Clostridium difficile infection (CDI) rates have been rising in recent years. We aimed to characterize CDI in lung transplant recipients in the modern era and hypothesized that CDI would increase the mortality risk. We performed a retrospective chart review of patients undergoing transplantation at our center from 1/2006 to 7/2011. Attributes of CDI+ and CDI- groups were compared using Student's t- and chi-square tests (α = 0.05). Multivariate Cox proportional hazard models were used to control for confounding factors. Overall CDI incidence was 22.5%. Seven of 151 patients (4.6%) developed CDI during the initial hospitalization after transplantation (mean time 10.6 ± 6 d) while 27 patients (19.7%) developed CDI after discharge (mean time 467 ± 471 d). Incidence rate was 224.6 cases/100 000 patient-days compared to 110 cases/100 000 patient-days (rate for entire hospital). CDI was not predictive of mortality (HR 2.06, 95% CI 0.94-4.52). CDI rates in lung transplant recipients are high in the modern era. No risk factors for CDI were identified. Although not statistically significant, CDI+ patients had a higher risk of death. The economic burden of CDI and trend toward worse outcomes for CDI patients have important implications for post-operative surveillance of CDI-related complications and need for CDI prophylaxis. © 2013 John Wiley & Sons A/S.

Economic Burden of Clostridium difficile Infection in European Countries.

PubMed

Reigadas Ramírez, Elena; Bouza, Emilio Santiago

2018-01-01

Clostridium difficile infection (CDI) remains a considerable challenge to health care systems worldwide. Although CDI represents a significant burden on healthcare systems in Europe, few studies have attempted to estimate the consumption of resources associated with CDI in Europe. The reported extra costs attributable to CDI vary widely according to the definitions, design, and methodologies used, making comparisons difficult to perform. In this chapter, the economic burden of healthcare facility-associated CDI in Europe will be assessed, as will other less explored areas such as the economic burden of recurrent CDI, community-acquired CDI, pediatric CDI, and CDI in outbreaks.

Clinical characteristics of central diabetes insipidus in Taiwanese children.

PubMed

Liu, Shih-Yao; Tung, Yi-Ching; Lee, Cheng-Ting; Liu, Hon-Man; Peng, Shinn-Forng; Wu, Mu-Zon; Kuo, Meng-Fai; Tsai, Wen-Yu

2013-10-01

Data on the clinical features of children with central diabetes insipidus (CDI) are lacking in Taiwan. This study investigated the clinical manifestations and etiology of CDI in Taiwanese children. From 1983 to 2012, 62 children with permanent diabetes insipidus were enrolled in the study. They were diagnosed at the Department of Pediatrics of National Taiwan University Hospital. Their medical records were thoroughly reviewed and their clinical symptoms and signs, laboratory data, and etiologies were analyzed. The patients' median age at diagnosis was 10 years and the median interval between initial manifestations and diagnosis was 0.5 years. The most common symptoms and signs were polyuria, polydipsia, nocturia, and growth retardation. Most patients had low urine osmolality and elevated plasma osmolality on diagnosis. Absence of a posterior pituitary hyperintense signal and thickening of the pituitary stalk were common findings on magnetic resonance imaging. Approximately 80% of the patients had anterior pituitary hormone deficiency and all patients had growth hormone deficiency. Approximately 60% of patients had intracranial lesions, the most common causes of which were germ cell tumor and Langerhans cell histiocytosis. Two patients were initially believed to have idiopathic CDI but intracranial lesions were detected during the follow-up period. Because a delayed diagnosis of CDI is common in Taiwanese children, a high index of suspicion is important. The underlying etiology of CDI in children may not initially be obvious. Long-term surveillance is therefore necessary, especially for the early detection of evolving treatable intracranial lesions. Copyright © 2013. Published by Elsevier B.V.

Risk factors for Clostridium difficile infections - an overview of the evidence base and challenges in data synthesis.

PubMed

Eze, Paul; Balsells, Evelyn; Kyaw, Moe H; Nair, Harish

2017-06-01

Recognition of a broad spectrum of disease and development of Clostridium difficile infection (CDI) and recurrent CDI (rCDI) in populations previously considered to be at low risk has renewed attention on differences in the risk profile of patients. In the absence of primary prevention for CDI and limited treatment options, it is important to achieve a deep understanding of the multiple factors that influence the risk of developing CDI and rCDI. We conducted a review of systematic reviews and meta-analyses on risk factors for CDI and rCDI published between 1990 and October 2016. 22 systematic reviews assessing risk factors for CDI (n = 19) and rCDI (n = 6) were included. Meta-analyses were conducted in 17 of the systematic reviews. Over 40 risk factors have been associated with CDI and rCDI and can be classified into three categories: pharmacological risk factors, host-related risk factors, and clinical characteristics or interventions. Most systematic reviews and meta-analyses have focused on antibiotic use (n = 8 for CDI, 3 for rCDI), proton pump inhibitors (n = 8 for CDI, 4 for rCDI), and histamine 2 receptor antagonists (n = 4 for CDI) and chronic kidney disease (n = 4 for rCDI). However, other risk factors have been assessed. We discuss the state of the evidence, methods, and challenges for data synthesis. Several studies, synthesized in different systematic review, provide valuable insights into the role of different risk factors for CDI. Meta-analytic evidence of association has been reported for factors such as antibiotics, gastric acid suppressants, non-selective NSAID, and some co-morbidities. However, despite statistical significance, issues of high heterogeneity, bias and confounding remain to be addressed effectively to improve overall risk estimates. Large, prospective primary studies on risk factors for CDI with standardised case definitions and stratified analyses are required to develop more accurate and robust estimates of risk effects that can inform targeted-CDI clinical management procedures, prevention, and research.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Kemin; Johnson, Parker M.; Stols, Lucy

Contact-dependent growth inhibition (CDI) is an important mechanism of intercellular competition between neighboring Gram-negative bacteria. CDI systems encode large surface-exposed CdiA effector proteins that carry a variety of C-terminal toxin domains (CdiA-CTs). All CDI +bacteria also produce CdiI immunity proteins that specifically bind to the cognate CdiA-CT and neutralize its toxin activity to prevent auto-inhibition. Here, the X-ray crystal structure of a CdiI immunity protein fromNeisseria meningitidisMC58 is presented at 1.45 Å resolution. The CdiI protein has structural homology to the Whirly family of RNA-binding proteins, but appears to lack the characteristic nucleic acid-binding motif of this family. Sequence homologymore » suggests that the cognate CdiA-CT is related to the eukaryotic EndoU family of RNA-processing enzymes. A homology model is presented of the CdiA-CT based on the structure of the XendoU nuclease fromXenopus laevis. Molecular-docking simulations predict that the CdiA-CT toxin active site is occluded upon binding to the CdiI immunity protein. Together, these observations suggest that the immunity protein neutralizes toxin activity by preventing access to RNA substrates.« less

The CDI toxin of Yersinia kristensenii is a novel bacterial member of the RNase A superfamily

DOE Office of Scientific and Technical Information (OSTI.GOV)

Batot, Gaëlle; Michalska, Karolina; Ekberg, Greg

Contact-dependent growth inhibition (CDI) is an important mechanism of inter-bacterial competition found in many Gram-negative pathogens. CDI+ cells express cell-surface CdiA proteins that bind neighboring bacteria and deliver C-terminal toxin domains (CdiA-CT) to inhibit target-cell growth. CDI+ bacteria also produce CdiI immunity proteins, which specifically neutralize cognate CdiA-CT toxins to prevent self-inhibition. Here, we present the crystal structure of the CdiA-CT/CdiI(Ykris) complex from Yersinia kris-tensenii ATCC 33638. CdiA-CTYkris adopts the same fold as angiogenin and other RNase A paralogs, but the toxin does not share sequence similarity with these nucleases and lacks the characteristic disulfide bonds of the superfamily. Consistentmore » with the structural homology, CdiA-CTYkris has potent RNase activity in vitro and in vivo. Structure-guided mutagenesis reveals that His175, Arg186, Thr276 and Tyr278 contribute to CdiA-CTYkris activity, suggesting that these residues participate in substrate binding and/or catalysis. CdiI(Ykris) binds directly over the putative active site and likely neutralizes toxicity by blocking access to RNA substrates. Significantly, CdiA-CTYkris is the first non-vertebrate protein found to possess the RNase A superfamily fold, and homologs of this toxin are associated with secretion systems in many Gram-negative and Gram-positive bacteria. These observations suggest that RNase Alike toxins are commonly deployed in inter-bacterial competition.« less

Hospital Clostridium difficile infection (CDI) incidence as a risk factor for hospital-associated CDI

PubMed Central

Miller, Aaron C.; Polgreen, Linnea A.; Cavanaugh, Joseph E.; Polgreen, Philip M.

2016-01-01

Background Environmental risk factors for Clostridium difficile infections (CDIs) have been described at the room or unit level but not the hospital level. To understand the environmental risk factors for CDI, we investigated the association between institutional- and individual-level CDI. Methods We performed a retrospective cohort study using the Healthcare Cost and Utilization Project state inpatient databases for California (2005–2011). For each patient’s hospital stay, we calculated the hospital CDI incidence rate corresponding to the patient’s quarter of discharge, while excluding each patient’s own CDI status. Adjusting for patient and hospital characteristics, we ran a pooled logistic regression to determine individual CDI risk attributable to the hospital’s CDI rate. Results There were 10,329,988 patients (26,086 cases and 10,303,902 noncases) who were analyzed. We found that a percentage point increase in the CDI incidence rate a patient encountered increased the odds of CDI by a factor of 1.182. Conclusions As a point of comparison, a 1-percentage point increase in the CDI incidence rate that the patient encountered had roughly the same impact on their odds of acquiring CDI as a 55.8-day increase in their length of stay or a 60-year increase in age. Patients treated in hospitals with a higher CDI rate are more likely to acquire CDI. PMID:26944007

National Surveillance of Central Diabetes Insipidus (CDI) in Denmark: results from 5 years registration of 9309 prescriptions of desmopressin to 1285 CDI patients.

PubMed

Juul, K V; Schroeder, M; Rittig, S; Nørgaard, J P

2014-06-01

Epidemiological data for central diabetes insipidus (CDI) are sparse. The purpose of this study was to provide accurate epidemiological data on CDI on a national level. This was a drug utilization and patient registry study during a 5-year period from 2007 to 2011. We used the Danish National Prescription Registry data linked with the Danish National Patient Registry to study the epidemiology of CDI using waiting time distribution and other pharmacoepidemiological methods. A total of 1285 patients with CDI were recorded in the observation period and given 9309 prescriptions for desmopressin in the nasal formulation, orodispersible tablet, or conventional tablet. The period prevalence rate of CDI in Denmark over the 5-year period investigated was 23 CDI patients per 100 000 inhabitants, with a higher prevalence in children and older adults (>80 years of age). The 1-year period prevalence rate of CDI decreased in Denmark over the 5 years from approximately 10 to 7 CDI patients per 100 000 inhabitants. The yearly incidence rate of new cases of CDI was found to be 3 to 4 patients per 100 000. The incidence of (presumable) congenital CDI was found to be 2 infants per 100 000 infants. Half of the patients with CDI prescribed as oral treatment were provided dosing instructions to only administer the drug before bedtime, and one third of the CDI patients either had no specific instructions or were instructed to use the drug as needed. Hospital admissions due to severe hyponatremia occurred in 0.9% of patients over a 5-year period, predominantly in females with an incidence ratio of women to men of 1.8:1. Half of the cases of CDI are acquired later in life. At least half of the patients with CDI are instructed to prevent nocturnal polyuria, but it is not clear whether their CDI remains uncontrolled during the daytime or, alternatively, whether they use desmopressin only as needed. Female patients with CDI had approximately twice the number of hospital admissions due to severe hyponatremia than male patients with CDI.

Cost of hospital management of Clostridium difficile infection in United States-a meta-analysis and modelling study.

PubMed

Zhang, Shanshan; Palazuelos-Munoz, Sarah; Balsells, Evelyn M; Nair, Harish; Chit, Ayman; Kyaw, Moe H

2016-08-25

Clostridium difficile infection (CDI) is the leading cause of infectious nosocomial diarrhoea but the economic costs of CDI on healthcare systems in the US remain uncertain. We conducted a systematic search for published studies investigating the direct medical cost associated with CDI hospital management in the past 10 years (2005-2015) and included 42 studies to the final data analysis to estimate the financial impact of CDI in the US. We also conducted a meta-analysis of all costs using Monte Carlo simulation. The average cost for CDI case management and average CDI-attributable costs per case were $42,316 (90 % CI: $39,886, $44,765) and $21,448 (90 % CI: $21,152, $21,744) in 2015 US dollars. Hospital-onset CDI-attributable cost per case was $34,157 (90 % CI: $33,134, $35,180), which was 1.5 times the cost of community-onset CDI ($20,095 [90 % CI: $4991, $35,204]). The average and incremental length of stay (LOS) for CDI inpatient treatment were 11.1 (90 % CI: 8.7-13.6) and 9.7 (90 % CI: 9.6-9.8) days respectively. Total annual CDI-attributable cost in the US is estimated US$6.3 (Range: $1.9-$7.0) billion. Total annual CDI hospital management required nearly 2.4 million days of inpatient stay. This review indicates that CDI places a significant financial burden on the US healthcare system. This review adds strong evidence to aid policy-making on adequate resource allocation to CDI prevention and treatment in the US. Future studies should focus on recurrent CDI, CDI in long-term care facilities and persons with comorbidities and indirect cost from a societal perspective. Health-economic studies for CDI preventive intervention are needed.

Healthcare resource utilization for recurrent Clostridium difficile infection in a large university hospital in Houston, Texas.

PubMed

Aitken, Samuel L; Joseph, Tiby B; Shah, Dhara N; Lasco, Todd M; Palmer, Hannah R; DuPont, Herbert L; Xie, Yang; Garey, Kevin W

2014-01-01

There are limited data examining healthcare resource utilization in patients with recurrent Clostridium difficile infection (CDI). Patients with CDI at a tertiary-care hospital in Houston, TX, were prospectively enrolled into an observational cohort study. Recurrence was assessed via follow-up phone calls. Patients with one or more recurrence were included in this study. The location at which healthcare was obtained by patients with recurrent CDI was identified along with hospital length of stay. CDI-attributable readmissions, defined as a positive toxin test within 48 hours of admission and a primary CDI diagnosis, were also assessed. 372 primary cases of CDI were identified of whom 64 (17.2%) experienced at least one CDI recurrence. Twelve of 64 patients experienced 18 further episodes of CDI recurrence. Of these 64 patients, 33 (50.8%) patients with recurrent CDI were readmitted of which 6 (18.2%) required ICU care, 29 (45.3%) had outpatient care only, and 2 (3.1%) had an ED visit. Nineteen (55.9%) readmissions were defined as CDI-attributable. For patients with CDI-attributable readmission, the average length of stay was 6 ± 6 days. Recurrent CDI leads to significant healthcare resource utilization. Methods of reducing the burden of recurrent CDI should be further studied.

Impact of recurrent Clostridium difficile infection: hospitalization and patient quality of life.

PubMed

Wilcox, Mark H; Ahir, Harblas; Coia, John E; Dodgson, Andrew; Hopkins, Susan; Llewelyn, Martin J; Settle, Chris; Mclain-Smith, Susan; Marcella, Stephen W

2017-09-01

Data quantifying outcomes of recurrent Clostridium difficile infection (rCDI) are lacking. We sought to determine the UK hospital resource use and health-related quality of life (HRQoL) associated with rCDI hospitalizations. A non-interventional study in six UK acute hospitals collected retrospective clinical and resource use data from medical records of 64 adults hospitalized for rCDI and 64 matched inpatient controls with a first episode only (f)CDI. Patients were observed from the index event (date rCDI/fCDI confirmed) for 28 days (or death, if sooner); UK-specific reference costs were applied. HRQoL was assessed prospectively in a separate cohort of 30 patients hospitalized with CDI, who completed the EQ-5D-3L questionnaire during their illness. The median total management cost (post-index) was £7539 and £6294 for rCDI and fCDI, respectively (cost difference, P = 0.075); median length of stay was 21 days and 15.5 days, respectively (P = 0.269). The median cost difference between matched rCDI and fCDI cases was £689 (IQR=£1873-£3954). Subgroup analysis demonstrated the highest median costs (£8542/patient) in severe rCDI cases. CDI management costs were driven primarily by hospital length of stay, which accounted for >85% of costs in both groups. Mean EQ-5D index values were 46% lower in CDI patients compared with UK population values (0.42 and 0.78, respectively); EQ visual analogue scale scores were 38% lower (47.82 and 77.3, respectively). CDI has considerable impact on patients and healthcare resources. This multicentre study provides a contemporaneous estimate of the real-world UK costs associated with rCDI management, which are substantial and comparable to fCDI costs. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Surgical biopsies in patients with central diabetes insipidus and thickened pituitary stalks.

PubMed

Jian, Fangfang; Bian, Liuguan; Sun, Shouyue; Yang, Jun; Chen, Xiao; Chen, Yufan; Ma, Qinyun; Miao, Fei; Wang, Weiqing; Ning, Guang; Sun, Qingfang

2014-09-01

Thickened pituitary stalks (TPSs) on magnetic resonance imaging (MRI) result from diverse pathologies; therefore, it is essential to make specific diagnoses for clinical decision-making. The diagnoses and indications for surgical biopsies in patients with central diabetes insipidus (CDI) and TPSs are thoroughly discussed in this paper. Thirty-seven patients with CDI and TPSs were retrospectively reviewed. The mean age at the diagnosis of CDI was 29.0 ± 15.9 years (range 8.0-63.3), and the median duration of follow-up was 5.5 ± 2.8 years (range 0.7-13.0). Anterior pituitary hormone deficiencies were documented in 26 (70.3 %) patients. All patients had a TPS on MRI at the diagnosis of CDI, and 21 (56.8 %) patients exhibited radiological changes during the follow-up. Of these 21 patients, 11 exhibited increases in the thickness of the stalk, and two patients exhibited reversals of the TPSs. Involvements of the hypothalamus, pituitary gland, basal ganglia or supersellar, and pineal gland were found in four, three, one, and 1 patient, respectively. Ultimately, clear diagnoses were established in 17 patients who underwent biopsies, nine of whom had germinomas, six of whom had Langerhans cell histiocytosis, one of whom had a granular cell tumor, and one of whom had Erdheim-Chester disease. Patients with CDI and TPSs should submit to periodic clinic follow-ups with serial MRI assessments to establish anterior pituitary deficiencies and to detect radiological progressions that are appropriate for surgical biopsies. Endoscopic-assisted microsurgery via the supraorbital keyhole approach is a good choice for the biopsy of pituitary stalk lesions.

Outcomes associated with Clostridium difficile infection in patients with chronic liver disease.

PubMed

Dotson, Kierra M; Aitken, Samuel L; Sofjan, Amelia K; Shah, Dhara N; Aparasu, Rajender R; Garey, Kevin W

2018-05-09

Patients with chronic liver disease (CLD) have frequent exposure to Clostridium difficile infection (CDI) risk factors but the incidence and aetiology of CDI on this population is poorly understood. The aim of this study was to assess the incidence, disease presentation and outcomes of CDI in patients with underlying CLD. The Health Care and Utilization Project National Inpatient Sample (HCUP-NIS) 2009 dataset was used to identify patients with CLD who developed CDI along with matched non-CLD patients with CDI. Using the NIS dataset, the incidence rate of CDI was 189.4/10 000 discharges in CLD patients vs. 83.7/10 000 discharges in the non-CLD matched cohort (P < 0.001). Compared with non-CLD, comorbidity-matched controls with CDI, CLD patients with CDI had higher likelihood of in-hospital mortality (8.8% vs. 18.6%, P < 0.001), increased length of stay by 1.19 days (P < 0.001) and increased total costs by $8632 (P < 0.001). In separate analyses using a tertiary case database of hospitalised patients in Houston, Texas (2006-2016) with CLD and CDI (n = 41) compared with patients with CDI but not CLD (n = 111), CLD patients had significantly higher Charlson comorbidity index (P < 0.0001) but similar risk factors for CDI and CDI-related disease presentation compared with non-CLD patients. In conclusion, CDI-related risk factors were almost universally present in the CLD population. CDI resulted in worse outcomes in this population.

Hospital Clostridium difficile infection (CDI) incidence as a risk factor for hospital-associated CDI.

PubMed

Miller, Aaron C; Polgreen, Linnea A; Cavanaugh, Joseph E; Polgreen, Philip M

2016-07-01

Environmental risk factors for Clostridium difficile infections (CDIs) have been described at the room or unit level but not the hospital level. To understand the environmental risk factors for CDI, we investigated the association between institutional- and individual-level CDI. We performed a retrospective cohort study using the Healthcare Cost and Utilization Project state inpatient databases for California (2005-2011). For each patient's hospital stay, we calculated the hospital CDI incidence rate corresponding to the patient's quarter of discharge, while excluding each patient's own CDI status. Adjusting for patient and hospital characteristics, we ran a pooled logistic regression to determine individual CDI risk attributable to the hospital's CDI rate. There were 10,329,988 patients (26,086 cases and 10,303,902 noncases) who were analyzed. We found that a percentage point increase in the CDI incidence rate a patient encountered increased the odds of CDI by a factor of 1.182. As a point of comparison, a 1-percentage point increase in the CDI incidence rate that the patient encountered had roughly the same impact on their odds of acquiring CDI as a 55.8-day increase in their length of stay or a 60-year increase in age. Patients treated in hospitals with a higher CDI rate are more likely to acquire CDI. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

A prospective cohort study on hospital mortality due to Clostridium difficile infection.

PubMed

Wenisch, J M; Schmid, D; Tucek, G; Kuo, H-W; Allerberger, F; Michl, V; Tesik, P; Laferl, H; Wenisch, C

2012-10-01

Although an increase in burden of disease has frequently been reported for Clostridium difficile infection (CDI), specific data on the effect of CDI on a patient's risk of death or overall hospital mortality are scarce. Therefore, we performed a prospective cohort study to analyse the effect of CDI on the risk of pre-discharge all-cause death in all inpatients with CDI compared to all inpatients without CDI during 2009 in a single hospital. Clostridium difficile infection was defined as by the European Society of Clinical Microbiology and Infectious Diseases. Data were collected from the medical charts of CDI patients and from the hospital discharge data of non-CDI and CDI patients. The effect measures of CDI used to compute the risk of pre-discharge all-cause death were risk ratio, attributable risk, mortality fraction (%) and population attributable risk percentage. Co-morbidity was categorized using the Charlson co-morbidity score in which a value of ≤2 was defined as low co-morbidity and that of >2 as moderate/severe co-morbidity. A stratified analysis and a Poisson regression model were applied to adjust for the effects of the risk factors sex, age and severity of co-morbidity. A total of 185 hospitalized patients with CDI were compared to 38,644 other hospitalized patients without CDI admitted between 1 January 2009 and 31 December 2009. The mean age of the CDI and non-CDI patients was 74.3 (range 72.3-76.4) and 51.9 (range 51.6-52.1) years, respectively. Of the 185 CDI, 136 (73.5%) and 49 (26.5%) were categorized with low and high co-morbidity, respectively, versus 32,107 (83.4%) and 6,352 (16.5%), respectively, in non-CDI patients. Overall, 24 of the 185 CDI patients (13%) versus 1,021 of the 38,459 non-CDI patients (2.7%) died during their hospital stay, resulting in a relative risk of pre-discharge death of 4.89 [95% confidence interval (CI) 3.35-7.13] for CDI patients, a CDI attributable risk of death of 10.3 per 100 patients and a CDI attributable fraction of 79.5 % (95% CI 70.1-86 %). After adjustment for age, sex and co-morbidity the relative risk of pre-discharge death was 2.74 (95% CI 1.82-4.10; p < 0.0001) for patients with CDI, and the proportion of hospital deaths due to CDI was 1.72 (95% CI 1.22-2.05). The results of this study lead to the conclusion that hospitalized patients with CDI are--independent of age, sex and co-morbidity severity--2.74-fold more likely to die during their hospital stay than all other hospitalized patients. The eradication of CDI in the hospital could have prevented 1.72% of in-hospital deaths in our study population during the 1 year of the study.

Factors associated with Clostridium difficile infection: A nested case-control study in a three year prospective cohort.

PubMed

Khanafer, Nagham; Vanhems, Philippe; Barbut, Frédéric; Luxemburger, Christine

2017-04-01

Clostridium difficile infection (CDI) is a serious medical condition that is associated with substantial morbidity and mortality. Identification of risk factors associated with CDI and prompt recognition of patients at risk is key to successfully preventing CDI. A 3-year prospective, observational, cohort study was conducted in a French university hospital and a nested case-control study was performed to identify risk factors for CDI. Inpatients aged 18 years or older, suffering from diarrhea suspected to be related to CDI, were asked to participate. A total of 945 patients were included, of which 233 cases had a confirmed CDI. CDI infection was more common in men (58.4%) (P = 0.04) compared with patients with diarrhea not related to C. difficile. Previous hospitalization (P < 0.001), prior treatment with antibiotics (P = 0.001) or antiperistaltics (P = 0.002), liver disease (P = 0.003), malnutrition (P < 0.001), and previous CDI (P < 0.001) were significantly more common in patients with CDI. Multivariate logistic regression analysis showed that exposure to antibiotics in the last 60 days (especially third generation cephalosporins and penicillins with β-lactamase inhibitor), chronic renal or liver disease, malnutrition or previous CDI, were associated with an independent high risk of CDI. Age was not related with CDI. This study showed that antibiotics and some comorbid conditions were predictors of CDI. Patients at high risk of acquiring CDI at the time of admission may benefit from careful monitoring of antibiotic prescriptions and early attention to infection control issues. In future, these "high-risk" patients may benefit from novel agents being developed to prevent CDI. Copyright © 2017 Elsevier Ltd. All rights reserved.

The burden of clostridium difficile infection: estimates of the incidence of CDI from U.S. Administrative databases.

PubMed

Olsen, Margaret A; Young-Xu, Yinong; Stwalley, Dustin; Kelly, Ciarán P; Gerding, Dale N; Saeed, Mohammed J; Mahé, Cedric; Dubberke, Erik R

2016-04-22

Many administrative data sources are available to study the epidemiology of infectious diseases, including Clostridium difficile infection (CDI), but few publications have compared CDI event rates across databases using similar methodology. We used comparable methods with multiple administrative databases to compare the incidence of CDI in older and younger persons in the United States. We performed a retrospective study using three longitudinal data sources (Medicare, OptumInsight LabRx, and Healthcare Cost and Utilization Project State Inpatient Database (SID)), and two hospital encounter-level data sources (Nationwide Inpatient Sample (NIS) and Premier Perspective database) to identify CDI in adults aged 18 and older with calculation of CDI incidence rates/100,000 person-years of observation (pyo) and CDI categorization (onset and association). The incidence of CDI ranged from 66/100,000 in persons under 65 years (LabRx), 383/100,000 in elderly persons (SID), and 677/100,000 in elderly persons (Medicare). Ninety percent of CDI episodes in the LabRx population were characterized as community-onset compared to 41 % in the Medicare population. The majority of CDI episodes in the Medicare and LabRx databases were identified based on only a CDI diagnosis, whereas almost ¾ of encounters coded for CDI in the Premier hospital data were confirmed with a positive test result plus treatment with metronidazole or oral vancomycin. Using only the Medicare inpatient data to calculate encounter-level CDI events resulted in 553 CDI events/100,000 persons, virtually the same as the encounter proportion calculated using the NIS (544/100,000 persons). We found that the incidence of CDI was 35 % higher in the Medicare data and fewer episodes were attributed to hospital acquisition when all medical claims were used to identify CDI, compared to only inpatient data lacking information on diagnosis and treatment in the outpatient setting. The incidence of CDI was 10-fold lower and the proportion of community-onset CDI was much higher in the privately insured younger LabRx population compared to the elderly Medicare population. The methods we developed to identify incident CDI can be used by other investigators to study the incidence of other infectious diseases and adverse events using large generalizable administrative datasets.

Economic healthcare costs of Clostridium difficile infection: a systematic review.

PubMed

Ghantoji, S S; Sail, K; Lairson, D R; DuPont, H L; Garey, K W

2010-04-01

Clostridium difficile infection (CDI) is the leading cause of infectious diarrhoea in hospitalised patients. CDI increases patient healthcare costs due to extended hospitalisation, re-hospitalisation, laboratory tests and medications. However, the economic costs of CDI on healthcare systems remain uncertain. The purpose of this study was to perform a systematic review to summarise available studies aimed at defining the economic healthcare costs of CDI. We conducted a literature search for peer-reviewed studies that investigated costs associated with CDI (1980 to present). Thirteen studies met inclusion and exclusion criteria. CDI costs in 2008 US dollars were calculated using the consumer price index. The total and incremental costs for primary and recurrent CDI were estimated. Of the 13, 10 were from the USA and one each from Canada, UK, and Ireland. In US-based studies incremental cost estimates ranged from $2,871 to $4,846 per case for primary CDI and from $13,655 to $18,067 per case for recurrent CDI. US-based studies in special populations (subjects with irritable bowel disease, surgical inpatients, and patients treated in the intensive care unit) showed an incremental cost range from $6,242 to $90,664. Non-US-based studies showed an estimated incremental cost of $5,243 to $8,570 per case for primary CDI and $13,655 per case for recurrent CDI. Economic healthcare costs of CDI were high for primary and recurrent cases. The high cost associated with CDI justifies the use of additional resources for CDI prevention and control. Copyright (c) 2009 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.

High Rate of Alternative Diagnoses in Patients Referred for Presumed Clostridium difficile Infection

PubMed Central

Jackson, Melissa; Olefson, Sidney; Machan, Jason T.; Kelly, Colleen R.

2015-01-01

Goals We evaluated a cohort of patients referred to our center for presumed recurrent Clostridium difficile infection (CDI) to determine final diagnoses and outcomes. Background As rates of CDI have increased, more patients are diagnosed with recurrent CDI and other sequelae of the infection. Distinguishing symptomatic patients with CDI from those who are colonized with an alternative etiology of diarrheal symptoms may be challenging. Methods We performed a retrospective review of 117 patients referred to our center for recurrent CDI between January 2013 and June 2014. Data collected included demographics, referring provider, previous anti-CDI treatment, and significant medical conditions. Additionally we gathered data on atypical features of CDI and investigations obtained to investigate etiology of symptoms. Outcomes included rates of alternative diagnoses and the accuracy of CDI diagnosis by referral source. Results The mean age was 61 years and 70% were female. 29 patients (25%) were determined to have a non-CDI diagnosis. Most common alternative diagnoses included irritable bowel syndrome (18 patients: 62%) and inflammatory bowel disease (3:10 %). Age was inversely correlated with rate of non-CDI diagnosis (p=0.016). Of the remaining 88 (75%) patients with a confirmed diagnosis of CDI, 25 (28%) received medical therapy alone and 63 (72%) underwent fecal microbiota transplantation (FMT). Conclusion Among patients referred to our center for recurrent CDI, a considerable percentage did not have CDI, but rather an alternative diagnosis, most commonly IBS. The rate of alternative diagnosis correlated inversely with age. Providers should consider other etiologies of diarrhea in patients presenting with features atypical of recurrent CDI. PMID:26565971

Burden of Clostridium difficile-associated disease among patients residing in nursing homes: a population-based cohort study.

PubMed

Yu, Holly; Baser, Onur; Wang, Li

2016-11-25

Clostridium difficile (C. difficile) infection (CDI) is the leading cause of nosocomial diarrhea in the United States. This study aimed to examine the incidence of CDI and evaluate mortality and economic burden of CDI in an elderly population who reside in nursing homes (NHs). This was a population-based retrospective cohort study focusing on US NHs by linking Medicare 5% sample, Medicaid, Minimum Data Set (MDS) (2008-10). NH residents aged ≥65 years with continuous enrollment in Medicare and/or Medicaid Fee-for-Service plan for ≥12 months and ≥2 quarterly MDS assessments were eligible for the study. The incidence rate was calculated as the number of CDI episodes by 100,000 person-years. A 1:4 propensity score matched sample of cohorts with and without CDI was generated to assess mortality and health care costs following the first CDI. Among 32,807 NH residents, 941 residents had ≥1 episode of CDI in 2009, with an incidence of 3359.9 per 100,000 person-years. About 30% CDI episodes occurred in the hospital setting. NH residents with CDI (vs without CDI) were more likely to have congestive heart failure, renal disease, cerebrovascular disease, hospitalizations, and outpatient antibiotic use. During the follow-up period, the 30-day (14.7% vs 4.3%, P < 0.001), 60-day (22.7% vs 7.5%, P < 0.001), 6-month (36.3% vs 18.3%, P < 0.001), and 1-year mortality rates (48.2% vs 31.1%, P < 0.001) were significantly higher among the CDI residents vs non-CDI residents. Total health care costs within 2 months following the first CDI episode were also significantly higher for CDI residents ($28,621 vs $13,644, P < 0.001). CDI presents a serious public health issue in NHs. Mortality, health care utilization, and associated costs were significant following incident CDI episodes.

Burden of Clostridium difficile on the healthcare system.

PubMed

Dubberke, Erik R; Olsen, Margaret A

2012-08-01

There are few high-quality studies of the costs of Clostridium difficile infection (CDI), and the majority of studies focus on the costs of CDI in acute-care facilities. Analysis of the best available data, from 2008, indicates that CDI may have resulted in $4.8 billion in excess costs in US acute-care facilities. Other areas of CDI-attributable excess costs that need to be investigated are costs of increased discharges to long-term care facilities, of CDI with onset in long-term care facilities, of recurrent CDI, and of additional adverse events caused by CDI.

European Practice for CDI Treatment.

PubMed

Fitzpatrick, Fidelma; Skally, Mairead; Brady, Melissa; Burns, Karen; Rooney, Christopher; Wilcox, Mark H

2018-01-01

Clostridium difficile infection (CDI) remains a significant cause of morbidity and mortality worldwide. Historically, two antibiotics (metronidazole and vancomycin) and a recent third (fidaxomicin) have been used routinely for CDI treatment; convincing data are now available showing that metronidazole is the least efficacious agent. The European Society of Clinical Microbiology and Infectious Diseases CDI treatment guidelines outline the treatment options for a variety of CDI clinical scenarios, including use of the more traditional anti-CDI therapies (e.g., metronidazole, vancomycin), the role of newer anti-CDI agents (e.g., fidaxomicin), indications for surgical intervention and for non-antimicrobial management (e.g., faecal microbiota transplantation, FMT). A 2017 survey of 20 European countries found that while the majority (n = 14) have national CDI guidelines that provide a variety of recommendations for CDI treatment, only five have audited guideline implementation. A variety of restrictions are in place in 13 (65%) countries prior to use of new anti-CDI treatments, including committee/infection specialist approval or economic review/restrictions. Novel anti-CDI agents are being evaluated in Phase III trials; it is not yet clear what will be the roles of these agents. Prophylaxis is an optimum approach to reduce the impact of CDI especially in high-risk populations; monoclonal antibodies, antibiotic blocking approaches and multiple vaccines are currently in advanced clinical trials. The treatment of recurrent CDI is particularly troublesome, and several different live bio therapeutics are being developed, in addition to FMT.

Emergence of community-acquired Clostridium difficile infection: the experience of a French hospital and review of the literature.

PubMed

Ogielska, Maja; Lanotte, Philippe; Le Brun, Cécile; Valentin, Anne Sophie; Garot, Denis; Tellier, Anne-Charlotte; Halimi, Jean Michel; Colombat, Philippe; Guilleminault, Laurent; Lioger, Bertrand; Vegas, Hélène; De Toffol, Bertrand; Constans, Thierry; Bernard, Louis

2015-08-01

Clostridium difficile infection (CDI) is a common cause of nosocomial diarrhoea. People in the general community are not usually considered to be at risk of CDI. CDI is associated with a high risk of morbidity and mortality. The risk of severity is defined by the Clostridium Severity Index (CSI). The cases of 136 adult patients with CDI treated at the University Hospital of Tours, France between 2008 and 2012 are described. This was a retrospective study. Among the 136 patients included, 62 were men and 74 were women. Their median age was 64.4 years (range 18-97 years). Twenty-six of the 136 (19%) cases were community-acquired (CA) and 110 (81%) were healthcare-acquired (HCA). The major risk factors for both groups were long-term treatment with proton pump inhibitors (54% of CA, 53% of HCA patients) and antibiotic treatment within the 2.5 months preceding the CDI (50% of CA, 91% of HCA). The CSI was higher in the CA-CDI group (1.56) than in the HCA-CDI group (1.39). Intensive care was required for 8% of CA-CDI and 16.5% of HCA-CDI patients. CDI can cause community-acquired diarrhoea, and CA-CDI may be more severe than HCA-CDI. Prospective studies of CDI involving people from the general community without risk factors are required to confirm this observation. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Attributable Cost of Clostridium difficile Infection in Pediatric Patients.

PubMed

Mehrotra, Preeti; Jang, Jisun; Gidengil, Courtney; Sandora, Thomas J

2017-12-01

OBJECTIVES The attributable cost of Clostridium difficile infection (CDI) in children is unknown. We sought to determine a national estimate of attributable cost and length of stay (LOS) of CDI occurring during hospitalization in children. DESIGN AND METHODS We analyzed discharge records of patients between 2 and 18 years of age from the Agency for Healthcare Research and Quality (AHRQ) Kids' Inpatient Database. We created a logistic regression model to predict CDI during hospitalization based on demographic and clinical characteristics. Predicted probabilities from the logistic regression model were then used as propensity scores to match 1:2 CDI to non-CDI cases. Charges were converted to costs and compared between patients with CDI and propensity-score-matched controls. In a sensitivity analysis, we adjusted for LOS as a confounder by including it in both the propensity score and a generalized linear model predicting cost. RESULTS We identified 8,527 pediatric hospitalizations (0.53%) with a diagnosis of CDI and 1,597,513 discharges without CDI. In our matched cohorts, the attributable cost of CDI occurring during a hospitalization ranged from $1,917 to $8,317, depending on whether model was adjusted for LOS. When not adjusting for LOS, CDI-associated hospitalizations cost 1.6 times more than non-CDI associated hospitalizations. Attributable LOS of CDI was approximately 4 days. CONCLUSIONS Clostridium difficile infection in hospitalized children is associated with an economic burden similar to adult estimates. This finding supports a continued focus on preventing CDI in children as a priority. Pediatric CDI cost analyses should account for LOS as an important confounder of cost. Infect Control Hosp Epidemiol 2017;38:1472-1477.

Clostridium difficile infection in patients hospitalized with type 2 diabetes mellitus and its impact on morbidity, mortality, and the costs of inpatient care.

PubMed

Olanipekun, Titilope O; Salemi, Jason L; Mejia de Grubb, Maria C; Gonzalez, Sandra J; Zoorob, Roger J

2016-06-01

Type 2 diabetes mellitus (T2DM) is often complicated by infections leading to hospitalization, increased morbidity, and mortality. Not much is known about the impact of Clostridium difficile infection (CDI) on health outcomes in hospitalized patients with T2DM. We estimated the prevalence and temporal trends of CDI; evaluated the associations between CDI and in-hospital mortality, length of stay (LOS), and the costs of inpatient care; and compared the impact of CDI with that of other infections commonly seen in patients with T2DM. We conducted a cross-sectional analysis using data from the Nationwide Inpatient Sample among patients ⩾18years with T2DM and generalized linear regression was used to analyze associations and jointpoint regression for trends. The prevalence of CDI was 6.8 per 1000 hospital discharges. Patients with T2DM and CDI had increased odds of in-hospital mortality (OR, 3.63; 95% CI 3.16, 4.17). The adjusted mean LOS was higher in patients with CDI than without CDI (11.9 vs. 4.7days). That translated to average hospital costs of $23,000 and $9100 for patients with and without CDI, respectively. The adjusted risk of mortality in patients who had CDI alone (OR 3.75; 95% CI 3.18, 4.41) was similar to patients who had CDI in addition to other common infections (OR 3.25; 95% CI 2.58, 4.10). CDI is independently associated with poorer health outcomes in patients with T2DM. We recommend close surveillance for CDI in hospitalized patients and further studies to determine the cost effectiveness of screening for CDI among patients with T2DM. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Contact-dependent growth inhibition toxins exploit multiple independent cell-entry pathways

PubMed Central

Willett, Julia L. E.; Gucinski, Grant C.; Fatherree, Jackson P.; Low, David A.; Hayes, Christopher S.

2015-01-01

Contact-dependent growth inhibition (CDI) systems function to deliver toxins into neighboring bacterial cells. CDI+ bacteria export filamentous CdiA effector proteins, which extend from the inhibitor-cell surface to interact with receptors on neighboring target bacteria. Upon binding its receptor, CdiA delivers a toxin derived from its C-terminal region. CdiA C-terminal (CdiA-CT) sequences are highly variable between bacteria, reflecting the multitude of CDI toxin activities. Here, we show that several CdiA-CT regions are composed of two domains, each with a distinct function during CDI. The C-terminal domain typically possesses toxic nuclease activity, whereas the N-terminal domain appears to control toxin transport into target bacteria. Using genetic approaches, we identified ptsG, metI, rbsC, gltK/gltJ, yciB, and ftsH mutations that confer resistance to specific CdiA-CTs. The resistance mutations all disrupt expression of inner-membrane proteins, suggesting that these proteins are exploited for toxin entry into target cells. Moreover, each mutation only protects against inhibition by a subset of CdiA-CTs that share similar N-terminal domains. We propose that, following delivery of CdiA-CTs into the periplasm, the N-terminal domains bind specific inner-membrane receptors for subsequent translocation into the cytoplasm. In accord with this model, we find that CDI nuclease domains are modular payloads that can be redirected through different import pathways when fused to heterologous N-terminal “translocation domains.” These results highlight the plasticity of CDI toxin delivery and suggest that the underlying translocation mechanisms could be harnessed to deliver other antimicrobial agents into Gram-negative bacteria. PMID:26305955

Clostridium difficile infection in hospitalized patients with inflammatory bowel disease: Prevalence, risk factors, and prognosis.

PubMed

Maharshak, Nitsan; Barzilay, Idan; Zinger, Hasya; Hod, Keren; Dotan, Iris

2018-02-01

To evaluate the frequency, possible risk factors, and outcome of Clostridium difficile infection (CDI) in inflammatory bowel disease (IBD) patients.There has been an upsurge of CDI in patients with IBD who has been associated with increased morbidity and mortality. Various risk factors have been found to predispose IBD patients to CDI.A retrospective case-control study on IBD patients admitted with exacerbation and tested for CDI at the Tel Aviv Medical Center in 2008 to 2013. Epidemiologic, laboratory, and prognostic data were retrieved from electronic files and compared between patients who tested positive (CDI+) or negative (CDI-) for CDI.CDI was identified in 28 of 311 (7.31%) IBD patients hospitalized with diarrhea. IBD-specific risk factors (univariate analysis) for CDI included: use of systemic steroids therapy (odds ratio [OR] = 3.6, 95% confidence interval [CI] 1.2-10.6) and combinations of ≥2 immunomodulator medications (OR = 2.6, 95% CI 1.1-6.3). Additional risk factors for CDI that are common in the general population were hospitalization in the preceding 2 months (OR = 6.0, 95% CI 2.6-14.1), use of antacids (OR = 3.8, 95% CI 1.7-8.4), and high Charlson comorbidity score (OR = 2.5, 95% CI 1.1-5.7). A multivariate analysis confirmed that only hospitalization within the preceding 2 months and use of antacids were significant risk factors for CDI. The prognosis of CDI+ patients was similar to that of CDI- patients.Hospitalized IBD patients with exacerbation treated with antacids or recently hospitalized are at increased risk for CDI and should be tested and empirically treated until confirmation or exclusion of the infection.

Determinants of Clostridium difficile Infection Incidence Across Diverse United States Geographic Locations

PubMed Central

Lessa, Fernanda C.; Mu, Yi; Winston, Lisa G.; Dumyati, Ghinwa K.; Farley, Monica M.; Beldavs, Zintars G.; Kast, Kelly; Holzbauer, Stacy M.; Meek, James I.; Cohen, Jessica; McDonald, L. Clifford; Fridkin, Scott K.

2014-01-01

Background  Clostridium difficile infection (CDI) is no longer restricted to hospital settings, and population-based incidence measures are needed. Understanding the determinants of CDI incidence will allow for more meaningful comparisons of rates and accurate national estimates. Methods  Data from active population- and laboratory-based CDI surveillance in 7 US states were used to identify CDI cases (ie, residents with positive C difficile stool specimen without a positive test in the prior 8 weeks). Cases were classified as community-associated (CA) if stool was collected as outpatients or ≤3 days of admission and no overnight healthcare facility stay in the past 12 weeks; otherwise, cases were classified as healthcare-associated (HA). Two regression models, one for CA-CDI and another for HA-CDI, were built to evaluate predictors of high CDI incidence. Site-specific incidence was adjusted based on the regression models. Results  Of 10 062 cases identified, 32% were CA. Crude incidence varied by geographic area; CA-CDI ranged from 28.2 to 79.1/100 000 and HA-CDI ranged from 45.7 to 155.9/100 000. Independent predictors of higher CA-CDI incidence were older age, white race, female gender, and nucleic acid amplification test (NAAT) use. For HA-CDI, older age and a greater number of inpatient-days were predictors. After adjusting for relevant predictors, the range of incidence narrowed greatly; CA-CDI rates ranged from 30.7 to 41.3/100 000 and HA-CDI rates ranged from 58.5 to 94.8/100 000. Conclusions  Differences in CDI incidence across geographic areas can be partially explained by differences in NAAT use, age, race, sex, and inpatient-days. Variation in antimicrobial use may contribute to the remaining differences in incidence. PMID:25734120

Determinants of Clostridium difficile Infection Incidence Across Diverse United States Geographic Locations.

PubMed

Lessa, Fernanda C; Mu, Yi; Winston, Lisa G; Dumyati, Ghinwa K; Farley, Monica M; Beldavs, Zintars G; Kast, Kelly; Holzbauer, Stacy M; Meek, James I; Cohen, Jessica; McDonald, L Clifford; Fridkin, Scott K

2014-09-01

Clostridium difficile infection (CDI) is no longer restricted to hospital settings, and population-based incidence measures are needed. Understanding the determinants of CDI incidence will allow for more meaningful comparisons of rates and accurate national estimates. Data from active population- and laboratory-based CDI surveillance in 7 US states were used to identify CDI cases (ie, residents with positive C difficile stool specimen without a positive test in the prior 8 weeks). Cases were classified as community-associated (CA) if stool was collected as outpatients or ≤3 days of admission and no overnight healthcare facility stay in the past 12 weeks; otherwise, cases were classified as healthcare-associated (HA). Two regression models, one for CA-CDI and another for HA-CDI, were built to evaluate predictors of high CDI incidence. Site-specific incidence was adjusted based on the regression models. Of 10 062 cases identified, 32% were CA. Crude incidence varied by geographic area; CA-CDI ranged from 28.2 to 79.1/100 000 and HA-CDI ranged from 45.7 to 155.9/100 000. Independent predictors of higher CA-CDI incidence were older age, white race, female gender, and nucleic acid amplification test (NAAT) use. For HA-CDI, older age and a greater number of inpatient-days were predictors. After adjusting for relevant predictors, the range of incidence narrowed greatly; CA-CDI rates ranged from 30.7 to 41.3/100 000 and HA-CDI rates ranged from 58.5 to 94.8/100 000. Differences in CDI incidence across geographic areas can be partially explained by differences in NAAT use, age, race, sex, and inpatient-days. Variation in antimicrobial use may contribute to the remaining differences in incidence.

Clostridium difficile infection in pediatric acute myeloid leukemia: from the Canadian Infections in Acute Myeloid Leukemia Research Group.

PubMed

Price, Victoria; Portwine, Carol; Zelcer, Shayna; Ethier, Marie-Chantal; Gillmeister, Biljana; Silva, Mariana; Schindera, Christina; Yanofsky, Rochelle; Mitchell, David; Johnston, Donna L; Lewis, Victor; Dix, David; Cellot, Sonia; Michon, Bruno; Bowes, Lynette; Stobart, Kent; Brossard, Josee; Beyene, Joseph; Sung, Lillian

2013-06-01

The prevalence and severity of Clostridium difficile infection (CDI) has increased over time in adult patients, but little is known about CDI in pediatric cancer. The primary objectives were to describe the incidence and characteristics of CDI in children with de novo acute myeloid leukemia (AML). The secondary objective was to describe factors associated with CDI. We performed a multicenter, retrospective cohort study of children with de novo AML and evaluated CDI. Recurrence, sepsis and infection-related death were examined. Factors associated with CDI were also evaluated. Forty-three CDI occurred in 37 of 341 (10.9%) patients during 42 of 1277 (3.3%) courses of chemotherapy. There were 6 children with multiple episodes of CDI. Three infections were associated with sepsis, and no children died of CDI. Only 2 children had an associated enterocolitis. Both days of broad-spectrum antibiotics (odds ratio 1.03, 95% confidence interval: 1.01 to 1.06; P = 0.003) and at least 1 microbiologically documented sterile site infection (odds ratio 10.81, 95% confidence interval: 5.88 to 19.89; P < 0.0001) were independently associated with CDI. CDI occurred in 11% of children receiving intensive chemotherapy for AML, and outcomes were not severe. CDI is not a prominent issue in pediatric AML in terms of prevalence, incidence or associated outcomes.

A Clostridium difficile infection (CDI) stewardship initiative improves adherence to practice guidelines for management of CDI.

PubMed

Jury, Lucy A; Tomas, Myreen; Kundrapu, Sirisha; Sitzlar, Brett; Donskey, Curtis J

2013-11-01

A Clostridium difficile infection (CDI) stewardship initiative reduced inappropriate prescription of empirical CDI therapy and improved timeliness of treatment and adherence to clinical practice guidelines for management of CDI. The initiative required minimal resources and could easily be incorporated into traditional antimicrobial stewardship programs.

Analysis of 43 cases of Langerhans cell histiocytosis (LCH)-induced central diabetes insipidus registered in the JLSG-96 and JLSG-02 studies in Japan.

PubMed

Shioda, Yoko; Adachi, Souichi; Imashuku, Shinsaku; Kudo, Kazuko; Imamura, Toshihiko; Morimoto, Akira

2011-12-01

To determine the ability of recent systemic chemotherapy protocols to reduce the incidence of central diabetes insipidus (CDI) in Langerhans cell histiocytosis (LCH), 43 CDI cases that belonged to a cohort of 348 pediatric patients with multi-focal LCH who were treated with the JLSG-96/-02 protocols were analyzed. The overall incidence of CDI was 12.4%, but in 24 cases CDI was already present at the time LCH was diagnosed. Thus, CDI developed during or after systemic chemotherapy over a follow-up period of 5.0 (0.2-14.7) years in only 19 patients (5.9%), with 7.4% at 5-year cumulative risk by Kaplan-Meier analysis. In two cases, complete resolution of CDI was noted. Anterior pituitary hormone deficiency was detected in 13 cases, while CDI-associated neurodegenerative disease was observed in six cases. The JLSG-96/-02 protocol appears to effectively reduce the occurrence of CDI. However, novel therapeutic measures are required to reverse pre-existing CDI and to prevent CDI-associated neurological complications.

High risk of post-infectious irritable bowel syndrome in patients with Clostridium difficile infection.

PubMed

Wadhwa, A; Al Nahhas, M F; Dierkhising, R A; Patel, R; Kashyap, P; Pardi, D S; Khanna, S; Grover, M

2016-09-01

Infectious enteritis is a commonly identified risk factor for irritable bowel syndrome (IBS). The incidence of Clostridium difficile infection (CDI) is on the rise. However, there is limited information on post-infectious IBS (PI-IBS) development following CDI and the host- and infection-related risk factors are not known. To determine the incidence and risk factors for PI-IBS following CDI. A total of 684 cases of CDI identified from September 2012 to November 2013 were surveyed. Participants completed the Rome III IBS questionnaire and details on the CDI episode. Predictive modelling was done using logistic regression to evaluate risk factors for PI-IBS development. A total of 315 CDI cases responded (46% response rate) and 205 were at-risk (no pre-CDI IBS) for PI-IBS development. A total of 52/205 (25%) met the Rome III criteria for IBS ≥6 months following CDI. IBS-mixed was most common followed by IBS-diarrhoea. In comparison to those without subsequent PI-IBS, greater percentage of PI-IBS patients had CDI symptoms >7 days, nausea, vomiting, abdominal pain during CDI, anxiety and a higher BMI. Using logistic regression, CDI symptoms >7 days [Odds ratio (OR): 2.96, P = 0.01], current anxiety (OR: 1.33, P < 0.0001) and a higher BMI (OR: 1.08, P = 0.004) were independently associated with PI-IBS development; blood in the stool during CDI was protective (OR: 0.44, P = 0.06). In this cohort study, new-onset IBS is common after CDI. Longer CDI duration, current anxiety and higher BMI are associated with the diagnosis of C. difficile PI-IBS. This chronic sequela should be considered during active management and follow-up of patients with CDI. © 2016 John Wiley & Sons Ltd.

Epidemiology of Clostridium difficile infections in Australia: enhanced surveillance to evaluate time trends and severity of illness in Victoria, 2010-2014.

PubMed

Worth, L J; Spelman, T; Bull, A L; Brett, J A; Richards, M J

2016-07-01

With epidemic strains of Clostridium difficile posing a substantial healthcare burden internationally, there is a need for longitudinal evaluation of Clostridium difficile infection (CDI) events in Australia. To evaluate time trends and severity of illness for CDI events in Australian healthcare facilities. All CDI events in patients admitted to Victorian public hospitals between 1(st) October 2010 and 31(st) December 2014 were reported to the Victorian Healthcare Associated Infection Surveillance System. CDI was defined as the isolation of a toxin-producing C. difficile organism in a diarrhoeal specimen, and classified as community-associated (CA-CDI) or healthcare-associated (HA-CDI). Severe disease was defined as admission to an intensive care unit, requirement for surgery and/or death due to infection. Time trends were examined using a mixed-effects Poisson regression model, and the Walter and Edward test of seasonality was applied to evaluate potential cyclical patterns. In total, 6736 CDI events were reported across 89 healthcare facilities. Of these, 4826 (71.6%) were HA-CDI, corresponding to a rate of 2.49/10,000 occupied bed days (OBDs). The incidence of HA-CDI was highest in the fifth quarter of surveillance (3.6/10,000 OBDs), followed by a reduction. Severe disease was reported in 1.66% of events, with the proportion being significantly higher for CA-CDI compared with HA-CDI (2.21 vs 1.45%, P = 0.03). The highest and lowest incidence of HA-CDI occurred in March and October, respectively. A low incidence of HA-CDI was reported in Victoria compared with US/European surveillance reports. Seasonality was evident, together with diminishing HA-CDI rates in 2012-2014. Severe infections were more common in CA-CDI, supporting future enhanced surveillance in community settings. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

CdiA Effectors from Uropathogenic Escherichia coli Use Heterotrimeric Osmoporins as Receptors to Recognize Target Bacteria

PubMed Central

Beck, Christina M.; Willett, Julia L. E.; Kim, Jeff J.; Low, David A.; Hayes, Christopher S.

2016-01-01

Many Gram-negative bacterial pathogens express contact-dependent growth inhibition (CDI) systems that promote cell-cell interaction. CDI+ bacteria express surface CdiA effector proteins, which transfer their C-terminal toxin domains into susceptible target cells upon binding to specific receptors. CDI+ cells also produce immunity proteins that neutralize the toxin domains delivered from neighboring siblings. Here, we show that CdiAEC536 from uropathogenic Escherichia coli 536 (EC536) uses OmpC and OmpF as receptors to recognize target bacteria. E. coli mutants lacking either ompF or ompC are resistant to CDIEC536-mediated growth inhibition, and both porins are required for target-cell adhesion to inhibitors that express CdiAEC536. Experiments with single-chain OmpF fusions indicate that the CdiAEC536 receptor is heterotrimeric OmpC-OmpF. Because the OmpC and OmpF porins are under selective pressure from bacteriophages and host immune systems, their surface-exposed loops vary between E. coli isolates. OmpC polymorphism has a significant impact on CDIEC536 mediated competition, with many E. coli isolates expressing alleles that are not recognized by CdiAEC536. Analyses of recombinant OmpC chimeras suggest that extracellular loops L4 and L5 are important recognition epitopes for CdiAEC536. Loops L4 and L5 also account for much of the sequence variability between E. coli OmpC proteins, raising the possibility that CDI contributes to the selective pressure driving OmpC diversification. We find that the most efficient CdiAEC536 receptors are encoded by isolates that carry the same cdi gene cluster as E. coli 536. Thus, it appears that CdiA effectors often bind preferentially to "self" receptors, thereby promoting interactions between sibling cells. As a consequence, these effector proteins cannot recognize nor suppress the growth of many potential competitors. These findings suggest that self-recognition and kin selection are important functions of CDI. PMID:27723824

Risk Factors, Clinical Characteristics, and Treatment Differences Between Residents With and Without Nursing Home- and Non-Nursing Home-Acquired Clostridium difficile Infection.

PubMed

Zarowitz, Barbara J; Allen, Carrie; O'Shea, Terrence; Strauss, Marcie E

2015-07-01

The incidence of Clostridium difficile infection (CDI) in nursing home residents is believed to be high because of the prevalence of predisposing factors such as decreased immune response, multiple comorbidities, medications, increased risk of infection, close proximity of residents, and recent hospitalization. Yet, specific information on CDI in this population is scarce.  To investigate differences in clinical and demographic characteristics, treatment, and underlying comorbidities in residents who acquired CDI preadmission (non-nursing home-acquired [NNH-Acquired]) compared with those who acquired CDI after admission to a nursing home (nursing home-acquired [NH-Acquired]) and matched controls. We conducted a retrospective case-control study of CDI in nursing home residents with a cross-sectional and longitudinal aspect of linked and de-identified pharmacy claims and Minimum Data Set data (MDS) 2.0 records from October 1, 2009, to September 30, 2010. The control group was frequency matched 1:1 for gender, race, and age range to residents with CDI.  Of 195,498 residents, 5,044 (2.6%) had a diagnosis of CDI. Compared with controls, CDI patients had less severe cognitive impairment (P  less than  0.01) and more severe functional impairment (P  less than  0.01), incontinence (P  less than  0.01), and diarrhea (P  less than  0.01). They were more likely to (a) have diabetes, stroke, heart failure, cancer, renal failure, and infections; (b) be treated with antibiotics, corticosteroids, megestrol, and proton pump inhibitors; and (c) be discharged to the hospital (29.3% vs. 14.7%, P = 0.001) than controls. NNH-Acquired CDI was 3 times more prevalent than NH-Acquired CDI. Most residents with NNH-Acquired CDI (85.0%) came from acute care hospitals and were more likely to have heart disease, cancer, and infections, while those with NH-Acquired CDI tended to have more cognitive impairment, reliance on staff for activities of daily living, incontinence, and stroke. Thirty-day retreatment rates for NH-Acquired CDI and NNH-Acquired CDI with metronidazole were 72.7% and 68.4%, and with vancomycin were 83.9% and 69.3%, respectively. The facility (Medicare Part A) was the payer for 93.6% of NNH-Acquired CDI and 75% of NH-Acquired CDI treatment; Medicare Part D was the prevalent secondary payer for NNH-Aquired CDI (19.4%) and NH-Acquired CDI (37.5%). Residents with CDI had more comorbidities, and the NNH-Acquired group bore a higher burden of illness, resulting in differing treatment patterns and outcomes than the NH-Acquired CDI group.

Bezlotoxumab: anti-toxin B monoclonal antibody to prevent recurrence of Clostridium difficile infection.

PubMed

Villafuerte Gálvez, Javier A; Kelly, Ciarán P

2017-07-01

Clostridium difficile infection (CDI) is the most common nosocomial infection in the U.S. 25% of CDI patients go on to develop recurrent CDI (rCDI) following current standard of care (SOC) therapy, leading to morbidity, mortality and economic loss. The first passive immunotherapy drug targeting C.difficile toxin B (bezlotoxumab) has been approved recently by the FDA and EMA for prevention of rCDI. Areas covered: A body of key studies was selected and reviewed by the authors. The unmet needs in CDI care were ascertained with emphasis in rCDI, including the epidemiology, pathophysiology and current management. The current knowledge about the immune response to C. difficile toxins and how this knowledge led to the development and the clinical use of bezlotoxumab is described. Current and potential future competitors to the drug were examined. Expert commentary: A single 10 mg/kg intravenous infusion of bezlotoxumab has been shown to decrease rCDI by ~40% (absolute reduction ~10%) in patients being treated for primary CDI or rCDI with SOC antibiotics. Targeting C.difficile toxins by passive immunotherapy is a novel mechanism for prevention of C.difficile infection. Bezlotoxumab will be a valuable adjunctive therapy to reduce the burden of CDI.

[Clinical characteristics of central diabetes insipidus: a retrospective analysis of 230 cases].

PubMed

Zhang, J P; Guo, Q H; Mu, Y M; Lyu, Z H; Gu, W J; Yang, G Q; Du, J; Ba, J M; Lu, J M

2018-03-01

Objective: To evaluate the clinical characteristics and etiologies of central diabetes insipidus (CDI). Methods: The clinical data of 230 patients with CDI in the Department of Endocrinology of Chinese PLA General Hospital from 2008 June to 2014 December were collected and analyzed retrospectively. Results: The three most common causes of CDI were idiopathic CDI, lymphocytic hypophysitis and intracranial germ cell tumors. Among all the CDI, the idiopathic CDI accounted for 37.48%. There were significant differences in age onset and gender distribution among the different causes of CDI. The patients with intracranial germ cell tumors [age of onset(19.2±10.2) years] were younger than the other types of CDI. Germ cell tumors patients were more common in male, and lymphocytic hypophysitis patients were more common in female. The most frequent abnormality of anterior pituitary in patients with CDI was growth hormone deficiency, followed by hypogonadism, adrenal insufficiency and hypothyroidism. The dysfunction of thyroid axis and adrenal axis in patients with germ cell tumor was more common than those in patients with idiopathic and lymphocytic hypophysitis. Conclusions: The most common causes of central diabetes insipidus were idiopathic CDI, lymphocytic hypophysitis and intracranial germ cell tumors. There were differences in age of onset, gender distribution and abnormal production of anterior pituitary hormones among all causes of CDI patients.

Fecal Microbiota Transplantation: Expanding Horizons for Clostridium difficile Infections and Beyond.

PubMed

Borody, Thomas J; Peattie, Debra; Mitchell, Scott W

2015-07-06

Fecal Microbiota Transplantation (FMT) methodology has been progressively refined over the past several years. The procedure has an extensive track record of success curing Clostridium difficile infection (CDI) with remarkably few adverse effects. It achieves similar levels of success whether the CDI occurs in the young or elderly, previously normal or profoundly ill patients, or those with CDI in Inflammatory Bowel Disease (IBD). While using FMT to treat CDI, however, we learned that using the procedure in other gastrointestinal (GI) diseases, such as IBD without CDI, generally fails to effect cure. To improve results in treating other non-CDI diseases, innovatively designed Randomized Controlled Trials (RCTs) will be required to address questions about mechanisms operating within particular diseases. Availability of orally deliverable FMT products, such as capsules containing lyophilised fecal microbiota, will simplify CDI treatment and open the door to convenient, prolonged FMT delivery to the GI tract and will likely deliver improved results in both CDI and non-CDI diseases.

Fecal Microbiota Transplantation: Expanding Horizons for Clostridium difficile Infections and Beyond

PubMed Central

Borody, Thomas J.; Peattie, Debra; Mitchell, Scott W.

2015-01-01

Fecal Microbiota Transplantation (FMT) methodology has been progressively refined over the past several years. The procedure has an extensive track record of success curing Clostridium difficile infection (CDI) with remarkably few adverse effects. It achieves similar levels of success whether the CDI occurs in the young or elderly, previously normal or profoundly ill patients, or those with CDI in Inflammatory Bowel Disease (IBD). While using FMT to treat CDI, however, we learned that using the procedure in other gastrointestinal (GI) diseases, such as IBD without CDI, generally fails to effect cure. To improve results in treating other non-CDI diseases, innovatively designed Randomized Controlled Trials (RCTs) will be required to address questions about mechanisms operating within particular diseases. Availability of orally deliverable FMT products, such as capsules containing lyophilised fecal microbiota, will simplify CDI treatment and open the door to convenient, prolonged FMT delivery to the GI tract and will likely deliver improved results in both CDI and non-CDI diseases. PMID:27025624

Color Doppler orbital hemodynamics in healthy individuals and patients with vascular disorders in Taiwan.

PubMed

Kahn, Mon-Te

2008-01-01

The main purpose of this study was to establish a data bank of orbital vasculature hemodynamics as assessed by color Doppler imaging (CDI) for normal Taiwanese. In addition, we compared the hemodynamic variables in subjects with a healthy orbital vasculature and 10 patients with various orbital disorders. From 1994 to 1995, we collected data from 90 age-and gender-matched (43 males, 47 females) healthy individuals, with age stratified by decades (ranging from 4 to 79 years). Ten patients with various orbital lesions were also examined by CDI. Peak systolic velocity (PSV), end diastolic velocity (EDV), mean velocity (MV), pulsatility index (PI), and resistivity index (RI) were obtained for the ophthalmic, central retinal, and posterior ciliary arteries. The MV was also measured in the ophthalmic, central retinal, and vortex veins. The mean and standard deviation of the values were calculated for each decade of age. There was no correlation between the CDI-generated values and gender. Student's t-test showed that the flow velocity in the group below age 10, compared with that of the other groups, is significantly higher (p < 0.05). The CDI values in diseased orbits could be classified as hyper-, iso-, or hypovascular in comparison with healthy orbits. On linear regression, there was a correlation between age and the PSV, EDV, and MV of healthy ophthalmic arteries.

Moderate to high use of opioid analgesics are associated with an increased risk of Clostridium difficile infection.

PubMed

Mora, Andrea L; Salazar, Miguel; Pablo-Caeiro, Juan; Frost, Craig P; Yadav, Yashoo; DuPont, Herbert L; Garey, Kevin W

2012-04-01

Risk factors for Clostridium difficile infection (CDI) include use of broad-spectrum antibiotics, advanced age and lack of an appropriate immune response. Whether antiperistaltics such as opioid analgesics also increase the risk of CDI is uncertain. The purpose of this preliminary study was to determine whether opioid analgesics increase the risk of developing CDI in hospitalized patients receiving broad-spectrum antibiotics. Hospitalized patients were assessed for incidence of CDI in relation to usage of opioid analgesics controlling for other known risk factors for CDI. During the study period, a total of 32,775 patients were identified of whom 192 had CDI. In univariate analysis, incidence of CDI increased significantly with moderate or high usage of opioids (P < 0.0001). One hundred of 21,396 (0.47%) patients who did not receive opioids developed CDI. Twenty-two of 6955 patients (0.32%) with mild usage of opioids developed CDI [odds ratio (OR): 0.68; 95% confidence interval (CI): 0.43-1.1; P = 0.10]. Thirty of 33,203 (0.93%) with moderate usage developed CDI (OR: 2.0; 95% CI: 1.3-3.0; P = 0.0009). Forty of 1029 (3.7%) patients with high usage of opioids developed CDI (OR: 8.3; 95% CI: 5.7-12.1; P < 0.0001). Similar results were observed using a multivariate Cox proportional hazard model. Moderate to high use of opioid analgesics were associated with an increased risk of CDI.

Assessment of treatment patterns and patient outcomes before vs after implementation of a severity-based Clostridium difficile infection treatment policy.

PubMed

Jardin, C G M; Palmer, H R; Shah, D N; Le, F; Beyda, N D; Jiang, Z; Garey, K W

2013-09-01

National guidelines recommend oral vancomycin for severe Clostridium difficile infection (CDI) based on results from recent clinical trials demonstrating improved clinical outcomes. However, real-world data to support these clinical trials are scant. To compare treatment patterns and patient outcomes of those treated for CDI before and after implementation of a severity-based CDI treatment policy at a tertiary teaching hospital. This study evaluated adult patients with a positive C. difficile toxin before and after implementation of a policy where patients with severe CDI given metronidazole were switched to oral vancomycin unless contra-indicated. Patients were stratified according to disease severity using a modified published severity score. Treatment patterns based on CDI severity and rates of refractory CDI were assessed. In total, 256 patients with CDI (mean age 66 years, standard deviation 17, 52% female) were evaluated (before implementation: N = 144; after implementation: N = 112). Use of oral vancomycin for severe CDI increased significantly from 14% (N = 8) to 91% (N = 48) following implementation of the policy (P < 0.0001). Refractory disease in patients with severe CDI decreased significantly from 37% to 15% following implementation of the policy (P = 0.035). No significant differences were noted among patients with mild to moderate CDI. A severity-based CDI treatment policy at a tertiary teaching hospital increased the use of oral vancomycin and was associated with decreased rates of refractory CDI. Copyright © 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Transient polyuria related to central diabetes insipidus caused by lymphocytic infundibulo-neurohypophysitis in a patient treated for Graves' disease.

PubMed

Yamazaki, Masanori; Sato, Ai; Nishio, Shin-ichi; Uehara, Takeshi; Komatsu, Mitsuhisa

2010-01-01

A 45-year-old man was hospitalized because of weight loss, finger tremor, thirst, polydipsia and increased urinary frequency. He was diagnosed with Graves' disease (GD) and central diabetes insipidus (CDI). Magnetic resonance imaging revealed the enlarged posterior pituitary with thickened stalk. Histological examination obtained from biopsy of the pituitary revealed lymphocytic infundibulo-neurohypophysitis. He received treatment with thiamazole (MMI) for GD and desmopressin acetate (DDAVP) for CDI. However, DDAVP administration could be discontinued as GD was gradually improved. This course indicates that not only the recovered renal response to arginine-vasopressin but also the immunomodulative effects of MMI might attribute to the improvement of polyuria.

Attributable inpatient costs of recurrent Clostridium difficile infections.

PubMed

Dubberke, Erik R; Schaefer, Eric; Reske, Kimberly A; Zilberberg, Marya; Hollenbeak, Christopher S; Olsen, Margaret A

2014-11-01

To determine the attributable inpatient costs of recurrent Clostridium difficile infections (CDIs). Retrospective cohort study. Academic, urban, tertiary care hospital. A total of 3,958 patients aged 18 years or more who developed an initial CDI episode from 2003 through 2009. Data were collected electronically from hospital administrative databases and were supplemented with chart review. Patients with an index CDI episode during the study period were followed up for 180 days from the end of their index hospitalization or the end of their index CDI antibiotic treatment (whichever occurred later). Total hospital costs during the outcome period for patients with recurrent versus a single episode of CDI were analyzed using zero-inflated lognormal models. There were 421 persons with recurrent CDI (recurrence rate, 10.6%). Recurrent CDI case patients were significantly more likely than persons without recurrence to have any hospital costs during the outcome period (P < .001). The estimated attributable cost of recurrent CDI was $11,631 (95% confidence interval, $8,937-$14,588). The attributable costs of recurrent CDI are considerable. Patients with recurrent CDI are significantly more likely to have inpatient hospital costs than patients who do not develop recurrences. Better strategies to predict and prevent CDI recurrences are needed.

Use of tigecycline for the management of Clostridium difficile colitis in oncology patients and case series of breakthrough infections.

PubMed

Brinda, B J; Pasikhova, Y; Quilitz, R E; Thai, C M; Greene, J N

2017-04-01

Clostridium difficile infection (CDI) is the most frequent cause of nosocomial diarrhoea in adults. Cancer patients, in particular, are at a higher risk for CDI. Limited clinical data exist regarding the use of tigecycline for the treatment of CDI, especially in patients with oncologic and haematologic malignancies. To characterize the use of tigecycline for treatment of CDI in oncology patients at an academic cancer centre. This was a retrospective, single-centre, single-arm, chart review evaluating the use of tigecycline for the management of CDI in oncology patients at an academic cancer centre. The median age of CDI diagnosis in this patient group (N=66) was 65 years (range: 16-84) and the majority of patients had solid tumour malignancies. Fifty-six percent of patients had severe CDI, 70.3% of which were classified as having severe complicated disease. The median time to initiation of tigecycline therapy was 2 days (mean: 3.83) and the median number of tigecycline doses was 13 (range: 1-50). Twelve non-CDI breakthrough infections were observed, and four patients developed CDI while receiving tigecycline for non-CDI indications. The rate of death was 18% and the recurrence rate was 15.2%. Tigecycline did not lead to overt benefits in outcomes of oncology patients with CDI when compared to historical data. In addition, several breakthrough CDIs were observed in patients who received the drug for a non-CDI indication. Further prospective research is needed to validate the use of tigecycline for management of CDI. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

The burden of healthcare-associated Clostridium difficile infection in a non-metropolitan setting.

PubMed

Bond, S E; Boutlis, C S; Yeo, W W; Pratt, W A B; Orr, M E; Miyakis, S

2017-04-01

Healthcare-associated Clostridium difficile infection (HCA-CDI) remains a major cause of morbidity and mortality in industrialized countries. However, few data exist on the burden of HCA-CDI in multi-site non-metropolitan settings. This study examined the introduction of an antimicrobial stewardship programme (ASP) in relation to HCA-CDI rates, and the effect of HCA-CDI on length of stay (LOS) and hospital costs. A comparative before-and-after intervention study of patients aged ≥16 years with HCA-CDI from December 2010 to April 2016 across the nine hospitals of a non-metropolitan health district in New South Wales, Australia was undertaken. The intervention comprised a multi-site ASP supported by a clinical decision support system, with subsequent introduction of email feedback of HCA-CDI cases to admitting medical officers. HCA-CDI rates, comparative LOS and hospital costs, prior use of antimicrobials and proton pump inhibitors, and appropriateness of CDI treatment. HCA-CDI rates rose from 3.07 to 4.60 cases per 10,000 occupied bed-days pre-intervention, and remained stable at 4 cases per 10,000 occupied bed-days post-intervention (P=0.24). Median LOS (17 vs six days; P<0.01) and hospital costs (AU$19,222 vs $7861; P<0.01) were significantly greater for HCA-CDI cases (N=91) than for matched controls (N=172). Half of the patients with severe HCA-CDI (4/8) did not receive initial appropriate treatment (oral vancomycin). HCA-CDI placed a significant burden on the regional and rural health service through increased LOS and hospital costs. Interventions targeting HCA-CDI could be employed to consolidate the effects of ASPs. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Risk for Clostridium difficile Infection After Allogeneic Hematopoietic Cell Transplant Remains Elevated in the Postengraftment Period.

PubMed

Dubberke, Erik R; Reske, Kimberly A; Olsen, Margaret A; Bommarito, Kerry M; Seiler, Sondra; Silveira, Fernanda P; Chiller, Tom M; DiPersio, John; Fraser, Victoria J

2017-04-01

Clostridium difficile infection (CDI) is a frequent cause of diarrhea among allogeneic hematopoietic cell transplant (HCT) recipients. It is unknown whether risk factors for CDI vary by time posttransplant. We performed a 3-year prospective cohort study of CDI in allogeneic HCT recipients. Participants were enrolled during their transplant hospitalizations. Clinical assessments were performed weekly during hospitalizations and for 12 weeks posttransplant, and monthly for 30 months thereafter. Data were collected through patient interviews and chart review, and included CDI diagnosis, demographics, transplant characteristics, medications, infections, and outcomes. CDI cases were included if they occurred within 1 year of HCT and were stratified by time from transplant. Multivariable logistic regression was used to determine risk factors for CDI. One hundred eighty-seven allogeneic HCT recipients were enrolled, including 63 (34%) patients who developed CDI. 38 (60%) CDI cases occurred during the preengraftment period (days 0-30 post-HCT) and 25 (40%) postengraftment (day >30). Lack of any preexisting comorbid disease was significantly associated with lower risk of CDI preengraftment (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.1-0.9). Relapsed underlying disease (OR, 6.7; 95% CI, 1.3-33.1), receipt of any high-risk antimicrobials (OR, 11.8; 95% CI, 2.9-47.8), and graft-versus-host disease (OR, 7.8; 95% CI, 2.0-30.2) were significant independent risk factors for CDI postengraftment. A large portion of CDI cases occurred during the postengraftment period in allogeneic HCT recipients, suggesting that surveillance for CDI should continue beyond the transplant hospitalization and preengraftment period. Patients with continued high underlying severity of illness were at increased risk of CDI postengraftment.

Recent Advances in the Diagnosis and Treatment of Clostridium Difficile Infection

PubMed Central

Avila, Meera B.; Avila, Nathaniel P.; Dupont, Andrew W.

2016-01-01

Clostridium difficile infection (CDI) has become the most frequently reported health care-associated infection in the United States [1]. As the incidence of CDI rises, so too does the burden it produces on health care and society. In an attempt to decrease the burden of CDI and provide the best outcomes for patients affected by CDI, there have been many recent advancements in the understanding, diagnosis, and management of CDI. In this article, we review the current recommendations regarding CDI testing and treatment strategies. PMID:26918176

Hospitalized Patients with Cirrhosis Should Be Screened for Clostridium difficile Colitis.

PubMed

Saab, Sammy; Alper, Theodore; Sernas, Ernesto; Pruthi, Paridhima; Alper, Mikhail A; Sundaram, Vinay

2015-10-01

Clostridium difficile infection (CDI) is an important public health problem in hospitalized patients. Patients with cirrhosis are particularly at risk of increased associated morbidity, mortality, and healthcare utilization from CDI. The aim of this study was to assess the pharmacoeconomic impact of CDI screening on hospitalized patients with cirrhosis. A Markov model was used to compare costs and outcomes of two strategies for the screening of CDI. The first strategy consisted of screening all patients for CDI and treating if detected (screening). In the second strategy, only patients found to have symptomatic CDI were treated (no screening). The probability of underlying CDI prevalence, symptomatic CDI infection, and likelihood of recurrent infection were varied in a sensitivity analysis. The costs of antibiotics and hospitalization were also assessed. Differences in outcome were expressed in ratio of the total costs associated with screening to the total costs associated without screening. The results of our model showed that screening for CDI was consistently associated with improved healthcare outcomes and decreased healthcare utilization across all variables in the one- and two-way sensitivity analyses. Using baseline assumptions, the costs associated with the no screening strategy were 3.54 times that of the screening strategy. Moreover, the mortality for symptomatic CDI was lower in the screening strategy than the no screening strategy. The screening strategy results in less healthcare utilization and improved clinical outcomes. Screening for CDI measures favorably.

Clostridium difficile infection after colorectal surgery: a rare but costly complication.

PubMed

Damle, Rachelle N; Cherng, Nicole B; Flahive, Julie M; Davids, Jennifer S; Maykel, Justin A; Sturrock, Paul R; Sweeney, W Brian; Alavi, Karim

2014-10-01

The incidence and virulence of Clostridium difficile infection (CDI) are on the rise. The characteristics of patients who develop CDI following colorectal resection have been infrequently studied. We utilized the University HealthSystem Consortium database to identify adult patients undergoing colorectal surgery between 2008 and 2012. We examined the patient-related risk factors for CDI and 30-day outcomes related to its occurrence. A total of 84,648 patients met our inclusion criteria, of which the average age was 60 years and 50% were female. CDI occurred in 1,266 (1.5%) patients during the years under study. The strongest predictors of CDI were emergent procedure, inflammatory bowel disease (IBD), and major/extreme APR-DRG severity of illness score. CDI was associated with a higher rate of complications, intensive care unit (ICU) admission, longer preoperative inpatient stay, 30-day readmission rate, and death within 30 days compared to non-CDI patients. Cost of the index stay was, on average, $14,130 higher for CDI patients compared with non-CDI patients. Emergent procedures, higher severity of illness, and inflammatory bowel disease are significant risk factors for postoperative CDI in patients undergoing colorectal surgery. Once established, CDI is associated with worse outcomes and higher costs. The poor outcomes of these patients and increased costs highlight the importance of prevention strategies targeting high-risk patients.

Risk Factors for Hospital-acquired Clostridium difficile Infection Among Pediatric Patients With Cancer.

PubMed

Daida, Atsuro; Yoshihara, Hiroki; Inai, Ikuko; Hasegawa, Daisuke; Ishida, Yasushi; Urayama, Kevin Y; Manabe, Atsushi

2017-04-01

Hospital-acquired Clostridium difficile infection (CDI) may cause life-threatening colitis for children with cancer, making identification of risk factors important. We described characteristics of pediatric cancer patients with primary and recurring CDI, and evaluated potential risk factors. Among 189 cancer patients, 51 cases (27%) of CDI and 94 matched controls of cancer patients without CDI were analyzed. Multivariable logistic regression was used to evaluate the association between CDI and several potential risk factors. Median age of CDI cases was lower (3.3 y; 0.60 to 16.2) than controls (7.7 y; 0.4 to 20.5). Median duration of neutropenia before CDI was longer for CDI cases (10.0 d; 0.0 to 30.0) compared with duration calculated from reference date in controls (6.0 d; 0.0 to 29.0). Multivariable analysis showed that older age was associated with reduced risk (≥7 vs. 0 to 3 y, odds ratio=0.11; 95% confidence interval, 0.02-0.54), and prolonged neutropenia was associated with increased risk (odds ratio=1.11; 95% confidence interval, 1.01-1.22). CDI recurred in 26% of cases. Younger age and prolonged neutropenia were risk factors for CDI in children with cancer. Increasing awareness to these risk factors will help to identify opportunities for CDI prevention in cancer patients.

Survey of Clostridium difficile infection surveillance systems in Europe, 2011.

PubMed

Kola, Axel; Wiuff, Camilla; Akerlund, Thomas; van Benthem, Birgit H; Coignard, Bruno; Lyytikäinen, Outi; Weitzel-Kage, Doris; Suetens, Carl; Wilcox, Mark H; Kuijper, Ed J; Gastmeier, Petra

2016-07-21

To develop a European surveillance protocol for Clostridium difficile infection (CDI), existing national CDI surveillance systems were assessed in 2011. A web-based electronic form was provided for all national coordinators of the European CDI Surveillance Network (ECDIS-Net). Of 35 national coordinators approached, 33 from 31 European countries replied. Surveillance of CDI was in place in 14 of the 31 countries, comprising 18 different nationwide systems. Three of 14 countries with CDI surveillance used public health notification of cases as the route of reporting, and in another three, reporting was limited to public health notification of cases of severe CDI. The CDI definitions published by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Centre for Disease Prevention and Control (ECDC) were widely used, but there were differing definitions to distinguish between community- and healthcare-associated cases. All CDI surveillance systems except one reported annual national CDI rates (calculated as number of cases per patient-days). Only four surveillance systems regularly integrated microbiological data (typing and susceptibility testing results). Surveillance methods varied considerably between countries, which emphasises the need for a harmonised European protocol to allow consistent monitoring of the CDI epidemiology at European level. The results of this survey were used to develop a harmonised EU-wide hospital-based CDI surveillance protocol. This article is copyright of The Authors, 2016.

Recurrent Clostridium difficile infections: The importance of the intestinal microbiota

PubMed Central

Zanella Terrier, Marie Céline; Simonet, Martine Louis; Bichard, Philippe; Frossard, Jean Louis

2014-01-01

Clostridium difficile infections (CDI) are a leading cause of antibiotic-associated and nosocomial diarrhea. Despite effective antibiotic treatments, recurrent infections are common. With the recent emergence of hypervirulent isolates of C. difficile, CDI is a growing epidemic with higher rates of recurrence, increasing severity and mortality. Fecal microbiota transplantation (FMT) is an alternative treatment for recurrent CDI. A better understanding of intestinal microbiota and its role in CDI has opened the door to this promising therapeutic approach. FMT is thought to resolve dysbiosis by restoring gut microbiota diversity thereby breaking the cycle of recurrent CDI. Since the first reported use of FMT for recurrent CDI in 1958, systematic reviews of case series and case report have shown its effectiveness with high resolution rates compared to standard antibiotic treatment. This article focuses on current guidelines for CDI treatment, the role of intestinal microbiota in CDI recurrence and current evidence about FMT efficacy, adverse effects and acceptability. PMID:24966611

Disproportionate rise in Clostridium difficile-associated hospitalizations among US youth with inflammatory bowel disease, 1997-2011.

PubMed

Sandberg, Kelly C; Davis, Matthew M; Gebremariam, Achamyeleh; Adler, Jeremy

2015-04-01

Our aim was to characterize the temporal changes in burden that Clostridium difficile infection (CDI) added to the hospital care of children and young adults with inflammatory bowel disease (IBD) in the United States. Retrospective analysis of annual, nationally representative samples of children and young adults with IBD. There was a 5-fold increase in IBD hospitalizations with CDI from 1997 to 2011 (P for trend <0.01). During the same period, IBD hospitalizations without CDI increased 2-fold (P for trend <0.01). Mean length of stay for IBD hospitalizations with CDI was consistently longer than that for hospitalizations without CDI and did not significantly change over time (P for trend = 0.47). CDI-related total hospital days in the United States rose from 1702 to 10,194 days per million individuals per year from 1997 to 2011 (P for trend <0.01). Children and young adults hospitalized with CDI had a significantly lower odds of colectomy (0.31) compared with those without CDI. Total charges for CDI-related hospitalizations among children and young adults in the United States rose from $8.7 million in 1997 to $68.2 million in 2011. A widening gap in burden has opened between IBD hospitalizations with and without CDI during the last decade and a half. CDI-related hospitalizations are associated with disproportionately longer lengths of stay, more hospital days, and more charges than hospitalizations without CDI over time. Further work within health systems, hospitals, and practices can help us better understand this enlarging gap to improve clinical care for this vulnerable population.

Risk Factors for Recurrent Clostridium difficile Infection in Pediatric Inpatients.

PubMed

Schwab, Elyse M; Wilkes, Jacob; Korgenski, Kent; Hersh, Adam L; Pavia, Andrew T; Stevens, Vanessa W

2016-06-01

The purpose of this study was to identify the risk factors during the incident Clostridium difficile infection (CDI) episode, associated with developing recurrent CDI within 60 days, among hospitalized children that may be amenable to intervention. This was a retrospective cohort study of pediatric patients hospitalized at a freestanding children's hospital from January 1, 2003, to December 31, 2010. Patients were eligible if they were <18 years of age at admission and had a new diagnosis of CDI. Patients <1 year of age and those with a history of CDI in the previous 60 days were excluded. Age, gender, race, complex chronic conditions, and other information were collected. Multivariable logistic regression was used to evaluate predictors of recurrent CDI. During the study period, there were 612 unique patients with an incident CDI episode; 65 (10.6%) experienced at least 1 recurrence. Patients with any complex chronic condition were 4.0 (95% confidence interval [CI]: 1.2-13.9) times more likely to experience recurrence. Patients with a malignancy and those who received non-CDI antibiotics at any time during CDI treatment were 2.3 (95% CI: 1.3-4.0) and 2.8 (95% CI: 1.2-6.9) times more likely to experience recurrence, respectively. The presence of underlying comorbidities, malignancies, and treatment with non-CDI antibiotics during CDI treatment were the most important risk factors for recurrence. Efforts to reduce unnecessary courses of non-CDI antibiotics could lower the risk of CDI recurrence. Copyright © 2016 by the American Academy of Pediatrics.

Current knowledge on the laboratory diagnosis of Clostridium difficile infection.

PubMed

Martínez-Meléndez, Adrián; Camacho-Ortiz, Adrián; Morfin-Otero, Rayo; Maldonado-Garza, Héctor Jesús; Villarreal-Treviño, Licet; Garza-González, Elvira

2017-03-07

Clostridium difficile ( C. difficile ) is a spore-forming, toxin-producing, gram-positive anaerobic bacterium that is the principal etiologic agent of antibiotic-associated diarrhea. Infection with C. difficile (CDI) is characterized by diarrhea in clinical syndromes that vary from self-limited to mild or severe. Since its initial recognition as the causative agent of pseudomembranous colitis, C. difficile has spread around the world. CDI is one of the most common healthcare-associated infections and a significant cause of morbidity and mortality among older adult hospitalized patients. Due to extensive antibiotic usage, the number of CDIs has increased. Diagnosis of CDI is often difficult and has a substantial impact on the management of patients with the disease, mainly with regards to antibiotic management. The diagnosis of CDI is primarily based on the clinical signs and symptoms and is only confirmed by laboratory testing. Despite the high burden of CDI and the increasing interest in the disease, episodes of CDI are often misdiagnosed. The reasons for misdiagnosis are the lack of clinical suspicion or the use of inappropriate tests. The proper diagnosis of CDI reduces transmission, prevents inadequate or unnecessary treatments, and assures best antibiotic treatment. We review the options for the laboratory diagnosis of CDI within the settings of the most accepted guidelines for CDI diagnosis, treatment, and prevention of CDI.

Quantitative Contrast-Enhanced Ultrasound Parameters in Crohn Disease: Their Role in Disease Activity Determination With Ultrasound.

PubMed

Medellin-Kowalewski, Alexandra; Wilkens, Rune; Wilson, Alexandra; Ruan, Ji; Wilson, Stephanie R

2016-01-01

The primary objective of our study was to examine the association between contrast-enhanced ultrasound (CEUS) parameters and established gray-scale ultrasound with color Doppler imaging (CDI) for the determination of disease activity in patients with Crohn disease. Our secondary objective was to develop quantitative time-signal intensity curve thresholds for disease activity. One hundred twenty-seven patients with Crohn disease underwent ultrasound with CDI and CEUS. Reviewers graded wall thickness, inflammatory fat, and mural blood flow as showing remission or inflammation (mild, moderate, or severe). If both gray-scale ultrasound and CDI predicted equal levels of disease activity, the studies were considered concordant. If ultrasound images suggested active disease not supported by CDI findings, the ultrasound results for disease activity were indeterminate. Time-signal intensity curves from CEUS were acquired with calculation of peak enhancement (PE), and AUCs. Interobserver variation and associations between PE and ultrasound parameters were examined. Multiclass ROC analysis was used to develop CEUS thresholds for activity. Ninety-six (76%) studies were concordant, 19 of which showed severe disease, and 31 (24%) studies were indeterminate. Kappa analyses revealed good interobserver agreement on grades for CDI (κ = 0.76) and ultrasound (κ = 0.80) assessments. PE values on CEUS and wall thickness showed good association with the Spearman rank correlation coefficient for the entire population (ρ = 0.62, p < 0.01) and for the concordant group (ρ = 0.70, p < 0.01). Multiclass ROC analyses of the concordant group using wall thickness alone as the reference standard showed cutoff points of 18.2 dB for differentiating mild versus moderate activity (sensitivity, 89.0% and specificity, 87.0%) and 23.0 dB for differentiating moderate versus severe (sensitivity, 90% and specificity, 86.8%). Almost identical cutoff points were observed when using ultrasound global assessment as the reference standard: using 18.2 dB to differentiate mild versus moderate activity yielded sensitivity of 89.2% and specificity of 90.9% and using 22.9 dB to differentiate moderate versus severe activity yielded sensitivity of 89.5% and specificity of 83.1%. Quantitative CEUS parameters integrated into inflammatory assessments with ultrasound reduce indeterminate results and improve disease activity level determinations.

Burden of Clostridium difficile infection: Associated hospitalization in a cohort of middle-aged and older adults.

PubMed

Chen, Yingxi; Glass, Kathryn; Liu, Bette; Korda, Rosemary J; Riley, Thomas V; Kirk, Martyn D

2017-05-01

Clostridium difficile is the principal cause of infectious diarrhea in hospitalized patients. The aim of this study was to describe and compare length of stay (LOS), costs, and in-hospital deaths for C difficile infection (CDI) and non-CDI hospitalizations, in a cohort of middle-aged and older Australians. We used survey data from the 45 and Up Study, linked to hospitalization and death data. We calculated the average LOS and costs per hospitalization, and the proportion of in-hospital deaths for CDI and non-CDI hospitalizations. We then compared hospitalizations with CDI as a secondary diagnosis to non-CDI hospitalizations by stratifying hospitalizations based on principal diagnosis and then using generalized linear models to compare LOS and in-hospital costs, and logistic regression for in-hospital deaths, adjusting for age and sex. There were 641 CDI hospitalizations during 2006-2012. The average LOS was 17 days; the average cost per hospitalization was AUD 12,704; and in 7.3% of admissions (47 out of 641) the patient died. After adjusting for age and sex, hospitalizations with CDI were associated with longer LOS, higher costs, and a greater proportion of in-hospital deaths compared with hospitalizations with similar principal diagnosis but without CDI. CDI places additional burden on the Australian hospital system, with CDI patients having relatively lengthy hospital stays and high costs. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

The emergence of Clostridium difficile infection in Asia: A systematic review and meta-analysis of incidence and impact.

PubMed

Borren, Nienke Z; Ghadermarzi, Shadi; Hutfless, Susan; Ananthakrishnan, Ashwin N

2017-01-01

Clostridium difficile infection (CDI) is the most common healthcare associated infection and is highly prevalent in Europe and North America. Limited data is available on the prevalence of CDI in Asia. However, secular increases in prevalence of risk factors for CDI suggest that it may be emerging as a major cause of morbidity, highlighting the urgent need for a systematic study of the prevalence of CDI in Asia. We systematically searched PubMed/Medline and Embase for publications from Asia between 2000-16 examining prevalence of CDI. A random-effects meta-analysis was performed to calculate the pooled prevalence of CDI in Asia and to identify subgroups and regions at high risk. Our meta-analysis included 51 studies from throughout Asia including 37,663 patients at risk among whom confirmed CDI was found in 4,343 patients. The pooled proportion of confirmed CDI among all patients with diarrhea was 14.8% with a higher prevalence in East Asia (19.5%), compared with South Asia (10.5%) or the Middle East (11.1%). There were an estimated 5.3 episodes of CDI per 10,000 patient days, similar to rates reported from Europe and North America. Infections due to hypervirulent strains were rare. CDI-related mortality was 8.9%. In a meta-analysis of 51 studies, we observed similar rates of CDI in Asia in comparison to Europe and North America. Increased awareness and improved surveillance of Clostridium difficile is essential to reduce incidence and morbidity.

Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections

PubMed Central

McFarland, Lynne Vernice; Ozen, Metehan; Dinleyici, Ener Cagri; Goh, Shan

2016-01-01

Antibiotic-associated diarrhea (AAD) and Clostridum difficile infections (CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases PubMed (June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications (required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar (discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics. PMID:27003987

Role of cephalosporins in the era of Clostridium difficile infection.

PubMed

Wilcox, Mark H; Chalmers, James D; Nord, Carl E; Freeman, Jane; Bouza, Emilio

2017-01-01

The incidence of Clostridium difficile infection (CDI) in Europe has increased markedly since 2000. Previous meta-analyses have suggested a strong association between cephalosporin use and CDI, and many national programmes on CDI control have focused on reducing cephalosporin usage. Despite reductions in cephalosporin use, however, rates of CDI have continued to rise. This review examines the potential association of CDI with cephalosporins, and considers other factors that influence CDI risk. EUCLID (the EUropean, multicentre, prospective biannual point prevalence study of CLostridium difficile Infection in hospitalized patients with Diarrhoea) reported an increase in the annual incidence of CDI from 6.6 to 7.3 cases per 10 000 patient bed-days from 2011-12 to 2012-13, respectively. While CDI incidence and cephalosporin usage varied widely across countries studied, there was no clear association between overall cephalosporin prescribing (or the use of any particular cephalosporin) and CDI incidence. Moreover, variations in the pharmacokinetic and pharmacodynamic properties of cephalosporins of the same generation make categorization by generation insufficient for predicting impact on gut microbiota. A multitude of additional factors can affect the risk of CDI. Antibiotic choice is an important consideration; however, CDI risk is associated with a range of antibiotic classes. Prescription of multiple antibiotics and a long duration of treatment are key risk factors for CDI, and risk also differs across patient populations. We propose that all of these are factors that should be taken into account when selecting an antibiotic, rather than focusing on the exclusion of individual drug classes. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Age-Stratified Treatment Response Rates in Hospitalized Patients with Clostridium difficile Infection Treated with Metronidazole

PubMed Central

Pham, Vy P.; Luce, Andrea M.; Ruppelt, Sara C.; Wei, Wenjing; Aitken, Samuel L.; Musick, William L.; Roux, Ryan K.

2015-01-01

Consensus on the optimal treatment of Clostridium difficile infection (CDI) is rapidly changing. Treatment with metronidazole has been associated with increased clinical failure rates; however, the reasons for this are unclear. The purpose of this study was to assess age-related treatment response rates in hospitalized patients with CDI treated with metronidazole. This was a retrospective, multicenter cohort study of hospitalized patients with CDI. Patients were assessed for refractory CDI, defined as persistent diarrhea after 7 days of metronidazole therapy, and stratified by age and clinical characteristics. A total of 242 individuals, aged 60 ± 18 years (Charlson comorbidity index, 3.8 ± 2.4; Horn's index, 1.7 ± 1.0) were included. One hundred twenty-eight patients (53%) had severe CDI. Seventy patients (29%) had refractory CDI, a percentage that increased from 22% to 28% and to 37% for patients aged less than 50 years, for patients from 50 to 70 years, and for patients aged >70 years, respectively (P = 0.05). In multivariate analysis, Horn's index (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.50 to 2.77; P < 0.001), severe CDI (OR, 2.25; 95% CI, 1.15 to 4.41; P = 0.018), and continued use of antibiotics (OR, 2.65; 95% CI, 1.30 to 5.39; P = 0.0072) were identified as significant predictors of refractory CDI. Age was not identified as an independent risk factor for refractory CDI. Therefore, hospitalized elderly patients with CDI treated with metronidazole had increased refractory CDI rates likely due to increased underlying severity of illness, severity of CDI, and concomitant antibiotic use. These results may help identify patients that may benefit from alternative C. difficile treatments other than metronidazole. PMID:26195522

Age-Stratified Treatment Response Rates in Hospitalized Patients with Clostridium difficile Infection Treated with Metronidazole.

PubMed

Pham, Vy P; Luce, Andrea M; Ruppelt, Sara C; Wei, Wenjing; Aitken, Samuel L; Musick, William L; Roux, Ryan K; Garey, Kevin W

2015-10-01

Consensus on the optimal treatment of Clostridium difficile infection (CDI) is rapidly changing. Treatment with metronidazole has been associated with increased clinical failure rates; however, the reasons for this are unclear. The purpose of this study was to assess age-related treatment response rates in hospitalized patients with CDI treated with metronidazole. This was a retrospective, multicenter cohort study of hospitalized patients with CDI. Patients were assessed for refractory CDI, defined as persistent diarrhea after 7 days of metronidazole therapy, and stratified by age and clinical characteristics. A total of 242 individuals, aged 60 ± 18 years (Charlson comorbidity index, 3.8 ± 2.4; Horn's index, 1.7 ± 1.0) were included. One hundred twenty-eight patients (53%) had severe CDI. Seventy patients (29%) had refractory CDI, a percentage that increased from 22% to 28% and to 37% for patients aged less than 50 years, for patients from 50 to 70 years, and for patients aged >70 years, respectively (P = 0.05). In multivariate analysis, Horn's index (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.50 to 2.77; P < 0.001), severe CDI (OR, 2.25; 95% CI, 1.15 to 4.41; P = 0.018), and continued use of antibiotics (OR, 2.65; 95% CI, 1.30 to 5.39; P = 0.0072) were identified as significant predictors of refractory CDI. Age was not identified as an independent risk factor for refractory CDI. Therefore, hospitalized elderly patients with CDI treated with metronidazole had increased refractory CDI rates likely due to increased underlying severity of illness, severity of CDI, and concomitant antibiotic use. These results may help identify patients that may benefit from alternative C. difficile treatments other than metronidazole. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

An environmental disinfection odyssey: evaluation of sequential interventions to improve disinfection of Clostridium difficile isolation rooms.

PubMed

Sitzlar, Brett; Deshpande, Abhishek; Fertelli, Dennis; Kundrapu, Sirisha; Sethi, Ajay K; Donskey, Curtis J

2013-05-01

OBJECTIVE. Effective disinfection of hospital rooms after discharge of patients with Clostridium difficile infection (CDI) is necessary to prevent transmission. We evaluated the impact of sequential cleaning and disinfection interventions by culturing high-touch surfaces in CDI rooms after cleaning. DESIGN. Prospective intervention. SETTING. A Veterans Affairs hospital. INTERVENTIONS. During a 21-month period, 3 sequential tiered interventions were implemented: (1) fluorescent markers to provide monitoring and feedback on thoroughness of cleaning facility-wide, (2) addition of an automated ultraviolet radiation device for adjunctive disinfection of CDI rooms, and (3) enhanced standard disinfection of CDI rooms, including a dedicated daily disinfection team and implementation of a process requiring supervisory assessment and clearance of terminally cleaned CDI rooms. To determine the impact of the interventions, cultures were obtained from CDI rooms after cleaning and disinfection. RESULTS. The fluorescent marker intervention improved the thoroughness of cleaning of high-touch surfaces (from 47% to 81% marker removal; P < .0001). Relative to the baseline period, the prevalence of positive cultures from CDI rooms was reduced by 14% (P=.024), 48% (P <.001), and 89% (P=.006) with interventions 1, 2, and 3, respectively. During the baseline period, 67% of CDI rooms had positive cultures after disinfection, whereas during interventions periods 1, 2, and 3 the percentages of CDI rooms with positive cultures after disinfection were reduced to 57%, 35%, and 7%, respectively. CONCLUSIONS. An intervention that included formation of a dedicated daily disinfection team and implementation of a standardized process for clearing CDI rooms achieved consistent CDI room disinfection. Culturing of CDI rooms provides a valuable tool to drive improvements in environmental disinfection.

A Comprehensive Study of Costs Associated With Recurrent Clostridium difficile Infection.

PubMed

Rodrigues, Rodrigo; Barber, Grant E; Ananthakrishnan, Ashwin N

2017-02-01

BACKGROUND Clostridium difficile infection (CDI) is the most common healthcare-associated infection and is associated with considerable morbidity. Recurrent CDI is a key contributing factor to this morbidity. Despite an estimated 83,000 recurrences annually in the United States, there are few accurate estimates of costs associated with recurrent CDI. OBJECTIVE We performed this study (1) to identify the health consequences of recurrent CDI including need for repeat hospitalization, intensive care unit (ICU) stay, and surgery; (2) to determine costs associated with recurrent CDI and identify determinants of such costs; and (3) to compare the outcomes and costs of recurrent CDI to those who develop reinfection. METHODS We identified all patients with confirmed recurrent CDI between January to December 2013 at a single referral center. Healthcare burden associated with recurrence including diagnostic testing, pharmacologic treatment, and inpatient and outpatient healthcare visits were identified in the 12 months following the first recurrence. Total healthcare costs were calculated, and the predictors of high healthcare utilization were identified. RESULTS Our study population included 98 patients with recurrent CDI. The median interval between the initial infection and recurrence was 37 days. The mean age of the cohort was 67 years, two-thirds were women (62%), and the mean Charlson index was 8.6. During the year following the first recurrence of CDI, each patient underwent a mean of 4.4 stool C. difficile toxin tests and received a mean of 2.5 prescriptions for oral vancomycin (range, 0-6). Most patients (84%) with recurrence had a CDI-related hospitalization, and 6% underwent colectomy. The mean total CDI-associated cost was $34,104 per patient, with hospitalization costs accounting for 68%, surgery 20%, and drug treatment 8% of this cost, respectively. Extrapolating to the United States overall, we estimate an annual cost of $2.8 billion related to recurrent CDI. CONCLUSION Recurrent CDI is associated with considerable morbidity and cost. Infect Control Hosp Epidemiol 2017;38:196-202.

Cost-effectiveness in Clostridium difficile treatment decision-making

PubMed Central

Nuijten, Mark JC; Keller, Josbert J; Visser, Caroline E; Redekop, Ken; Claassen, Eric; Speelman, Peter; Pronk, Marja H

2015-01-01

AIM: To develop a framework for the clinical and health economic assessment for management of Clostridium difficile infection (CDI). METHODS: CDI has vast economic consequences emphasizing the need for innovative and cost effective solutions, which were aim of this study. A guidance model was developed for coverage decisions and guideline development in CDI. The model included pharmacotherapy with oral metronidazole or oral vancomycin, which is the mainstay for pharmacological treatment of CDI and is recommended by most treatment guidelines. RESULTS: A design for a patient-based cost-effectiveness model was developed, which can be used to estimate the cost-effectiveness of current and future treatment strategies in CDI. Patient-based outcomes were extrapolated to the population by including factors like, e.g., person-to-person transmission, isolation precautions and closing and cleaning wards of hospitals. CONCLUSION: The proposed framework for a population-based CDI model may be used for clinical and health economic assessments of CDI guidelines and coverage decisions for emerging treatments for CDI. PMID:26601096

Cost-effectiveness in Clostridium difficile treatment decision-making.

PubMed

Nuijten, Mark Jc; Keller, Josbert J; Visser, Caroline E; Redekop, Ken; Claassen, Eric; Speelman, Peter; Pronk, Marja H

2015-11-16

To develop a framework for the clinical and health economic assessment for management of Clostridium difficile infection (CDI). CDI has vast economic consequences emphasizing the need for innovative and cost effective solutions, which were aim of this study. A guidance model was developed for coverage decisions and guideline development in CDI. The model included pharmacotherapy with oral metronidazole or oral vancomycin, which is the mainstay for pharmacological treatment of CDI and is recommended by most treatment guidelines. A design for a patient-based cost-effectiveness model was developed, which can be used to estimate the cost-effectiveness of current and future treatment strategies in CDI. Patient-based outcomes were extrapolated to the population by including factors like, e.g., person-to-person transmission, isolation precautions and closing and cleaning wards of hospitals. The proposed framework for a population-based CDI model may be used for clinical and health economic assessments of CDI guidelines and coverage decisions for emerging treatments for CDI.

Detection of Clostridium difficile infection clusters, using the temporal scan statistic, in a community hospital in southern Ontario, Canada, 2006-2011.

PubMed

Faires, Meredith C; Pearl, David L; Ciccotelli, William A; Berke, Olaf; Reid-Smith, Richard J; Weese, J Scott

2014-05-12

In hospitals, Clostridium difficile infection (CDI) surveillance relies on unvalidated guidelines or threshold criteria to identify outbreaks. This can result in false-positive and -negative cluster alarms. The application of statistical methods to identify and understand CDI clusters may be a useful alternative or complement to standard surveillance techniques. The objectives of this study were to investigate the utility of the temporal scan statistic for detecting CDI clusters and determine if there are significant differences in the rate of CDI cases by month, season, and year in a community hospital. Bacteriology reports of patients identified with a CDI from August 2006 to February 2011 were collected. For patients detected with CDI from March 2010 to February 2011, stool specimens were obtained. Clostridium difficile isolates were characterized by ribotyping and investigated for the presence of toxin genes by PCR. CDI clusters were investigated using a retrospective temporal scan test statistic. Statistically significant clusters were compared to known CDI outbreaks within the hospital. A negative binomial regression model was used to identify associations between year, season, month and the rate of CDI cases. Overall, 86 CDI cases were identified. Eighteen specimens were analyzed and nine ribotypes were classified with ribotype 027 (n = 6) the most prevalent. The temporal scan statistic identified significant CDI clusters at the hospital (n = 5), service (n = 6), and ward (n = 4) levels (P ≤ 0.05). Three clusters were concordant with the one C. difficile outbreak identified by hospital personnel. Two clusters were identified as potential outbreaks. The negative binomial model indicated years 2007-2010 (P ≤ 0.05) had decreased CDI rates compared to 2006 and spring had an increased CDI rate compared to the fall (P = 0.023). Application of the temporal scan statistic identified several clusters, including potential outbreaks not detected by hospital personnel. The identification of time periods with decreased or increased CDI rates may have been a result of specific hospital events. Understanding the clustering of CDIs can aid in the interpretation of surveillance data and lead to the development of better early detection systems.

Burden of Clostridium difficile infection between 2010 and 2013: Trends and outcomes from an academic center in Eastern Europe.

PubMed

Kurti, Zsuzsanna; Lovasz, Barbara D; Mandel, Michael D; Csima, Zoltan; Golovics, Petra A; Csako, Bence D; Mohas, Anna; Gönczi, Lorant; Gecse, Krisztina B; Kiss, Lajos S; Szathmari, Miklos; Lakatos, Peter L

2015-06-07

To analyze the incidence and possible risk factors in hospitalized patients treated with Clostridium difficile infection (CDI). A total of 11751 patients were admitted to our clinic between 1 January 2010 and 1 May 2013. Two hundred and forty-seven inpatients were prospectively diagnosed with CDI. For the risk analysis a 1:3 matching was used. Data of 732 patients matched for age, sex, and inpatient care period and unit were compared to those of the CDI population. Inpatient records were collected from an electronic hospital database and comprehensively reviewed. Incidence of CDI was 21.0/1000 admissions (2.1% of all-cause hospitalizations and 4.45% of total inpatient days). The incidence of severe CDI was 12.6% (2.63/1000 of all-cause hospitalizations). Distribution of CDI cases was different according to the unit type, with highest incidence rates in hematology, gastroenterology and nephrology units (32.9, 25 and 24.6/1000 admissions, respectively) and lowest rates in 1.4% (33/2312) in endocrinology and general internal medicine (14.2 and 16.9/1000 admissions) units. Recurrence of CDI was 11.3% within 12 wk after discharge. Duration of hospital stay was longer in patients with CDI compared to controls (17.6 ± 10.8 d vs 12.4 ± 7.71 d). CDI accounted for 6.3% of all-inpatient deaths, and 30-d mortality rate was 21.9% (54/247 cases). Risk factors for CDI were antibiotic therapy [including third-generation cephalosporins or fluoroquinolones, odds ratio (OR) = 4.559; P < 0.001], use of proton pump inhibitors (OR = 2.082, P < 0.001), previous hospitalization within 12 mo (OR = 3.167, P < 0.001), previous CDI (OR = 15.32; P < 0.001), while presence of diabetes mellitus was associated with a decreased risk for CDI (OR = 0.484; P < 0.001). Treatment of recurrent cases was significantly different from primary infections with more frequent use of vancomycin alone or in combination (P < 0.001), and antibiotic therapy duration was longer (P < 0.02). Severity, mortality and outcome of primary infections and relapsing cases did not significantly differ. CDI was accounted for significant burden with longer hospitalization and adverse outcomes. Antibiotic, PPI therapy and previous hospitalization or CDI were risk factors for CDI.

Burden of Clostridium difficile infection between 2010 and 2013: Trends and outcomes from an academic center in Eastern Europe

PubMed Central

Kurti, Zsuzsanna; Lovasz, Barbara D; Mandel, Michael D; Csima, Zoltan; Golovics, Petra A; Csako, Bence D; Mohas, Anna; Gönczi, Lorant; Gecse, Krisztina B; Kiss, Lajos S; Szathmari, Miklos; Lakatos, Peter L

2015-01-01

AIM: To analyze the incidence and possible risk factors in hospitalized patients treated with Clostridium difficile infection (CDI). METHODS: A total of 11751 patients were admitted to our clinic between 1 January 2010 and 1 May 2013. Two hundred and forty-seven inpatients were prospectively diagnosed with CDI. For the risk analysis a 1:3 matching was used. Data of 732 patients matched for age, sex, and inpatient care period and unit were compared to those of the CDI population. Inpatient records were collected from an electronic hospital database and comprehensively reviewed. RESULTS: Incidence of CDI was 21.0/1000 admissions (2.1% of all-cause hospitalizations and 4.45% of total inpatient days). The incidence of severe CDI was 12.6% (2.63/1000 of all-cause hospitalizations). Distribution of CDI cases was different according to the unit type, with highest incidence rates in hematology, gastroenterology and nephrology units (32.9, 25 and 24.6/1000 admissions, respectively) and lowest rates in 1.4% (33/2312) in endocrinology and general internal medicine (14.2 and 16.9/1000 admissions) units. Recurrence of CDI was 11.3% within 12 wk after discharge. Duration of hospital stay was longer in patients with CDI compared to controls (17.6 ± 10.8 d vs 12.4 ± 7.71 d). CDI accounted for 6.3% of all-inpatient deaths, and 30-d mortality rate was 21.9% (54/247 cases). Risk factors for CDI were antibiotic therapy [including third-generation cephalosporins or fluoroquinolones, odds ratio (OR) = 4.559; P < 0.001], use of proton pump inhibitors (OR = 2.082, P < 0.001), previous hospitalization within 12 mo (OR = 3.167, P < 0.001), previous CDI (OR = 15.32; P < 0.001), while presence of diabetes mellitus was associated with a decreased risk for CDI (OR = 0.484; P < 0.001). Treatment of recurrent cases was significantly different from primary infections with more frequent use of vancomycin alone or in combination (P < 0.001), and antibiotic therapy duration was longer (P < 0.02). Severity, mortality and outcome of primary infections and relapsing cases did not significantly differ. CONCLUSION: CDI was accounted for significant burden with longer hospitalization and adverse outcomes. Antibiotic, PPI therapy and previous hospitalization or CDI were risk factors for CDI. PMID:26074711

Community for Data Integration 2016 annual report

USGS Publications Warehouse

Langseth, Madison L.; Hsu, Leslie; Amberg, Jon J.; Bliss, Norman; Bock, Andrew R.; Bolus, Rachel T.; Bristol, R. Sky; Chase, Katherine J.; Crimmins, Theresa M.; Earle, Paul S.; Erickson, Richard; Everette, A. Lance; Falgout, Jeff T.; Faundeen, John L.; Fienen, Michael N.; Griffin, Rusty; Guy, Michelle R.; Henry, Kevin D.; Hoebelheinrich, Nancy J.; Hunt, Randall; Hutchison, Vivian B.; Ignizio, Drew A.; Infante, Dana M.; Jarnevich, Catherine; Jones, Jeanne M.; Kern, Tim; Leibowitz, Scott; Lightsom, Francis L.; Marsh, R. Lee; McCalla, S. Grace; McNiff, Marcia; Morisette, Jeffrey T.; Nelson, John C.; Norkin, Tamar; Preston, Todd M.; Rosemartin, Alyssa; Sando, Roy; Sherba, Jason T.; Signell, Richard P.; Sleeter, Benjamin M.; Sundquist, Eric T.; Talbert, Colin B.; Viger, Roland J.; Weltzin, Jake F.; Waltman, Sharon; Weber, Marc; Wieferich, Daniel J.; Williams, Brad; Windham-Myers, Lisamarie

2017-05-19

The Community for Data Integration (CDI) represents a dynamic community of practice focused on advancing science data and information management and integration capabilities across the U.S. Geological Survey and the CDI community. This annual report describes the various presentations, activities, and outcomes of the CDI monthly forums, working groups, virtual training series, and other CDI-sponsored events in fiscal year 2016. The report also describes the objectives and accomplishments of the 13 CDI-funded projects in fiscal year 2016.

Current knowledge on the laboratory diagnosis of Clostridium difficile infection

PubMed Central

Martínez-Meléndez, Adrián; Camacho-Ortiz, Adrián; Morfin-Otero, Rayo; Maldonado-Garza, Héctor Jesús; Villarreal-Treviño, Licet; Garza-González, Elvira

2017-01-01

Clostridium difficile (C. difficile) is a spore-forming, toxin-producing, gram-positive anaerobic bacterium that is the principal etiologic agent of antibiotic-associated diarrhea. Infection with C. difficile (CDI) is characterized by diarrhea in clinical syndromes that vary from self-limited to mild or severe. Since its initial recognition as the causative agent of pseudomembranous colitis, C. difficile has spread around the world. CDI is one of the most common healthcare-associated infections and a significant cause of morbidity and mortality among older adult hospitalized patients. Due to extensive antibiotic usage, the number of CDIs has increased. Diagnosis of CDI is often difficult and has a substantial impact on the management of patients with the disease, mainly with regards to antibiotic management. The diagnosis of CDI is primarily based on the clinical signs and symptoms and is only confirmed by laboratory testing. Despite the high burden of CDI and the increasing interest in the disease, episodes of CDI are often misdiagnosed. The reasons for misdiagnosis are the lack of clinical suspicion or the use of inappropriate tests. The proper diagnosis of CDI reduces transmission, prevents inadequate or unnecessary treatments, and assures best antibiotic treatment. We review the options for the laboratory diagnosis of CDI within the settings of the most accepted guidelines for CDI diagnosis, treatment, and prevention of CDI. PMID:28321156

Identification of target risk groups for population-based Clostridium difficile infection prevention strategies using a population attributable risk approach.

PubMed

Oh, Sung-Hee; Kang, Hye-Young

2018-01-01

We aimed to determine risk factors associated with Clostridium difficile infection (CDI) and assess the contributions of these factors on CDI burden. We conducted a 1:4 matched case-control study using a national claims dataset. Cases were incident CDI without a history of CDI in the previous 84 days, and were age- and sex-matched with control patients. We ascertained exposure, defined as a history of morbidities and drug use within 90 days. The population attributable risk (PAR) percent for risk factors was estimated using odds ratios (ORs) obtained from the case-control study. Overall, the strongest CDI-associated risk factors, which have significant contributions to the CDI burden as well, were the experience of gastroenteritis (OR=5.08, PAR%=17.09%) and use of antibiotics (OR=1.69, PAR%=19.00%), followed by the experiences of female pelvic infection, irritable bowel syndrome, inflammatory bowel disease, and pneumonia, and use of proton-pump inhibitors (OR=1.52-2.37, PAR%=1.95-2.90). The control of risk factors that had strong association with CDI and affected large proportions of total CDI cases would be beneficial for CDI prevention. We suggest performing CDI testing for symptomatic patients with gastroenteritis and implementing antibiotics stewardship. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Early central diabetes insipidus: An ominous sign in post-cardiac arrest patients.

PubMed

Chae, Minjung Kathy; Lee, Jeong Hoon; Lee, Tae Rim; Yoon, Hee; Hwang, Sung Yeon; Cha, Won Chul; Shin, Tae Gun; Sim, Min Seob; Jo, Ik Joon; Song, Keun Jeong; Rhee, Joong Eui; Jeong, Yeon Kwon

2016-04-01

Central diabetes insipidus (CDI) after cardiac arrest is not well described. Thus, we aim to study the occurrences, outcomes, and risk factors of CDI of survivors after out-of-hospital cardiac arrest (OHCA). We retrospectively analyzed post-OHCA patients treated at a single center. Central diabetes insipidus was retrospectively defined by diagnostic criteria. One-month cerebral performance category (CPC) scores were collected for outcomes. Of the 169 patients evaluated, 36 patients (21.3%) were diagnosed with CDI. All CDI patients had a poor neurologic outcome of either CPC 4 (13.9%) or CPC 5 (86.1%), and CDI was strongly associated with mortality. Age (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.93-0.99), respiratory arrest (OR, 6.62; 95% CI, 1.23-35.44), asphyxia (OR, 9.26; 95% CI, 2.17-34.61), and gray to white matter ratio on brain computed tomogram (OR, 0.88; 95% CI, 0.81-0.95) were associated with the development of CDI. The onset of CDI was earlier (P < .001) and the maximum 24-hour urine output was larger (P = .03) in patients with worst outcomes. All patients diagnosed with CDI had poor neurologic outcomes, and occurrence of CDI was associated with mortality. Central diabetes insipidus patients with death or brain death had earlier occurrence of CDI and more maximum urine output. Copyright © 2015 Elsevier Inc. All rights reserved.

Prevention of Clostridium difficile infection in rural hospitals.

PubMed

Haun, Nicholas; Hofer, Adam; Greene, M Todd; Borlaug, Gwen; Pritchett, Jenny; Scallon, Tina; Safdar, Nasia

2014-03-01

Prevention of Clostridium difficile infection (CDI) remains challenging across the spectrum of health care. There are limited data on prevention practices for CDI in the rural health care setting. An electronic survey was administered to 21 rural facilities in Wisconsin, part of the Rural Wisconsin Health Cooperative. Data were collected on hospital characteristics and practices to prevent endemic CDI. Fifteen facilities responded (71%). Nearly all respondent facilities reported regular use of dedicated patient care items, use of gown and gloves, private patient rooms, hand hygiene, and room cleaning. Facilities in which the infection preventionist thought the support of his/her leadership to be "Very good" or "Excellent" employed significantly more CDI practices (13.3 ± 2.4 [standard deviation]) compared with infection preventionists who thought there was less support from leadership (9.8 ± 3.0, P = .033). Surveillance for CDI was highly variable. The most frequent barriers to implementation of CDI prevention practices included lack of adequate resources, lack of a physician champion, and difficulty keeping up with new recommendations. Although most rural facilities in our survey reported using evidence-based practices for prevention of CDI, surveillance practices were highly variable, and data regarding the impact of these practices on CDI rates were limited. Future efforts that correlate CDI prevention initiatives and CDI incidence will help develop evidence-based practices in these resource-limited settings. Published by Mosby, Inc.

The presence of IL-8 +781 T/C polymorphism is associated with the parameters of severe Clostridium difficile infection.

PubMed

Czepiel, Jacek; Biesiada, Grażyna; Dróżdż, Mirosław; Gdula-Argasińska, Joanna; Żurańska, Justyna; Marchewka, Jakub; Perucki, William; Wołkow, Paweł; Garlicki, Aleksander

2018-01-01

There is large variation in the clinical manifestations of Clostridium difficile infection (CDI). We also still can not predict which patients are more susceptible to reinfection with CDI. The aim of our study was to evaluate the effect of gene single nucleotide polymorphisms (SNP) of proinflammatory cytokines, specifically IL-1β, IL-8 on the development, clinical course and recurrence of CDI. We performed a prospective study of adults (130 people ≥ 18 years) including 65 patients with CDI treated in tertiary hospital and 65 healthy persons. The following 3 variants were analyzed for the occurrence of gene polymorphisms in patients with CDI versus the control group: IL-1β +3953 A/G (rs1143634), IL-1β -31 A/G (rs1143627), and IL-8 +781 T/C (rs2227306). Then, we assessed the correlation between these genetic polymorphisms and biochemical parameters important in CDI course, CDI severity as well as CDI recurrence. The presence of genetic polymorphisms of IL-1β +3953 A/G, -31 A/G and IL-8 +781 T/C did not have an effect on the development or recurrence of CDI. The presence of IL-8 +781 T/C polymorphism is associated with the severe CDI. Copyright © 2017 Elsevier Ltd. All rights reserved.

INCIDENCE OF CENTRAL DIABETES INSIPIDUS IN CHILDREN PRESENTING WITH POLYDIPSIA AND POLYURIA.

PubMed

Haddad, Nadine G; Nabhan, Zeina M; Eugster, Erica A

2016-12-01

Polydipsia and polyuria are common reasons for referral to the Pediatric Endocrine clinic. In the absence of hyperglycemia, diabetes insipidus (DI) should be considered. The objectives of the study were to determine the prevalence of central DI (CDI) in a group of children presenting for evaluation of polydipsia and polyuria, and to determine if predictive features were present in patients in whom the diagnosis of DI was made. The study was a retrospective chart review of children presenting to the endocrine clinic with complaints of polydipsia and polyuria over a 5-year period. The charts of 41 patients (mean age 4.9 ± 3.7 years, 28 males) were reviewed. CDI was diagnosed in 8 (20%) children based on abnormal water deprivation test (WDT) results. All but one patient had abnormal magnetic resonance imaging (MRI) findings, the most common being pituitary stalk thickening. Children with DI were older (7.86 ± 4.40 vs. 4.18 ± 3.20 years, P = .01) and had a higher propensity for cold beverages intake and unusual water-seeking behaviors compared to those without DI. Baseline WDT also revealed higher serum sodium (Na) and osmolality. The incidence of CDI in children presenting with polydipsia and polyuria is low. Factors associated with higher likelihood of pathology include older age, propensity for cold beverage intake, and higher baseline serum Na and osmolality on a WDT. BMI = body mass index CDI = central diabetes insipidus DI = diabetes insipidus Na = sodium WDT = water deprivation test.

Management of diabetes insipidus in children

PubMed Central

Mishra, Garima; Chandrashekhar, Sudha Rao

2011-01-01

Diabetes Insipidus (DI) is a heterogeneous clinical syndrome of disturbance in water balance, characterized by polyuria (urine output > 4 ml/kg/hr), polydypsia (water intake > 2 L/m2/d) and failure to thrive. In children, Nephrogenic DI (NDI) is more common than Central DI (CDI), and is often acquired. The signs and symptoms vary with etiology, age at presentation and mode of onset. Neonates and infants with NDI are severely affected and difficult to treat. Diagnosis is based on the presence of high plasma osmolality and low urinary osmolality with significant water diuresis. Water deprivation test with vasopressin challenge, though has limitations, is done to differentiate NDI and CDI and diagnose their partial forms. Measurement of urinary aquaporin 2 and serum copeptin levels are being studied and show promising diagnostic potential. Magnetic Resonance Imaging (MRI) pituitary helps in the etiological diagnosis of CDI, absence of posterior pituitary bright signal being the pathognomic sign. If pituitary stalk thickening of < 2 mm is present, these children need to be monitored for evolving lesion. Neonates and young infants are better managed with fluids alone. Older children with CDI are treated with desmopressin. The oral form is safe, highly effective, with more flexibility of dosing and has largely replaced the intranasal form. In NDI besides treatment of the underlying cause, use of high calorie low solute diet and drugs to ameliorate water excretion (thiazide, amelioride, indomethacin) are useful. Children with NDI however well treated, remain short and have mental retardation on follow up. PMID:22029022

Is Clostridium difficile infection a risk factor for subsequent bloodstream infection?

PubMed

Ulrich, Robert J; Santhosh, Kavitha; Mogle, Jill A; Young, Vincent B; Rao, Krishna

2017-12-01

Clostridium difficile infection (CDI) is a common nosocomial diarrheal illness increasingly associated with mortality in United States. The underlying factors and mechanisms behind the recent increases in morbidity from CDI have not been fully elucidated. Murine models suggest a mucosal barrier breakdown leads to bacterial translocation and subsequent bloodstream infection (BSI). This study tests the hypothesis that CDI is associated with subsequent BSI in humans. We conducted a retrospective cohort study on 1132 inpatients hospitalized >72 h with available stool test results for toxigenic C. difficile. The primary outcome was BSI following CDI. Secondary outcomes included 30-day mortality, colectomy, readmission, and ICU admission. Unadjusted and adjusted logistic regression models were developed. CDI occurred in 570 of 1132 patients (50.4%). BSI occurred in 86 (7.6%) patients. Enterococcus (14%) and Klebsiella (14%) species were the most common organisms. Patients with BSI had higher comorbidity scores and were more likely to be male, on immunosuppression, critically ill, and have a central venous catheter in place. Of the patients with BSI, 36 (42%) had CDI. CDI was not associated with subsequent BSI (OR 0.69; 95% CI 0.44-1.08; P = 0.103) in unadjusted analysis. In multivariable modeling, CDI appeared protective against subsequent BSI (OR 0.57; 95% CI 0.34-0.96; P = 0.036). Interaction modeling suggests a complicated relationship among CDI, BSI, antibiotic exposure, and central venous catheter use. In this cohort of inpatients that underwent testing for CDI, CDI was not a risk factor for developing subsequent BSI. Copyright © 2017 Elsevier Ltd. All rights reserved.

The emergence of Clostridium difficile infection in Asia: A systematic review and meta-analysis of incidence and impact

PubMed Central

Borren, Nienke Z.; Ghadermarzi, Shadi; Hutfless, Susan

2017-01-01

Background Clostridium difficile infection (CDI) is the most common healthcare associated infection and is highly prevalent in Europe and North America. Limited data is available on the prevalence of CDI in Asia. However, secular increases in prevalence of risk factors for CDI suggest that it may be emerging as a major cause of morbidity, highlighting the urgent need for a systematic study of the prevalence of CDI in Asia. Methods We systematically searched PubMed/Medline and Embase for publications from Asia between 2000–16 examining prevalence of CDI. A random-effects meta-analysis was performed to calculate the pooled prevalence of CDI in Asia and to identify subgroups and regions at high risk. Results Our meta-analysis included 51 studies from throughout Asia including 37,663 patients at risk among whom confirmed CDI was found in 4,343 patients. The pooled proportion of confirmed CDI among all patients with diarrhea was 14.8% with a higher prevalence in East Asia (19.5%), compared with South Asia (10.5%) or the Middle East (11.1%). There were an estimated 5.3 episodes of CDI per 10,000 patient days, similar to rates reported from Europe and North America. Infections due to hypervirulent strains were rare. CDI-related mortality was 8.9%. Conclusions In a meta-analysis of 51 studies, we observed similar rates of CDI in Asia in comparison to Europe and North America. Increased awareness and improved surveillance of Clostridium difficile is essential to reduce incidence and morbidity. PMID:28463987

Body image in patients with adolescent idiopathic scoliosis: validation of the Body Image Disturbance Questionnaire--Scoliosis Version.

PubMed

Auerbach, Joshua D; Lonner, Baron S; Crerand, Canice E; Shah, Suken A; Flynn, John M; Bastrom, Tracey; Penn, Phedra; Ahn, Jennifer; Toombs, Courtney; Bharucha, Neil; Bowe, Whitney P; Newton, Peter O

2014-04-16

Appearance concerns in individuals with adolescent idiopathic scoliosis can result in impairment in daily functioning, or body image disturbance. The Body Image Disturbance Questionnaire (BIDQ) is a self-reported, seven-question instrument that measures body image disturbance in general populations; no studies have specifically examined body image disturbance in those with adolescent idiopathic scoliosis. This study aimed to validate a modified version of the BIDQ in a population with adolescent idiopathic scoliosis and to establish discriminant validity by comparing responses of operatively and nonoperatively treated patients with those of normal controls. In the first phase, a multicenter study of forty-nine patients (mean age, fourteen years; thirty-seven female) with adolescent idiopathic scoliosis was performed to validate the BIDQ-Scoliosis version (BIDQ-S). Participants completed the BIDQ-S, Scoliosis Research Society (SRS)-22, Children's Depression Index (CDI), and Body Esteem Scale for Adolescents and Adults (BESAA) questionnaires. Descriptive statistics and Pearson correlation coefficients were calculated. In the second phase, ninety-eight patients with adolescent idiopathic scoliosis (mean age, 15.7 years; seventy-five female) matched by age and sex with ninety-eight healthy adolescents were enrolled into a single-center study to evaluate the discriminant validity of the BIDQ-S. Subjects completed the BIDQ-S and a demographic form before treatment. Independent-sample t tests and Pearson correlation coefficients were calculated. The BIDQ-S was internally consistent (Cronbach alpha = 0.82), and corrected item total correlations ranged from 0.47 to 0.67. The BIDQ-S was significantly correlated with each domain of the SRS-22 and the total score (r = -0.50 to -0.72, p ≤ 0.001), with the CDI (r = 0.31, p = 0.03), and with the BESAA (r = 0.60, p < 0.001). BIDQ-S scores differed significantly between patients (1.50) and controls (1.06, p < 0.005), establishing discriminant validity. The BIDQ-S is an internally consistent outcomes instrument that correlated with the SRS-22, CDI, and BESAA outcomes instruments in a scoliosis population. The scores of the patients with scoliosis indicated greater back-related body image disturbance compared with healthy controls. To our knowledge, this user-friendly instrument is the first to examine body image disturbance in adolescent idiopathic scoliosis, and it provides a comprehensive evaluation of how scoliosis-related appearance concerns impact psychosocial and daily functioning.

76 FR 58045 - Amended Certification Regarding Eligibility To Apply for Worker Adjustment Assistance; Applied...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-19

... Leased Workers From Adecco Employment Services, Aerotek, Inc., CDI IT Solutions, Inc. (CDI Corporation..., Aerotek, Inc., CDI IT Solutions, D&Z Microelectronics, Pentagon Technology, Proactive Business Solution... include the Unemployment Insurance (UI) wages for on-site leased workers from CDI IT Solutions is reported...

Clostridium difficile Infection in Children: Current State and Unanswered Questions

PubMed Central

Tamma, Pranita D.; Sandora, Thomas J.

2012-01-01

The incidence of Clostridium difficile infection (CDI) in children has increased over the past decade. In recent years, new and intriguing data on pediatric CDI have emerged. Community-onset infections are increasingly recognized, even in children who have not previously received antibiotics. A hypervirulent strain is responsible for up to 20% of pediatric CDI cases. Unique risk factors for CDI in children have been identified. Advances in diagnostic testing strategies, including the use of nucleic acid amplification tests, have raised new questions about the optimal approach to diagnosing CDI in children. Novel therapeutic options are available for adult patients with CDI, raising questions about the use of these agents in children. Updated recommendations about infection prevention and control measures are now available. We summarize these recent developments in pediatric CDI in this review and also highlight remaining knowledge gaps that should be addressed in future research efforts. PMID:23687578

Central diabetes insipidus as a very late relapse limited to the pituitary stalk in Langerhans cell histiocytosis.

PubMed

Nakagawa, Shunsuke; Shinkoda, Yuichi; Hazeki, Daisuke; Imamura, Mari; Okamoto, Yasuhiro; Kawakami, Kiyoshi; Kawano, Yoshifumi

2016-07-01

Central diabetes insipidus (CDI) and relapse are frequently seen in multifocal Langerhans cell histiocytosis (LCH). We present two females with multifocal LCH who developed CDI 9 and 5 years after the initial diagnosis, respectively, as a relapse limited to the pituitary stalk. Combination chemotherapy with cytarabine reduced the mass in the pituitary stalk. Although CDI did not improve, there has been no anterior pituitary hormone deficiency (APHD), neurodegenerative disease in the central nervous system (ND-CNS) or additional relapse for 2 years after therapy. It was difficult to predict the development of CDI in these cases. CDI might develop very late in patients with multifocal LCH, and therefore strict follow-up is necessary, especially with regard to symptoms of CDI such as polydipsia and polyuria. For new-onset CDI with LCH, chemotherapy with cytarabine might be useful for preventing APHD and ND-CNS.

Risk factors for the development of Clostridium difficile infection in hospitalized children.

PubMed

Samady, Waheeda; Pong, Alice; Fisher, Erin

2014-10-01

This article defines the risk factors for Clostridium difficile infection (CDI) in hospitalized children in light of recent studies demonstrating a change in the epidemiology of these infections in both adults and children. Antibiotic exposure within the past 4-12 weeks was noted in a majority of published cases of pediatric CDI, and that remains a key risk factor for infection. Past and/or prolonged hospitalization increase a child's risk for CDI as they increase potential contact with C. difficile spores. Of all CDI, hospital-acquired infection remains more common. Many comorbid conditions have been linked with CDI, with the strongest association existing in children with cancer and inflammatory bowel disease. Severe infections occur infrequently in pediatric patients. Markers established in adults for severe CDI resulting in colectomy or transfer to ICU have not been shown to correlate in pediatric patients. Recent antibiotic exposure and hospitalization remain key risk factors for CDI in the hospitalized pediatric patient. Patients with comorbid conditions such as malignancy and inflammatory bowel disease are at higher risk for CDI. Resistant infections and severe outcomes are not common in the pediatric population.

Hospitalization stay and costs attributable to Clostridium difficile infection: a critical review.

PubMed

Gabriel, L; Beriot-Mathiot, A

2014-09-01

In most healthcare systems, third-party payers fund the costs for patients admitted to hospital for Clostridium difficile infection (CDI) whereas, for CDI cases arising as complications of hospitalization, not all related costs are refundable to the hospital. We therefore aimed to critically review and categorize hospital costs and length of hospital stay (LOS) attributable to Clostridium difficile infection and to investigate the economic burden associated with it. A comprehensive literature review selected papers describing the costs and LOS for hospitalized patients as outcomes of CDI, following the use of statistics to identify costs and LOS solely attributable to CDI. Twenty-four studies were selected. Estimated attributable costs, all ranges expressed in US dollars, were $6,774-$10,212 for CDI requiring admission, $2,992-$29,000 for hospital-acquired CDI, and $2,454-$12,850 where no categorization was made. The ranges for LOS values were 5-13.6, 2.7-21.3, and 2.8-17.9 days, respectively. The categorization of CDI attributable costs allows budget holders to anticipate the cost per CDI case, a perspective that should enrich the design of appropriate incentives for the various budget holders to invest in prevention so that CDI prevention is optimized globally. Copyright © 2014 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Clostridium difficile in the ICU: the struggle continues.

PubMed

Bobo, Linda D; Dubberke, Erik R; Kollef, Marin

2011-12-01

Clostridium difficile infection (CDI) management has become more daunting over the past decade because of alarming increases in CDI incidence and severity both in the hospital and in the community. This increase has concomitantly caused significant escalation of the health-care economic burden caused by CDI, and it will likely be translated to increased ICU admission and attributable mortality. Some possible causes for difficulty in management of CDI are as follows: (1) inability to predict and prevent development of severe/complicated or relapsing CDI in patients who initially present with mild symptoms; (2) lack of a method to determine who would have benefited a priori from initiating vancomycin treatment first instead of treatment with metronidazole; (3) lack of sensitive and specific CDI diagnostics; (4) changing epidemiology of CDI, including the emergence of a hypervirulent, epidemic C difficile strain associated with increased morbidity and mortality; (5) association of certain high-usage nonantimicrobial medications with CDI; and (6) lack of treatment regimens that leave the normal intestinal flora undisturbed while treating the primary infection. The objective of this article is to present current management and prevention guidelines for CDI based on recommendations by the Society for Healthcare Epidemiology of America and Infectious Diseases Society of America and potential new clinical management strategies on the horizon.

Clostridium difficile in the ICU

PubMed Central

Dubberke, Erik R.; Kollef, Marin

2011-01-01

Clostridium difficile infection (CDI) management has become more daunting over the past decade because of alarming increases in CDI incidence and severity both in the hospital and in the community. This increase has concomitantly caused significant escalation of the health-care economic burden caused by CDI, and it will likely be translated to increased ICU admission and attributable mortality. Some possible causes for difficulty in management of CDI are as follows: (1) inability to predict and prevent development of severe/complicated or relapsing CDI in patients who initially present with mild symptoms; (2) lack of a method to determine who would have benefited a priori from initiating vancomycin treatment first instead of treatment with metronidazole; (3) lack of sensitive and specific CDI diagnostics; (4) changing epidemiology of CDI, including the emergence of a hypervirulent, epidemic C difficile strain associated with increased morbidity and mortality; (5) association of certain high-usage nonantimicrobial medications with CDI; and (6) lack of treatment regimens that leave the normal intestinal flora undisturbed while treating the primary infection. The objective of this article is to present current management and prevention guidelines for CDI based on recommendations by the Society for Healthcare Epidemiology of America and Infectious Diseases Society of America and potential new clinical management strategies on the horizon. PMID:22147824

Clinical manifestations of Clostridium difficile infection in a medical center in Taiwan.

PubMed

Lai, Chih-Cheng; Lin, Sheng-Hsiang; Tan, Che-Kim; Liao, Chun-Hsing; Huang, Yu-Tsung; Hsueh, Po-Ren

2014-12-01

To investigate the clinical characteristics of Clostridium difficile infection (CDI) at a medical center in Taiwan. Patients with CDI were identified from medical records at the National Taiwan University Hospital (Taipei, Taiwan). The following information was gathered and analyzed to better understand the clinical manifestations of CDI: age; sex; underlying immunocompromised conditions; laboratory data; in-hospital mortality; and previous use of drugs such as antimicrobial agents, steroids, and antipeptic ulcer agents. During the years 2000-2010, 122 patients were identified as having CDI. This included 92 patients with nontoxigenic CDI (i.e., positive stool culture for C. difficile but negative results for toxins A and B) and 30 patients with toxigenic CDI (i.e., positive stool culture cultures for C. difficile and positive results for toxins A and B). Of the 122 patients, 48 (39%) patients were older than 65 years and most patients acquired the CDI while in the hospital. Active cancer was the most common reason for hospitalization, followed by diabetes mellitus, and end-stage renal disease. More than 90% of the patients had received antibiotics before acquiring CDI. The results of fecal leukocyte examinations were positive in 33 (27%) patients. The overall in-hospital mortality rate was 26.2%. There were no significant differences between patients with nontoxigenic CDI and patients with toxigenic CDI. Clostridium difficile infection can develop in healthcare facilities and in community settings, especially in immunocompromised patients. Copyright © 2013. Published by Elsevier B.V.

Predictors of failure after single faecal microbiota transplantation in patients with recurrent Clostridium difficile infection: results from a 3-year, single-centre cohort study.

PubMed

Ianiro, G; Valerio, L; Masucci, L; Pecere, S; Bibbò, S; Quaranta, G; Posteraro, B; Currò, D; Sanguinetti, M; Gasbarrini, A; Cammarota, G

2017-05-01

Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI). Although a single faecal infusion is usually sufficient to eradicate CDI, a considerable number of patients need multiple infusions to be cured. The aim of this study was to identify predictors of failure after single faecal infusion in patients with recurrent CDI. We included patients with recurrent CDI prospectively treated with FMT by colonoscopy. By means of univariate and multivariate analysis, variables including female gender, age, number of CDI recurrences, severity of CDI, hospitalization, inadequate bowel preparation, unrelated donor, and use of frozen faeces, were assessed to predict failure after single faecal infusion. Sixty-four patients (39 women; mean age 74 years) were included. Of them, 44 (69%) were cured by a single faecal infusion, whereas 20 (31%) needed repeat infusions. Overall, FMT cured 62 of 64 (97%) patients. In the subgroup of patients with severe CDI, only eight of 26 (30%) were cured with a single infusion. At multivariate analysis, severe CDI (OR 24.66; 95% CI 4.44-242.08; p 0.001) and inadequate bowel preparation (OR 11.53; 95% CI 1.71-115.51; p 0.019) were found to be independent predictors of failure after single faecal infusion. Severe CDI and inadequate bowel preparation appear to be independent predictors of failure after single faecal infusion in patients treated with FMT by colonoscopy for recurrent CDI. Our results may help to optimize protocols and outcomes of FMT in patients with recurrent CDI. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Predicting the risk for hospital-onset Clostridium difficile infection (HO-CDI) at the time of inpatient admission: HO-CDI risk score.

PubMed

Tabak, Ying P; Johannes, Richard S; Sun, Xiaowu; Nunez, Carlos M; McDonald, L Clifford

2015-06-01

To predict the likelihood of hospital-onset Clostridium difficile infection (HO-CDI) based on patient clinical presentations at admission Retrospective data analysis Six US acute care hospitals Adult inpatients We used clinical data collected at the time of admission in electronic health record (EHR) systems to develop and validate a HO-CDI predictive model. The outcome measure was HO-CDI cases identified by a nonduplicate positive C. difficile toxin assay result with stool specimens collected >48 hours after inpatient admission. We fit a logistic regression model to predict the risk of HO-CDI. We validated the model using 1,000 bootstrap simulations. Among 78,080 adult admissions, 323 HO-CDI cases were identified (ie, a rate of 4.1 per 1,000 admissions). The logistic regression model yielded 14 independent predictors, including hospital community onset CDI pressure, patient age ≥65, previous healthcare exposures, CDI in previous admission, admission to the intensive care unit, albumin ≤3 g/dL, creatinine >2.0 mg/dL, bands >32%, platelets ≤150 or >420 109/L, and white blood cell count >11,000 mm3. The model had a c-statistic of 0.78 (95% confidence interval [CI], 0.76-0.81) with good calibration. Among 79% of patients with risk scores of 0-7, 19 HO-CDIs occurred per 10,000 admissions; for patients with risk scores >20, 623 HO-CDIs occurred per 10,000 admissions (P<.0001). Using clinical parameters available at the time of admission, this HO-CDI model demonstrated good predictive ability, and it may have utility as an early risk identification tool for HO-CDI preventive interventions and outcome comparisons.

Epidemiological and economic burden of Clostridium difficile in the United States: estimates from a modeling approach.

PubMed

Desai, Kamal; Gupta, Swati B; Dubberke, Erik R; Prabhu, Vimalanand S; Browne, Chantelle; Mast, T Christopher

2016-06-18

Despite a large increase in Clostridium difficile infection (CDI) severity, morbidity and mortality in the US since the early 2000s, CDI burden estimates have had limited generalizability and comparability due to widely varying clinical settings, populations, or study designs. A decision-analytic model incorporating key input parameters important in CDI epidemiology was developed to estimate the annual number of initial and recurrent CDI cases, attributable and all-cause deaths, economic burden in the general population, and specific number of high-risk patients in different healthcare settings and the community in the US. Economic burden was calculated adopting a societal perspective using a bottom-up approach that identified healthcare resources consumed in the management of CDI. Annually, a total of 606,058 (439,237 initial and 166,821 recurrent) episodes of CDI were predicted in 2014: 34.3 % arose from community exposure. Over 44,500 CDI-attributable deaths in 2014 were estimated to occur. High-risk susceptible individuals representing 5 % of the total hospital population accounted for 23 % of hospitalized CDI patients. The economic cost of CDI was $5.4 billion ($4.7 billion (86.7 %) in healthcare settings; $725 million (13.3 %) in the community), mostly due to hospitalization. A modeling framework provides more comprehensive and detailed national-level estimates of CDI cases, recurrences, deaths and cost in different patient groups than currently available from separate individual studies. As new treatments for CDI are developed, this model can provide reliable estimates to better focus healthcare resources to those specific age-groups, risk-groups, and care settings in the US where they are most needed. (Trial Identifier ClinicaTrials.gov: NCT01241552).

Excess Length of Stay Attributable to Clostridium difficile Infection (CDI) in the Acute Care Setting: A Multistate Model.

PubMed

Stevens, Vanessa W; Khader, Karim; Nelson, Richard E; Jones, Makoto; Rubin, Michael A; Brown, Kevin A; Evans, Martin E; Greene, Tom; Slade, Eric; Samore, Matthew H

2015-09-01

Standard estimates of the impact of Clostridium difficile infections (CDI) on inpatient lengths of stay (LOS) may overstate inpatient care costs attributable to CDI. In this study, we used multistate modeling (MSM) of CDI timing to reduce bias in estimates of excess LOS. A retrospective cohort study of all hospitalizations at any of 120 acute care facilities within the US Department of Veterans Affairs (VA) between 2005 and 2012 was conducted. We estimated the excess LOS attributable to CDI using an MSM to address time-dependent bias. Bootstrapping was used to generate 95% confidence intervals (CI). These estimates were compared to unadjusted differences in mean LOS for hospitalizations with and without CDI. During the study period, there were 3.96 million hospitalizations and 43,540 CDIs. A comparison of unadjusted means suggested an excess LOS of 14.0 days (19.4 vs 5.4 days). In contrast, the MSM estimated an attributable LOS of only 2.27 days (95% CI, 2.14-2.40). The excess LOS for mild-to-moderate CDI was 0.75 days (95% CI, 0.59-0.89), and for severe CDI, it was 4.11 days (95% CI, 3.90-4.32). Substantial variation across the Veteran Integrated Services Networks (VISN) was observed. CDI significantly contributes to LOS, but the magnitude of its estimated impact is smaller when methods are used that account for the time-varying nature of infection. The greatest impact on LOS occurred among patients with severe CDI. Significant geographic variability was observed. MSM is a useful tool for obtaining more accurate estimates of the inpatient care costs of CDI.

Clostridium difficile infection is associated with increased risk of death and prolonged hospitalization in children.

PubMed

Sammons, Julia Shaklee; Localio, Russell; Xiao, Rui; Coffin, Susan E; Zaoutis, Theoklis

2013-07-01

Clostridium difficile infection (CDI) is associated with significant morbidity and mortality among adults. However, outcomes are poorly defined among children. A retrospective cohort study was performed among hospitalized children at 41 children's hospitals between January 2006 and August 2011. Patients with CDI (exposed) were matched 1:2 to patients without CDI (unexposed) based on the probability of developing CDI (propensity score derived from patient characteristics). Exposed subjects were stratified by C. difficile test date, suggestive of community-onset (CO) versus hospital-onset (HO) CDI. Outcomes were analyzed for matched subjects. We identified 5107 exposed and 693 409 unexposed subjects. Median age was 6 years (interquartile range [IQR], 2-13 years) for exposed and 8 years (IQR, 3-14 years) for unexposed subjects. Of these, 4474 exposed were successfully matched to 8821 unexposed by propensity score. In-hospital mortality differed significantly (CDI, 1.43% vs matched unexposed, 0.66%; P < .001). Mortality rates were similar between CO-CDI and matched subjects. However, mortality rates were significantly greater among HO-CDI compared with matched unexposed (odds ratio, 6.73 [95% confidence interval {CI}, 3.77-12.02]). Mean differences in length of stay (LOS) and total cost were significant: 5.55 days (95% CI, 4.54-6.56 days) and $18 900 (95% CI, $15 100-$22 700) for CO-CDI, and 21.60 days (95% CI, 19.29-23.90 days) and $93 600 (95% CI, $80 000-$107 200) for HO-CDI. Pediatric CDI is associated with increased mortality, longer LOS, and higher costs. These findings underscore the importance of antibiotic stewardship and infection control programs to prevent this disease in children.

Mortality, Hospital Costs, Payments, and Readmissions Associated With Clostridium difficile Infection Among Medicare Beneficiaries.

PubMed

Drozd, Edward M; Inocencio, Timothy J; Braithwaite, Shamonda; Jagun, Dayo; Shah, Hemal; Quon, Nicole C; Broderick, Kelly C; Kuti, Joseph L

2015-11-01

The management of Clostridium difficile infection (CDI) among hospitalized patients is costly, and ongoing payment reform is compelling hospitals to reduce its burden. To assess the impact of CDI on mortality, hospital costs, healthcare use, and Medicare payments for beneficiaries who were discharged with CDI listed as a secondary International Classification of Diseases , Ninth Revision , Clinical Modification claim diagnosis. Data were analyzed from the 2009 to 2010 5% random sample Medicare Standard Analytic Files of beneficiary claims. Patients with index hospitalizations with CDI as a secondary diagnosis and no previous hospitalization within 30 days were identified. Outcomes included inpatient and 30-day mortality, inpatient costs, index hospital payments, all-provider payments, net hospital losses, payment to cost ratio, length of stay (LOS), and 30-day readmission; outcomes were each risk adjusted using propensity score matching and regression modeling techniques. A total of 3262 patients with CDI were identified after matching to patients without a CDI diagnosis. After risk adjustment, secondary CDI was associated with statistically significantly (all P < 0.05) greater inpatient mortality (3.1% vs. 1.7%), 30-day mortality (4.1% vs. 2.2%), longer LOS (7.0 days vs. 3.8 days), higher rates of 30-day hospital readmissions (14.8% vs. 10.4%), and greater hospital costs ($16,184 vs. $13,954) compared with the non-CDI cohort. The risk-adjusted payment-to-cost ratio was shown to be lower for patients with CDI than those without (0.76 vs. 0.85). Secondary CDI is associated with greater adjusted mortality, costs, LOS, and hospital readmissions, while receiving similar hospital reimbursement compared with patients without CDI in a Medicare population.

Consequences of Clostridium difficile infection: understanding the healthcare burden.

PubMed

Bouza, E

2012-12-01

Clostridium difficile is the leading cause of infectious nosocomial diarrhoea in developed countries, with a measured incidence of approximately five episodes per 10,000 days of hospital stay in Europe. Accurate diagnosis of C. difficile infection (CDI) is a prerequisite for obtaining reliable epidemiological data, but in many European countries diagnosis is probably suboptimal. A significant percentage of CDI cases are missed because clinicians often fail to request tests for C. difficile toxins in cases of unexplained diarrhoea. In addition, some laboratories continue to use tests of low sensitivity or apply them inappropriately. In one study in Spain, failure to request CDI testing in more than two-thirds of patients with unexplained diarrhoea led to significant underdiagnosis of cases. A recent pan-European survey revealed huge discrepancies in the rate of CDI testing across Europe, which suggests that epidemiological reports underestimate the true incidence of CDI in many parts of Europe. This is important because, as this review of the clinical and economic burden of CDI illustrates, infection with C. difficile imposes a significant burden not only on patients, owing to increased morbidity and mortality, but also on healthcare systems and society in general. On the basis of current incidence rates, annual costs for management of CDI amount to approximately $800 million in the USA and €3000 million in Europe. Moreover, estimates suggest that costs associated with recurrent CDI can exceed those of primary CDI. Measures to more effectively prevent CDI and reduce CDI recurrence rates may help to reduce this burden. © 2012 The Author Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

Mortality and Costs in Clostridium difficile Infection Among the Elderly in the United States.

PubMed

Shorr, Andrew F; Zilberberg, Marya D; Wang, Li; Baser, Onur; Yu, Holly

2016-11-01

OBJECTIVE To examine attributable mortality and costs of Clostridium difficile infection (CDI) in the Medicare population. DESIGN A population-based cohort study among US adults aged at least 65 years in the 2008-2010 Medicare 5% sample, with follow-up of 12 months. PATIENTS Incident CDI episode was defined by the International Classification of Diseases, Ninth Revision, Clinical Modification code of 008.45 and no other occurrences within the preceding 12 months. To quantify the adjusted mortality and costs we developed a 1:1 propensity-matched sample of CDI and non-CDI patients. RESULTS Among 1,165,165 patients included, 6,838 (0.6%) had a CDI episode in 2009 (82.5% healthcare-associated). Patients with CDI were older (mean [SD] age, 81.0±8.0 vs 77.0±7.7 years, P<.001), were more likely to come from the Northeast (27.4% vs 18.6%, P<.001), and had a higher comorbidity burden (Charlson score, 4.6±3.3 vs 1.7±2.1, P<.001). Hospitalizations (63.2% vs 6.0%, P<.001) and antibiotics (33.9% vs 12.5%, P<.001) within the prior 90 days were more common in the group with CDI. In the propensity-adjusted analysis, CDI was associated with near doubling of both mortality (42.6% vs 23.4%, P<.001) and total healthcare costs ($64,807±$66,480 vs $38,128±$46,485, P<.001). CONCLUSIONS Among elderly patients, CDI is associated with an increase in adjusted mortality and healthcare costs following a CDI episode. Nationwide annually this equals 240,000 patients with CDI, 46,000 potential deaths, and more than $6 billion in costs. Infect Control Hosp Epidemiol 2016;1-6.

Clostridium difficile and inflammatory bowel disease: role in pathogenesis and implications in treatment.

PubMed

Nitzan, Orna; Elias, Mazen; Chazan, Bibiana; Raz, Raul; Saliba, Walid

2013-11-21

Clostridium difficile (C. difficile) is the leading cause of antibiotic associated colitis and nosocomial diarrhea. Patients with inflammatory bowel disease (IBD) are at increased risk of developing C. difficile infection (CDI), have worse outcomes of CDI-including higher rates of colectomy and death, and experience higher rates of recurrence. However, it is still not clear whether C. difficile is a cause of IBD or a consequence of the inflammatory state in the intestinal environment. The burden of CDI has increased dramatically over the past decade, with severe outbreaks described in many countries, which have been attributed to a new and more virulent strain. A parallel rise in the incidence of CDI has been noted in patients with IBD. IBD patients with CDI tend be younger, have less prior antibiotic exposure, and most cases of CDI in these patients represent outpatient acquired infections. The clinical presentation of CDI in these patients can be unique-including diversion colitis, enteritis and pouchitis, and typical findings on colonoscopy are often absent. Due to the high prevalence of CDI in patients hospitalized with an IBD exacerbation, and the prognostic implications of CDI in these patients, it is recommended to test all IBD patients hospitalized with a disease flare for C. difficile. Treatment includes general measures such as supportive care and infection control measures. Antibiotic therapy with either oral metronidazole, vancomycin, or the novel antibiotic-fidaxomicin, should be initiated as soon as possible. Fecal macrobiota transplantation constitutes another optional treatment for severe/recurrent CDI. The aim of this paper is to review recent data on CDI in IBD: role in pathogenesis, diagnostic methods, optional treatments, and outcomes of these patients.

Mortality, Hospital Costs, Payments, and Readmissions Associated With Clostridium difficile Infection Among Medicare Beneficiaries

PubMed Central

Drozd, Edward M.; Inocencio, Timothy J.; Braithwaite, Shamonda; Jagun, Dayo; Shah, Hemal; Quon, Nicole C.; Broderick, Kelly C.; Kuti, Joseph L.

2015-01-01

Background The management of Clostridium difficile infection (CDI) among hospitalized patients is costly, and ongoing payment reform is compelling hospitals to reduce its burden. To assess the impact of CDI on mortality, hospital costs, healthcare use, and Medicare payments for beneficiaries who were discharged with CDI listed as a secondary International Classification of Diseases, Ninth Revision, Clinical Modification claim diagnosis. Methods Data were analyzed from the 2009 to 2010 5% random sample Medicare Standard Analytic Files of beneficiary claims. Patients with index hospitalizations with CDI as a secondary diagnosis and no previous hospitalization within 30 days were identified. Outcomes included inpatient and 30-day mortality, inpatient costs, index hospital payments, all-provider payments, net hospital losses, payment to cost ratio, length of stay (LOS), and 30-day readmission; outcomes were each risk adjusted using propensity score matching and regression modeling techniques. Results A total of 3262 patients with CDI were identified after matching to patients without a CDI diagnosis. After risk adjustment, secondary CDI was associated with statistically significantly (all P < 0.05) greater inpatient mortality (3.1% vs. 1.7%), 30-day mortality (4.1% vs. 2.2%), longer LOS (7.0 days vs. 3.8 days), higher rates of 30-day hospital readmissions (14.8% vs. 10.4%), and greater hospital costs ($16,184 vs. $13,954) compared with the non-CDI cohort. The risk-adjusted payment-to-cost ratio was shown to be lower for patients with CDI than those without (0.76 vs. 0.85). Conclusions Secondary CDI is associated with greater adjusted mortality, costs, LOS, and hospital readmissions, while receiving similar hospital reimbursement compared with patients without CDI in a Medicare population. PMID:27885315

Clostridium difficile Infection Is Associated With Increased Risk of Death and Prolonged Hospitalization in Children

PubMed Central

Sammons, Julia Shaklee; Localio, Russell; Xiao, Rui; Coffin, Susan E.; Zaoutis, Theoklis

2013-01-01

Background Clostridium difficile infection (CDI) is associated with significant morbidity and mortality among adults. However, outcomes are poorly defined among children. Methods A retrospective cohort study was performed among hospitalized children at 41 children's hospitals between January 2006 and August 2011. Patients with CDI (exposed) were matched 1:2 to patients without CDI (unexposed) based on the probability of developing CDI (propensity score derived from patient characteristics). Exposed subjects were stratified by C. difficile test date, suggestive of community-onset (CO) versus hospital-onset (HO) CDI. Outcomes were analyzed for matched subjects. Results We identified 5107 exposed and 693 409 unexposed subjects. Median age was 6 years (interquartile range [IQR], 2–13 years) for exposed and 8 years (IQR, 3–14 years) for unexposed subjects. Of these, 4474 exposed were successfully matched to 8821 unexposed by propensity score. In-hospital mortality differed significantly (CDI, 1.43% vs matched unexposed, 0.66%; P < .001). Mortality rates were similar between CO-CDI and matched subjects. However, mortality rates were significantly greater among HO-CDI compared with matched unexposed (odds ratio, 6.73 [95% confidence interval {CI}, 3.77–12.02]). Mean differences in length of stay (LOS) and total cost were significant: 5.55 days (95% CI, 4.54–6.56 days) and $18 900 (95% CI, $15 100–$22 700) for CO-CDI, and 21.60 days (95% CI, 19.29–23.90 days) and $93 600 (95% CI, $80 000–$107 200) for HO-CDI. Conclusions Pediatric CDI is associated with increased mortality, longer LOS, and higher costs. These findings underscore the importance of antibiotic stewardship and infection control programs to prevent this disease in children. PMID:23532470

Use of prophylactic Saccharomyces boulardii to prevent Clostridium difficile infection in hospitalized patients: a controlled prospective intervention study.

PubMed

Carstensen, Jeppe West; Chehri, Mahtab; Schønning, Kristian; Rasmussen, Steen Christian; Anhøj, Jacob; Godtfredsen, Nina Skavlan; Andersen, Christian Østergaard; Petersen, Andreas Munk

2018-05-03

Clostridium difficile infection (CDI) is a common complication to antibiotic use. Saccharomyces boulardii has shown effect as a prophylactic agent. We aimed to evaluate the efficacy of S. boulardii in preventing CDI in unselected hospitalized patients treated with antibiotics. We conducted a 1 year controlled prospective intervention study aiming to prescribe Sacchaflor (S. boulardii 5 × 10 9 , Pharmaforce ApS) twice daily to hospitalized patients treated with antibiotics. Comparable departments from three other hospitals in our region were included as controls. All occurrences of CDI in patients receiving antibiotics were reported and compared to a baseline period defined as 2 years prior to intervention. Results were analyzed using run chart tests for non-random variation in CDI rates. In addition, odds ratios for CDI were calculated. S. boulardii compliance reached 44% at the intervention hospital, and 1389 patients were treated with Sacchaflor. Monthly CDI rates dropped from a median of 3.6% in the baseline period to 1.5% in the intervention period. S. boulardii treatment was associated with a reduced risk of CDI at the intervention hospital: OR = 0.06 (95% CI 0.02-0.16). At two control hospitals, CDI rates did not change. At one control hospital, the median CDI rate dropped from 3.5 to 2.4%, possibly reflecting the effects of simultaneous multifaceted intervention against CDI at that hospital. The results from this controlled prospective interventional study indicate that S. boulardii is effective for the prevention of CDI in an unselected cohort of mainly elderly patients from departments of internal medicine.

Diverticular disease of the colon does not increase risk of repeat C. difficile infection.

PubMed

Feuerstadt, Paul; Das, Rohit; Brandt, Lawrence J

2013-01-01

Studies have suggested that colonic diverticulosis might increase the likelihood of repeat Clostridium difficile infection (CDI). Our study was designed to compare rates of repeat infection in patients with and without colon diverticula. Patients who had a positive C. difficile toxin assay and colonoscopic evidence of diverticulosis were classified as CDI and diverticulosis (CDI-D), whereas those with a positive toxin assay but no such colonoscopic evidence were classified as CDI and no diverticulosis (CDI-ND). Various clinical and epidemiologic factors were recorded for each patient. Primary outcomes were "relapse" (repeat CDI within 3 mo of initial infection) and "recurrent" infection (repeat CDI≥3 mo after initial infection). Secondary outcomes 30 days after diagnosis were mortality, intensive care unit transfer, and continuous hospitalization. A total of 128 patients were classified as CDI-D, whereas 137 had CDI-ND. There were no significant differences between CDI-D and CDI-ND when comparing frequencies of repeat infection and its subclassifications, relapse or recurrence. There were, however, statistical associations seen between diverticulosis of the ascending colon and increased recurrence rates [hazard ratio (HR): 1.4±0.38, P<0.05] and decreased rates of relapse in diverticular disease of the descending (HR: 0.40±0.46, P<0.05), and sigmoid colon (HR: 0.39±0.49, P<0.05). The ascending colon association is limited by a small patient population. There were no significant differences in any of the 30-day outcomes including intensive care unit requirement, hospitalization stay, or mortality. Patients with diverticular disease of the colon are not at increased risk of repeat CDI.

High-throughput screening using the differential radial capillary action of ligand assay identifies ebselen as an inhibitor of diguanylate cyclases.

PubMed

Lieberman, Ori J; Orr, Mona W; Wang, Yan; Lee, Vincent T

2014-01-17

The rise of bacterial resistance to traditional antibiotics has motivated recent efforts to identify new drug candidates that target virulence factors or their regulatory pathways. One such antivirulence target is the cyclic-di-GMP (cdiGMP) signaling pathway, which regulates biofilm formation, motility, and pathogenesis. Pseudomonas aeruginosa is an important opportunistic pathogen that utilizes cdiGMP-regulated polysaccharides, including alginate and pellicle polysaccharide (PEL), to mediate virulence and antibiotic resistance. CdiGMP activates PEL and alginate biosynthesis by binding to specific receptors including PelD and Alg44. Mutations that abrogate cdiGMP binding to these receptors prevent polysaccharide production. Identification of small molecules that can inhibit cdiGMP binding to the allosteric sites on these proteins could mimic binding defective mutants and potentially reduce biofilm formation or alginate secretion. Here, we report the development of a rapid and quantitative high-throughput screen for inhibitors of protein-cdiGMP interactions based on the differential radial capillary action of ligand assay (DRaCALA). Using this approach, we identified ebselen as an inhibitor of cdiGMP binding to receptors containing an RxxD domain including PelD and diguanylate cyclases (DGC). Ebselen reduces diguanylate cyclase activity by covalently modifying cysteine residues. Ebselen oxide, the selenone analogue of ebselen, also inhibits cdiGMP binding through the same covalent mechanism. Ebselen and ebselen oxide inhibit cdiGMP regulation of biofilm formation and flagella-mediated motility in P. aeruginosa through inhibition of diguanylate cyclases. The identification of ebselen provides a proof-of-principle that a DRaCALA high-throughput screening approach can be used to identify bioactive agents that reverse regulation of cdiGMP signaling by targeting cdiGMP-binding domains.

An agent-based simulation model for Clostridium difficile infection control.

PubMed

Codella, James; Safdar, Nasia; Heffernan, Rick; Alagoz, Oguzhan

2015-02-01

Control of Clostridium difficile infection (CDI) is an increasingly difficult problem for health care institutions. There are commonly recommended strategies to combat CDI transmission, such as oral vancomycin for CDI treatment, increased hand hygiene with soap and water for health care workers, daily environmental disinfection of infected patient rooms, and contact isolation of diseased patients. However, the efficacy of these strategies, particularly for endemic CDI, has not been well studied. The objective of this research is to develop a valid, agent-based simulation model (ABM) to study C. difficile transmission and control in a midsized hospital. We develop an ABM of a midsized hospital with agents such as patients, health care workers, and visitors. We model the natural progression of CDI in a patient using a Markov chain and the transmission of CDI through agent and environmental interactions. We derive input parameters from aggregate patient data from the 2007-2010 Wisconsin Hospital Association and published medical literature. We define a calibration process, which we use to estimate transition probabilities of the Markov model by comparing simulation results to benchmark values found in published literature. In a comparison of CDI control strategies implemented individually, routine bleach disinfection of CDI-positive patient rooms provides the largest reduction in nosocomial asymptomatic colonization (21.8%) and nosocomial CDIs (42.8%). Additionally, vancomycin treatment provides the largest reduction in relapse CDIs (41.9%), CDI-related mortalities (68.5%), and total patient length of stay (21.6%). We develop a generalized ABM for CDI control that can be customized and further expanded to specific institutions and/or scenarios. Additionally, we estimate transition probabilities for a Markov model of natural CDI progression in a patient through calibration. © The Author(s) 2014.

Microbiologic factors affecting Clostridium difficile recurrence.

PubMed

Chilton, C H; Pickering, D S; Freeman, J

2018-05-01

Recurrent Clostridium difficile infection (rCDI) places a huge economic and practical burden on healthcare facilities. Furthermore, rCDI may affect quality of life, leaving patients in an rCDI cycle and dependant on antibiotic therapy. To discuss the importance of microbiologic factors in the development of rCDI. Literature was drawn from a search of PubMed from 2000 onwards with the search term 'recurrent Clostridium difficile infection' and further references cited within these articles. Meta-analyses and systematic reviews have shown that CDI and rCDI risk factors are similar. Development of rCDI is attendant on many factors, including immune status or function, comorbidities and concomitant treatments. Studies suggest that poor bacterial diversity is correlated with clinical rCDI. Narrow-spectrum gut microflora-sparing antimicrobials (e.g. surotomycin, cadazolid, ridinilazole) are in development for CDI treatment, while microbiota therapeutics (faecal microbiota transplantation, nontoxigenic C. difficile, stool substitutes) are increasingly being explored. rCDI can only occur when viable C. difficile spores are present, either within the gut lumen after infection or when reacquired from the environment. C. difficile spore germination can be influenced by gut environmental factors resulting from dysbiosis, and spore outgrowth may be affected stage by some antimicrobials (e.g. fidaxomicin, ramoplanin, oritavancin). rCDI is a significant challenge for healthcare professionals, requiring a multifaceted approach; optimized infection control to minimize reinfection; C. difficile-targeted antibiotics to minimize dysbiosis; and gut microflora restoration to promote colonization resistance. These elements should be informed by our understanding of the microbiologic factors involved in both C. difficile itself and the gut microbiome. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Differences in caregiver daily impression by sex, education and career length.

PubMed

Ae, Ryusuke; Kojo, Takao; Kotani, Kazuhiko; Okayama, Masanobu; Kuwabara, Masanari; Makino, Nobuko; Aoyama, Yasuko; Sano, Takashi; Nakamura, Yosikazu

2017-03-01

We previously proposed the concept of caregiver daily impression (CDI) as a practical tool for emergency triage. We herein assessed how CDI varies by sex, education and career length by determining CDI scores as quantitative outcome measures. We carried out a cross-sectional study using a self-reported questionnaire among caregivers in 20 long-term care facilities in Hyogo, Japan. A total of 10 CDI variables measured participants' previous experience of emergency transfers using a scale from 0-10. The resulting total was defined as the CDI score. We hypothetically considered that higher scores indicated greater caregiver focus. The CDI scores were compared by sex, education and career length using analysis of covariance. A total of 601 personal caregivers were evaluated (mean age 36.7 years; 36% men). The mean career length was 6.9 years, with the following groupings: 1-4 years (38%), 5-9 years (37%) and >10 years (24%). After adjustment for sex and education, the CDI scores for the variable, "poor eye contact," significantly differed between caregivers with ≥10 and <5 years of experience (scores of 5.0 ± 3.1 and 4.0 ± 2.7, respectively). The CDI scores for variables related to eyes tended to increase with experience, whereas other CDI scores decreased. Male caregivers focused on residents' eyes significantly more than did female caregivers. We found that the CDI variable, "poor eye contact," is influenced by career length. Caregivers with more experience attach more importance to their impression of residents' eyes than do those with less experience. Sex-related differences in CDI might also exist. Geriatr Gerontol Int 2016; 17: 410-415. © 2016 Japan Geriatrics Society.

Risk factors and outcomes associated with severe clostridium difficile infection in children.

PubMed

Kim, Jason; Shaklee, Julia F; Smathers, Sarah; Prasad, Priya; Asti, Lindsey; Zoltanski, Joan; Dul, Michael; Nerandzic, Michelle; Coffin, Susan E; Toltzis, Philip; Zaoutis, Theoklis

2012-02-01

The incidence and severity of Clostridium difficile infection (CDI) is increasing among adults; however, little is known about the epidemiology of CDI among children. We conducted a nested case-control study to identify the risk factors for and a prospective cohort study to determine the outcomes associated with severe CDI at 2 children's hospitals. Severe CDI was defined as CDI and at least 1 complication or ≥2 laboratory or clinical indicators consistent with severe disease. Studied outcomes included relapse, treatment failure, and CDI-related complications. Isolates were tested to determine North American pulsed-field gel electrophoresis type 1 lineage. We analyzed 82 patients with CDI, of whom 48 had severe disease. Median age in years was 5.93 (1.78-12.16) and 1.83 (0.67-8.1) in subjects with severe and nonsevere CDI, respectively (P = 0.012). All patients with malignancy and CDI had severe disease. Nine subjects (11%) had North American pulsed-field gel electrophoresis type 1 isolates. Risk factors for severe disease included age (adjusted odds ratio [95% confidence interval]: 1.12 [1.02, 1.24]) and receipt of 3 antibiotic classes in the 30 days before infection (3.95 [1.19, 13.11]). If infants less than 1 year of age were excluded, only receipt of 3 antibiotic classes remained significantly associated with severe disease. Neither the rate of relapse nor treatment failure differed significantly between patients with severe and nonsevere CDI. There was 1 death. Increasing age and exposure to multiple antibiotic classes were risk factors for severe CDI. Although most patients studied had severe disease, complications were infrequent. Relapse rates were similar to those reported in adults.

Burden of Clostridium difficile Infections in French Hospitals in 2014 From the National Health Insurance Perspective.

PubMed

Leblanc, Soline; Blein, Cécile; Andremont, Antoine; Bandinelli, Pierre-Alain; Galvain, Thibaut

2017-08-01

OBJECTIVE To describe the hospital stays of patients with Clostridium difficile infection (CDI) and to measure the hospitalization costs of CDI (as primary and secondary diagnoses) from the French national health insurance perspective DESIGN Burden of illness study SETTING All acute-care hospitals in France METHODS Data were extracted from the French national hospitalization database (PMSI) for patients covered by the national health insurance scheme in 2014. Hospitalizations were selected using the International Classification of Diseases, 10 th revision (ICD-10) code for CDI. Hospital stays with CDI as the primary diagnosis or the secondary diagnosis (comorbidity) were studied for the following parameters: patient sociodemographic characteristics, mortality, length of stay (LOS), and related costs. A retrospective case-control analysis was performed on stays with CDI as the secondary diagnosis to assess the impact of CDI on the LOS and costs. RESULTS Overall, 5,834 hospital stays with CDI as the primary diagnosis were included in this study. The total national insurance costs were €30.7 million (US $33,677,439), and the mean cost per hospital stay was €5,267±€3,645 (US $5,777±$3,998). In total, 10,265 stays were reported with CDI as the secondary diagnosis. The total national insurance additional costs attributable to CDI were estimated to be €85 million (US $93,243,725), and the mean additional cost attributable to CDI per hospital stay was €8,295±€17,163, median, €4,797 (US $9,099±$8,827; median, $5,262). CONCLUSION CDI has a high clinical and economic burden in the hospital, and it represents a major cost for national health insurance. When detected as a comorbidity, CDI was significantly associated with increased LOS and economic burden. Preventive approaches should be implemented to avoid CDIs. Infect Control Hosp Epidemiol 2017;38:906-911.

Prevalence and Clinical Outcomes of Clostridium difficile Infection in the Intensive Care Unit: A Systematic Review and Meta-Analysis

PubMed Central

Karanika, Styliani; Paudel, Suresh; Zervou, Fainareti N.; Grigoras, Christos; Zacharioudakis, Ioannis M.; Mylonakis, Eleftherios

2016-01-01

Background. Intensive care unit (ICU) patients are at higher risk for Clostridium difficile infection (CDI). Methods. We performed a systematic review and meta-analysis of published studies from 1983 to 2015 using the PubMed, EMBASE, and Google Scholar databases to study the prevalence and outcomes of CDI in this patient population. Among the 9146 articles retrieved from the studies, 22 articles, which included a total of 80 835 ICU patients, were included in our final analysis. Results. The prevalence of CDI among ICU patients was 2% (95% confidence interval [CI], 1%–2%), and among diarrheic ICU patients the prevalence was 11% (95% CI, 6%–17%). Among CDI patients, 25% (95% CI, 5%–51%) were diagnosed with pseudomembranous colitis, and the estimated length of ICU stay before CDI acquisition was 10.74 days (95% CI, 5%–51%). The overall hospital mortality among ICU patients with CDI was 32% (95% CI, 26%–39%), compared with 24% (95% CI, 14%–36%) among those without CDI presenting a statistically significant difference in mortality risk (P = .030). It is worth noting that the length of ICU and hospital stay among CDI patients was significantly longer, compared with non-CDI patients (standardized mean of difference [SMD] = 0.49, 95% CI, .39%–.6%, P = .00 and SMD = 1.15, 95% CI, .44%–1.91%, P = .003, respectively). It is noteworthy that the morbidity score at ICU admission (Acute Physiology and Chronic Health Evaluation II [APACHE II]) was not statistically different between the 2 groups (P = .911), implying that the differences in outcomes can be attributed to CDI. Conclusions. The ICU setting is associated with higher prevalence of CDI. In this setting, CDI is associated with increased hospital mortality and prolonged ICU and overall hospital stay. These findings highlight the need for additional prevention and treatment studies in this setting. PMID:26788544

Effects of Clostridium difficile infection in patients with alcoholic hepatitis.

PubMed

Sundaram, Vinay; May, Folasade P; Manne, Vignan; Saab, Sammy

2014-10-01

Infection increases mortality in patients with alcoholic hepatitis (AH). Little is known about the association between Clostridium difficile infection (CDI) and AH. We examined the prevalence and effects of CDI in patients with AH, compared with those of other infections. We performed a cross-sectional analysis using data collected from the Nationwide Inpatient Sample, from 2008 through 2011. International Classification of Diseases, 9th revision, Clinical Modification codes were used to identify patients with AH. We used multivariable logistic regression to determine risk factors that affect mortality, negative binomial regression to evaluate the effects of CDI on predicted length of stay (LOS), and Poisson regression to determine the effects of CDI on predicted hospital charges. Chi-square and Wilcoxon rank-sum analyses were used to compare mortality, LOS, and hospital charges associated with CDI with those associated with urinary tract infection (UTI) and spontaneous bacterial peritonitis (SBP). Of 10,939 patients with AH, 177 had CDI (1.62%). Patients with AH and CDI had increased odds of inpatient mortality (adjusted odds ratio, 1.75; P = .04), a longer predicted LOS (10.63 vs 5.75 d; P < .001), and greater predicted hospital charges ($36,924.30 vs $29,136.58; P < .001), compared with those without CDI. Compared with UTI, CDI was associated with similar mortality but greater LOS (9 vs 6 d; P < .001) and hospital charges ($45,607 vs $32,087; P < .001). SBP was associated with higher mortality than CDI (17.3% vs 10.1%; P = .045), but similar LOS and hospital charges. In patients with AH, CDI is associated with greater mortality and health care use. These effects appear similar to those for UTI and SBP. We propose further studies to determine the cost effectiveness of screening for CDI among patients with AH. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Trend, Risk Factors, and Costs of Clostridium difficile Infections in Vascular Surgery.

PubMed

Egorova, Natalia N; Siracuse, Jeffrey J; McKinsey, James F; Nowygrod, Roman

2015-01-01

Starting in December 2013, the Hospital Inpatient Quality Reporting Program included Clostridium difficile infection (CDI) rates as a new publically reported quality measure. Our goal was to review the trend, hospital variability in CDI rates, and associated risk factors and costs in vascular surgery. The rates of CDI after major vascular procedures including aortic abdominal aneurysm (AAA) repair, carotid endarterectomy or stenting, lower extremity revascularization (LER), and LE amputation were identified using Nationwide Inpatient Sample database for 2000-2011. Risk factors associated with CDI were analyzed with hierarchical multivariate logistic regression. Extra costs, length of stay (LOS), and mortality were assessed for propensity-matched hospitalizations with and without CDI. During the study period, the rates of CDI after vascular procedures had increased by 74% from 0.6 in 2000 to 1.05% in 2011, whereas the case fatality rate was stable at 9-11%. In 2011, the highest rates were after ruptured aortic abdominal aneurysm (rAAA) repair (3.3%), followed by lower extremity amputations (2.3%) and elective open AAA (1.3%). The rates of CDI increased after all vascular procedures during the 12 years. The highest increase was after endovascular LER (151.8%) and open rAAA repair (135.7%). In 2011, patients who had experienced CDI had median LOS of 15 days (interquartile range, 9-25 days) compared with 8.3 days for matched patients without CDI, in-hospital mortality 9.1% (compared with 5.0%), and $13,471 extra cost per hospitalization. The estimated cost associated with CDI in vascular surgery in the United States was ∼$98 million in 2011. Hospital rates of CDI varied from 0 to 50% with 3.5% of hospitals having infection rates ≥5%. Factors associated with CDI included multiple chronic conditions, female gender, surgery type, emergent and weekend hospitalizations, hospital transfers, and urban locations. Despite potential reduction of infection rates as evidenced by the experience of hospitals with effective interventions, CDI is increasing among vascular surgery patients. It is associated with prolonged LOS, increased mortality, and higher costs. Copyright © 2015 Elsevier Inc. All rights reserved.

[Clostridium difficile infection (CDI) in the course of time - an issue only for the internist?].

PubMed

Weis, S; John, E; Lippmann, N; Mössner, J; Lübbert, C

2014-08-01

Toxigenic strains of Clostridium (C.) difficile are the most prevalent pathogens of antibiotic associated intestinal disease and nosocomial diarrhoea. During the last 10 years, incidences of C. difficile infection (CDI) have increased worldwide. With clinical and microbiological original data for 2002-2012 from the University Hospitals Leipzig and Halle (Saale), Germany, the authors illustrate the current situation regarding CDI in the states of Saxony and Saxony-Anhalt and exemplify the latest developments in terms of incidence, prevalence of resistance, diagnosis and treatment strategies regarding CDI with an emphasis on surgical options. Following the general trend, at the University Hospitals of Leipzig and Halle (Saale) there was also an increase in incidence of CDI, especially of severe clinical courses. In primary and secondary care facilities, prevention of CDI is based on hygiene management and restricted usage of antibiotics, preferably as "Antibiotic Stewardship" programmes. In 2012, the new macrocyclic antibiotic Fidaxomicin was approved in the European Union for the treatment of CDI. The therapeutic armamentarium, previously based on metronidazole or vancomycin, has now been enriched by a substance that presumably will reduce the rate of recurrence of CDI. Moreover, early data from case series and controlled trials suggest that the re-establishment of eubiosis in the colon of patients with recurrent CDI by stool transplantation from healthy donors is an alternative to antibiotics. Standard surgical intervention for refractory CDI is subtotal colectomy with terminal ileostomy. In patients with adequate life expectancy and without organ dysfunction, a colon-saving surgical technique should be considered. Taking antibiotics for most remains the main risk factor for suffering from symptomatic CDI. With the introduction of Fidaxomicin there is hope for an improvement in the conservative treatment of CDI. Stool transplants from healthy donors are now considered to be better than giving antibiotics for severe CDI, but this treatment has not found broad acceptance yet. In cases with a lack of early treatment success, the surgeon must be consulted. Here, the evidence for preferably colon-saving surgical procedures is so far unfortunately low. Georg Thieme Verlag KG Stuttgart · New York.

Evaluating the Effectiveness of an Antimicrobial Stewardship Program on Reducing the Incidence Rate of Healthcare-Associated Clostridium difficile Infection: A Non-Randomized, Stepped Wedge, Single-Site, Observational Study.

PubMed

DiDiodato, Giulio; McArthur, Leslie

2016-01-01

The incidence rate of healthcare-associated Clostridium difficile infection (HA-CDI) is estimated at 1 in 100 patients. Antibiotic exposure is the most consistently reported risk factor for HA-CDI. Strategies to reduce the risk of HA-CDI have focused on reducing antibiotic utilization. Prospective audit and feedback is a commonly used antimicrobial stewardship intervention (ASi). The impact of this ASi on risk of HA-CDI is equivocal. This study examines the effectiveness of a prospective audit and feedback ASi on reducing the risk of HA-CDI. Single-site, 339 bed community-hospital in Barrie, Ontario, Canada. Primary outcome is HA-CDI incidence rate. Daily prospective and audit ASi is the exposure variable. ASi implemented across 6 wards in a non-randomized, stepped wedge design. Criteria for ASi; any intravenous antibiotic use for ≥ 48 hrs, any oral fluoroquinolone or oral second generation cephalosporin use for ≥ 48 hrs, or any antimicrobial use for ≥ 5 days. HA-CDI cases and model covariates were aggregated by ward, year and month starting September 2008 and ending February 2016. Multi-level mixed effect negative binomial regression analysis was used to model the primary outcome, with intercept and slope coefficients for ward-level random effects estimated. Other covariates tested for inclusion in the final model were derived from previously published risk factors. Deviance residuals were used to assess the model's goodness-of-fit. The dataset included 486 observation periods, of which 350 were control periods and 136 were intervention periods. After accounting for all other model covariates, the estimated overall ASi incidence rate ratio (IRR) was 0.48 (95% 0.30, 0.79). The ASi effect was independent of antimicrobial utilization. The ASi did not seem to reduce the risk of Clostridium difficile infection on the surgery wards (IRR 0.87, 95% CI 0.45, 1.69) compared to the medicine wards (IRR 0.42, 95% CI 0.28, 0.63). The ward-level burden of Clostridium difficile as measured by the ward's previous month's total CDI cases (CDI Lag) and the ward's current month's community-associated CDI cases (CA-CDI) was significantly associated with an increased risk of HA-CDI, with the estimated CDI Lag IRR of 1.21 (95% 1.15, 1.28) and the estimated CA-CDI IRR of 1.10 (95% CI 1.01, 1.20). The ward-level random intercept and slope coefficients were not significant. The final model demonstrated good fit. In this study, a daily prospective audit and feedback ASi resulted in a significant reduction in the risk of HA-CDI on the medicine wards, however, this effect was independent of an overall reduction in antibiotic utilization. In addition, the ward-level burden of Clostridium difficile was shown to significantly increase the risk of HA-CDI, reinforcing the importance of the environment as a source of HA-CDI.

Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis

PubMed Central

Grewal, Suman; LaComb, Joseph F.; Park, Jiyhe; Channer, Breana; Rajapakse, Ramona; Bucobo, Juan Carlos; Buscaglia, Jonathan M.; Monzur, Farah; Chawla, Anupama; Yang, Jie; Robertson, Charlie E.; Frank, Daniel N.; Li, Ellen

2018-01-01

Background Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only). Method V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group. Results Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the CDI-only and CDI + UC recipients, were restored after FMT. Conclusion The results from this pilot study suggest that the microbial imbalances in the CDI + UC recipients more closely resemble those of the CDI-only recipients than the UC-only recipients. PMID:29385143

Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis.

PubMed

Mintz, Michael; Khair, Shanawaj; Grewal, Suman; LaComb, Joseph F; Park, Jiyhe; Channer, Breana; Rajapakse, Ramona; Bucobo, Juan Carlos; Buscaglia, Jonathan M; Monzur, Farah; Chawla, Anupama; Yang, Jie; Robertson, Charlie E; Frank, Daniel N; Li, Ellen

2018-01-01

Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only). V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group. Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the CDI-only and CDI + UC recipients, were restored after FMT. The results from this pilot study suggest that the microbial imbalances in the CDI + UC recipients more closely resemble those of the CDI-only recipients than the UC-only recipients.

CD-I: From Boob Tube to Teacher's Assistant--The Birth of the Smart TV.

ERIC Educational Resources Information Center

Luskin, Bernard J.

1993-01-01

Explains compact disc interactive (CD-I) and discusses possible uses in education. Advances in technology are considered; the current status of CD-I and recent developments are described, including marketing and costs; and future possibilities of CD-I in education are suggested, including digital technology and electronic and optical publishing.…

Predicting the Risk of Clostridium difficile Infection upon Admission: A Score to Identify Patients for Antimicrobial Stewardship Efforts.

PubMed

Kuntz, Jennifer L; Smith, David H; Petrik, Amanda F; Yang, Xiuhai; Thorp, Micah L; Barton, Tracy; Barton, Karen; Labreche, Matthew; Spindel, Steven J; Johnson, Eric S

2016-01-01

Increasing morbidity and health care costs related to Clostridium difficile infection (CDI) have heightened interest in methods to identify patients who would most benefit from interventions to mitigate the likelihood of CDI. To develop a risk score that can be calculated upon hospital admission and used by antimicrobial stewards, including pharmacists and clinicians, to identify patients at risk for CDI who would benefit from enhanced antibiotic review and patient education. We assembled a cohort of Kaiser Permanente Northwest patients with a hospital admission from July 1, 2005, through December 30, 2012, and identified CDI in the six months following hospital admission. Using Cox regression, we constructed a score to identify patients at high risk for CDI on the basis of preadmission characteristics. We calculated and plotted the observed six-month CDI risk for each decile of predicted risk. We identified 721 CDIs following 54,186 hospital admissions-a 6-month incidence of 13.3 CDIs/1000 patient admissions. Patients with the highest predicted risk of CDI had an observed incidence of 53 CDIs/1000 patient admissions. The score differentiated between patients who do and do not develop CDI, with values for the extended C-statistic of 0.75. Predicted risk for CDI agreed closely with observed risk. Our risk score accurately predicted six-month risk for CDI using preadmission characteristics. Accurate predictions among the highest-risk patient subgroups allow for the identification of patients who could be targeted for and who would likely benefit from review of inpatient antibiotic use or enhanced educational efforts at the time of discharge planning.

Prevention program for Clostridium difficile infection: a single-centre Serbian experience.

PubMed

Brkic, Snezana; Pellicano, Rinaldo; Turkulov, Vesna; Radovanovic, Marija; Abenavoli, Ludovico

2016-06-01

Clostridium difficile (C. difficile) diarrhea is a common, iatrogenic, nosocomial disease with a worldwide diffusion. Recent studies reported that the incidence of C. difficile infection (CDI) is rising, due to aging of the population and to greater prevalence of hypervirulent strains. We investigated whether the application of a prevention program lead to a decline in the incidence of intrahospital CDI. The study was designed as observational, to compare the efficacy of Schülke preventive program with the standard protocols, in a period of 4 months. For every patient with community-onset healthcare facility-associated (HCFA) CDI, we randomly selected four controls (1:4) with the same ICD code but without HCFA CDI. For statistical analysis the nonparametric, one-way ANOVA, univariate regression analysis, univariate analysis of variance, and Welch and Brown-Forsythe Test were used. Clinical features of HCFA CDI were typical. HCFA CDI group was significantly older than control group (P=0.008 and F=6.686; Partial Eta Square=0.013). Patients with HCFA CDI stayed significantly longer in hospital (P=0.000 and F=69.379; Partial Eta Square=0.117). Acquiring CDI prolonged the hospitalization of 14.52 days. HCFA CDI significantly increases the total cost of hospitalization as well as each element of the price respectively. With the application of the prevention program the annual incidence of CDI dropped from 49.01 in 2013 to 18.22/10000 bed days in 2014. Applying Schülke preventive program, implemented in 2014, has led to significant savings for the hospital compared to previous methods.

European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection.

PubMed

Crobach, M J T; Planche, T; Eckert, C; Barbut, F; Terveer, E M; Dekkers, O M; Wilcox, M H; Kuijper, E J

2016-08-01

In 2009 the first European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guideline for diagnosing Clostridium difficile infection (CDI) was launched. Since then newer tests for diagnosing CDI have become available, especially nucleic acid amplification tests. The main objectives of this update of the guidance document are to summarize the currently available evidence concerning laboratory diagnosis of CDI and to formulate and revise recommendations to optimize CDI testing. This update is essential to improve the diagnosis of CDI and to improve uniformity in CDI diagnosis for surveillance purposes among Europe. An electronic search for literature concerning the laboratory diagnosis of CDI was performed. Studies evaluating a commercial laboratory test compared to a reference test were also included in a meta-analysis. The commercial tests that were evaluated included enzyme immunoassays (EIAs) detecting glutamate dehydrogenase, EIAs detecting toxins A and B and nucleic acid amplification tests. Recommendations were formulated by an executive committee, and the strength of recommendations and quality of evidence were graded using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. No single commercial test can be used as a stand-alone test for diagnosing CDI as a result of inadequate positive predictive values at low CDI prevalence. Therefore, the use of a two-step algorithm is recommended. Samples without free toxin detected by toxins A and B EIA but with positive glutamate dehydrogenase EIA, nucleic acid amplification test or toxigenic culture results need clinical evaluation to discern CDI from asymptomatic carriage. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Hospital-onset Clostridium difficile infection among solid organ transplant recipients.

PubMed

Donnelly, J P; Wang, H E; Locke, J E; Mannon, R B; Safford, M M; Baddley, J W

2015-11-01

Clostridium difficile infection (CDI) is a considerable health issue in the United States and represents the most common healthcare-associated infection. Solid organ transplant recipients are at increased risk of CDI, which can affect both graft and patient survival. However, little is known about the impact of CDI on health services utilization posttransplantation. We examined hospital-onset CDI from 2012 to 2014 among transplant recipients in the University HealthSystem Consortium, which includes academic medical center-affiliated hospitals in the United States. Infection was five times more common among transplant recipients than among general medicine inpatients (209 vs 40 per 10 000 discharges), and factors associated with CDI among transplant recipients included transplant type, risk of mortality, comorbidities, and inpatient complications. Institutional risk-standardized CDI varied more than 3-fold across high-volume hospitals (infection ratio 0.54-1.82, median 1.04, interquartile range 0.78-1.28). CDI was associated with increased 30-day readmission, transplant organ complications, cytomegalovirus infection, inpatient costs, and lengths of stay. Total observed inpatient days and direct costs for those with CDI were substantially higher than risk-standardized expected values (40 094 vs 22 843 days, costs $198 728 368 vs $154 020 528). Further efforts to detect, prevent, and manage CDI among solid organ transplant recipients are warranted. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Bezlotoxumab: A Review in Preventing Clostridium difficile Infection Recurrence.

PubMed

Deeks, Emma D

2017-10-01

Bezlotoxumab (Zinplava™) is a fully human monoclonal antibody against Clostridium difficile toxin B indicated for the prevention of C. difficile infection (CDI) recurrence in patients with a high recurrence risk. It is the first agent approved for recurrence prevention and is administered as a single intravenous infusion in conjunction with standard-of-care (SoC) antibacterial treatment for CDI. In well-designed, placebo-controlled, phase 3 trials (MODIFY 1 and 2), a single infusion of bezlotoxumab, given in combination with SoC antibacterial therapy for CDI in adults, was effective in reducing CDI recurrence in the 12 weeks post-treatment, with this benefit being seen mainly in the patients at high recurrence risk. Bezlotoxumab did not impact the efficacy of the antibacterials being used to treat the CDI and, consistent with its benefits on CDI recurrence, appeared to reduce the need for subsequent antibacterials, thus minimizing further gut microbiota disruption. Longer term, there were no further CDI recurrences over 12 months' follow-up among patients who had received bezlotoxumab in MODIFY 2 and entered an extension substudy. Bezlotoxumab has low immunogenicity and is generally well tolerated, although the potential for heart failure in some patients requires consideration; cost-effectiveness data for bezlotoxumab are awaited with interest. Thus, a single intravenous infusion of bezlotoxumab during SoC antibacterial treatment for CDI is an emerging option for reducing CDI recurrence in adults at high risk of recurrence.

Decreasing Clostridium difficile Infections by an Antimicrobial Stewardship Program That Reduces Moxifloxacin Use

PubMed Central

Equiluz-Bruck, Susanne; Fudel, Marta; Reiter, Ingun; Schmid, Andrea; Singer, Erna; Chott, Andreas

2014-01-01

Clostridium difficile infections (CDI) in hospitalized patients are known to be closely related to antibiotic exposure. Although several substances can cause CDI, the risk differs between individual agents. In Vienna and other eastern parts of Austria, CDI ribotype 027 is currently highly prevalent. This ribotype has the characteristic of intrinsic moxifloxacin resistance. Therefore, we hypothesized that moxifloxacin restriction can decrease the number of CDI cases in hospitalized patients. Our antibiotic stewardship (ABS) group applied an information campaign on CDI and formal restriction of moxifloxacin in Wilhelminenspital (Vienna, Austria), a 1,000- bed tertiary care hospital. The preintervention period (period 1) was January through May 2013, and the intervention period (period 2) was June through December 2013. We recorded the defined daily doses (DDD) of moxifloxacin and the number of CDI patients/month. Moxifloxacin use was reduced from a mean (± standard error of the mean [SEM]) of 1,038 ± 109 DDD per month (period 1) to 42 ± 10 DDD per month (period 2) (P = 0.0045). Total antibiotic use was not affected. The mean (±SEM) numbers of CDI cases in period 1 were 59 ± 3 per month and in period 2 were 32 ± 3 per month (46% reduction; P = 0.0044). Reducing moxifloxacin use in combination with providing structured information on CDI was associated with an immediate decrease in CDI rates in this large community teaching hospital. PMID:24936597

Investigation of a cluster of Clostridium difficile infections in a pediatric oncology setting.

PubMed

Dantes, Raymund; Epson, Erin E; Dominguez, Samuel R; Dolan, Susan; Wang, Frank; Hurst, Amanda; Parker, Sarah K; Johnston, Helen; West, Kelly; Anderson, Lydia; Rasheed, James K; Moulton-Meissner, Heather; Noble-Wang, Judith; Limbago, Brandi; Dowell, Elaine; Hilden, Joanne M; Guh, Alice; Pollack, Lori A; Gould, Carolyn V

2016-02-01

We investigated an increase in Clostridium difficile infection (CDI) among pediatric oncology patients. CDI cases were defined as first C difficile positive stool tests between December 1, 2010, and September 6, 2012, in pediatric oncology patients receiving inpatient or outpatient care at a single hospital. A case-control study was performed to identify CDI risk factors, infection prevention and antimicrobial prescribing practices were assessed, and environmental sampling was conducted. Available isolates were strain-typed by pulsed-field gel electrophoresis. An increase in hospital-onset CDI cases was observed from June-August 2012. Independent risk factors for CDI included hospitalization in the bone marrow transplant ward and exposure to computerized tomography scanning or cefepime in the prior 12 weeks. Cefepime use increased beginning in late 2011, reflecting a practice change for patients with neutropenic fever. There were 13 distinct strain types among 22 available isolates. Hospital-onset CDI rates decreased to near-baseline levels with enhanced infection prevention measures, including environmental cleaning and prolonged contact isolation. C difficile strain diversity associated with a cluster of CDI among pediatric oncology patients suggests a need for greater understanding of modes and sources of transmission and strategies to reduce patient susceptibility to CDI. Further research is needed on the risk of CDI with cefepime and its use as primary empirical treatment for neutropenic fever. Published by Elsevier Inc.

Epidemiology of Clostridium difficile infection: results of a hospital-based study in Krakow, Poland.

PubMed

Czepiel, J; Kędzierska, J; Biesiada, G; Birczyńska, M; Perucki, W; Nowak, P; Garlicki, A

2015-11-01

Over the past two decades Clostridium difficile infection (CDI) has appeared as a major public health threat. We performed a retrospective study based on the records of patients hospitalized for CDI at the University Hospital in Krakow, Poland, between 2008 and 2014. In the study period, CDI occurred in 1009 individuals. There were 790 (78%) individuals who developed infection only once, whereas 219 (22%) developed infection more than once. The percentage of deaths within 14 days of CDI confirmation was 2·4%, with a mean age of 74·2 ± 15·9 years. Crude mortality was 12·9% in medical wards, 5·6% for surgical wards and 27·7% in the ICU setting. The time span between diagnosis and death was 5·1 days on average. Between 2008 and 2012 a 6·5-fold increase of CDI frequency with a posterior stabilization and even reduction in 2013 and 2014 was observed. According to the data analysed, 2/3 patients in our population developed CDI during their hospitalization even though they were admitted for different reasons. Medical wards pose a significantly higher risk of CDI than the surgical ones. Age is a risk factor for CDI recurrence. In the case of patients who died, death occurred shortly after diagnosis. The first CDI episode poses much higher risk of mortality than the consecutive ones.

n-3 and n-6 Fatty Acid Changes in the Erythrocyte Membranes of Patients with 658240251 Clostridium difficile Infection.

PubMed

Czepiel, Jacek; Gdula-Argasińska, Joanna; Garlicki, Aleksander

2016-01-01

The implications of circulating essential fatty acids (FA) on the inflammatory risk profile and clinical outcome are still unclear. In order to gain a deeper understanding of the role of polyunsaturated fatty acids (PUFA) in the pathogenesis of acute infection, we analyzed the FA content in red blood cell (RBC) membranes of patients with Clostridium difficile infection (CDI) and controls. We prospectively studied 60 patients including 30 patients with CDI and 30 controls to assess lipid concentrations in erythrocyte membranes using gas chromatography. We observed a higher level of saturated fatty acids (SFA) in RBC membranes from patients with CDI. In patients with CDI, we also noticed a higher level of 20:4 n-6 FA and only a small amounts of C20:2n-6, C20:3n-6 FAs, arachidonic acid (AA) precursors, which suggest an intense inflammatory reaction in the organism during infection. We also noticed low levels of n-3 FA in the RBC membranes of patients infected with CDI. There is a deficit of n-3 FA in patients with CDI. n-3 FA are probably used during CDI as precursors of pro-resolving mediators that may indicate a therapeutic role of n-3 PUFAs in CDI. The changes in fatty acids in erythrocyte membranes during CDI alter their functions which may have an impact on the clinical outcome.

The Need for European Surveillance of CDI.

PubMed

Wiuff, Camilla; Banks, A-Lan; Fitzpatrick, Fidelma; Cottom, Laura

2018-01-01

Since the turn of the millennium, the epidemiology of Clostridium difficile infection (CDI) has continued to challenge. Over the last decade there has been a growing awareness that improvements to surveillance are needed. The increasing rate of CDI and emergence of ribotype 027 precipitated the implementation of mandatory national surveillance of CDI in the UK. Changes in clinical presentation, severity of disease, descriptions of new risk factors and the occurrence of outbreaks all emphasised the importance of early diagnosis and surveillance.However a lack of consensus on case definitions, clinical guidelines and optimal laboratory diagnostics across Europe has lead to the underestimation of CDI and impeded comparison between countries. These inconsistencies have prevented the true burden of disease from being appreciated.Acceptance that a multi-country surveillance programme and optimised diagnostic strategies are required not only to detect and control CDI in Europe, but for a better understanding of the epidemiology, has built the foundations for a more robust, unified surveillance. The concerted efforts of the European Centre for Disease Prevention and Control (ECDC) CDI networks, has lead to the development of an over-arching long-term CDI surveillance strategy for 2014-2020. Fulfilment of the ECDC priorities and targets will no doubt be challenging and will require significant investment however the hope is that both a national and Europe-wide picture of CDI will finally be realised.

Epidemiology of Clostridium difficile infection.

PubMed

Depestel, Daryl D; Aronoff, David M

2013-10-01

There has been dramatic change in the epidemiology of Clostridium difficile infection (CDI) since the turn of the 21st century noted by a marked increase in incidence and severity, occurring at a disproportionately higher frequency in older patients. Historically considered a nosocomial infection associated with antibiotic exposure, CDI has now also emerged in the community in populations previously considered low risk. Emerging risk factors and disease recurrence represent continued challenges in the management of CDI. The increased incidence and severity associated with CDI has coincided with the emergence and rapid spread of a previously rare strain, ribotype 027. Recent data from the United States and Europe suggest that the incidence of CDI may have reached a crescendo in the recent years and is perhaps beginning to plateau. The acute care direct costs of CDI were estimated to be US$4.8 billion in 2008. However, nearly all the published studies have focused on CDI diagnosed and treated in the acute care hospital setting and fail to measure the burden outside the hospital, including recently discharged patients, outpatients, and those in long-term care facilities. Enhanced surveillance methods are needed to monitor the incidence, to identify populations at risk, and to characterize the molecular epidemiology of strains causing CDI.

Epidemiology of Clostridium difficile Infection

PubMed Central

DePestel, Daryl D.; Aronoff, David M.

2014-01-01

There has been dramatic change in the epidemiology of Clostridium difficile infection (CDI) since the turn of the 21st Century noted by a marked increase in incidence and severity, occurring at a disproportionately higher frequency in older patients. Historically considered a nosocomial infection associated with antibiotic exposure, CDI has now also emerged in the community in populations previously considered low risk. Emerging risk factors and disease recurrence represent continued challenges in the management of CDI. The increased incidence and severity associated with CDI has coincided with the emergence and rapid spread of a previously rare strain, ribotype 027. Recent data from the U.S. and Europe suggest the incidence of CDI may have reached a crescendo in recent years and is perhaps beginning to plateau. The acute-care direct costs of CDI were estimated to be $4.8 billion in 2008. However, nearly all the published studies have focused on CDI diagnosed and treated in acute-care hospital setting and fail to measure the burden outside the hospital, including recently discharged patients, outpatients, and those in long-term care facilities. Enhanced surveillance methods are needed to monitor the incidence, identify populations at risk, and characterize the molecular epidemiology of strains causing CDI. PMID:24064435

Epidemiology, Diagnosis, and Management of Clostridium difficile Infection in Patients with Inflammatory Bowel Disease

PubMed Central

Rao, Krishna; Higgins, Peter D. R.

2016-01-01

Clostridium difficile infection (CDI) is a major source of morbidity and mortality for the US healthcare system, and frequently complicates the course of inflammatory bowel disease (IBD). Patients with IBD are more likely to be colonized with C. difficile and develop active infection than the general population. They are also more likely to have severe CDI and develop subsequent complications such as IBD flare, colectomy, or death. Even after successful initial treatment and recovery, recurrent CDI is common. Management of CDI in IBD is fraught with diagnostic and therapeutic challenges, since the clinical presentations of CDI and IBD flare have considerable overlap. Fecal microbiota transplantation can be successful in curing recurrent CDI when other treatments have failed, but may also trigger IBD flare and this warrants caution. New, experimental treatments including vaccines, monoclonal antibodies, and non-toxigenic strains of C. difficile offer promise but are not yet available for clinicians. A better understanding of the complex relationship between the gut microbiota, CDI, and IBD is needed. PMID:27120571

Discordance of SHEA/IDSA Clostridium difficile Disease Severity Scale in Solid Organ Transplant Patients

PubMed Central

Lee, Tiffany; McCoy, Christopher; Alonso, Carolyn D; Snyder, Graham M; Rogers, Christin; Richards, Katelyn; Hirsch, Elizabeth B; Mahoney, Monica V

2017-01-01

Abstract Background Solid organ transplant (SOT) patients are at high risk for Clostridium difficile infections (CDI) due to chronic immunosuppression and a propensity to receive antimicrobials. Management of CDI in SOT patients poses unique challenges as this population has disease-altered clinical and laboratory parameters. The objective of this study was to assess concordance between various CDI severity scales and the Society for Healthcare Epidemiology of America/Infectious Diseases Society of America (SHEA/IDSA) guidelines. Methods This retrospective study included all SOT recipients with a first CDI episode following transplant and time-matched (2:1) to non-SOT patients experiencing first CDI episodes between 2008 and 2016. The primary endpoint was concordance rates of CDI episodes considered mild-moderate or severe/severe-complicated in published CDI scales compared with the SHEA/IDSA guidelines. We also sought to compare the distribution of CDI severity across all scales between SOT and non-SOT patients. Results Overall, 32 SOT patients and 64 non-SOT patients were included. The SOT group had significantly higher leukopenia rates at CDI diagnosis; however, the magnitude of serum creatinine change did not differ between groups. According to the SHEA/IDSA scale, CDI episodes in SOT recipients were categorized as mild-moderate and severe/severe-complicated in 23 (72%) and 9 (28%) patients, respectively. Overall concordance rates among SHEA/IDSA guidelines and other scales ranged from 28% to 72%. Concordance rates were highest for mild-moderate CDI with Belmares and for severe/severe-complicated CDI with ESCMID (Table 1). No scale evenly categorized SOT and non-SOT patients across all severities (Figure 1). Conclusion Severity scales with heavy emphasis on white blood cell counts may not adequately categorize SOT patients. Immunocompromised status may need to be considered on its own when categorizing CDI severity and prescribing therapy. Table 1 Number (%) of Severity Classification-Concordant CDI Episodes, in Comparison to SHEA/IDSA Guidelines Overall n = 32 Mild/Moderate n = 23 Severe or Severe-Complicated n = 9 AST 23 (71.9) 18 (78.3) 5 (55.6) ESCMID 9 (28.1) 0 9 (100) Zar 20 (62.5) 13 (56.5) 7 (77.8) Belmares 22 (68.8) 22 (95.7) 0 Disclosures C. D. Alonso, Merck: Grant Investigator and Scientific Advisor, Research grant sanofi pasteur: Investigator and Scientific Advisor, Research support GSK: Investigator, Research support; E. B. Hirsch, Merck: Grant Investigator, Grant recipient The Medicines Company: Speaker’s Bureau, Speaker honorarium

Outcomes in children with Clostridium difficile infection: results from a nationwide survey.

PubMed

Gupta, Arjun; Pardi, Darrell S; Baddour, Larry M; Khanna, Sahil

2016-11-01

Hospital- and population-based studies demonstrate an increasing incidence of Clostridium difficile infection (CDI) in adults and children; although pediatric CDI outcomes are incompletely understood. We analysed United States National Hospital Discharge Survey (NHDS) data to study CDI in hospitalized children. NHDS data for 2005-2009 (demographics, diagnoses and discharge status) were obtained; cases and comorbidities were identified using ICD-9 codes. Weighted univariate and multivariate analyses were performed to ascertain incidence of CDI; associations between CDI and outcomes [length of stay (LOS), colectomy, all-cause in-hospital mortality and discharge to a care facility (DTCF)]. Of an estimated 13.8 million pediatric inpatients; 46 176 had CDI; median age was 3 years; overall incidence was 33.5/10 000 hospitalizations. The annual frequency of CDI did not vary from 2005 to 2009 (0.24-0.43%; P = 0.64). On univariate analyses, children with CDI had a longer median LOS (6 vs 2 days), higher rates of colectomy [odds ratio (OR) 2.0; 95% confidence interval (CI) 1.7-2.4], mortality (OR 2.5; 95% CI 2.3-2.7), and DTCF (OR 1.6; 95% CI 1.6-1.7) (all P < 0.0001). After adjusting for age, sex and comorbidities, CDI was an independent and the strongest predictor of increased LOS (adjusted mean difference, 6.4 days; 95% CI 5.4-7.4), higher rates of colectomy (OR 2.1; 95% CI 1.8-2.5), mortality (OR 2.3; 95% CI 2.2-2.5), and DTCF (OR 1.7; 95% CI 1.6-1.8) (all P < 0.0001). On excluding infants from the analysis, children with CDI had higher rates of mortality, DTCF and longer LOS than children without CDI. Despite increased awareness and advancements in management, CDI remains a significant problem and is associated with increased LOS, colectomy, in-hospital mortality and DTCF in hospitalized children. © The Author(s) 2016. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-Sen University.

Evaluation of fixed and variable hospital costs due to Clostridium difficile infection: institutional incentives and directions for future research.

PubMed

Ryan, P; Skally, M; Duffy, F; Farrelly, M; Gaughan, L; Flood, P; McFadden, E; Fitzpatrick, F

2017-04-01

Economic analysis of Clostridium difficile infection (CDI) should consider the incentives facing institutional decision-makers. To avoid overstating the financial benefits of infection prevention, fixed and variable costs should be distinguished. To quantify CDI fixed and variable costs in a tertiary referral hospital during August 2015. A micro-costing analysis estimated CDI costs per patient, including the additional costs of a CDI outbreak. Resource use was quantified after review of patient charts, pharmacy data, administrative resource input, and records of salary and cleaning/decontamination expenditure. The incremental cost of CDI was €75,680 (mean: €5,820 per patient) with key cost drivers being cleaning, pharmaceuticals, and length of stay (LOS). Additional LOS ranged from 1.75 to 22.55 days. For seven patients involved in a CDI outbreak, excluding the value of the 58 lost bed-days (€34,585); costs were 30% higher (€7,589 per patient). Therefore, total spending on CDI was €88,062 (mean: €6,773 across all patients). Potential savings from variable costs were €1,026 (17%) or €1,768 (26%) if outbreak costs were included. Investment in an antimicrobial pharmacist would require 47 CDI cases to be prevented annually. Prevention of 5%, 10% and 20% CDI would reduce attributable costs by €4,403, €8,806 and €17,612. Increasing the incremental LOS attributable to CDI to seven days per patient would have increased costs to €7,478 or €8,431 (if outbreak costs were included). As much CDI costs are fixed, potential savings from infection prevention are limited. Future analysis must consider more effectively this distinction and its impact on institutional decision-making. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Clostridium difficile Diarrhea in the Elderly: Current Issues and Management Options.

PubMed

Mizusawa, Masako; Doron, Shira; Gorbach, Sherwood

2015-08-01

Clostridium difficile infection (CDI) is the most common cause of infectious diarrhea in healthcare settings. Along with antimicrobial exposure, advanced age has been shown to be a significant risk factor for the development and recurrence of, and mortality from, CDI. The substantial burden of CDI in the elderly may be related to frequent healthcare exposure, the necessity for more medications, altered intestinal microbiota, and complicated comorbidities. A diagnosis of CDI is based on evidence of toxin, or the C. difficile organism itself, in a stool sample in the presence of clinical signs and symptoms. Only symptomatic patients should be tested for CDI, and routine surveillance or repeat testing on asymptomatic patients as a test of cure is discouraged. Antibiotic discontinuation alone can improve or resolve CDI in some patients, and concomitant use of antibiotics is associated with decreased response to CDI treatment. Metronidazole, vancomycin, and fidaxomicin are the therapeutic agents currently available for CDI, with the selection of these agents being based on disease severity, history of recurrence, and cost. The recurrence rate after initial treatment is 20-30%. The first recurrence can be treated with the same therapeutic agent and, for subsequent recurrences, vancomycin in a tapered and/or pulsed regimen is recommended. Fecal microbiota transplantation has shown remarkable effectiveness for recurrent anti-refractory CDI, although caution is advised in treating immunocompromised hosts and those with toxic megacolon. C. difficile can be transmitted directly and indirectly via contact with patients or their environment; therefore, isolation precautions should be initiated at the first suspicion of CDI. C. difficile spores can survive for a long time on environmental surfaces, and the patient's room and all equipment used in the room should be disinfected. In order to manage CDI in the elderly, timely diagnosis, appropriate treatment based on severity of illness, and effective infection control are essential.

Comparative epidemiology of Clostridium difficile infection: England and the USA.

PubMed

King, Alice; Mullish, Benjamin H; Williams, Horace R T; Aylin, Paul

2017-10-01

To examine whether there is an epidemiological difference between Clostridium difficile infection (CDI) inpatient populations in England and the United States. A cross-sectional study. National administrative inpatient discharge data from England (Hospital Episode Statistics) and the USA (National Inpatient Sample) in 2012. De-identifiable non-obstetric inpatient discharges from the national datasets were used to estimate national CDI incidence in the United States and England using ICD9-CM(008.45) and ICD10(A04.7) respectively. The rate of CDI was calculated per 100 000 population using national population estimates. Rate per 100 000 inpatient discharges was also calculated separated by primary and secondary diagnosis of CDI. Age, sex and Elixhauser comorbidities profiles were examined. The USA had a higher rate of CDI compared to England: 115.1/100 000 vs. 19.3/100 000 population (P < 0.001). CDI age profiles differed between the countries (P < 0.001): in England, patients ≥75 years constitute a larger proportion of CDI cases, whilst those aged 25-70 constitute more cases in the US (P < 0.001). Overall adjusted odds of CDI in females compared to males was elevated in both England (odds ratios (OR) 1.26 95% CI [1.21,1.31] P < 0.001) and the USA (OR 1.20 95% CI [1.18,1.22] P < 0.001). The proportion of CDI patients with comorbidities was greater in the USA compared to England apart from dementia, which was greater in England (9.63% vs. 1.25%, P < 0.0001). The 2012 inpatient CDI rate within the USA was much higher than in England. Age and comorbidity profiles also differed between CDI patients in both countries. The reasons for this are likely multi-factorial but may reflect national infection control policy. © The Author 2017. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

The Campus Demotechnic Index: A comparison of technological energy consumption at U.S. colleges and universities

NASA Astrophysics Data System (ADS)

Vance, Leisha Ann

The Campus Demotechnic Index (CDI) is a normalized metric developed to provide universities with a method for tracking progress toward or retreat from sustainability in their energy consumption. The CDI is modified after the Demotechnic Index of Mata et al. (1994). CDI values assess the total campus energy consumed against the total energy required to meet the campus population's basal metabolism. Like the D-Index, the CDI is thus a measure of the scalar quantity of energy consumed in excess of the quantity of energy required for simple survival on a per capita basis. For this research, data were collected from an on-line survey designed for U.S. colleges and universities, which requested information related to campus demographics and campus built and mobile environmental energy consumption. Data were requested for the years of 2000 to 2005. Wilcoxon signed rank test analyses were conducted to determine if CDI values significantly increased over time. ANOVAs, GLMs, correlations and regressions were conducted to determine if climate and campus size significantly influenced CDI. ANOVAs, correlations and regressions were conducted to determine the effect of acreage on mobile fuel consumption and to ascertain whether differing proportions between the built and mobile environments significantly influenced CDI values. Correlations and regressions were carried out to which variables best predicted CDI, and cluster analyses were conducted to find out if any significant groups existed based on CDI values, fossil fuel consumption and population per square foot. The knowledge gained from results of these analyses not only provides a depiction of campus energy consumption, but also puts campus energy consumption into context in that CDI scores allow peer institutional comparisons. Awareness of factors that contribute to campus energy use (and CDI ranks) could also facilitate prioritization of sustainability-related issues, as well as the design and establishment of sustainable management systems.

Clinical and Healthcare Burden of Multiple Recurrences of Clostridium difficile Infection.

PubMed

Sheitoyan-Pesant, Caroline; Abou Chakra, Claire Nour; Pépin, Jacques; Marcil-Héguy, Anaïs; Nault, Vincent; Valiquette, Louis

2016-03-01

Clostridium difficile infection (CDI) is associated with a high risk of recurrence (rCDI). Few studies have focused on multiple recurrences. To evaluate the potential of novel treatments targeting recurrence, we assessed the burden and severity of rCDI. This was a retrospective cohort of adults diagnosed with CDI in a hospital in Sherbrooke, Canada (1998-2013). An rCDI episode was defined by the reappearance of diarrhea leading to a treatment, with or without a positive toxin assay, within 14-60 days after the previous episode. We included 1527 patients. The probability of developing a first rCDI was 25% (354/1418); a second, 38% (128/334); a third, 29% (35/121); and a fourth or more, 27% (9/33). Two or more rCDIs were observed in 9% (128/1389) of patients. The risk of a first recurrence fluctuated over time, but there was no such variation for second or further recurrences. The proportion of severe cases decreased (47% for initial episodes, 31% for first recurrences, 25% for second, 17% for third), as did the risk of complicated CDI (5.8% to 2.8%). The severity and risk of complications of first recurrences decreased over time, while oral vancomycin was used more systemically. A hospital admission was needed for 34% (148/434) of recurrences. This study documented the clinical and healthcare burden of rCDI: 34% of patients with rCDI needed admission, 28% developed severe CDI, and 4% developed a complication. Secular changes in the severity of recurrences could reflect variations in the predominant strain, or better management. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Recurrent Clostridium difficile infection among Medicare patients in nursing homes: A population-based cohort study.

PubMed

Zilberberg, Marya D; Shorr, Andrew F; Jesdale, William M; Tjia, Jennifer; Lapane, Kate

2017-03-01

We explored the epidemiology and outcomes of Clostridium difficile infection (CDI) recurrence among Medicare patients in a nursing home (NH) whose CDI originated in acute care hospitals.We conducted a retrospective, population-based matched cohort combining Medicare claims with Minimum Data Set 3.0, including all hospitalized patients age ≥65 years transferred to an NH after hospitalization with CDI 1/2011-11/2012. Incident CDI was defined as ICD-9-CM code 008.45 with no others in prior 60 days. CDI recurrence was defined as (within 60 days of last day of CDI treatment): oral metronidazole, oral vancomycin, or fidaxomicin for ≥3 days in part D file; or an ICD-9-CM code for CDI (008.45) during a rehospitalization. Cox proportional hazards and linear models, adjusted for age, gender, race, and comorbidities, examined mortality within 60 days and excess hospital days and costs, in patients with recurrent CDI compared to those without.Among 14,472 survivors of index CDI hospitalization discharged to an NH, 4775 suffered a recurrence. Demographics and clinical characteristics at baseline were similar, as was the risk of death (24.2% with vs 24.4% without). Median number of hospitalizations was 2 (IQR 1-3) among those with and 0 (IQR 0-1) among those without recurrence. Adjusted excess hospital days per patient were 20.3 (95% CI 19.1-21.4) and Medicare reimbursements $12,043 (95% CI $11,469-$12,617) in the group with a recurrence.Although recurrent CDI did not increase the risk of death, it was associated with a far higher risk of rehospitalization, excess hospital days, and costs to Medicare.

Hospital cost of Clostridium difficile infection including the contribution of recurrences in French acute-care hospitals.

PubMed

Le Monnier, A; Duburcq, A; Zahar, J-R; Corvec, S; Guillard, T; Cattoir, V; Woerther, P-L; Fihman, V; Lalande, V; Jacquier, H; Mizrahi, A; Farfour, E; Morand, P; Marcadé, G; Coulomb, S; Torreton, E; Fagnani, F; Barbut, F

2015-10-01

The impact of Clostridium difficile infection (CDI) on healthcare costs is significant due to the extra costs of associated inpatient care. However, the specific contribution of recurrences has rarely been studied. The aim of this study was to estimate the hospital costs of CDI and the fraction attributable to recurrences in French acute-care hospitals. A retrospective study was performed for 2011 on a sample of 12 large acute-care hospitals. CDI costs were estimated from both hospital and public insurance perspectives. For each stay, CDI additional costs were estimated by comparison to controls without CDI extracted from the national DRG (diagnosis-related group) database and matched on DRG, age and sex. When CDI was the primary diagnosis, the full cost of stay was used. A total of 1067 bacteriological cases of CDI were identified corresponding to 979 stays involving 906 different patients. Recurrence(s) were identified in 118 (12%) of these stays with 51.7% of them having occurred within the same stay as the index episode. Their mean length of stay was 63.8 days compared to 25.1 days for stays with an index case only. The mean extra cost per stay with CDI was estimated at €9,575 (median: €7,514). The extra cost of CDI in public acute-care hospitals was extrapolated to €163.1 million at the national level, of which 12.5% was attributable to recurrences. The economic burden of CDI is substantial and directly impacts healthcare systems in France. Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Economic impact of Clostridium difficile infection in a multihospital cohort of academic health centers.

PubMed

Pakyz, Amy; Carroll, Norman V; Harpe, Spencer E; Oinonen, Michael; Polk, Ronald E

2011-06-01

To assess the economic impact of Clostridium difficile infection (CDI) in a large multihospital cohort. Retrospective case-control study. Administrative claims data from 45 academic medical centers. A total of 10,857 patients who developed health care-associated CDI and were discharged between April 1, 2002, and March 31, 2007 (cases); each case patient was matched by hospital, age, quarter and year of hospital discharge, and diagnosis related group to at least one control patient who did not develop health care-associated CDI (19,214 controls). Patients with health care-associated CDI were identified by using a previously validated method combining the International Classification of Diseases, Ninth Revision, Clinical Modification code for CDI with specific CDI drug therapy (oral or intravenous metronidazole, or oral vancomycin). Costs were determined from charges by using standardized cost:charges ratios and were adjusted for age, All Patient Refined-Diagnosis Related Group (APR-DRG) severity of illness level, race, and sex with use of multivariable linear regression. The adjusted mean cost for cases was significantly higher than that for controls ($55,769 vs $28,609), and adjusted mean length of stay was twice as long (21.1 vs 10.0 days). The interaction between CDI and APR-DRG severity of illness level was significant; the effect of CDI on costs and length of stay decreased as severity of illness increased. This large CDI economic evaluation confirms that health care-associated cases of CDI are associated with significantly higher mean cost and longer length of stay than those of matched controls, with the greatest effect on costs at the lowest level of severity of illness.

Health care burden of Clostridium difficile infection in hospitalized children with inflammatory bowel disease.

PubMed

Pant, Chaitanya; Anderson, Michael P; Deshpande, Abhishek; Altaf, Muhammad A; Grunow, John E; Atreja, Ashish; Sferra, Thomas J

2013-04-01

Children with inflammatory bowel disease (IBD), similar to adults, are at increased risk of acquiring a Clostridium difficile infection (CDI). Our objective was to characterize the health care burden associated with CDI in hospitalized pediatric patients with IBD. We extracted and analyzed cases with a discharge diagnosis of IBD or CDI from the U.S. Healthcare Cost and Utilization Project Kids' Inpatient Database. In our primary analysis, we evaluated pediatric cases with a principal diagnosis of IBD or CDI. For the year 2009, we identified 12,610 weighted cases with IBD of which 3.5% had CDI. In children with IBD, CDI was independently associated with lengthier hospital stays (8.0 versus 6.0 days; adjusted regression coefficient, 2.1 days; 95% confidence interval [CI], 1.4-2.8), higher charges ($45,126 versus $34,703; adjusted regression coefficient, $11,506; 95% CI, 6192-16,820), and greater need for parenteral nutrition (15.9% versus 12.1%; adjusted odds ratio, 1.5; 95% CI, 1.1-2.0) and blood transfusion (17.7% versus 9.8%; adjusted odds ratio, 1.8; 95% CI, 1.4-2.4). There were no deaths. We made similar observations in a subanalysis of cases with principal or secondary diagnoses of IBD or CDI. The incidence of CDI in patients with IBD increased between 2000 and 2009 from 21.7 to 28.0 cases per 1000 IBD cases per year (P < 0.001). There was a significant increase in CDI complicating ulcerative colitis (28.1 versus 42.2, P < 0.001) but not for Crohn's disease (18.3 versus 20.3). CDI represents a significant health care burden in hospitalized children with IBD.

The Epidemiology and Clinical Features of Clostridium difficile Infection in Liver Transplant Recipients.

PubMed

Sullivan, Timothy; Weinberg, Alan; Rana, Meenakshi; Patel, Gopi; Huprikar, Shirish

2016-09-01

Clostridium difficile infection (CDI) is common after liver transplantation (LT); however, few studies have examined the risk factors, clinical manifestations, and outcomes of CDI in this population. A retrospective study of adults who underwent LT between January 1, 2011, and April 4, 2013, at The Mount Sinai Hospital was conducted. Potential risk factors were evaluated via univariate and multivariable analysis to determine predictors of CDI in this population. The clinical manifestations of CDI and patient outcomes were also reviewed. Clostridium difficile infection occurred in 27 (14%) of 192 patients after LT. In multivariable analysis, CDI was associated with having a model for end-stage liver disease score of 20 or greater (hazards ratio, 2.90; 95% confidence interval, 1.29-6.52; P = 0.010), and receiving a LT from a living donor (hazards ratio, 3.77; 95% confidence interval, 1.47-9.67; P = 0.006). Forty-one percent of CDI cases occurred within 1 week of LT. Seven percent of patients with CDI had a serum white blood cell count greater than 12 000 cells per μL, and 26% had a temperature greater than 38.0°C. After treatment 6 (22%) patients developed CDI relapse, and all were successfully treated. No patients died of CDI after a mean follow-up time of 1.8 years; however, overall survival was significantly lower among those with CDI (78% vs 92%; P = 0.033). Clostridium difficile infection after LT was associated with higher model for end-stage liver disease scores and receiving a LT from a living donor. Clostridium difficile infection often occurred soon after LT and was infrequently associated with leukocytosis or fever. Clostridium difficile infection in LT recipients was associated with lower overall survival.

Incidence of Clostridium difficile infection in patients receiving high-risk antibiotics with or without a proton pump inhibitor.

PubMed

Gordon, D; Young, L R; Reddy, S; Bergman, C; Young, J D

2016-02-01

Considering the incidence and severity of Clostridium difficile infection (CDI), risk reduction strategies are crucial. Prior studies suggest that proton pump inhibitor (PPI) use can increase the risk of CDI over antibiotics alone; however, data and guidelines have been conflicting. The aim was to compare CDI incidence in patients receiving high-risk antibiotics, comparing rates in those prescribed a PPI versus those without overlapping PPI exposure. This retrospective cohort study assessed the incidence of CDI in veterans receiving high-risk antibiotics over an approximately three-year period. High-risk antibiotics were defined as: ciprofloxacin, levofloxacin, moxifloxacin, clindamycin, ceftriaxone, cefotaxime, ceftazidime, or cefixime. We identified subjects who were prescribed any high-risk antibiotic, finding 3513 on a concomitant PPI and 6149 not taking a PPI. Of these subjects, 111 were diagnosed with CDI and met inclusion criteria. Baseline characteristics, CDI severity, length of hospitalization and antibiotic therapy prior to infection were similar in both groups. The incidence of CDI was significantly higher in patients prescribed a PPI (odds ratio: 2.2; 95% confidence interval: 1.52-3.23; P=0.0001). A strong association was found between concurrent PPI use with fluoroquinolones (P=0.005) and clindamycin (P=0.045). The use of PPIs together with high-risk antibiotics was associated with a significantly higher incidence of CDI. Our study provides further support for the CDI prevention strategy of judicious PPI use, especially in patients receiving high-risk antibiotics. Prudent avoidance of PPIs may reduce the incidence of CDI, a major cause of morbidity and mortality worldwide. Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Prevalence of Clostridium difficile infection in hospitalized patients with diarrhoea: Results of a Polish multicenter, prospective, biannual point-prevalence study.

PubMed

Pituch, Hanna; Obuch-Woszczatyński, Piotr; Lachowicz, Dominika; Kuthan, Robert; Dzierżanowska-Fangrat, Katarzyna; Mikucka, Agnieszka; Jermakow, Katarzyna; Pituch-Zdanowska, Aleksandra; Davies, Kerrie

2018-04-13

We aimed to measure the underdiagnosis of Clostridium difficile infection across Poland and the distribution of PCR-ribotypes of C. difficile. Twenty seven Polish healthcare facilities (HCFs) participated in this prospective study. Each HCF systematically sent all diarrhoeal stools received from inpatients at their laboratories on two days (one in January 2013 and one in July 2013), independently of CDI test request, to the National Coordinating Laboratory (NCL) for standardized testing of CDI. Positive samples (using two-stage algorithm), had CDI, confirmed by qPCR and toxigenic culture. C. difficile isolates were characterized by PCR-ribotyping. Hospitals were questioned about their methods and testing policy for CDI during the study period: September 2011 to August 2013. During the study period, participating hospitals reported a mean of 33.2 tests for CDI per 10 000 patient-days and a mean of 8.4 cases of CDI per 10 000 patient-days. The overall prevalence of positive CDI patients at NCL was 16.5%. Due to absence of clinical suspicion, 19.1% of these patients were not diagnosed by the local diagnostic laboratory. We identified 23 different PCR-ribotypes among 87C. difficile strains isolated from patients. PCR-ribotype 027 (48%) was the most prevalent. The incidence of CDI in Poland in study period was very high. It should be noted however, that there is a lack of clinical suspicion and underestimation of the need to perform diagnostic tests for CDI in hospitalized patients. This will have an impact on the reported epidemiological status of CDI in Poland. Copyright © 2018 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

Economic burden and cost-effective management of Clostridium difficile infections.

PubMed

Heimann, S M; Cruz Aguilar, M R; Mellinghof, S; Vehreschild, M J G T

2018-02-01

Clostridium difficile infection (CDI) is the most important cause of healthcare-associated infectious diarrhea in industrialized countries. We performed a literature review of the overall economic burden of initial and recurrent CDI as well as of the cost-effectiveness of the various treatment strategies applied in these settings. Even though analysis of health economic data is complicated by the limited comparability of results, our review identified several internationally consistent results. Authors from different countries have shown that recurrent CDI disproportionally contributes to the overall economic burden of CDI and therefore offers considerable saving potential. Subsequent cost-effectiveness analyses almost exclusively identified fidaxomicin as the preferred treatment option for initial CDI and fecal microbiota transplant (FMT) for recurrent CDI. Among the various FMT protocols, optimum results were obtained using early colonoscopy-based FMT. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Recent Progress for the Effective Prevention and Treatment of Recurrent Clostridium difficile Infection.

PubMed

Ramsay, Isobel; Brown, Nicholas M; Enoch, David A

2018-01-01

Recurrence occurs in approximately 25% of all cases of Clostridium difficile infection (CDI) and poses a unique clinical challenge. Traditionally, treatment options of CDI have been limited to regimes of established antibiotics (eg, pulsed/tapered vancomycin) but faecal transplantation is emerging as a useful alternative. In recent years, promising new strategies have emerged for effective prevention of recurrent CDI (rCDI) including new antimicrobials (eg, fidaxomicin) and monoclonal antibodies (eg, bezlotoxumab). Despite promising progress in this area, obstacles remain for making the best use of these resources due to uncertainty over patient selection. This commentary describes the current epidemiology of rCDI, its clinical impact and risk factors, some of the measures used for treating and preventing rCDI, and some of the emerging treatment options. It then describes some of the obstacles that need to be overcome.

The impact of Clostridium difficile infection on resource use and costs in hospitals in Spain and Italy: a matched cohort study.

PubMed

Asensio, Angel; Di Bella, Stefano; Lo Vecchio, Andrea; Grau, Santiago; Hart, Warren M; Isidoro, Beatriz; Scotto, Ricardo; Petrosillo, Nicola; Watt, Maureen; Nazir, Jameel

2015-07-01

To assess the impact of Clostridium difficile infection (CDI) on hospital resources and costs in Spain and Italy. CDI data were collected from institutions in Spain and Italy. Each patient was matched with two randomly selected uninfected controls in the same institution. Patient outcomes were assessed for the first and second episodes of CDI and for patients aged ≤65 and >65 years. The impact of CDI on hospital length of stay (LOS) was used to calculate CDI-attributable costs. A multivariate analysis using duration of stay as the continuous outcome variable assessed the independent effect of CDI on hospital costs and LOS. LOS attributable to CDI ranged from 7.6-19.0 days in adults and was 5.0 days in children; the increases were greater in adults in Italy than in Spain. Attributable costs per adult patient ranged from €4396 in Madrid to €14 023 in Rome, with the majority of the cost being due to hospitalization. For children, the total attributable cost was €3545/patient. These data show that the burden of CDI is considerable in Spain and Italy. Treatments that can reduce LOS, disease severity, and recurrence rates, as well as effective infection control measures to prevent transmission, have the potential to reduce the burden of CDI. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Decreasing Clostridium difficile infections by an antimicrobial stewardship program that reduces moxifloxacin use.

PubMed

Wenisch, Judith Maria; Equiluz-Bruck, Susanne; Fudel, Marta; Reiter, Ingun; Schmid, Andrea; Singer, Erna; Chott, Andreas

2014-09-01

Clostridium difficile infections (CDI) in hospitalized patients are known to be closely related to antibiotic exposure. Although several substances can cause CDI, the risk differs between individual agents. In Vienna and other eastern parts of Austria, CDI ribotype 027 is currently highly prevalent. This ribotype has the characteristic of intrinsic moxifloxacin resistance. Therefore, we hypothesized that moxifloxacin restriction can decrease the number of CDI cases in hospitalized patients. Our antibiotic stewardship (ABS) group applied an information campaign on CDI and formal restriction of moxifloxacin in Wilhelminenspital (Vienna, Austria), a 1,000- bed tertiary care hospital. The preintervention period (period 1) was January through May 2013, and the intervention period (period 2) was June through December 2013. We recorded the defined daily doses (DDD) of moxifloxacin and the number of CDI patients/month. Moxifloxacin use was reduced from a mean (±standard error of the mean [SEM]) of 1,038±109 DDD per month (period 1) to 42±10 DDD per month (period 2) (P=0.0045). Total antibiotic use was not affected. The mean (±SEM) numbers of CDI cases in period 1 were 59±3 per month and in period 2 were 32±3 per month (46% reduction; P=0.0044). Reducing moxifloxacin use in combination with providing structured information on CDI was associated with an immediate decrease in CDI rates in this large community teaching hospital. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Probiotics in Clostridium difficile infection: reviewing the need for a multistrain probiotic.

PubMed

Hell, M; Bernhofer, C; Stalzer, P; Kern, J M; Claassen, E

2013-03-01

In the past two years an enormous amount of molecular, genetic, metabolomic and mechanistic data on the host-bacterium interaction, a healthy gut microbiota and a possible role for probiotics in Clostridium difficile infection (CDI) has been accumulated. Also, new hypervirulent strains of C. difficile have emerged. Yet, clinical trials in CDI have been less promising than in antibiotic associated diarrhoea in general, with more meta-analysis than primary papers on CDI-clinical-trials. The fact that C. difficile is a spore former, producing at least three different toxins has not yet been incorporated in the rational design of probiotics for (recurrent) CDI. Here we postulate that the plethora of effects of C. difficile and the vast amount of data on the role of commensal gut residents and probiotics point towards a multistrain mixture of probiotics to reduce CDI, but also to limit (nosocomial) transmission and/or endogenous reinfection. On the basis of a retrospective chart review of a series of ten CDI patients where recurrence was expected, all patients on adjunctive probiotic therapy with multistrain cocktail (Ecologic®AAD/OMNiBiOTiC® 10) showed complete clinical resolution. This result, and recent success in faecal transplants in CDI treatment, are supportive for the rational design of multistrain probiotics for CDI.

Antibiotic Treatment of Hospitalized Patients with Pneumonia Complicated by Clostridium Difficile Infection.

PubMed

Zycinska, K; Chmielewska, M; Lenartowicz, B; Hadzik-Blaszczyk, M; Cieplak, M; Kur, Z; Krupa, R; Wardyn, K A

2016-01-01

Clostridium difficile infection (CDI) is one of the most common gastrointestinal complication after antimicrobial treatment. It is estimated that CDI after pneumonia treatment is connected with a higher mortality than other causes of hospitalization. The aim of the study was to assess the relationship between the kind of antibiotic used for pneumonia treatment and mortality from post-pneumonia CDI. We addressed the issue by examining retrospectively the records of 217 patients who met the diagnostic criteria of CDI. Ninety four of those patients (43.3 %) came down with CDI infection after pneumonia treatment. Fifty of the 94 patients went through severe or severe and complicated CDI. The distribution of antecedent antibiotic treatment of pneumonia in these 50 patients was as follows: ceftriaxone in 14 (28 %) cases, amoxicillin with clavulanate in 9 (18 %), ciprofloxacin in 8 (16.0 %), clarithromycin in 7 (14 %), and cefuroxime and imipenem in 6 (12 %) each. The findings revealed a borderline enhancement in the proportion of deaths due to CDI in the ceftriaxone group compared with the ciprofloxacin, cefuroxime, and imipenem groups. The corollary is that ceftriaxone should be shunned in pneumonia treatment. The study demonstrates an association between the use of a specific antibiotic for pneumonia treatment and post-pneumonia mortality in patients who developed CDI.

In-vivo measurement of relationship between applied current amplitude and current density magnitude from 10 mA to 110 mA.

PubMed

DeMonte, Tim P; Wang, Dinghui; Ma, Weijing; Gao, Jia-Hong; Joy, Michael L G

2009-01-01

Current density imaging (CDI) is a magnetic resonance imaging (MRI) technique used to quantitatively measure current density vectors throughout the volume of an object/subject placed in the MRI system. Electrical current pulses are applied externally to the object/subject and are synchronized with the MRI sequence. In this work, CDI is used to measure average current density magnitude in the torso region of an in-vivo piglet for applied current pulse amplitudes ranging from 10 mA to 110 mA. The relationship between applied current amplitude and current density magnitude is linear in simple electronic elements such as wires and resistors; however, this relationship may not be linear in living tissue. An understanding of this relationship is useful for research in defibrillation, human electro-muscular incapacitation (e.g. TASER(R)) and other bioelectric stimulation devices. This work will show that the current amplitude to current density magnitude relationship is slightly nonlinear in living tissue in the range of 10 mA to 110 mA.

A case of Clostridium difficile infection complicated by acute respiratory distress syndrome treated with fecal microbiota transplantation.

PubMed

Kim, Ji Eun; Gweon, Tae-Geun; Yeo, Chang Dong; Cho, Young-Seok; Kim, Gi Jun; Kim, Jae Young; Kim, Jong Wook; Kim, Hyunho; Lee, Hye Won; Lim, Taeseok; Ham, Hyoju; Oh, Hyun Jin; Lee, Yeongbok; Byeon, Jaeho; Park, Sung Soo

2014-09-21

Acute respiratory distress syndrome is a life-threatening disorder caused mainly by pneumonia. Clostridium difficile infection (CDI) is a common nosocomial diarrheal disease. Disruption of normal intestinal flora by antibiotics is the main risk factor for CDI. The use of broad-spectrum antibiotics for serious medical conditions can make it difficult to treat CDI complicated by acute respiratory distress syndrome. Fecal microbiota transplantation is a highly effective treatment in patients with refractory CDI. Here we report on a patient with refractory CDI and acute respiratory distress syndrome caused by pneumonia who was treated with fecal microbiota transplantation.

Ridinilazole: a novel therapy for Clostridium difficile infection.

PubMed

Vickers, Richard J; Tillotson, Glenn; Goldstein, Ellie J C; Citron, Diane M; Garey, Kevin W; Wilcox, Mark H

2016-08-01

Clostridium difficile infection (CDI) is the leading cause of infectious healthcare-associated diarrhoea. Recurrent CDI increases disease morbidity and mortality, posing a high burden to patients and a growing economic burden to the healthcare system. Thus, there exists a significant unmet and increasing medical need for new therapies for CDI. This review aims to provide a concise summary of CDI in general and a specific update on ridinilazole (formerly SMT19969), a novel antibacterial currently under development for the treatment of CDI. Owing to its highly targeted spectrum of activity and ability to spare the normal gut microbiota, ridinilazole provides significant advantages over metronidazole and vancomycin, the mainstay antibiotics for CDI. Ridinilazole is bactericidal against C. difficile and exhibits a prolonged post-antibiotic effect. Furthermore, treatment with ridinilazole results in decreased toxin production. A phase 1 trial demonstrated that oral ridinilazole is well tolerated and specifically targets clostridia whilst sparing other faecal bacteria. Phase 2 and 3 trials will hopefully further our understanding of the clinical utility of ridinilazole for the treatment of CDI. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Management of inflammatory bowel disease with Clostridium difficile infection.

PubMed

D'Aoust, Julie; Battat, Robert; Bessissow, Talat

2017-07-21

To address the management of Clostridium difficile ( C. difficile ) infection (CDI) in the setting of suspected inflammatory bowel disease (IBD)-flare. A systematic search of the Ovid MEDLINE and EMBASE databases by independent reviewers identified 70 articles including a total of 932141 IBD patients or IBD-related hospitalizations. In those with IBD, CDI is associated with increased morbidity, including subsequent escalation in IBD medical therapy, urgent colectomy and increased hospitalization, as well as excess mortality. Vancomycin-containing regimens are effective first-line therapies for CDI in IBD inpatients. No prospective data exists with regards to the safety or efficacy of initiating or maintaining corticosteroid, immunomodulator, or biologic therapy to treat IBD in the setting of CDI. Corticosteroid use is a risk factor for the development of CDI, while immunomodulators and biologics are not. Strong recommendations regarding when to initiate IBD specific therapy in those with CDI are precluded by a lack of evidence. However, based on expert opinion and observational data, initiation or resumption of immunosuppressive therapy after 48-72 h of targeted antibiotic treatment for CDI may be considered.

Emerging therapies for Clostridium difficile infections.

PubMed

McFarland, Lynne V

2011-09-01

Clostridium difficile infection (CDI) is the leading identifiable gastrointestinal disease in healthcare institutions, but the response rates to the two standard therapies for CDI are declining and so innovative therapies are being developed for CDI. The purpose of this paper is to review the data on the efficacy and safety of emerging therapies for CDI and assess their potential for effectiveness based on the clinical phase of development and marketing challenges. Emerging therapies for CDI are reviewed including new antibiotics, peptides, immune regulators, probiotics and toxin binders. PubMed, Medline and Google Scholar and online clinical trial registers are searched from 1976 to 2010 for articles unrestricted by language. Secondary searches by author, manufacturing companies and FDA websites are also performed. Of the emerging therapies for CDI, several may ultimately reduce the incidence of CDI and the economic burden of this disease on the healthcare system. Several emerging treatments (fidaxomicin, rifaximin and mAbs) show the most promise, although only one is currently being actively developed. Use of other clostridial strains, probiotic strains and immune enhancers have great potential as therapies, but require further development.

Systemic thrombolysis increases hemorrhagic stroke risk without survival benefit compared with catheter-directed intervention for the treatment of acute pulmonary embolism.

PubMed

Liang, Nathan L; Avgerinos, Efthymios D; Singh, Michael J; Makaroun, Michel S; Chaer, Rabih A

2017-03-01

Systemic thrombolysis (ST) and catheter-directed intervention (CDI) are both used in the treatment of acute pulmonary embolism (PE), but the comparative outcomes of these two therapies remain unclear. The objective of this study was to compare short-term mortality and safety outcomes between the two treatments using a large national database. Patients presenting with acute PE were identified in the National Inpatient Sample (NIS) from 2009 to 2012. Comorbidities, clinical characteristics, and invasive procedures were identified using International Classification of Diseases, Ninth Revision (ICD) codes and the Elixhauser comorbidity index. To adjust for anticipated baseline differences between the two treatment groups, propensity score matching was used to create a matched ST cohort with clinical and comorbid characteristics similar to those of the CDI cohort. Subgroups of patients with and without hemodynamic shock were analyzed separately. Primary outcomes were in-hospital mortality, overall bleeding risk, and hemorrhagic stroke risk. Of 263,955 subjects with acute PE, 1.63% (n = 4272) received ST and 0.55% (n = 1455) received CDI. ST subjects were older, had more chronic comorbidities, and had higher rates of respiratory failure (ST, 27.9% [n = 1192]; CDI, 21.2% [n = 308]; P < .001) and shock (ST, 18.2% [n = 779]; CDI, 12% [n = 174]; P < .001). CDI subjects had higher rates of concurrent deep venous thrombosis (ST, 35.8% [n = 1530]; CDI, 45.9% [n = 668]; P < .001) and vena cava filter placement (ST, 31.1% [n = 1328]; CDI, 57% [n = 830]; P < .001). In the unmatched cohort, ST subjects had higher in-hospital mortality (ST, 16.7% [n = 714]; CDI, 9.4% [n = 136]; P < .001) and hemorrhagic stroke rates (ST, 2.2% [n = 96]; CDI, 1.4% [n = 20]; P = .041). After propensity matching, 1430 patients remained in each cohort; baseline characteristics of the matched cohorts did not differ significantly using standardized difference comparisons. Analysis of the matched cohorts did not demonstrate a significant effect of CDI on in-hospital mortality or overall bleeding risk but did show a significant protective effect against hemorrhagic stroke compared with ST (odds ratio, 0.47; 95% confidence interval, 0.27-0.82; P = .01). Subgroup analysis showed decreased odds of hemorrhagic stroke for CDI in the nonshock subgroup and increased procedural bleeding for CDI but no difference in hemorrhagic stroke risk in the shock subgroup. ST for acute PE may not improve in-hospital mortality compared with CDI but increases the overall risk of hemorrhagic stroke compared with CDI. Further prospective studies should examine the comparative effectiveness and safety of these two treatments. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Thirty-Day Readmissions in Hospitalized Patients Who Received Bezlotoxumab With Antibacterial Drug Treatment for Clostridium difficile Infection

PubMed Central

Prabhu, Vimalanand S; Cornely, Oliver A; Golan, Yoav; Dubberke, Erik R; Heimann, Sebastian M; Hanson, Mary E; Liao, Jane; Pedley, Alison; Dorr, Mary Beth; Marcella, Stephen

2017-01-01

Abstract We estimated 30-day all-cause and Clostridium difficile infection (CDI)–associated hospital readmissions in participants at high risk of recurrent CDI enrolled in MODIFY I/II. Bezlotoxumab-treated inpatients experienced fewer CDI-associated readmissions compared with placebo-treated inpatients, notably in participants aged ≥65 years and with severe CDI. Clinical Trials Registration. NCT01241552 (MODIFY I) and NCT01513239 (MODIFY II).

Comparing productive vocabulary measures from the CDI and a systematic diary study.

PubMed

Robinson, B F; Mervis, C B

1999-02-01

Expressive vocabulary data gathered during a systematic diary study of one male child's early language development are compared to data that would have resulted from longitudinal administration of the MacArthur Communicative Development Inventories spoken vocabulary checklist (CDI). Comparisons are made for (1) the number of words at monthly intervals (9; 10.15 to 2; 0.15), (2) proportion of words by lexical class (i.e. noun, predicate, closed class, 'other'), (3) growth curves. The CDI underestimates the number of words in the diary study, with the underestimation increasing as vocabulary size increases. The proportion of diary study words appearing on the CDI differed as a function of lexical class. Finally, despite the differences in vocabulary size, logistic curves proved to be the best fitting model to characterize vocabulary development as measured by both the diary study and the CDI. Implications for the longitudinal use of the CDI are discussed.

Recent Progress for the Effective Prevention and Treatment of Recurrent Clostridium difficile Infection

PubMed Central

Ramsay, Isobel; Brown, Nicholas M; Enoch, David A

2018-01-01

Recurrence occurs in approximately 25% of all cases of Clostridium difficile infection (CDI) and poses a unique clinical challenge. Traditionally, treatment options of CDI have been limited to regimes of established antibiotics (eg, pulsed/tapered vancomycin) but faecal transplantation is emerging as a useful alternative. In recent years, promising new strategies have emerged for effective prevention of recurrent CDI (rCDI) including new antimicrobials (eg, fidaxomicin) and monoclonal antibodies (eg, bezlotoxumab). Despite promising progress in this area, obstacles remain for making the best use of these resources due to uncertainty over patient selection. This commentary describes the current epidemiology of rCDI, its clinical impact and risk factors, some of the measures used for treating and preventing rCDI, and some of the emerging treatment options. It then describes some of the obstacles that need to be overcome. PMID:29535530

Epidemiology and healthcare costs of incident Clostridium difficile infections identified in the outpatient healthcare setting.

PubMed

Kuntz, Jennifer L; Johnson, Eric S; Raebel, Marsha A; Petrik, Amanda F; Yang, Xiuhai; Thorp, Micah L; Spindel, Steven J; Neil, Nancy; Smith, David H

2012-10-01

To describe the epidemiology and healthcare costs of Clostridium difficile infection (CDI) identified in the outpatient setting. Population-based, retrospective cohort study. Kaiser Permanente Colorado and Kaiser Permanente Northwest members between June 1, 2005, and September 30, 2008. We identified persons with incident CDI and classified CDI by whether it was identified in the outpatient or inpatient healthcare setting. We collected information about baseline variables and follow-up healthcare utilization, costs, and outcomes among patients with CDI. We compared characteristics of patients with CDI identified in the outpatient versus inpatient setting. We identified 3,067 incident CDIs; 56% were identified in the outpatient setting. Few strong, independent predictors of diagnostic setting were identified, although a previous stay in a nonacute healthcare institution (odds ratio [OR], 1.45 [95% confidence interval (CI), 1.13-1.86]) was statistically associated with outpatient-identified CDI, as was age from 50 to 59 years (OR, 1.64 [95% CI, 1.18-2.29]), 60 to 69 years (OR, 1.37 [95% CI, 1.03-1.82]), and 70 to 79 years (OR, 1.36 [95% CI, 1.06-1.74]), when compared with persons aged 80-89 years. We found that more than one-half of incident CDIs in this population were identified in the outpatient setting. Patients with outpatient-identified CDI were younger with fewer comorbidities, although they frequently had previous exposure to healthcare. These data suggest that practitioners should be aware of CDI and obtain appropriate diagnostic testing on outpatients with CDI symptoms.

Clostridium difficile: Investigating Transmission Patterns between Infected and Colonized Patients using whole Genome Sequencing.

PubMed

Kong, L Y; Eyre, D W; Corbeil, J; Raymond, F; Walker, A S; Wilcox, M H; Crook, D W; Michaud, S; Toye, B; Frost, E; Dendukuri, N; Schiller, I; Bourgault, A M; Dascal, A; Oughton, M; Longtin, Y; Poirier, L; Brassard, P; Turgeon, N; Gilca, R; Loo, V G

2018-05-28

Whole genome sequencing (WGS) studies can enhance our understanding of the role of patients with asymptomatic Clostridium difficile colonization in transmission. Isolates obtained from patients with Clostridium difficile infection (CDI) and colonization identified in a study conducted during 2006 - 2007 at six Canadian hospitals underwent typing by pulsed-field gel electrophoresis, multilocus sequence typing, and WGS. Isolates from incident CDI cases not in the initial study were also sequenced where possible. Ward movement and typing data were combined to identify plausible donors for each CDI case, as defined by shared time and space within predefined limits. Proportions of plausible donors for CDI cases that were colonized, infected, or both were examined. Five hundred and fifty-four isolates were sequenced successfully, 353 from colonized and 201 from CDI cases. The NAP1/027/ST1 strain was the most common strain, found in 124 (62%) of infected and 92 (26%) of colonized patients. A donor with a plausible ward link was found for 81 CDI cases (40%) using WGS with a threshold of ≤2 single nucleotide variants to determine relatedness. Sixty-five (32%) CDI cases could be linked to both infected and colonized donors. Exclusive linkages to infected and colonized donors were found for 28 (14%) and 12 (6%) CDI cases, respectively. Colonized patients contribute to transmission, but CDI cases are more likely linked to other infected patients than colonized patients in this cohort with high rates of NAP1/027/ST1 strain, highlighting the importance of local prevalence of virulent strains in determining transmission dynamics.

Epidemiology, risk factors, and outcome of Clostridium difficile infection in heart and heart-lung transplant recipients.

PubMed

Bruminhent, Jackrapong; Cawcutt, Kelly A; Thongprayoon, Charat; Petterson, Tanya M; Kremers, Walter K; Razonable, Raymund R

2017-06-01

Clostridium difficile is a major cause of diarrhea in thoracic organ transplant recipients. We investigated the epidemiology, risk factors, and outcome of Clostridium difficile infection (CDI) in heart and heart-lung transplant (HT) recipients. This is a retrospective study from 2004 to 2013. CDI was defined by diarrhea and a positive toxigenic C. difficile in stool measured by toxin enzyme immunoassay (2004-2006) or polymerase chain reaction (2007-2013). Cox proportional hazards regression was used to model the association of risk factors with time to CDI and survival with CDI following transplantation. There were 254 HT recipients, with a median age of 53 years (IQR, 45-60); 34% were female. During the median follow-up of 3.1 years (IQR, 1.3-6.1), 22 (8.7%) patients developed CDI. In multivariable analysis, risk factors for CDI were combined heart-lung transplant (HR 4.70; 95% CI, 1.30-17.01 [P=.02]) and retransplantation (HR 7.19; 95% CI, 1.61-32.12 [P=.01]). Acute cellular rejection was associated with a lower risk of CDI (HR 0.34; 95% CI, 0.11-0.94 [P=.04]). CDI was found to be an independent risk factor for mortality (HR 7.66; 95% CI, 3.41-17.21 [P<.0001]). Clostridium difficile infection after HT is more common among patients with combined heart-lung and those undergoing retransplantation. CDI was associated with a higher risk of mortality in HT recipients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Perceptions of Clostridium difficile infections among infection control professionals in Taiwan.

PubMed

Hung, Yuan-Pin; Lee, Jen-Chieh; Lin, Hsiao-Ju; Chiu, Chun-Wei; Wu, Jia-Ling; Liu, Hsiao-Chieh; Huang, I-Hsiu; Tsai, Pei-Jane; Ko, Wen-Chien

2017-08-01

High Clostridium difficile colonization and infection rates among hospitalized patients had been noted in Taiwan. Nevertheless, the cognition about clinical diagnosis and management of CDI among infection control professionals in Taiwan is not clear. A 24-item survey questionnaire about the diagnosis, therapy, or infection control policies toward CDI was distributed in the annual meeting of the Infectious Disease Society of Taiwan (IDST) in October 2015 and Infectious Control Society of Taiwan (ICST) in April 2016. Totally 441 individuals responded to the survey, and 280 (63.5%) participants would routinely monitor the prevalence of CDI and 347 (78.7%) reported the formulation of infection control policies of CDI in their hospital, including contact precaution (75.7%), wearing gloves (88.9%) or dressing (80.0%) at patient care, single room isolation (49.7%), preference of soap or disinfectant-based sanitizer (83.2%) and avoidance of alcohol-based sanitizer (63.3%), and environmental disinfection with 1000 ppm bleach (87.1%). For the timing of contact precaution discontinuation isolation for CDI patients, most (39.9%) participants suggested the time point of the absence of C. difficile toxin in feces. To treat mild CDI, most (61.9%) participants preferred oral metronidazole, and for severe CDI 26.1% would prescribe oral vancomycin as the drug of choice. There were substantial gaps in infection control polices and therapeutic choices for CDI between international guidelines and the perceptions of medical professionals in Taiwan. Professional education program and the setup of guideline for CDI should be considered in Taiwan. Copyright © 2017. Published by Elsevier B.V.

Awareness about clostridium difficile infection among internal medicine residents in the United States.

PubMed

Navaneethan, U; Schauer, D; Giannella, R

2011-09-01

Clostridium difficile infection (CDI) is the leading infective cause of antibiotic associated diarrhea. The principal objective of this study was to assess the knowledge and awareness of internal medicine (IM) residents regarding the epidemiology, clinical recognition, diagnosis and management of CDI. A 20-question survey was distributed to 90 IM residents in all three years of their post graduate training in a university-based program. The survey instrument assessed the resident's knowledge of the current epidemiological trend, clinical recognition and presentation, diagnosis and management of CDI. Forty two out of 90 (48%) residents completed the questionnaire. Only 10/42 (23.8%) of the residents recommended the gold standard investigation for diagnosing CDI. The majority of residents 29/42 (69%) were not aware of the existence of CDI in the outpatient setting and would not test for CDI. Only 50% of the residents were aware of the worse outcome of CDI in inflammatory bowel disease patients and only 12/42 (28.6%) would appropriately risk stratify and treat patients. Almost all of the residents (97.6%) knew about the appropriate time to consult surgery. There was no significant difference in the awareness with respect to the year of training (interns vs. residents), their career choices (primary care vs. fellowship) nor did the knowledge correlate with the United States medical licensing examination (USMLE) scores. IM residents had suboptimal knowledge of many aspects of the common problem of CDI. Educational efforts should be directed at IM residents, many of whom plan careers as primary care/hospitalists, who will encounter patients with CDI.

Evaluation of a Clostridium difficile infection management policy with clinical pharmacy and medical microbiology involvement at a major Canadian teaching hospital.

PubMed

Yeung, S S T; Yeung, J K; Lau, T T Y; Forrester, L A; Steiner, T S; Bowie, W R; Bryce, E A

2015-12-01

Clostridium difficile infection (CDI) represents a spectrum of disease and is a significant concern for healthcare institutions. Our study objective was to assess whether implementation of a regional CDI management policy with Clinical Pharmacy and Medical Microbiology and Infection Control involvement would lead to an improvement in concordance in prescribing practices to an evidence-based CDI disease severity assessment and pharmacological treatment algorithm. Conducted at a tertiary care teaching hospital, this two-phase quality assurance study consisted of a baseline retrospective healthcare record review of patients with CDI prior to the implementation of a regional CDI management policy followed by a prospective evaluation post-implementation. One hundred and forty-one CDI episodes in the pre-implementation group were compared to 283 episodes post-implementation. Overall treatment concordance to the CDI treatment algorithm was achieved in 48 of 141 cases (34%) pre-implementation compared with 136 of 283 cases (48·1%) post-implementation (P = 0·01). The median time to treatment with vancomycin was reduced from five days to one day (P < 0·01), with median length of hospital stay decreasing from 30 days to 21 days (P = 0·01) post-implementation. There was no difference in 30-day all-cause mortality. A comprehensive approach with appropriate stakeholder involvement in the development of clinical pathways, education to healthcare workers and prospective audit with intervention and feedback can ensure patients diagnosed with CDI are optimally managed and prescribed the most appropriate therapy based on CDI disease severity. © 2015 John Wiley & Sons Ltd.

Derivation and Validation of a Clostridium difficile Infection Recurrence Prediction Rule in a National Cohort of Veterans.

PubMed

Reveles, Kelly R; Mortensen, Eric M; Koeller, Jim M; Lawson, Kenneth A; Pugh, Mary Jo V; Rumbellow, Sarah A; Argamany, Jacqueline R; Frei, Christopher R

2018-03-01

Prior studies have identified risk factors for recurrent Clostridium difficile infection (CDI), but few studies have integrated these factors into a clinical prediction rule that can aid clinical decision-making. The objectives of this study were to derive and validate a CDI recurrence prediction rule to identify patients at risk for first recurrence in a national cohort of veterans. Retrospective cohort study. Veterans Affairs Informatics and Computing Infrastructure. A total of 22,615 adult Veterans Health Administration beneficiaries with first-episode CDI between October 1, 2002, and September 30, 2014; of these patients, 7538 were assigned to the derivation cohort and 15,077 to the validation cohort. A 60-day CDI recurrence prediction rule was created in a derivation cohort using backward logistic regression. Those variables significant at p<0.01 were assigned an integer score proportional to the regression coefficient. The model was then validated in the derivation cohort and a separate validation cohort. Patients were then split into three risk categories, and rates of recurrence were described for each category. The CDI recurrence prediction rule included the following predictor variables with their respective point values: prior third- and fourth-generation cephalosporins (1 point), prior proton pump inhibitors (1 point), prior antidiarrheals (1 point), nonsevere CDI (2 points), and community-onset CDI (3 points). In the derivation cohort, the 60-day CDI recurrence risk for each score ranged from 7.5% (0 points) to 57.9% (8 points). The risk score was strongly correlated with recurrence (R 2  = 0.94). Patients were split into low-risk (0-2 points), medium-risk (3-5 points), and high-risk (6-8 points) classes and had the following recurrence rates: 8.9%, 20.2%, and 35.0%, respectively. Findings were similar in the validation cohort. Several CDI and patient-specific factors were independently associated with 60-day CDI recurrence risk. When integrated into a clinical prediction rule, higher risk scores and risk classes were strongly correlated with CDI recurrence. This clinical prediction rule can be used by providers to identify patients at high risk for CDI recurrence and help guide preventive strategy decisions, while accounting for clinical judgment. © 2018 Pharmacotherapy Publications, Inc.

Successful Fecal Microbiota Transplantation in a Patient with Severe Complicated Clostridium difficile Infection after Liver Transplantation.

PubMed

Schneider, Kai Markus; Wirtz, Theresa H; Kroy, Daniela; Albers, Stefanie; Neumann, Ulf Peter; Strowig, Till; Sellge, Gernot; Trautwein, Christian

2018-01-01

Clostridium difficile infection (CDI) represents one of the most common healthcare-associated infections. Due to increasing numbers of recurrences and therapy failures, CDI has become a major disease burden. Studies have shown that fecal microbiota transplantation (FMT) can both be a safe and highly efficacious therapy for patients with therapy-refractory CDI. However, patients undergoing solid organ transplantation are at high risk for CDI due to long-term immunosuppression, previous antibiotic therapy, and proton pump inhibitor use. Additionally, these patients may be especially prone to adverse events related to FMT. Here, we report a successful FMT in a patient with severe therapy-refractory CDI after liver transplantation.

A review of the economics of treating Clostridium difficile infection.

PubMed

Mergenhagen, Kari A; Wojciechowski, Amy L; Paladino, Joseph A

2014-07-01

Clostridium difficile infection (CDI) is a costly result of antibiotic use, responsible for an estimated 14,000 deaths annually in the USA according to the Centers for Disease Control and Prevention. Annual costs attributable to CDI are in excess of $US 1 billion. This review summarizes appropriate utilization of prevention and treatment methods for CDI that have the potential to reduce the economic and humanistic costs of the disease. Some cost-effective strategies to prevent CDI include screening and isolation of hospital admissions based on C. difficile carriage to reduce transmission in the inpatient setting, and probiotics, which are potentially efficacious in preventing CDI in the appropriate patient population. The most extensively studied agents for treatment of CDI are metronidazole, vancomycin, and fidaxomicin. Most economic comparisons between metronidazole and vancomycin favor vancomycin, especially with the emergence of metronidazole-resistant C. difficile strains. Metronidazole can only be recommended for mild disease. Moderate to severe CDI should be treated with vancomycin, preferably the compounded oral solution, which provides the most cost-effective therapeutic option. Fidaxomicin offers a clinically effective and potentially cost-effective alternative for treating moderate CDI in patients who do not have the NAP1/BI/027 strain of C. difficile. Probiotics and fecal microbiota transplant have variable efficacy and the US FDA does not currently regulate the content; the potential economic advantages of these treatment modalities are currently unknown.

A population-based longitudinal study of Clostridium difficile infection-related hospitalization in mid-age and older Australians.

PubMed

Chen, Y; Glass, K; Liu, B; Riley, T V; Korda, R; Kirk, M D

2017-02-01

Clostridium difficile is the principal cause of infectious diarrhoea in hospitalized patients. We investigated the incidence and risk factors for hospitalization due to C. difficile infection (CDI) in older Australians. We linked data from a population-based prospective cohort study (the 45 and Up Study) of 266 922 adults aged ⩾45 years recruited in New South Wales, Australia to hospitalization and death records for 2006-2012. We estimated the incidence of CDI hospitalization and calculated days in hospital and costs per hospitalization. We also estimated hazard ratios (HR) for CDI hospitalization using Cox regression with age as the underlying time variable. Over a total follow-up of 1 126 708 person-years, 187 adults had an incident CDI hospitalization. The crude incidence of CDI hospitalization was 16·6/100 000 person-years, with a median hospital stay of 6 days, and a median cost of AUD 6102 per admission. Incidence increased with age and year of follow-up, with a threefold increase for 2009-2012. After adjustment, CDI hospitalization rates were significantly lower in males than females (adjusted HR 0·6, 95% confidence interval 0·4-0·7). CDI hospitalization rates increased significantly over 2009-2012. There is a need to better understand the increasing risk of CDI hospitalization in women.

Update on Clostridium difficile infections.

PubMed

Le Monnier, A; Zahar, J-R; Barbut, F

2014-08-01

Clostridium difficile infections (CDI) occur primarily in hospitalized patients with risk factors such as concomitant or recent use of antibiotics. CDI related additional costs are important for the global population and health-care facilities. CDI epidemiology has changed since 2003: they became more frequent boosted by large outbreaks, more severe, more resistant to antibiotic treatment, and spread to new groups of population without any risk factor. This is partly due to the emergence and worldwide dissemination of new and more virulent C. difficile strains such as the epidemic clone 027/NAP1/BI. The host immune response plays a central role in the pathogenesis of CDI and could also be involved in the occurrence of recurrent or severe forms. New guidelines including new molecular tests (NAAT) have recently clarified and simplified the diagnostic strategies for the microbiological diagnosis of CDI. The CDI incidence was proven to be related to the level of clinical suspicion and the frequency of microbiological screening for C. difficile. The current recommendations for the treatment of CDI mention oral metronidazole as the first line treatment for mild to moderate diarrhea. Oral vancomycin use should be restricted to severe cases. In the absence of consensus, the treatment of multiple recurrences remains a major concern. New and more targeted antibiotics and innovative therapeutic strategies (fecal transplantation, monoclonal antibodies, and vaccination) have emerged as new therapies for CDI. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Community-acquired Clostridium difficile infection in children: A retrospective study.

PubMed

Borali, Elena; Ortisi, Giuseppe; Moretti, Chiara; Stacul, Elisabetta Francesca; Lipreri, Rita; Gesu, Giovanni Pietro; De Giacomo, Costantino

2015-10-01

Community acquired-Clostridium difficile infection (CDI) has increased also in children in the last years. To determine the incidence of community-acquired CDI and to understand whether Clostridium difficile could be considered a symptom-triggering pathogen in infants. A five-year retrospective analysis (January 2007-December 2011) of faecal specimens from 124 children hospitalized in the Niguarda Ca' Granda Hospital for prolonged or muco-haemorrhagic diarrhoea was carried out. Stool samples were evaluated for common infective causes of diarrhoea and for Clostridium difficile toxins. Patients with and without CDI were compared for clinical characteristics and known risk factors for infection. Twenty-two children with CDI were identified in 5 years. An increased incidence of community-acquired CDI was observed, ranging from 0.75 per 1000 hospitalizations in 2007 to 9.8 per 1000 hospitalizations in 2011. Antimicrobial treatment was successful in all 19 children in whom it was administered; 8/22 CDI-positive children were younger than 2 years. No statistically significant differences in clinical presentation were observed between patients with and without CDI, nor in patients with and without risk factors for CDI. Our study shows that Clostridium difficile infection is increasing and suggests a possible pathogenic role in the first 2 years of life. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Clostridium difficile – From Colonization to Infection

PubMed Central

Schäffler, Holger; Breitrück, Anne

2018-01-01

Clostridium difficile is the most frequent cause of nosocomial antibiotic-associated diarrhea. The incidence of C. difficile infection (CDI) has been rising worldwide with subsequent increases in morbidity, mortality, and health care costs. Asymptomatic colonization with C. difficile is common and a high prevalence has been found in specific cohorts, e.g., hospitalized patients, adults in nursing homes and in infants. However, the risk of infection with C. difficile differs significantly between these cohorts. While CDI is a clear indication for therapy, colonization with C. difficile is not believed to be a direct precursor for CDI and therefore does not require treatment. Antibiotic therapy causes alterations of the intestinal microbial composition, enabling C. difficile colonization and consecutive toxin production leading to disruption of the colonic epithelial cells. Clinical symptoms of CDI range from mild diarrhea to potentially life-threatening conditions like pseudomembranous colitis or toxic megacolon. While antibiotics are still the treatment of choice for CDI, new therapies have emerged in recent years such as antibodies against C. difficile toxin B and fecal microbial transfer (FMT). This specific therapy for CDI underscores the role of the indigenous bacterial composition in the prevention of the disease in healthy individuals and its role in the pathogenesis after alteration by antibiotic treatment. In addition to the pathogenesis of CDI, this review focuses on the colonization of C. difficile in the human gut and factors promoting CDI. PMID:29692762

Compliance with Clostridium difficile treatment guidelines: effect on patient outcomes.

PubMed

Crowell, K T; Julian, K G; Katzman, M; Berg, A S; Tinsley, A; Williams, E D; Koltun, W A; Messaris, E

2017-08-01

Guidelines for the severity classification and treatment of Clostridium difficile infection (CDI) were published by Infectious Diseases Society of America (IDSA)/Society for Healthcare Epidemiology of America (SHEA) in 2010; however, compliance and efficacy of these guidelines has not been widely investigated. This present study assessed compliance with guidelines and its effect on CDI patient outcomes as compared with before these recommendations. A retrospective study included all adult inpatients with an initial episode of CDI treated in a single academic center from January 2009 to August 2014. Patients after guideline publication were compared with patients treated in 2009-2010. Demographic, clinical, and laboratory data were collected to stratify for disease severity. Outcome measures included compliance with guidelines, mortality, length of stay (LOS), and surgical intervention for CDI. A total of 1021 patients with CDI were included. Based upon the 2010 guidelines, 42 (28·8%) of 146 patients treated in 2009 would have been considered undertreated, and treatment progressively improved over time, as inadequate treatment decreased to 10·0% (15/148 patients) in 2014 (P = 0·0005). Overall, patient outcomes with guideline-adherent treatment decreased CDI attributable mortality twofold (P = 0·006) and CDI-related LOS by 1·9 days (P = 0·0009) when compared with undertreated patients. Compliance with IDSA/SHEA guidelines was associated with a decreased risk of mortality and LOS in hospitalized patients with CDI.

Assessment of Data Fusion Algorithms for Earth Observation Change Detection Processes

PubMed Central

Molina, Iñigo; Martinez, Estibaliz; Morillo, Carmen; Velasco, Jesus; Jara, Alvaro

2016-01-01

In this work a parametric multi-sensor Bayesian data fusion approach and a Support Vector Machine (SVM) are used for a Change Detection problem. For this purpose two sets of SPOT5-PAN images have been used, which are in turn used for Change Detection Indices (CDIs) calculation. For minimizing radiometric differences, a methodology based on zonal “invariant features” is suggested. The choice of one or the other CDI for a change detection process is a subjective task as each CDI is probably more or less sensitive to certain types of changes. Likewise, this idea might be employed to create and improve a “change map”, which can be accomplished by means of the CDI’s informational content. For this purpose, information metrics such as the Shannon Entropy and “Specific Information” have been used to weight the changes and no-changes categories contained in a certain CDI and thus introduced in the Bayesian information fusion algorithm. Furthermore, the parameters of the probability density functions (pdf’s) that best fit the involved categories have also been estimated. Conversely, these considerations are not necessary for mapping procedures based on the discriminant functions of a SVM. This work has confirmed the capabilities of probabilistic information fusion procedure under these circumstances. PMID:27706048

Management of central diabetes insipidus with oral desmopressin lyophilisate in infants.

PubMed

Korkmaz, Hüseyin Anıl; Demir, Korcan; Kılıç, Fatma Kaya; Terek, Demet; Arslanoğlu, Sertaç; Dizdarer, Ceyhun; Ozkan, Behzat

2014-09-01

To assess the efficiency of oral desmopressin lyophilisate (ODL) in neonatal central diabetes insipidus (CDI). The characteristics of four newborns with CDI treated with ODL were evaluated. Four newborns with polyuria and hypernatremia were included [male, 2 (50%); mean postnatal age, 19±17 days]. At the time of hypernatremia, the mean serum and urine osmolality values were 310±16 and 179±48 mOsm/kg, respectively. Antidiuretic hormone levels were undetectable (<0.5 pmol/L) in all cases. Magnetic resonance imaging revealed anatomical malformations in all cases. ODL (60 μg/tablet) dissolved in water (3-5 mL) was initiated with a dose of 5 μg/kg/day in two equal doses, together with limitation of water intake to avoid hyponatremia. Serum sodium levels returned to normal in a mean duration of 58±9.9 h with a mean decline rate of 0.37±0.1 mEq/L/h after desmopressin administration. Rehospitalization was required for one of the infants because of hypernatremia due to non-compliance. No episode of hyponatremia was encountered. Weight gain and growth of the infants were normal during the mean follow-up duration of 8.5±1 months. ODL appears to be practical and safe in the treatment of CDI during the first year of life.

Changes in microbial ecology after fecal microbiota transplantation for recurrent C. difficile infection affected by underlying inflammatory bowel disease.

PubMed

Khanna, Sahil; Vazquez-Baeza, Yoshiki; González, Antonio; Weiss, Sophie; Schmidt, Bradley; Muñiz-Pedrogo, David A; Rainey, John F; Kammer, Patricia; Nelson, Heidi; Sadowsky, Michael; Khoruts, Alexander; Farrugia, Stefan L; Knight, Rob; Pardi, Darrell S; Kashyap, Purna C

2017-05-15

Gut microbiota play a key role in maintaining homeostasis in the human gut. Alterations in the gut microbial ecosystem predispose to Clostridium difficile infection (CDI) and gut inflammatory disorders such as inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) from a healthy donor can restore gut microbial diversity and pathogen colonization resistance; consequently, it is now being investigated for its ability to improve inflammatory gut conditions such as IBD. In this study, we investigated changes in gut microbiota following FMT in 38 patients with CDI with or without underlying IBD. There was a significant change in gut microbial composition towards the donor microbiota and an overall increase in microbial diversity consistent with previous studies after FMT. FMT was successful in treating CDI using a diverse set of donors, and varying degrees of donor stool engraftment suggesting that donor type and degree of engraftment are not drivers of a successful FMT treatment of CDI. However, patients with underlying IBD experienced an increased number of CDI relapses (during a 24-month follow-up) and a decreased growth of new taxa, as compared to the subjects without IBD. Moreover, the need for IBD therapy did not change following FMT. These results underscore the importance of the existing gut microbial landscape as a decisive factor to successfully treat CDI and potentially for improvement of the underlying pathophysiology in IBD. FMT leads to a significant change in microbial diversity in patients with recurrent CDI and complete resolution of symptoms. Stool donor type (related or unrelated) and degree of engraftment are not the key for successful treatment of CDI by FMT. However, CDI patients with IBD have higher proportion of the original community after FMT and lack of improvement of their IBD symptoms and increased episodes of CDI on long-term follow-up.

Prediction of specific depressive symptom clusters in youth with epilepsy: The NDDI-E-Y versus Neuro-QOL SF.

PubMed

Kellermann, Tanja S; Mueller, Martina; Carter, Emma G; Brooks, Byron; Smith, Gigi; Kopp, Olivia J; Wagner, Janelle L

2017-08-01

Proper assessment and early identification of depressive symptoms are essential to initiate treatment and minimize the risk for poor outcomes in youth with epilepsy (YWE). The current study examined the predictive utility of the Neurological Disorders Depression Inventory-Epilepsy for Youth (NDDI-E-Y) and the Neuro-QOL Depression Short Form (Neuro-QOL SF) in explaining variance in overall depressive symptoms and specific symptom clusters on the gold standard Children's Depression Inventory-2 (CDI-2). Cross-sectional study examining 99 YWE (female 68, mean age 14.7 years) during a routine epilepsy visit, who completed self-report measures of depressive symptoms, including the NDDI-E-Y, CDI-2, and the Neuro-QOL SF. Caregivers completed a measure of seizure severity. All sociodemographic and medical information was evaluated through electronic medical record review. After accounting for seizure and demographic variables, the NDDI-E-Y accounted for 45% of the variance in the CDI-2 Total score and the CDI-2 Ineffectiveness subscale. Furthermore, the NDDI-E-Y predicted CDI-2 Total scores and subscales similarly, with the exception of explaining significantly more variance in the CDI-2 Ineffectiveness subscale compared to the Negative Mood subscale. The NDDI-E-Y explained greater variance compared to Neuro-QOL SF across the Total (48% vs. 37%) and all CDI-2 subscale scores; however, the NDDI-E-Y emerged as a stronger predictor of only CDI-2 Ineffectiveness. Both the NDDI-E-Y and Neuro-QOL SF accounted for the lowest amount of variance in CDI-2 Negative Mood. Sensitivity was poor for the Neuro-QOL SF in predicting high versus low CDI-2 scores. The NDDI-E-Y has strong psychometrics and can be easily integrated into routine epilepsy care for quick, brief screening of depressive symptoms in YWE. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

National epidemiology of initial and recurrent Clostridium difficile infection in the Veterans Health Administration from 2003 to 2014.

PubMed

Reveles, Kelly R; Lawson, Kenneth A; Mortensen, Eric M; Pugh, Mary Jo V; Koeller, Jim M; Argamany, Jacqueline R; Frei, Christopher R

2017-01-01

Prior studies demonstrated marked increases in Clostridium difficile infection (CDI) in the United States (U.S.) in recent years. The objective of this study was to describe the epidemiology of initial and recurrent CDI in a national Veterans Health Administration (VHA) cohort over a 12-year period. This was a retrospective cohort study of all adult VHA beneficiaries with CDI (ICD-9-CM code 008.45) plus a positive CDI stool test between October 1, 2002 and September 30, 2014. Data were obtained from the VA Informatics and Computing Infrastructure. Recurrence was defined as a second ICD-9-CM code plus a new course of CDI therapy following a minimum three-day gap after the initial therapy was completed. CDI incidence and outcomes were presented descriptively and longitudinally. Overall, 30,326 patients met study inclusion criteria. CDI incidence increased from FY 2003 (1.6 per 10,000) to FY 2013 (5.1 per 10,000). Thereafter, CDI incidence decreased through FY 2014 (4.6 per 10,000). A total of 5,011 patients (17%) experienced a first recurrence and, of those, 1,713 (34%) experienced a second recurrence. Recurrence incidence increased 10-fold over the study period, from (0.1 per 10,000) in FY 2003, to (1.0 per 10,000) in FY 2014. Overall, 30-day mortality and median hospital length of stay (LOS) decreased among initial episodes over the study period. Mortality was higher for initial episodes (21%) compared to first recurrences (11%) and second recurrences (7%). Median hospital LOS was longer for first episodes (13 days) compared to first (9 days) and second recurrences (8 days). Initial and recurrent CDI episodes increased among veterans over a 12-year period. Outcomes, such as mortality and hospital LOS improved in recent years; both of these outcomes are worse for initial CDI episodes than recurrent episodes.

Association Between Outpatient Antibiotic Prescribing Practices and Community-Associated Clostridium difficile Infection

PubMed Central

Dantes, Raymund; Mu, Yi; Hicks, Lauri A.; Cohen, Jessica; Bamberg, Wendy; Beldavs, Zintars G.; Dumyati, Ghinwa; Farley, Monica M.; Holzbauer, Stacy; Meek, James; Phipps, Erin; Wilson, Lucy; Winston, Lisa G.; McDonald, L. Clifford; Lessa, Fernanda C.

2015-01-01

Background. Antibiotic use predisposes patients to Clostridium difficile infections (CDI), and approximately 32% of these infections are community-associated (CA) CDI. The population-level impact of antibiotic use on adult CA-CDI rates is not well described. Methods. We used 2011 active population- and laboratory-based surveillance data from 9 US geographic locations to identify adult CA-CDI cases, defined as C difficile-positive stool specimens (by toxin or molecular assay) collected from outpatients or from patients ≤3 days after hospital admission. All patients were surveillance area residents and aged ≥20 years with no positive test ≤8 weeks prior and no overnight stay in a healthcare facility ≤12 weeks prior. Outpatient oral antibiotic prescriptions dispensed in 2010 were obtained from the IMS Health Xponent database. Regression models examined the association between outpatient antibiotic prescribing and adult CA-CDI rates. Methods. Healthcare providers prescribed 5.2 million courses of antibiotics among adults in the surveillance population in 2010, for an average of 0.73 per person. Across surveillance sites, antibiotic prescription rates (0.50–0.88 prescriptions per capita) and unadjusted CA-CDI rates (40.7–139.3 cases per 100 000 persons) varied. In regression modeling, reducing antibiotic prescribing rates by 10% among persons ≥20 years old was associated with a 17% (95% confidence interval, 6.0%–26.3%; P = .032) decrease in CA-CDI rates after adjusting for age, gender, race, and type of diagnostic assay. Reductions in prescribing penicillins and amoxicillin/clavulanic acid were associated with the greatest decreases in CA-CDI rates. Conclusions and Relevance. Community-associated CDI prevention should include reducing unnecessary outpatient antibiotic use. A modest reduction of 10% in outpatient antibiotic prescribing can have a disproportionate impact on reducing CA-CDI rates. PMID:26509182

New cadmium(II) halides modified by N-heterocyclic molecules

NASA Astrophysics Data System (ADS)

Wang, Tie-Gang; Li, Su; Yu, Jie-Hui; Xu, Ji-Qing

2015-03-01

Under the solvothermal condition, the reaction of CdI2, bpp and KI at pH = 8 afforded compound [CdI2(bpp)] (bpp = 1,2-bis(4-pyridyl)propane) 1, while at the ambient conditions, the reactions of CdX2, dabco and KX at pH = 4-5 produced compounds [H2(dabco)][CdBr4]·H2O (dabco = 1,4-diazabicyclo[2,2,2]octane) 2 and [(Hdabco)CdI3] 3. X-ray single-crystal diffraction analysis reveals that (i) compound 1 possesses a one-dimensional (1-D) zigzag chain structure. The large volume bpp molecule controls the Cd2+ ion to adopt a tetrahedral geometric configuration; (ii) both compounds 2 and 3 are mononuclear. Interestingly, in the same pH environments, dabco was in situ diprotonated in compound 2, while dabco was in situ monoprotonated in compound 3. The templating effect as well as the X- ion maybe plays a key role in the protonated degree for dabco in an acidic environment. The photoluminescence analysis indicates that compound 1 emits the strong green light, which should be attributed to a combination of two types of charge transfers: the charge transfer between Cd2+ and I-; the charge transfer between Cd2+ and bpp.

Clostridium difficile infection seasonality: patterns across hemispheres and continents - a systematic review.

PubMed

Furuya-Kanamori, Luis; McKenzie, Samantha J; Yakob, Laith; Clark, Justin; Paterson, David L; Riley, Thomas V; Clements, Archie C

2015-01-01

Studies have demonstrated seasonal variability in rates of Clostridium difficile infection (CDI). Synthesising all available information on seasonality is a necessary step in identifying large-scale epidemiological patterns and elucidating underlying causes. Three medical and life sciences publication databases were searched from inception to October 2014 for longitudinal epidemiological studies written in English, Spanish or Portuguese that reported the incidence of CDI. The monthly frequency of CDI were extracted, standardized and weighted according to the number of follow-up months. Cross correlation coefficients (XCORR) were calculated to examine the correlation and lag between the year-month frequencies of reported CDI across hemispheres and continents. The search identified 13, 5 and 2 studies from North America, Europe, and Oceania, respectively that met the inclusion criteria. CDI had a similar seasonal pattern in the Northern and Southern Hemisphere characterized by a peak in spring and lower frequencies of CDI in summer/autumn with a lag of 8 months (XCORR = 0.60) between hemispheres. There was no difference between the seasonal patterns across European and North American countries. CDI demonstrates a distinct seasonal pattern that is consistent across North America, Europe and Oceania. Further studies are required to identify the driving factors of the observed seasonality.

Factors predictive of severe Clostridium difficile infection depend on the definition used.

PubMed

Khanafer, Nagham; Barbut, Frédéric; Eckert, Catherine; Perraud, Michel; Demont, Clarisse; Luxemburger, Christine; Vanhems, Philippe

2016-02-01

Clostridium difficile infection (CDI) produces a variety of clinical presentations ranging from mild diarrhea to severe infection with fulminant colitis, septic shock, and death. Over the past decade, the emergence of the BI/NAP1/027 strain has been linked to higher prevalence and severity of CDI. The guidelines to treat patients with CDI are currently based on severity factors identified in the literature and on expert opinion and have not been systematically evaluated. The objective of this study was to identify factors associated with severe CDI defined according to four different severity definitions (Def): the 2010 SHEA/IDSA guidelines (Def1), the 2014 ESCMID guidelines (Def2), complicated CDI at the end of diarrhea (Def3), and our hospital-specific guidelines (white blood cell (WBC) count ≥15 × 10(9)/L, serum creatinine concentration >50% above baseline, pseudomembranous colitis, megacolon, intestinal perforation, or septic shock requiring intensive care unit admission. A three-year cohort study was conducted in a university hospital in Lyon, France. All hospitalized (≥48 h) patients ≥18 years old, suffering from CDI, and agreeing to participate were included. Patients were followed-up for 60 days after CDI diagnosis. After bivariate regression analyses, factors associated with severe CDI during the course of disease were identified by a multivariate logistic regression. Statistical significance was reached with a two-sided p-value <0.05. 233 CDI patients diagnosed between 2011 and 2014 were included for a mean incidence rate of 2.15 cases/1000 hospitalized patients or 3.16 cases/10,000 patient days. Mean age was 65.3 years and 52.5% were men. Death occurred in 37 patients (15.9%) within 60 days of diagnosis. Death was related to CDI in 15 patients (40.5%). Frequency of severe CDI ranges from 11.6% to 59.2% depending on the case-definition. Factors independently associated with severe CDI were: age ≥68 years, male gender, renal disease, and serum albumin <30 g/L according to Def1 (n = 106, 45.5%); exposure to antivirals in the previous 4 weeks, renal disease, and blood neutrophils >7,5 × 10(9)/L in patients with Def2 (n = 138, 59.2%); abdominal pain, serum albumin <30 g/L, and WBC >10 × 10(9)/L according to Def3 (n = 27, 11.6%); age ≥68 years, renal disease, serum albumin <30 g/L, serum lactate dehydrogenase >248 IU/L, and blood neutrophils >7,5 × 10(9)/L were associated with severe CDI in patients with Def4 (n = 113, 48.5%). Our results indicate that appropriate case definition is needed for characterizing patients at risk of developing severe CDI. Our study suggest that serum albumin and the presence of renal disease, associated with severe CDI in three definitions, may be useful for identifying patients at risk of a poor outcome. Copyright © 2015 Elsevier Ltd. All rights reserved.

Customer Dissatisfaction Index and its Improvement Costs

NASA Astrophysics Data System (ADS)

Lvovs, Aleksandrs; Mutule, Anna

2010-01-01

The paper gives description of customer dissatisfaction index (CDI) that can be used as reliability level characterizing factor. The factor is directly joined with customer satisfaction of power supply and can be used for control of reliability level of power supply for residential customers. CDI relations with other reliability indices are shown. Paper also gives a brief overview of legislation of Latvia in power industry that is the base for CDI introduction. Calculations of CDI improvement costs are performed in the paper too.

A Perception Test of Infrared Images of Soldiers in Camouflaged Uniforms

DTIC Science & Technology

1998-03-09

psychology ," Science, pp. 990- 1000, 1973. 3.) Macmillan, N.A., and Creelman , C.D.,I991, Detection Theory: A User’s Guide, Cambridge University Press. 4...levels, using the rating scale method shown in McMillan and Creelman ( 1996). The estimated true d was calculated as the mean of the liberal and

Incidence and Costs of Clostridium difficile Infections in Canada.

PubMed

Levy, Adrian R; Szabo, Shelagh M; Lozano-Ortega, Greta; Lloyd-Smith, Elisa; Leung, Victor; Lawrence, Robin; Romney, Marc G

2015-09-01

Background.  Limited data are available on direct medical costs and lost productivity due to Clostridium difficile infection (CDI) in Canada. Methods.  We developed an economic model to estimate the costs of managing hospitalized and community-dwelling patients with CDI in Canada. The number of episodes was projected based on publicly available national rates of hospital-associated CDI and the estimate that 64% of all CDI is hospital-associated. Clostridium difficile infection recurrences were classified as relapses or reinfections. Resource utilization data came from published literature, clinician interviews, and Canadian CDI surveillance programs, and this included the following: hospital length of stay, contact with healthcare providers, pharmacotherapy, laboratory testing, and in-hospital procedures. Lost productivity was considered for those under 65 years of age, and the economic impact was quantified using publicly available labor statistics. Unit costs were obtained from published sources and presented in 2012 Canadian dollars. Results.  There were an estimated 37 900 CDI episodes in Canada in 2012; 7980 (21%) of these were relapses, out of a total of 10 900 (27%) episodes of recurrence. The total cost to society of CDI was estimated at $281 million; 92% ($260 million) was in-hospital costs, 4% ($12 million) was direct medical costs in the community, and 4% ($10 million) was due to lost productivity. Management of CDI relapses alone accounted for $65.1 million (23%). Conclusions.  The largest proportion of costs due to CDI in Canada arise from extra days of hospitalization. Interventions reducing the severity of infection and/or relapses leading to rehospitalizations are likely to have the largest absolute effect on direct medical costs.

Comparison of Clostridium difficile Ribotypes Circulating in Australian Hospitals and Communities.

PubMed

Furuya-Kanamori, Luis; Riley, Thomas V; Paterson, David L; Foster, Niki F; Huber, Charlotte A; Hong, Stacey; Harris-Brown, Tiffany; Robson, Jenny; Clements, Archie C A

2017-01-01

Clostridium difficile infection (CDI) is becoming less exclusively a health care-associated CDI (HA-CDI). The incidence of community-associated CDI (CA-CDI) has increased over the past few decades. It has been postulated that asymptomatic toxigenic C. difficile (TCD)-colonized patients may play a role in the transfer of C. difficile between the hospital setting and the community. Thus, to investigate the relatedness of C. difficile across the hospital and community settings, we compared the characteristics of symptomatic and asymptomatic host patients and the pathogens from these patients in these two settings over a 3-year period. Two studies were simultaneously conducted; the first study enrolled symptomatic CDI patients from two tertiary care hospitals and the community in two Australian states, while the second study enrolled asymptomatic TCD-colonized patients from the same tertiary care hospitals. A total of 324 patients (96 with HA-CDI, 152 with CA-CDI, and 76 colonized with TCD) were enrolled. The predominant C. difficile ribotypes isolated in the hospital setting corresponded with those isolated in the community, as it was found that for 79% of the C. difficile isolates from hospitals, an isolate with a matching ribotype was isolated in the community, suggesting that transmission between these two settings is occurring. The toxigenic C. difficile strains causing symptomatic infection were similar to those causing asymptomatic infection, and patients exposed to antimicrobials prior to admission were more likely to develop a symptomatic infection (odds ratio, 2.94; 95% confidence interval, 1.20 to 7.14). Our findings suggest that the development of CDI symptoms in a setting without establishment of hospital epidemics with binary toxin-producing C. difficile strains may be driven mainly by host susceptibility and exposure to antimicrobials, rather than by C. difficile strain characteristics. Copyright © 2016 American Society for Microbiology.

Isolation of C. difficile Carriers Alone and as Part of a Bundle Approach for the Prevention of Clostridium difficile Infection (CDI): A Mathematical Model Based on Clinical Study Data.

PubMed

Grigoras, Christos A; Zervou, Fainareti N; Zacharioudakis, Ioannis M; Siettos, Constantinos I; Mylonakis, Eleftherios

2016-01-01

Clostridium difficile infection is the most common hospital-acquired infection. Besides infected patients, carriers have emerged as a key player in C. difficile epidemiology. In this study, we evaluated the impact of identifying and isolating carriers upon hospital admission on the incidence of CDI incidence and hospital-acquired C. difficile colonization, as a single policy and as part of bundle approaches. We simulated C. difficile transmission using a stochastic mathematical approach, considering the contribution of carriers based on published literature. In the baseline scenario, CDI incidence was 6.18/1,000 admissions (95% CI, 5.72-6.65), simulating reported estimates from U.S. hospital discharges. The acquisition rate of C. difficile carriage was 9.72/1,000 admissions (95% CI, 9.15-10.31). Screening and isolation of colonized patients on admission to the hospital decreased CDI incidence to 4.99/1,000 admissions (95% CI, 4.59-5.42; relative reduction (RR) = 19.1%) and led to 36.2% reduction in the rate of hospital-acquired colonization. Simulating an antimicrobial stewardship program reduced CDI rate to 2.35/1,000 admissions (95% CI, 2.07-2.65). In sensitivity analysis, CDI incidence was less than 2.32/1,000 admissions (RR = 62.4%) in 95% of 1,000 simulations. The combined bundle, focusing on reducing C. difficile transmission from colonized patients and the individual risk of these patients to develop CDI, decreased significantly the incidence of both CDI and hospital-acquired colonization. Implementation of this bundle to current practice is expected to have an important impact in containing CDI.

Incidence and Costs of Clostridium difficile Infections in Canada

PubMed Central

Levy, Adrian R.; Szabo, Shelagh M.; Lozano-Ortega, Greta; Lloyd-Smith, Elisa; Leung, Victor; Lawrence, Robin; Romney, Marc G.

2015-01-01

Background. Limited data are available on direct medical costs and lost productivity due to Clostridium difficile infection (CDI) in Canada. Methods. We developed an economic model to estimate the costs of managing hospitalized and community-dwelling patients with CDI in Canada. The number of episodes was projected based on publicly available national rates of hospital-associated CDI and the estimate that 64% of all CDI is hospital-associated. Clostridium difficile infection recurrences were classified as relapses or reinfections. Resource utilization data came from published literature, clinician interviews, and Canadian CDI surveillance programs, and this included the following: hospital length of stay, contact with healthcare providers, pharmacotherapy, laboratory testing, and in-hospital procedures. Lost productivity was considered for those under 65 years of age, and the economic impact was quantified using publicly available labor statistics. Unit costs were obtained from published sources and presented in 2012 Canadian dollars. Results. There were an estimated 37 900 CDI episodes in Canada in 2012; 7980 (21%) of these were relapses, out of a total of 10 900 (27%) episodes of recurrence. The total cost to society of CDI was estimated at $281 million; 92% ($260 million) was in-hospital costs, 4% ($12 million) was direct medical costs in the community, and 4% ($10 million) was due to lost productivity. Management of CDI relapses alone accounted for $65.1 million (23%). Conclusions. The largest proportion of costs due to CDI in Canada arise from extra days of hospitalization. Interventions reducing the severity of infection and/or relapses leading to rehospitalizations are likely to have the largest absolute effect on direct medical costs. PMID:26191534

Isolation of C. difficile Carriers Alone and as Part of a Bundle Approach for the Prevention of Clostridium difficile Infection (CDI): A Mathematical Model Based on Clinical Study Data

PubMed Central

Grigoras, Christos A.; Zervou, Fainareti N.; Zacharioudakis, Ioannis M.; Siettos, Constantinos I.; Mylonakis, Eleftherios

2016-01-01

Clostridium difficile infection is the most common hospital-acquired infection. Besides infected patients, carriers have emerged as a key player in C. difficile epidemiology. In this study, we evaluated the impact of identifying and isolating carriers upon hospital admission on the incidence of CDI incidence and hospital-acquired C. difficile colonization, as a single policy and as part of bundle approaches. We simulated C. difficile transmission using a stochastic mathematical approach, considering the contribution of carriers based on published literature. In the baseline scenario, CDI incidence was 6.18/1,000 admissions (95% CI, 5.72–6.65), simulating reported estimates from U.S. hospital discharges. The acquisition rate of C. difficile carriage was 9.72/1,000 admissions (95% CI, 9.15–10.31). Screening and isolation of colonized patients on admission to the hospital decreased CDI incidence to 4.99/1,000 admissions (95% CI, 4.59–5.42; relative reduction (RR) = 19.1%) and led to 36.2% reduction in the rate of hospital-acquired colonization. Simulating an antimicrobial stewardship program reduced CDI rate to 2.35/1,000 admissions (95% CI, 2.07–2.65). In sensitivity analysis, CDI incidence was less than 2.32/1,000 admissions (RR = 62.4%) in 95% of 1,000 simulations. The combined bundle, focusing on reducing C. difficile transmission from colonized patients and the individual risk of these patients to develop CDI, decreased significantly the incidence of both CDI and hospital-acquired colonization. Implementation of this bundle to current practice is expected to have an important impact in containing CDI. PMID:27258068

Implementation of a Clinical Documentation Improvement Curriculum Improves Quality Metrics and Hospital Charges in an Academic Surgery Department.

PubMed

Reyes, Cynthia; Greenbaum, Alissa; Porto, Catherine; Russell, John C

2017-03-01

Accurate clinical documentation (CD) is necessary for many aspects of modern health care, including excellent communication, quality metrics reporting, and legal documentation. New requirements have mandated adoption of ICD-10-CM coding systems, adding another layer of complexity to CD. A clinical documentation improvement (CDI) and ICD-10 training program was created for health care providers in our academic surgery department. We aimed to assess the impact of our CDI curriculum by comparing quality metrics, coding, and reimbursement before and after implementation of our CDI program. A CDI/ICD-10 training curriculum was instituted in September 2014 for all members of our university surgery department. The curriculum consisted of didactic lectures, 1-on-1 provider training, case reviews, e-learning modules, and CD queries from nurse CDI staff and hospital coders. Outcomes parameters included monthly documentation completion rates, severity of illness (SOI), risk of mortality (ROM), case-mix index (CMI), all-payer refined diagnosis-related groups (APR-DRG), and Surgical Care Improvement Program (SCIP) metrics. Financial gain from responses to CDI queries was determined retrospectively. Surgery department delinquent documentation decreased by 85% after CDI implementation. Compliance with SCIP measures improved from 85% to 97%. Significant increases in surgical SOI, ROM, CMI, and APR-DRG (all p < 0.01) were found after CDI/ICD-10 training implementation. Provider responses to CDI queries resulted in an estimated $4,672,786 increase in charges. Clinical documentation improvement/ICD-10 training in an academic surgery department is an effective method to improve documentation rates, increase the hospital estimated reimbursement based on more accurate CD, and provide better compliance with surgical quality measures. Copyright © 2016 American College of Surgeons. All rights reserved.

Prevalence and risk factors for central diabetes insipidus in cardiac arrest survivor treated with targeted temperature management.

PubMed

Lee, Dong Hun; Lee, Byung Kook; Song, Kyoung Hwan; Jung, Yong Hun; Park, Jung Soo; Lee, Sung Min; Cho, Yong Soo; Kim, Jin Woong; Jeung, Kyung Woon

2016-08-01

Central diabetes insipidus (CDI) is a marker of severe brain injury. Here we aimed to investigate the prevalence and risk factors of CDI in cardiac arrest survivors treated with targeted temperature management (TTM). This retrospective observational study included consecutive adult cardiac arrest survivors treated with TTM between 2008 and 2014. Central diabetes insipidus was confirmed if all of the following criteria were met: urine volume >50 cc kg(-1) d(-1), serum osmolarity >300 mmol/L, urine osmolarity <300 mmol/L, and serum sodium >145 mEq/L. The primary outcome was the incidence of CDI. Of the 385 included patients, 45 (11.7%) had confirmed central CDI. Univariate analysis showed that younger age, nonwitness of collapse, nonshockable rhythm, a high incidence of asphyxia arrest, longer downtime, and lower initial core temperature were associated with CDI development. Patients with CDI had a higher incidence of poor neurologic outcomes at discharge and higher in-hospital mortality rate (20/45 vs 76/340, P= .001) as well as 180-day mortality (44/45 vs 174/340, P< .001). Multivariate analysis revealed that age (odds ratio [OR], 0.963; 95% confidence interval [CI], 0.942-0.984), shockable rhythm (OR, 0.077; 95% CI, 0.009-0.662), downtime (OR, 1.025; 95% CI, 1.006-1.044), and asphyxia etiology (OR, 6.815; 95% CI, 2.457-18.899) were independently associated with CDI development. Central diabetes insipidus developed in 12% of cardiac arrest survivors treated with TTM, and those with CDI showed poor neurologic outcomes and high mortality rates. Younger age, nonshockable rhythm, long downtime, and asphyxia arrest were significant risk factors for development of CDI. Copyright © 2016 Elsevier Inc. All rights reserved.

Cost-effectiveness of Bezlotoxumab Compared With Placebo for the Prevention of Recurrent Clostridium difficile Infection.

PubMed

Prabhu, Vimalanand S; Dubberke, Erik R; Dorr, Mary Beth; Elbasha, Elamin; Cossrow, Nicole; Jiang, Yiling; Marcella, Stephen

2018-01-18

Clostridium difficile infection (CDI) is the most commonly recognized cause of recurrent diarrhea. Bezlotoxumab, administered concurrently with antibiotics directed against C. difficile (standard of care [SoC]), has been shown to reduce the recurrence of CDI, compared with SoC alone. This study aimed to assess the cost-effectiveness of bezlotoxumab administered concurrently with SoC, compared with SoC alone, in subgroups of patients at risk of recurrence of CDI. A computer-based Markov health state transition model was designed to track the natural history of patients infected with CDI. A cohort of patients entered the model with either a mild/moderate or severe CDI episode, and were treated with SoC antibiotics together with either bezlotoxumab or placebo. The cohort was followed over a lifetime horizon, and costs and utilities for the various health states were used to estimate incremental cost-effectiveness ratios (ICERs). Both deterministic and probabilistic sensitivity analyses were used to test the robustness of the results. The cost-effectiveness model showed that, compared with placebo, bezlotoxumab was associated with 0.12 quality-adjusted life-years (QALYs) gained and was cost-effective in preventing CDI recurrences in the entire trial population, with an ICER of $19824/QALY gained. Compared with placebo, bezlotoxumab was also cost-effective in the subgroups of patients aged ≥65 years (ICER of $15298/QALY), immunocompromised patients (ICER of $12597/QALY), and patients with severe CDI (ICER of $21430/QALY). Model-based results demonstrated that bezlotoxumab was cost-effective in the prevention of recurrent CDI compared with placebo, among patients receiving SoC antibiotics for treatment of CDI. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Preparation and Application of Electrodes in Capacitive Deionization (CDI): a State-of-Art Review.

PubMed

Jia, Baoping; Zhang, Wei

2016-12-01

As a promising desalination technology, capacitive deionization (CDI) have shown practicality and cost-effectiveness in brackish water treatment. Developing more efficient electrode materials is the key to improving salt removal performance. This work reviewed current progress on electrode fabrication in application of CDI. Fundamental principal (e.g. EDL theory and adsorption isotherms) and process factors (e.g. pore distribution, potential, salt type and concentration) of CDI performance were presented first. It was then followed by in-depth discussion and comparison on properties and fabrication technique of different electrodes, including carbon aerogel, activated carbon, carbon nanotubes, graphene and ordered mesoporous carbon. Finally, polyaniline as conductive polymer and its potential application as CDI electrode-enhancing materials were also discussed.

Clinical update for the diagnosis and treatment of Clostridium difficile infection

PubMed Central

IV, Edward C Oldfield; III, Edward C Oldfield; Johnson, David A

2014-01-01

Clostridium difficile infection (CDI) presents a rapidly evolving challenge in the battle against hospital-acquired infections. Recent advances in CDI diagnosis and management include rapid changes in diagnostic approach with the introduction of newer tests, such as detection of glutamate dehydrogenase in stool and polymerase chain reaction to detect the gene for toxin production, which will soon revolutionize the diagnostic approach to CDI. New medications and multiple medical society guidelines have introduced changing concepts in the definitions of severity of CDI and the choice of therapeutic agents, while rapid expansion of data on the efficacy of fecal microbiota transplantation heralds a revolutionary change in the management of patients suffering multiple relapses of CDI. Through a comprehensive review of current medical literature, this article aims to offer an intensive review of the current state of CDI diagnosis, discuss the strengths and limitations of available laboratory tests, compare both current and future treatments options and offer recommendations for best practice strategies. PMID:24729930

A Wireless Text Messaging System Improves Communication for Neonatal Resuscitation.

PubMed

Hughes Driscoll, Colleen A; Schub, Jamie A; Pollard, Kristi; El-Metwally, Dina

Handoffs for neonatal resuscitation involve communicating critical delivery information (CDI). The authors sought to achieve ≥95% communication of CDI during resuscitation team requests. CDI included name of caller, urgency of request, location of delivery, gestation of fetus, status of amniotic fluid, and indication for presence of the resuscitation team. Three interventions were implemented: verbal scripted handoff, Spök text messaging, and Engage text messaging. Percentages of CDI communications were analyzed using statistical process control. Following implementation of Engage, the communication of all CDI, except for indication, was ≥95%; communication of indication occurred 93% of the time. Control limits for most CDI were narrower with Engage, indicating greater reliability of communication compared to the verbal handoff and Spök. Delayed resuscitation team arrival, a countermeasure, was not higher with text messaging compared to verbal handoff ( P = 1.00). Text messaging improved communication during high-risk deliveries, and it may represent an effective tool for other delivery centers.

Prevalence of and Factors Associated with Clostridium difficile Co-infection Among Patients with Candidemia, United States, 2014–2016

PubMed Central

Tsay, Sharon; Benedict, Kaitlin; Beldavs, Zintars G; Farley, Monica M; Harrison, Lee H; Schaffner, William; Gerth, Taryn; Chiller, Tom; Vallabhaneni, Snigdha

2017-01-01

Abstract Background Candidemia and Clostridium difficile infection (CDI) are two common healthcare-associated infections (HAIs) and share risk factors such as antibiotic use and prolonged hospitalization. CDI and CDI treatment disrupt gut microbial diversity, allowing Candida overgrowth and translocation to the bloodstream. We describe CDI co-infection among patients with candidemia. Methods Population-based surveillance for candidemia was conducted through CDC’s Emerging Infections Program during 2014–2016. A case of candidemia was defined as a blood culture positive for Candida species collected from a surveillance area resident. Demographic and medical information, including occurrence of CDI was collected. We defined co-infection as CDI within 90 days of candidemia and performed bivariable analysis to assess factors associated with co-infection. Results Among 2129 cases of candidemia, 190 (9%) had CDI co-infection; 116 (5%) had CDI in the 90 days before candidemia (median: 10 days) and 60 (3%) had CDI following candidemia (median: 8 days). The median age of those with CDI-candidemia co-infection was 61 years and 100 (53%) were male. Compared with candidemia alone, the odds of CDI-candidemia co-infection was significantly greater for patients of black race (OR 1.41, 95% CI 1.05–1.90), those with diabetes (OR 1.68, 1.24–2.27), pancreatitis (OR 1.91, 1.01–3.61), or solid organ transplant (OR 4.15, 2.09–8.22). Those with co-infection had higher odds of certain healthcare exposures: hemodialysis (OR 2.27, 1.57–3.28), hospital stay in the past 90 days (OR 1.9, 1.37–2.64), ICU admission in the past 14 days (OR 1.78, 1.20–2.66), and central venous catheter (CVC) at the time of candidemia (OR 1.71, 1.19–2.46). There were no significant differences in 30-day mortality or in type of Candida species, although C. parapsilosis was less common in the co-infection group (8% vs. 13%). Conclusion Nearly one in ten patients with candidemia also had CDI co-infection. Black race, certain underlying conditions, hemodialysis, previous hospitalization, ICU stay, and the presence of a CVC were associated with co-infection. Clinicians should be vigilant for coinfection of CDI and candidemia, particularly in situations with associated risk factors. Disclosures W. Schaffner, Pfizer: Scientific Advisor, Consulting fee; Merck: Scientific Advisor, Consulting fee; Novavax: Consultant, Consulting fee; Dynavax: Consultant, Consulting fee; Sanofi-pasteur: Consultant, Consulting fee; GSK: Consultant, Consulting fee; Seqirus: Consultant, Consulting fee

Reducing Clostridium difficile in the inpatient setting: A systematic review of the adherence to and effectiveness of C. difficile prevention bundles

PubMed Central

Barker, Anna; Ngam, Caitlyn; Musuuza, Jackson; Vaughn, Valerie M.; Safdar, Nasia

2017-01-01

Background Clostridium difficile infection (CDI) is the most common infectious cause of nosocomial diarrhea and its prevention is an urgent public health priority. However, reduction of CDI is challenging, because of its complex pathogenesis, large reservoirs of colonized patients, and persistence of infectious spores. The literature lacks high quality evidence for evaluating interventions, and many hospitals have implemented bundled interventions to reduce CDI with variable results. Thus, we conducted a systematic review to examine the components of CDI bundles, their implementation processes, and their impact on CDI rates. Methods We conducted a comprehensive literature search of multiple computerized databases from their date of inception through April 30, 2016. The protocol was registered in PROSPERO. Bundle effectiveness, adherence, and study quality was assessed for each study meeting criteria for inclusion. Results In the 26 studies that met inclusion criteria for this review, we found that implementation and adherence factors to interventions were variably and incompletely reported, making study reproducibility and replicability challenging. Despite contextual differences and the variety of bundle components utilized, all 26 studies reported an improvement in CDI rates. However, given the lack of randomized controlled trials in the literature, assessing a causal relationship between bundled interventions and CDI rates is currently impossible. Conclusions Cluster randomized trials that include a rigorous assessment of the implementation of bundled interventions are urgently needed to causally test the effect of intervention bundles on CDI rates. PMID:28343455

High morbidity and mortality of Clostridium difficile infection and its associations with ribotype 002 in Hong Kong.

PubMed

Wong, Sunny H; Ip, Margaret; Hawkey, Peter M; Lo, Norman; Hardy, Katie; Manzoor, Susan; Hui, Wyman W M; Choi, Kin-Wing; Wong, Rity Y K; Yung, Irene M H; Cheung, Catherine S K; Lam, Kelvin L Y; Kwong, Thomas; Wu, William K K; Ng, Siew C; Wu, Justin C Y; Sung, Joseph J Y; Lee, Nelson

2016-08-01

We aim to study the disease burden, risk factors and severity of Clostridium difficile infection (CDI) in Hong Kong. We conducted a prospective, case-control study in three acute-care hospitals in Hong Kong. Adult inpatients who developed CDI diarrhoea confirmed by PCR (n = 139) were compared with the non-CDI controls (n = 114). Ribotyping of isolates and antimicrobial susceptibility testing were performed. The estimated crude annual incidence of CDI was 23-33/100,000 population, and 133-207/100,000 population among those aged ≥65 years. The mean age of CDI patients was 71.5. Nursing home care, recent hospitalization, antibiotics exposure (adjusted OR 3.0, 95% CI 1.3-7.1) and proton-pump inhibitors use (adjusted OR 2.2, 95% CI 1.2-3.9) were risk factors. Severe CDI occurred in 41.7%. Overall mortality was 16.5% (among severe CDI, 26.5%). The commonest ribotypes were 002 (22.8%), 014 (14.1%), 012 and 046; ribotype 027 was absent. Ribotype 002 was associated with fluoroquinolone resistance and higher mortality (47.6% vs. 12.7%; adjusted HR 2.8, 95% CI 1.1-7.0). Our findings show high morbidity and mortality of CDI in the older adults, and identify ribotype 002 as a possible virulent strain causing serious infections in this cohort. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Cost analysis of an outbreak of Clostridium difficile infection ribotype 027 in a Dutch tertiary care centre.

PubMed

van Beurden, Y H; Bomers, M K; van der Werff, S D; Pompe, E A P M; Spiering, S; Vandenbroucke-Grauls, C M J E; Mulder, C J J

2017-04-01

The economic impact of Clostridium difficile infection (CDI) on the healthcare system is significant. From May 2013 to May 2014, an outbreak of C. difficile ribotype 027 occurred in a Dutch tertiary care hospital, involving 72 patients. The primary aim of this study was to provide insight into the financial burden that this CDI outbreak brought upon this hospital. A retrospective analysis was performed to estimate the costs of a one-year-long C. difficile ribotype 027 outbreak. Medical charts were reviewed for patient data. In addition, all costs associated with the outbreak control measures were collected. The attributable costs of the whole outbreak were estimated to be €1,222,376. The main contributing factor was missed revenue due to increased length of stay of CDI patients and closure of beds to enable contact isolation of CDI patients (36%). A second important cost component was extra surveillance and activities of the Department of Medical Microbiology and Infection Control (25%). To the authors' knowledge, this is the first study to provide insight into the attributable costs of CDI in an outbreak setting, and to delineate the major cost items. It is clear that the economic consequences of CDI are significant. The high costs associated with a CDI outbreak should help to justify the use of additional resources for CDI prevention and control. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Clostridium difficile infection is associated with graft loss in solid organ transplant recipients.

PubMed

Cusini, A; Béguelin, C; Stampf, S; Boggian, K; Garzoni, C; Koller, M; Manuel, O; Meylan, P; Mueller, N J; Hirsch, H H; Weisser, M; Berger, C; van Delden, C

2018-01-19

Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea in solid organ transplant recipients (SOT). We aimed to assess incidence, risk factors, and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We performed a case-control study of SOT recipients in the STCS diagnosed with CDI between May 2008 and August 2013. We matched 2 control subjects per case by age at transplantation, sex, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors and evaluate outcome of CDI. Two thousand one hundred fifty-eight SOT recipients, comprising 87 cases of CDI and 174 matched controls were included. The overall CDI rate per 10 000 patient days was 0.47 (95% confidence interval ([CI] 0.38-0.58), with the highest rate in lung (1.48, 95% CI 0.93-2.24). In multivariable analysis, proven infections (hazard ratio [HR] 2.82, 95% CI 1.29-6.19) and antibiotic treatments (HR 4.51, 95% CI 2.03-10.0) during the preceding 3 months were independently associated with the development of CDI. Despite mild clinical presentations, recipients acquiring CDI posttransplantation had an increased risk of graft loss (HR 2.24, 95% CI 1.15-4.37; P = .02). These findings may help to improve the management of SOT recipients. © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.

Standardised surveillance of Clostridium difficile infection in European acute care hospitals: a pilot study, 2013.

PubMed

van Dorp, Sofie M; Kinross, Pete; Gastmeier, Petra; Behnke, Michael; Kola, Axel; Delmée, Michel; Pavelkovich, Anastasia; Mentula, Silja; Barbut, Frédéric; Hajdu, Agnes; Ingebretsen, André; Pituch, Hanna; Macovei, Ioana S; Jovanović, Milica; Wiuff, Camilla; Schmid, Daniela; Olsen, Katharina Ep; Wilcox, Mark H; Suetens, Carl; Kuijper, Ed J

2016-07-21

Clostridium difficile infection (CDI) remains poorly controlled in many European countries, of which several have not yet implemented national CDI surveillance. In 2013, experts from the European CDI Surveillance Network project and from the European Centre for Disease Prevention and Control developed a protocol with three options of CDI surveillance for acute care hospitals: a 'minimal' option (aggregated hospital data), a 'light' option (including patient data for CDI cases) and an 'enhanced' option (including microbiological data on the first 10 CDI episodes per hospital). A total of 37 hospitals in 14 European countries tested these options for a three-month period (between 13 May and 1 November 2013). All 37 hospitals successfully completed the minimal surveillance option (for 1,152 patients). Clinical data were submitted for 94% (1,078/1,152) of the patients in the light option; information on CDI origin and outcome was complete for 94% (1,016/1,078) and 98% (294/300) of the patients in the light and enhanced options, respectively. The workload of the options was 1.1, 2.0 and 3.0 person-days per 10,000 hospital discharges, respectively. Enhanced surveillance was tested and was successful in 32 of the hospitals, showing that C. difficile PCR ribotype 027 was predominant (30% (79/267)). This study showed that standardised multicountry surveillance, with the option of integrating clinical and molecular data, is a feasible strategy for monitoring CDI in Europe. This article is copyright of The Authors, 2016.

The roles of host and pathogen factors and the innate immune response in the pathogenesis of Clostridium difficile infection

PubMed Central

Sun, Xingmin; Hirota, Simon A.

2014-01-01

Clostridium difficile (C. difficile) is the most common cause of nosocomial antibiotic-associated diarrhea and the etiologic agent of pseudomembranous colitis. The clinical manifestation of Clostridium difficile infection (CDI) is highly variable, from asymptomatic carriage, to mild self-limiting diarrhea, to the more severe pseudomembranous colitis. Furthermore, in extreme cases, colonic inflammation and tissue damage can lead to toxic megacolon, a condition requiring surgical intervention. C. difficile expresses two key virulence factors; the exotoxins, toxin A (TcdA) and toxin B (TcdB), which are glucosyltransferases that target host-cell monomeric GTPases. In addition, some hypervirulent strains produce a third toxin, binary toxin or C. difficile transferase (CDT), which may contribute to the pathogenesis of CDI. More recently, other factors such as surface layer proteins (SLPs) and flagellin have also been linked to the inflammatory responses observed in CDI. Although the adaptive immune response can influence the severity of CDI, the innate immune responses to C. difficile and its toxins play crucial roles in CDI onset, progression, and overall prognosis. Despite this, the innate immune responses in CDI have drawn relatively little attention from clinical researchers. Targeting these responses may prove useful clinically as adjuvant therapies, especially in refractory and/or recurrent CDI. This review will focus on recent advances in our understanding of how C. difficile and its toxins modulate innate immune responses that contribute to CDI pathogenesis. PMID:25242213

Risk factors associated with Clostridium difficile infection in kidney transplant recipients.

PubMed

Spinner, M L; Stephany, B R; Cerrato, P M; Lam, S W; Neuner, E A; Patel, K S

2018-05-24

Solid organ transplant recipients are especially vulnerable to Clostridium difficile infection (CDI) due to cumulative risk factors including increased exposure to healthcare settings, persistent immunosuppression, and higher rates of antimicrobial exposure. We aimed to identify risk factors associated with CDI development in kidney transplant recipients including implications of immunosuppressive therapies and acid-suppressing agents. This was a single-center, non-interventional, retrospective case-control study of adult subjects between June 1, 2009 and June 30, 2013. During this time, 728 patients underwent kidney transplantation. Overall, 22 developed CDI (cases) and were matched 1:3 with 66 controls. Cases and controls were also matched for induction agent, kidney allograft type (living or deceased), and time from transplant to CDI result (±60 days). The majority of subjects received a deceased donor kidney (77.3%) and basiliximab induction therapy (86.4%). The overall CDI incidence was 3%. Factors independently associated with CDI were average tacrolimus trough (AOR = 1.25, 95% CI = 1.00-1.56, P = .048) and antibiotic exposure for urinary tract infections (UTI) (AOR = 4.17, 95% CI = 1.12-15.54, P = .034). Proton pump inhibitor use was not associated with CDI (OR = 0.81, 95% CI = 0.29-2.29, P = .691). Maintaining a clinically appropriate tacrolimus trough and judicious antibiotic use and selection for UTI treatment could potentially reduce CDI in the kidney transplant population. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Breakthrough Clostridium difficile Infection in Cirrhotic Patients Receiving Rifaximin.

PubMed

Reigadas, Elena; Alcalá, Luis; Gómez, Javier; Marín, Mercedes; Martin, Adoración; Onori, Raffaella; Muñoz, Patricia; Bouza, Emilio

2018-03-19

Patients with cirrhosis are at high risk of Clostridium difficile infection (CDI). Rifaximin is commonly used in cirrhotic patients as prophylaxis for hepatic encephalopathy (HE). Several studies have demonstrated the efficacy of rifaximin in the treatment of CDI; however, resistance to rifaximin has also been reported. Few studies have assessed the risk of developing CDI in cirrhotic patients receiving rifaximin. Our objective was to assess the incidence and characteristics of CDI in patients with cirrhosis, especially in those who received rifaximin. We assessed the incidence and clinical characteristics of CDI in cirrhotic patients over a 6-year period in our hospital. Medical charts were retrospectively reviewed. Ribotyping and antimicrobial susceptibility testing of all strains against rifaximin were performed. A total of 388 cirrhotic patients were included, of whom 127 patients had at least 1 episode of diarrhea in which a sample was sent to the laboratory. CDI was detected in 46 patients. Fourteen patients (30.4%) were receiving rifaximin as prophylaxis for HE. The main ribotypes detected were 001 (30.4%), followed by 014 (19.6%). Resistance to rifaximin was 34.1% overall, and 84.6% in patients who had received rifaximin. Multivariate analysis showed that rifamycin therapy and ribotype 001 were significant risk factors for having a rifaximin-resistant C. difficile strain. A high percentage of CDI cases were detected in cirrhotic patients receiving rifaximin, mostly owing to selection of rifaximin-resistant C. difficile strains. Clinicians should be aware of the risk of CDI in cirrhotic patients, even in those receiving rifaximin.

Inflammatory bowel disease and Clostridium difficile infection: contrasting views of international clinical professionals.

PubMed

Stallmach, Andreas; Anttila, Veli-Jukka; Hell, Markus; Gwynn, Simon; Merino-Amador, Paloma; Petrosillo, Nicola; Ráčil, Zdenek; Warren, Tim; Wenisch, Christoph; Wilcox, Mark

2018-02-09

 In patients with inflammatory bowel disease (IBD), Clostridium difficile infection (CDI) is a risk factor for both morbidity and mortality. Currently, appropriate management is unclear. Guidance on best practice in the diagnosis and treatment of CDI in IBD patients is therefore needed.  A multidisciplinary group of clinicians involved in the treatment of patients with IBD and CDI developed 27 consensus statements. Respondents were asked to rate their agreement with each statement using a 4-point Likert scale. A modified Delphi methodology was used to review responses of 442 physicians from different specialties (including infectious disease specialists [n = 104], microbiologists [n = 95], and gastroenterologists [n = 73]). A threshold of 75 % agreement was predefined as consensus.  Consensus was achieved for 17 of the 27 statements. Unprompted recognition of risk factors for CDI was low. Intensification of immunosuppressive therapy in the absence of clinical improvement was controversial. Clear definitions of treatment failure of antibiotic therapy in CDI and recurrence of CDI in IBD are needed. Respondents require further clarity regarding the place of fecal microbiota transplantation in CDI patients with IBD. Differences were observed between the perceptions of microbiologists and gastroenterologists, as well as between countries.  Different perceptions both between specialties and geographical locations complicate the development of an internationally accepted algorithm for the diagnosis and treatment of CDI in patients with IBD. This study highlights the need for future studies in this area. © Georg Thieme Verlag KG Stuttgart · New York.

76 FR 14021 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-15

... Project Clostridium difficile Infection (CDI) Surveillance--New--National Center for Emerging and Zoonotic... Description Steady increases in the rate and severity of Clostridium difficile infection (CDI) indicate a clear need to conduct longitudinal assessments of the impact of CDI in the United States. C. difficile...

78 FR 65322 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... days of this notice. Proposed Project Clostridium difficile Infection (CDI) Surveillance (0920-0892... rate and severity of Clostridium difficile infection (CDI) indicate a clear need to conduct longitudinal assessments to continue to monitor changes in CDI epidemiology, including changes in risk factors...

78 FR 66779 - United States Enrichment Corporation, Paducah Gaseous Diffusion Plant, Including On-Site Leased...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-06

..., KB Consultants, Henry, Meisenheimer, & Grende, SR Martin Group And CDI Corporation, Paducah, Kentucky.... Petter Supply, KB Consultants, Henry, Meisenheimer & Grende, SR Martin Group and CDI Corporation were... Services, Henry A. Petter Supply, KB Consultants, Henry, Meisenheimer & Grende, SR Martin Group and CDI...

75 FR 21372 - Calvert Social Investment Fund, et al.; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-23

... Management Company, Inc. (``CAMCO'') and Calvert Distributors, Inc. (``CDI''). Filing Dates: The application... adviser under the Investment Advisers Act of 1940, as amended. CDI, a Delaware corporation, is a... entity controlling, controlled by or under common control with CAMCO or CDI that now or in the future...

Systematic Assessment of a High-Impact Course Design Institute

ERIC Educational Resources Information Center

Palmer, Michael S.; Streifer, Adriana C.; Williams-Duncan, Stacy

2016-01-01

Herein, we describe an intensive, week-long course design institute (CDI) designed to introduce participants to the scholarly and evidence-driven process of learning-focused course design. Impact of this intervention is demonstrated using a multifaceted approach: (a) post-CDI satisfaction and perception surveys, (b) pre-/post-CDI surveys probing…

CD-I and Full Motion Video.

ERIC Educational Resources Information Center

Chen, Ching-chih

1991-01-01

Describes compact disc interactive (CD-I) as a multimedia home entertainment system that combines audio, visual, text, graphic, and interactive capabilities. Full-screen video and full-motion video (FMV) are explained, hardware for FMV decoding is described, software is briefly discussed, and CD-I titles planned for future production are listed.…

The Cost-efficiency and Care Effectiveness of Probiotic Administration with Antibiotics to Prevent Hospital-Acquired Clostridium difficile Infection.

PubMed

Starn, Emily S; Hampe, Holly; Cline, Thomas

Health care facility-acquired Clostridium difficile infections (HCFA-CDI) have increased over the last several decades despite facilities developing protocols for prescribing probiotics with antibiotics to prevent HCFA-CDI. The literature does not consistently support this. A retrospective medical record review evaluated the care effectiveness of this practice. Care effectiveness was not found; patients receiving probiotics with antibiotics were twice as likely to develop HCFA-CDI (P = .004). Except with glycopeptides, patients were 1.88 times less likely to experience HCFA-CDI (P = .05).

Clostridium difficile infection: management strategies for a difficult disease

PubMed Central

Pardi, Darrell S.

2014-01-01

Clostridium difficile was first described as a cause of diarrhea in 1978 and in the last three decades has reached an epidemic state with increasing incidence and severity in both healthcare and community settings. There also has been a rise in severe outcomes from C. difficile infection (CDI). There have been tremendous advancements in the field of CDI with the identification of newer risk factors, recognition of CDI in populations previously thought not at risk and development of better diagnostic modalities. Several treatment options are available for CDI apart from metronidazole and vancomycin, and include new drugs such as fidaxomicin and other options such as fecal microbiota transplantation. This review discusses the epidemiology, risk factors and outcomes from CDI, and focuses primarily on existing and evolving treatment modalities. PMID:24587820

The economic impact of Clostridium difficile infection: a systematic review.

PubMed

Nanwa, Natasha; Kendzerska, Tetyana; Krahn, Murray; Kwong, Jeffrey C; Daneman, Nick; Witteman, William; Mittmann, Nicole; Cadarette, Suzanne M; Rosella, Laura; Sander, Beate

2015-04-01

With Clostridium difficile infection (CDI) on the rise, knowledge of the current economic burden of CDI can inform decisions on interventions related to CDI. We systematically reviewed CDI cost-of-illness (COI) studies. We performed literature searches in six databases: MEDLINE, Embase, the Health Technology Assessment Database, the National Health Service Economic Evaluation Database, the Cost-Effectiveness Analysis Registry, and EconLit. We also searched gray literature and conducted reference list searches. Two reviewers screened articles independently. One reviewer abstracted data and assessed quality using a modified guideline for economic evaluations. The second reviewer validated the abstraction and assessment. We identified 45 COI studies between 1988 and June 2014. Most (84%) of the studies were from the United States, calculating costs of hospital stays (87%), and focusing on direct costs (100%). Attributable mean CDI costs ranged from $8,911 to $30,049 for hospitalized patients. Few studies stated resource quantification methods (0%), an epidemiological approach (0%), or a justified study perspective (16%) in their cost analyses. In addition, few studies conducted sensitivity analyses (7%). Forty-five COI studies quantified and confirmed the economic impact of CDI. Costing methods across studies were heterogeneous. Future studies should follow standard COI methodology, expand study perspectives (e.g., patient), and explore populations least studied (e.g., community-acquired CDI).

Clostridium difficile infection in the elderly: an update on management.

PubMed

Asempa, Tomefa E; Nicolau, David P

2017-01-01

The burden of Clostridium difficile infection (CDI) is profound and growing. CDI now represents a common cause of health care-associated diarrhea, and is associated with significant morbidity, mortality, and health care costs. CDI disproportionally affects the elderly, possibly explained by the following risk factors: age-related impairment of the immune system, increasing antibiotic utilization, and frequent health care exposure. In the USA, recent epidemiological studies estimate that two out of every three health care-associated CDIs occur in patients 65 years or older. Additionally, the elderly are at higher risk for recurrent CDI. Existing therapeutic options include metronidazole, oral vancomycin, and fidaxomicin. Choice of agent depends on disease severity, history of recurrence, and, increasingly, the drug cost. Bezlotoxumab, a recently approved monoclonal antibody targeting C. difficile toxin B, offers an exciting advancement into immunologic therapies. Similarly, fecal microbiota transplantation is gaining popularity as an effective option mainly for recurrent CDI. The challenge of decreasing CDI burden in the elderly involves adopting preventative strategies, optimizing initial treatment, and decreasing the risk of recurrence. Expanded strategies are certainly needed to improve outcomes in this high-risk population. This review considers available data from prospective and retrospective studies as well as case reports to illustrate the merits and gaps in care related to the management of CDI in the elderly.

Clostridium difficile Infection Seasonality: Patterns across Hemispheres and Continents – A Systematic Review

PubMed Central

Furuya-Kanamori, Luis; McKenzie, Samantha J.; Yakob, Laith; Clark, Justin; Paterson, David L.; Riley, Thomas V.; Clements, Archie C.

2015-01-01

Background Studies have demonstrated seasonal variability in rates of Clostridium difficile infection (CDI). Synthesising all available information on seasonality is a necessary step in identifying large-scale epidemiological patterns and elucidating underlying causes. Methods Three medical and life sciences publication databases were searched from inception to October 2014 for longitudinal epidemiological studies written in English, Spanish or Portuguese that reported the incidence of CDI. The monthly frequency of CDI were extracted, standardized and weighted according to the number of follow-up months. Cross correlation coefficients (XCORR) were calculated to examine the correlation and lag between the year-month frequencies of reported CDI across hemispheres and continents. Results The search identified 13, 5 and 2 studies from North America, Europe, and Oceania, respectively that met the inclusion criteria. CDI had a similar seasonal pattern in the Northern and Southern Hemisphere characterized by a peak in spring and lower frequencies of CDI in summer/autumn with a lag of 8 months (XCORR = 0.60) between hemispheres. There was no difference between the seasonal patterns across European and North American countries. Conclusion CDI demonstrates a distinct seasonal pattern that is consistent across North America, Europe and Oceania. Further studies are required to identify the driving factors of the observed seasonality. PMID:25775463

Point-Counterpoint: What Is the Optimal Approach for Detection of Clostridium difficile Infection?

PubMed Central

Wilcox, Mark H.

2017-01-01

INTRODUCTION In 2010, we published an initial Point-Counterpoint on the laboratory diagnosis of Clostridium difficile infection (CDI). At that time, nucleic acid amplification tests (NAATs) were just becoming commercially available, and the idea of algorithmic approaches to CDI was being explored. Now, there are numerous NAATs in the marketplace, and based on recent proficiency test surveys, they have become the predominant method used for CDI diagnosis in the United States. At the same time, there is a body of literature that suggests that NAATs lack clinical specificity and thus inflate CDI rates. Hospital administrators are taking note of institutional CDI rates because they are publicly reported. They have become an important metric impacting hospital safety ratings and value-based purchasing; hospitals may have millions of dollars of reimbursement at risk. In this Point-Counterpoint using a frequently asked question approach, Ferric Fang of the University of Washington, who has been a consistent advocate for a NAAT-only approach for CDI diagnosis, will discuss the value of a NAAT-only approach, while Christopher Polage of the University of California Davis and Mark Wilcox of Leeds University, Leeds, United Kingdom, each of whom has recently written important articles on the value of toxin detection in the diagnosis, will discuss the impact of toxin detection in CDI diagnosis. PMID:28077697

Clostridium difficile infection in the elderly: an update on management

PubMed Central

Asempa, Tomefa E; Nicolau, David P

2017-01-01

The burden of Clostridium difficile infection (CDI) is profound and growing. CDI now represents a common cause of health care–associated diarrhea, and is associated with significant morbidity, mortality, and health care costs. CDI disproportionally affects the elderly, possibly explained by the following risk factors: age-related impairment of the immune system, increasing antibiotic utilization, and frequent health care exposure. In the USA, recent epidemiological studies estimate that two out of every three health care–associated CDIs occur in patients 65 years or older. Additionally, the elderly are at higher risk for recurrent CDI. Existing therapeutic options include metronidazole, oral vancomycin, and fidaxomicin. Choice of agent depends on disease severity, history of recurrence, and, increasingly, the drug cost. Bezlotoxumab, a recently approved monoclonal antibody targeting C. difficile toxin B, offers an exciting advancement into immunologic therapies. Similarly, fecal microbiota transplantation is gaining popularity as an effective option mainly for recurrent CDI. The challenge of decreasing CDI burden in the elderly involves adopting preventative strategies, optimizing initial treatment, and decreasing the risk of recurrence. Expanded strategies are certainly needed to improve outcomes in this high-risk population. This review considers available data from prospective and retrospective studies as well as case reports to illustrate the merits and gaps in care related to the management of CDI in the elderly. PMID:29123385

Prevalence of depressive symptoms among schoolchildren in Cyprus: a cross-sectional descriptive correlational study.

PubMed

Sokratis, Sokratous; Christos, Ζilides; Despo, Panagi; Maria, Karanikola

2017-01-01

Depressive symptoms in the young constitute a public health issue. The current study aims to estimate: (a) the frequency of depressive symptoms in a sample of final grade elementary-school children in Cyprus, (b) the association among frequency of depressive symptoms, gender and nationality and, (c) the metric properties of the Greek-Cypriot version of the children's depression inventory (CDI). A descriptive cross-sectional study with internal comparison was performed. The occurrence of depressive symptoms was assessed with the CDI, which includes 5 subscales: depressive mood, interpersonal difficulties, ineffectiveness, anhedonia and negative self-esteem. Clinical depressive symptoms were reported as CDI score ≥19. CDI was anonymously and voluntarily completed by 439 schoolchildren [mean age 12.3 (±0.51) years old] from fifteen public elementary schools (217 boys and 222 girls), yielding a response rate of 58.2%. The metric properties of the CDI were assessed in terms of internal consistency reliability and construct validity via exploratory factor analysis (rotated and unrotated principal component analysis). Descriptive and inferential statistics were explored. 10.25% of Cypriot schoolchildren reported clinical depressive symptoms (CDI score ≥19). Statistically significant differences were reported between boys and girls in all five subscales of the CDI. Girls reported higher scores in "Depressive mood", "Negative self-esteem" and "Anhedonia" subscales, while boys scored higher in "Interpersonal difficulties" and "Ineffectiveness" subscales. There were no statistically significant differences among ethnicity groups regarding the entire CDI or the subscales of it. Concerning the metric properties of the Greek-Cypriot version of the CDI, internal consistency reliability was adequate (Cronbach's alpha = 0.84). Factor analysis with varimax rotation resulted in five factors explaining 42% of the variance. The Greek-Cypriot version of the CDI is a reliable tool for the assessment of the severity of depressive symptoms in schoolchildren. Institutional counseling services, as well as interventions aiming to empower the young need to address the different psychological needs of boys and girls. Longitudinal studies within this cultural context may be warranted, with special attention to other factors related to depressive symptoms and low self-esteem in schoolchildren, such as suicidality or bullying.

[Characteristics of the course of gastric and duodenal ulcer disease concurrent with duodenal insufficiency].

PubMed

Busygina, M S; Vakhrushev, Ya M

To comprehensively study the course of gastric ulcer disease (GUD) and duodenal ulcer disease (DUD) concurrent with chronic duodenal insufficiency (CDI). Ulcer disease (UD) was verified on the basis of the results of clinical and fibrogastroduodenoscopic examinations. The data of contrast duodenography and cavitary manometry were used to identify CDI. Gastroduodenal motor activity was investigated using the peripheral electrogastrograph EGG-4M. The results of pH measurements were employed to assess the state of gastric acid secretion and duodenal pH values. A comprehensive examination was made in 106 patients with UD concurrent with CDI (a study group) and 30 UD patients without CDI (a comparison group). Epigastric pain was noted in the patients with GUD in the study and comparison groups (91.5 and 84.6%, respectively), but the pain was mainly aching in the patients with concomitant CDI and more intense (77.8%) in those without this condition. In the study group, heartburn was more common in patients with GUD and DUD (75.3 and 71.4%, respectively) than in those with UD in the comparison group (28.5 and 37.5%, respectively). Helicobacter pylori tests were positive in 23.8% of the patients in the study group and in 57.2% in the comparison group. Electrogastrography indicated that the patients with GUD and CDI had bradygastria and hypokinesis on an empty stomach; the electrical activity was reduced after eating. In the comparison group, tachygastria and hyperkinesis were detected on an empty stomach; these postprandial indicators were elevated. H. pylori tests were positive in 34.7% of the patients with DUD and CDI and in 63.6% of those with DUD without CDI. The postprandial electrical activity increased in patients with DUD and decreased in the comparison group. The specific features of changes in gastric and duodenal pH values in GUD and DUD concurrent with CDI in comparison with the isolated course of UD. The immediate and long-term follow-ups show that GUD and DUD concurrent with CDI run a more persistent course; the time of ulcer healing increases and the periods of remission decrease.

Mathematical Modeling of the Transmission Dynamics of Clostridium difficile Infection and Colonization in Healthcare Settings: A Systematic Review

PubMed Central

Gingras, Guillaume; Guertin, Marie-Hélène; Laprise, Jean-François; Drolet, Mélanie; Brisson, Marc

2016-01-01

Background We conducted a systematic review of mathematical models of transmission dynamic of Clostridium difficile infection (CDI) in healthcare settings, to provide an overview of existing models and their assessment of different CDI control strategies. Methods We searched MEDLINE, EMBASE and Web of Science up to February 3, 2016 for transmission-dynamic models of Clostridium difficile in healthcare settings. The models were compared based on their natural history representation of Clostridium difficile, which could include health states (S-E-A-I-R-D: Susceptible-Exposed-Asymptomatic-Infectious-Resistant-Deceased) and the possibility to include healthcare workers and visitors (vectors of transmission). Effectiveness of interventions was compared using the relative reduction (compared to no intervention or current practice) in outcomes such as incidence of colonization, CDI, CDI recurrence, CDI mortality, and length of stay. Results Nine studies describing six different models met the inclusion criteria. Over time, the models have generally increased in complexity in terms of natural history and transmission dynamics and number/complexity of interventions/bundles of interventions examined. The models were categorized into four groups with respect to their natural history representation: S-A-I-R, S-E-A-I, S-A-I, and S-E-A-I-R-D. Seven studies examined the impact of CDI control strategies. Interventions aimed at controlling the transmission, lowering CDI vulnerability and reducing the risk of recurrence/mortality were predicted to reduce CDI incidence by 3–49%, 5–43% and 5–29%, respectively. Bundles of interventions were predicted to reduce CDI incidence by 14–84%. Conclusions Although CDI is a major public health problem, there are very few published transmission-dynamic models of Clostridium difficile. Published models vary substantially in the interventions examined, the outcome measures used and the representation of the natural history of Clostridium difficile, which make it difficult to synthesize results and provide a clear picture of optimal intervention strategies. Future modeling efforts should pay specific attention to calibration, structural uncertainties, and transparent reporting practices. PMID:27690247

Critical Aspects of the Coastal Drought Index: Length of Salinity Data Record and Ecological Response Data

NASA Astrophysics Data System (ADS)

Conrads, P. A.; Tufford, D. L.; Darby, L. S.

2015-12-01

The phenomenon of coastal drought has a different dynamic from upland droughts that are typically characterized by agricultural, hydrologic, meteorological, and(or) socio-economic impacts. Because of the uniqueness of drought impacts on coastal ecosystems, a coastal drought index (CDI) that uses existing salinity datasets for sites in South Carolina, Georgia, and Florida was developed using an approach similar to the Standardized Precipitation Index (SPI). CDIs characterizing the 1- to 24-month salinity conditions were developed and the evaluation of the CDI indicates that the index can be used for different estuary types (for example, brackish, olioghaline, or mesohaline), for regional comparison between estuaries, and as an index for wet conditions (high freshwater inflow) in addition to drought conditions. Unlike the SPI where long-term precipitation datasets of 50 to 100 years are available for computing the index, there are a limited number of salinity data sets of greater than 10 or 15 years for computing the CDI. To evaluate the length of salinity record necessary to compute the CDI, a 29-year dataset was resampled into 5-, 10-, 15-, and 20-year interval datasets. Comparison of the CDI for the different periods of record show that the range of salinity conditions in the 10-, 15-, and 20-year datasets were similar and results were a close approximation to the CDI computed by using the full period of record. The CDI computed with the 5-year dataset had the largest differences with the CDI computed with the 29-year dataset but did provide useful information on coastal drought and freshwater conditions. An ongoing National Integrated Drought Information System (NIDIS) drought early warning project in the Carolinas is developing ecological linkages to the CDI and evaluating the effectiveness of the CDI as a prediction tool for adaptation planning for future droughts. However, identifying potential coastal drought response datasets is a challenge. Coastal drought is a relatively new concept and existing datasets may not have been collected or understood as "drought response" datasets. We have considered drought response datasets including tree growth and liter fall, harmful algal blooms occurrence, Vibrio infection occurrence, shellfish harvesting data, and shark attacks.

Cost-effectiveness of competing strategies for management of recurrent Clostridium difficile infection: a decision analysis.

PubMed

Konijeti, Gauree G; Sauk, Jenny; Shrime, Mark G; Gupta, Meera; Ananthakrishnan, Ashwin N

2014-06-01

Clostridium difficile infection (CDI) is an important cause of morbidity and healthcare costs, and is characterized by high rates of disease recurrence. The cost-effectiveness of newer treatments for recurrent CDI has not been examined, yet would be important to inform clinical practice. The aim of this study was to analyze the cost effectiveness of competing strategies for recurrent CDI. We constructed a decision-analytic model comparing 4 treatment strategies for first-line treatment of recurrent CDI in a population with a median age of 65 years: metronidazole, vancomycin, fidaxomicin, and fecal microbiota transplant (FMT). We modeled up to 2 additional recurrences following the initial recurrence. We assumed FMT delivery via colonoscopy as our base case, but conducted sensitivity analyses based on different modes of delivery. Willingness-to-pay threshold was set at $50 000 per quality-adjusted life-year. At our base case estimates, initial treatment of recurrent CDI using FMT colonoscopy was the most cost-effective strategy, with an incremental cost-effectiveness ratio of $17 016 relative to oral vancomycin. Fidaxomicin and metronidazole were both dominated by FMT colonoscopy. On sensitivity analysis, FMT colonoscopy remained the most cost-effective strategy at cure rates >88.4% and CDI recurrence rates <14.9%. Fidaxomicin required a cost <$1359 to meet our cost-effectiveness threshold. In clinical settings where FMT is not available or applicable, the preferred strategy appears to be initial treatment with oral vancomycin. In this decision analysis examining treatment strategies for recurrent CDI, we demonstrate that FMT colonoscopy is the most cost-effective initial strategy for management of recurrent CDI.

Clinical and economic consequences of vancomycin and fidaxomicin for the treatment of Clostridium difficile infection in Canada.

PubMed

Wagner, Monika; Lavoie, Louis; Goetghebeur, Mireille

2014-03-01

Clostridium difficile infection (CDI) represents a public health problem with increasing incidence and severity. To evaluate the clinical and economic consequences of vancomycin compared with fidaxomicin in the treatment of CDI from the Canadian health care system perspective. A decision-tree model was developed to compare vancomycin and fidaxomicin for the treatment of severe CDI. The model assumed identical initial cure rates and included first recurrent episodes of CDI (base case). Treatment of patients presenting with recurrent CDI was examined as an alternative analysis. Costs included were for study medication, physician services and hospitalization. Cost effectiveness was measured as incremental cost per recurrence avoided. Sensitivity analyses of key input parameters were performed. In a cohort of 1000 patients with an initial episode of severe CDI, treatment with fidaxomicin led to 137 fewer recurrences at an incremental cost of $1.81 million, resulting in an incremental cost of $13,202 per recurrence avoided. Among 1000 patients with recurrent CDI, 113 second recurrences were avoided at an incremental cost of $18,190 per second recurrence avoided. Incremental costs per recurrence avoided increased with increasing proportion of cases caused by the NAP1/B1/027 strain. Results were sensitive to variations in recurrence rates and treatment duration but were robust to variations in other parameters. The use of fidaxomicin is associated with a cost increase for the Canadian health care system. Clinical benefits of fidaxomicin compared with vancomycin depend on the proportion of cases caused by the NAP1/B1/027 strain in patients with severe CDI.

RO brine treatment and recovery by biological activated carbon and capacitive deionization process.

PubMed

Tao, Guihe; Viswanath, Bala; Kekre, Kiran; Lee, Lai Yoke; Ng, How Yong; Ong, Say Leong; Seah, Harry

2011-01-01

The generation of brine solutions from dense membrane (reverse osmosis, RO or nanofiltration, NF) water reclamation systems has been increasing worldwide, and the lack of cost effective disposal options is becoming a critical water resources management issue. In Singapore, NEWater is the product of a multiple barrier water reclamation process from secondary treated domestic effluent using MF/UF-RO and UV technologies. The RO brine (concentrates) accounts for more than 20% of the total flow treated. To increase the water recovery and treat the RO brine, a CDI based process with BAC as pretreatment was tested. The results show that ion concentrations in CDI product were low except SiO2 when compared with RO feed water. CDI product was passed through a RO and the RO permeate was of better quality including low SiO2 as compared to NEWater quality. It could be beneficial to use a dedicated RO operated at optimum conditions with better performance to recover the water. BAC was able to achieve 15-27% TOC removal of RO brine. CDI had been tested at a water recovery ranging from 71.6 to 92.3%. CDI based RO brine treatment could improve overall water recovery of NEWater production over 90%. It was found that calcium phosphate scaling and organic fouling was the major cause of CDI pressure increase. Ozone disinfection and sodium bisulfite dosing were able to reduce CDI fouling rate. For sustainable operation of CDI organic fouling control and effective organic fouling cleaning should be further studied.

Epidemiology and outcomes of Clostridium difficile infection in allogeneic hematopoietic cell and lung transplant recipients.

PubMed

Dubberke, E R; Reske, K A; Olsen, M A; Bommarito, K; Cleveland, A A; Silveira, F P; Schuster, M G; Kauffman, C A; Avery, R K; Pappas, P G; Chiller, T M

2018-04-01

Clostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described. We performed a prospective, multicenter study of CDI within 365 days post-allogeneic HCT or lung transplantation. Data were collected via patient interviews and medical chart review. Participants were followed weekly in the 12 weeks post-transplant and while hospitalized and contacted monthly up to 18 months post-transplantation. Six sites participated in the study with 614 total participants; 4 enrolled allogeneic HCT (385 participants) and 5 enrolled lung transplant recipients (229 participants). One hundred and fifty CDI cases occurred within 1 year of transplantation; the incidence among lung transplant recipients was 13.1% and among allogeneic HCTs was 31.2%. Median time to CDI was significantly shorter among allogeneic HCT than lung transplant recipients (27 days vs 90 days; P = .037). CDI was associated with significantly higher mortality from 31 to 180 days post-index date among the allogeneic HCT recipients (Hazard ratio [HR] = 1.80; P = .007). There was a trend towards increased mortality among lung transplant recipients from 120 to 180 days post-index date (HR = 4.7, P = .09). The epidemiology and outcomes of CDI vary by transplant population; surveillance for CDI should continue beyond the immediate post-transplant period. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

CLOSTRIDIUM DIFFICILE INFECTION IN ACUTE CARE HOSPITALS: SYSTEMATIC REVIEW AND BEST PRACTICES FOR PREVENTION

PubMed Central

Louh, Irene K.; Greendyke, William G.; Hermann, Emilia A.; Davidson, Karina W.; Falzon, Louise; Vawdrey, David K.; Shaffer, Jonathan A.; Calfee, David P.; Furuya, E. Yoko; Ting, Henry H.

2017-01-01

Objective Prevention of Clostridium difficile infection (CDI) in acute care hospitals is a priority for hospitals and clinicians. We performed a qualitative systematic review to update the evidence on interventions to prevent CDI published since 2009. Design We searched Ovid, MEDLINE, EMBASE, The Cochrane Library, CINAHL, ISI Web of Knowledge, and grey literature databases from January 1, 2009 to August 1, 2015. Setting We included studies performed in acute care hospitals. Patients or participants We included studies conducted on hospitalized patients that investigated the impact of specific interventions on CDI rates. Interventions We used the QI-Minimum Quality Criteria Set (QI-MQCS) to assess the quality of included studies. Interventions were grouped thematically: environmental disinfection, antimicrobial stewardship, hand hygiene, chlorhexidine bathing, probiotics, bundled approaches, and others. A meta-analysis was performed when possible. Results Of 3236 articles screened, 261 met the criteria for full-text review and 46 studies were ultimately included. The average quality rating was 82% on the QI-MQCS. The most effective interventions, resulting in a 45% to 85% reduction in CDI, included daily to twice daily disinfection of high-touch surfaces (including bed rails) and terminal cleaning of patient rooms with chlorine-based products. Bundled interventions and antimicrobial stewardship showed promise for reducing CDI rates. Chlorhexidine bathing and intensified hand hygiene practices were not effective for reducing CDI rates. Conclusions Daily and terminal cleaning of patient rooms using chlorine-based products were most effective in reducing CDI rates in hospitals. Further studies are needed to identify the components of bundled interventions that reduce CDI rates. PMID:28300019

A population-based spatio-temporal analysis of Clostridium difficile infection in Queensland, Australia over a 10-year period.

PubMed

Furuya-Kanamori, Luis; Robson, Jenny; Soares Magalhães, Ricardo J; Yakob, Laith; McKenzie, Samantha J; Paterson, David L; Riley, Thomas V; Clements, Archie C A

2014-11-01

To identify the spatio-temporal patterns and environmental factors associated with Clostridium difficile infection (CDI) in Queensland, Australia. Data from patients tested for CDI were collected from 392 postcodes across Queensland between May 2003 and December 2012. A binomial logistic regression model, with CDI status as the outcome, was built in a Bayesian framework, incorporating fixed effects for sex, age, source of the sample (healthcare facility or community), elevation, rainfall, land surface temperature, seasons of the year, time in months and spatially unstructured random effects at the postcode level. C. difficile was identified in 13.1% of the samples, the proportion significantly increased over the study period from 5.9% in 2003 to 18.8% in 2012. CDI peaked in summer (14.6%) and was at its lowest in autumn (10.1%). Other factors significantly associated with CDI included female sex (OR: 1.08; 95%CI: 1.01-1.14), community source samples (OR: 1.12; 95%CI: 1.05-1.20), and higher rainfall (OR: 1.09; 95%CI: 1.02-1.17). There was no significant spatial variation in CDI after accounting for the fixed effects in the model. There was an increasing annual trend in CDI in Queensland from 2003 to 2012. Peaks of CDI were found in summer (December-February), which is at odds with the current epidemiological pattern described for northern hemisphere countries. Epidemiologically plausible explanations for this disparity require further investigation. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Treatment of pediatric Clostridium difficile infection: a review on treatment efficacy and economic value.

PubMed

D'Ostroph, Amanda R; So, Tsz-Yin

2017-01-01

The incidence of Clostridium difficile infection (CDI) in pediatric patients continues to rise. Most of the pediatric recommendations for CDI treatment are extrapolated from the literature and guidelines for adults. The American Academy of Pediatrics recommends oral metronidazole as the first-line treatment option for an initial CDI and the first recurrence if they are mild to moderate in severity. Oral vancomycin is recommended to be used for severe CDI and the second recurrent infection. Additional pulsed regimen of oral vancomycin, which is tapered, may increase efficacy in refractory patients. However, there is lack of large studies evaluating the use of fidaxomicin in pediatrics to know whether it could be a safe and effective treatment option for difficult-to-treat patients. Fidaxomicin is associated with higher total drug costs compared to metronidazole and vancomycin, but the literature supports its use due to a lower rate of CDI recurrence, which may result in cost savings. Further studies are warranted to evaluate the use of fidaxomicin in patients <18 years old and to understand its role in the standard of care for pediatric patients with CDI.

Normative data for female adolescents with eating disorders on the Children's Depression Inventory.

PubMed

Watson, Hunna J; Egan, Sarah J; Limburg, Karina; Hoiles, Kimberley J

2014-09-01

Given the importance of assessing depressive symptoms and suicidal ideation in adolescents with eating disorders (EDs), the aim was to provide normative data on the Children's Depression Inventory (CDI) for female adolescents presenting for treatment of an ED. The data source was the Helping to Outline Paediatric Eating Disorders (HOPE) Project registry (N = 1000), a prospective, ongoing registry study comprising consecutive pediatric tertiary ED referrals. Females (N = 256; 12-17 years) with DSM-5 EDs completed the CDI at intake. Results on the CDI revealed a pattern of increasing depressive scores with age and higher scores among patients with anorexic spectrum disorders. The prevalence of suicidal ideation was high and had the same pattern as CDI scores. The mean score on the CDI in the sample was higher than community samples and clinical samples of adolescents with post-traumatic stress disorder, obsessive compulsive disorder, and other clinical disorders. Females adolescents with EDs are at high-risk of depression and suicidal ideation. These data provide information about variation in CDI scores to guide clinicians in interpretation of scores. © 2014 Wiley Periodicals, Inc.

Contact-dependent growth inhibition induces high levels of antibiotic-tolerant persister cells in clonal bacterial populations.

PubMed

Ghosh, Anirban; Baltekin, Özden; Wäneskog, Marcus; Elkhalifa, Dina; Hammarlöf, Disa L; Elf, Johan; Koskiniemi, Sanna

2018-05-02

Bacterial populations can use bet-hedging strategies to cope with rapidly changing environments. One example is non-growing cells in clonal bacterial populations that are able to persist antibiotic treatment. Previous studies suggest that persisters arise in bacterial populations either stochastically through variation in levels of global signalling molecules between individual cells, or in response to various stresses. Here, we show that toxins used in contact-dependent growth inhibition (CDI) create persisters upon direct contact with cells lacking sufficient levels of CdiI immunity protein, which would otherwise bind to and neutralize toxin activity. CDI-mediated persisters form through a feedforward cycle where the toxic activity of the CdiA toxin increases cellular (p)ppGpp levels, which results in Lon-mediated degradation of the immunity protein and more free toxin. Thus, CDI systems mediate a population density-dependent bet-hedging strategy, where the fraction of non-growing cells is increased only when there are many cells of the same genotype. This may be one of the mechanisms of how CDI systems increase the fitness of their hosts. © 2018 The Authors.

Antimicrobial Resistance and Reduced Susceptibility in Clostridium difficile: Potential Consequences for Induction, Treatment, and Recurrence of C. difficile Infection

PubMed Central

Baines, Simon D.; Wilcox, Mark H.

2015-01-01

Clostridium difficile infection (CDI) remains a substantial burden on healthcare systems and is likely to remain so given our reliance on antimicrobial therapies to treat bacterial infections, especially in an aging population in whom multiple co-morbidities are common. Antimicrobial agents are a key component in the aetiology of CDI, both in the establishment of the infection and also in its treatment. The purpose of this review is to summarise the role of antimicrobial agents in primary and recurrent CDI; assessing why certain antimicrobial classes may predispose to the induction of CDI according to a balance between antimicrobial activity against the gut microflora and C. difficile. Considering these aspects of CDI is important in both the prevention of the infection and in the development of new antimicrobial treatments. PMID:27025625

The Reliability and Validity of the Computerized Double Inclinometer in Measuring Lumbar Mobility

PubMed Central

MacDermid, Joy Christine; Arumugam, Vanitha; Vincent, Joshua Israel; Carroll, Krista L

2014-01-01

Study Design : Repeated measures reliability/validity study. Objectives : To determine the concurrent validity, test-retest, inter-rater and intra-rater reliability of lumbar flexion and extension measurements using the Tracker M.E. computerized dual inclinometer (CDI) in comparison to the modified-modified Schober (MMS) Summary of Background : Numerous studies have evaluated the reliability and validity of the various methods of measuring spinal motion, but the results are inconsistent. Differences in equipment and techniques make it difficult to correlate results. Methods : Twenty subjects with back pain and twenty without back pain were selected through convenience sampling. Two examiners measured sagittal plane lumbar range of motion for each subject. Two separate tests with the CDI and one test with the MMS were conducted. Each test consisted of three trials. Instrument and examiner order was randomly assigned. Intra-class correlations (ICCs 2, 2 and 2, 2) and Pearson correlation coefficients (r) were used to calculate reliability and concurrent validity respectively. Results : Intra-trial reliability was high to very high for both the CDI (ICCs 0.85 - 0.96) and MMS (ICCs 0.84 - 0.98). However, the reliability was poor to moderate, when the CDI unit had to be repositioned either by the same rate (ICCs 0.16 - 0.59) or a different rater (ICCs 0.45 - 0.52). Inter-rater reliability for the MMS was moderate to high (ICCs 0.75 - 0.82) which bettered the moderate correlation obtained for the CDI (ICCs 0.45 - 0.52). Correlations between the CDI and MMS were poor for flexion (0.32; p<0.05) and poor to moderate (-0.42 - -0.51; p<0.05) for extension measurements. Conclusion : When using the CDI, an average of subsequent tests is required to obtain moderate reliability. The MMS was highly reliable than the CDI. The MMS and the CDI measure lumbar movement on a different metric that are not highly related to each other. PMID:25352928

Cost-Effectiveness of Competing Treatment Strategies for Clostridium difficile Infection: A Systematic Review.

PubMed

Le, Phuc; Nghiem, Van T; Mullen, Patricia Dolan; Deshpande, Abhishek

2018-04-01

BACKGROUND Clostridium difficile infection (CDI) presents a substantial economic burden and is associated with significant morbidity. While multiple treatment strategies have been evaluated, a cost-effective management strategy remains unclear. OBJECTIVE We conducted a systematic review to assess cost-effectiveness analyses of CDI treatment and to summarize key issues for clinicians and policy makers to consider. METHODS We searched PubMed and 5 other databases from inception to August 2016. These searches were not limited by study design or language of publication. Two reviewers independently screened the literature, abstracted data, and assessed methodological quality using the Drummond and Jefferson checklist. We extracted data on study characteristics, type of CDI, treatment characteristics, and model structure and inputs. RESULTS We included 14 studies, and 13 of these were from high-income countries. More than 90% of these studies were deemed moderate-to-high or high quality. Overall, 6 studies used a decision-tree model and 7 studies used a Markov model. Cost of therapy, time horizon, treatment cure rates, and recurrence rates were common influential factors in the study results. For initial CDI, fidaxomicin was a more cost-effective therapy than metronidazole or vancomycin in 2 of 3 studies. For severe initial CDI, 2 of 3 studies found fidaxomicin to be the most cost-effective therapy. For recurrent CDI, fidaxomicin was cost-effective in 3 of 5 studies, while fecal microbiota transplantation (FMT) by colonoscopy was consistently cost-effective in 4 of 4 studies. CONCLUSIONS The cost-effectiveness of fidaxomicin compared with other pharmacologic therapies was not definitive for either initial or recurrent CDI. Despite its high cost, FMT by colonoscopy may be a cost-effective therapy for recurrent CDI. A consensus on model design and assumptions are necessary for future comparison of CDI treatment. Infect Control Hosp Epidemiol 2018;39:412-424.

Central Diabetes Insipidus in Infancy With or Without Hypothalamic Adipsic Hypernatremia Syndrome: Early Identification and Outcome.

PubMed

Djermane, Adel; Elmaleh, Monique; Simon, Dominique; Poidvin, Amélie; Carel, Jean-Claude; Léger, Juliane

2016-02-01

Neonatal central diabetes insipidus (CDI) with or without adipsia is a very rare complication of various complex hypothalamic disorders. It is associated with greater morbidity and a high risk of developing both hypernatremia and hyponatremia, due to the condition itself or secondary to treatment with vasopressin analogs or fluid administration. Its outcomes have yet to be evaluated. To investigate the clinical outcomes of patients with neonatal-onset CDI or adipsic CDI with hypernatremia. All patients diagnosed with neonatal CDI in a university hospital-based observational study and followed between 2005 and 2015 were included and analyzed retrospectively. The various causes of CDI were grouped. Clinical outcome and comorbidities were analyzed. Ten of the 12 patients had an underlying condition with brain malformations: optic nerve hypoplasia (n = 3), septo-optic dysplasia (n = 2), semilobar holoprosencephaly (n = 1), ectopic neurohypophysis (n = 3), and unilateral absence of the internal carotid artery (n = 1). The other two were idiopathic cases. During the median follow-up period of 7.8 (4.9-16.8) years, all but one patient displayed anterior pituitary deficiency. Transient CDI was found in three (25%) patients for whom a posterior pituitary hyperintense signal was observed with (n = 2) and without (n = 1) structural hypothalamic pituitary abnormalities, and with no other underlying cerebral malformations. Patients with permanent CDI with persistent adipsia (n = 4) and without adipsia (n = 5) required adequate fluid intake and various doses of desamino-D-arginine-8-vasopressin. Those with adipsia were more likely to develop hypernatremia (45 vs 33%), hyponatremia (16 vs 4%) (P < .0001), and severe neurodevelopmental delay (P < .05) than those without adipsia. Comorbidities were common. The underlying cause remains unknown at the age of 23 years for one patient with CDI and normal thirst. Neonatal CDI may be transient or permanent. These vulnerable patients have high rates of comorbidity and require careful monitoring.

Modelling the factor structure of the Child Depression Inventory in a population of apparently healthy adolescents in Nigeria.

PubMed

Olorunju, Samson Bamidele; Akpa, Onoja Matthew; Afolabi, Rotimi Felix

2018-01-01

Childhood and adolescent depression is common and often persists into adulthood with negative implications for school performances, peer relationship and behavioural functioning. The Child Depression Inventory (CDI) has been used to assess depression among adolescents in many countries including Nigeria but it is uncertain if the theoretical structure of CDI appropriately fits the experiences of adolescents in Nigeria. This study assessed varying theoretical modelling structure of the CDI in a population of apparently healthy adolescents in Benue state, Nigeria. Data was extracted on CDI scale and demographic information from a total of 1, 963 adolescents (aged 10-19 years), who participated in a state wide study assessing adolescent psychosocial functioning. In addition to descriptive statistics and reliability tests, Exploratory Factor Analysis (EFA) and Confirmatory Factor analysis (CFA) were used to model the underlying factor structure and its adequacy. The suggested new model was compared with existing CDI models as well as the CDI's original theoretical model. A model is considered better, if it has minimum Root Mean Square Error of Approximation (RMSEA<0.05), Minimum value of Discrepancy (CMIN/DF<3.0) and Akaike information criteria. All analyses were performed at 95% confidence level, using the version 21 of AMOS and the R software. Participants were 14.7±2.1 years and mostly male (54.3%), from Monogamous homes (67.9%) and lived in urban areas (52.2%). The measure of the overall internal consistency of the 2-factor CDI was α = 0.84. The 2-factor model had the minimum RMSEA (0.044), CMIN/DF (2.87) and least AIC (1037.996) compared to the other five CDI models. The child depression inventory has a 2-factor structure in a non-clinical general population of adolescents in Nigeria. Future use of the CDI in related setting may consider the 2-factor model.

Correlation between hospital-level antibiotic consumption and incident health care facility-onset Clostridium difficile infection.

PubMed

Crew, Page E; Rhodes, Nathaniel J; O'Donnell, J Nicholas; Miglis, Cristina; Gilbert, Elise M; Zembower, Teresa R; Qi, Chao; Silkaitis, Christina; Sutton, Sarah H; Scheetz, Marc H

2018-03-01

The purpose of this single-center, ecologic study is to characterize the relationship between facility-wide (FacWide) antibiotic consumption and incident health care facility-onset Clostridium difficile infection (HO-CDI). FacWide antibiotic consumption and incident HO-CDI were tallied on a monthly basis and standardized, from January 2013 through April 2015. Spearman rank-order correlation coefficients were calculated using matched-months analysis and a 1-month delay. Regression analyses were performed, with P < .05 considered statistically significant. FacWide analysis identified a matched-months correlation between ceftriaxone and HO-CDI (ρ = 0.44, P = .018). A unit of stem cell transplant recipients did not have significant correlation between carbapenems and HO-CDI in matched months (ρ = 0.37, P = .098), but a significant correlation was observed when a 1-month lag was applied (ρ = 0.54, P = .014). Three statistically significant lag associations were observed between FacWide/unit-level antibiotic consumption and HO-CDI, and 1 statistically significant nonlagged association was observed FacWide. Antibiotic consumption may convey extended ward-level risk for incident CDI. Consumption of antibiotic agents may have immediate and prolonged influence on incident CDI. Additional studies are needed to investigate the immediate and delayed associations between antibiotic consumption and C difficile colonization, infection, and transmission at the hospital level. Published by Elsevier Inc.

Accurate determination of segmented X-ray detector geometry

PubMed Central

Yefanov, Oleksandr; Mariani, Valerio; Gati, Cornelius; White, Thomas A.; Chapman, Henry N.; Barty, Anton

2015-01-01

Recent advances in X-ray detector technology have resulted in the introduction of segmented detectors composed of many small detector modules tiled together to cover a large detection area. Due to mechanical tolerances and the desire to be able to change the module layout to suit the needs of different experiments, the pixels on each module might not align perfectly on a regular grid. Several detectors are designed to permit detector sub-regions (or modules) to be moved relative to each other for different experiments. Accurate determination of the location of detector elements relative to the beam-sample interaction point is critical for many types of experiment, including X-ray crystallography, coherent diffractive imaging (CDI), small angle X-ray scattering (SAXS) and spectroscopy. For detectors with moveable modules, the relative positions of pixels are no longer fixed, necessitating the development of a simple procedure to calibrate detector geometry after reconfiguration. We describe a simple and robust method for determining the geometry of segmented X-ray detectors using measurements obtained by serial crystallography. By comparing the location of observed Bragg peaks to the spot locations predicted from the crystal indexing procedure, the position, rotation and distance of each module relative to the interaction region can be refined. We show that the refined detector geometry greatly improves the results of experiments. PMID:26561117

The morbidity, mortality, and costs associated with Clostridium difficile infection.

PubMed

Kwon, Jennie H; Olsen, Margaret A; Dubberke, Erik R

2015-03-01

Clostridium difficile infection (CDI) is the most common cause of infectious health care-associated diarrhea and is a major burden to patients and the health care system. The incidence and severity of CDI remain at historically high levels. This article reviews the morbidity, mortality, and costs associated with CDI. Copyright © 2015 Elsevier Inc. All rights reserved.

The Use of the Internet in Collecting CDI Data -- An Example from Norway

ERIC Educational Resources Information Center

Kristoffersen, Kristian E.; Simonsen, Hanne Gram; Bleses, Dorthe; Wehberg, Sonja; Jorgensen, Rune Norgard; Eiesland, Eli Anne; Henriksen, Laila Yvonne

2013-01-01

This article presents the methodology used in a population-based study of early communicative development in Norwegian children using an adaptation of the MacArthur-Bates communicative development inventories (CDI), comprising approximately 6500 children aged between 0 ; 8 and 3 ; 0. To our knowledge, this is the first CDI study collecting data…

Definition of a CDI metadata profile and its ISO 19139 based encoding

NASA Astrophysics Data System (ADS)

Boldrini, Enrico; de Korte, Arjen; Santoro, Mattia; Schaap, Dick M. A.; Nativi, Stefano; Manzella, Giuseppe

2010-05-01

The Common Data Index (CDI) is the middleware service adopted by SeaDataNet for discovery and query. The primary goal of the EU funded project SeaDataNet is to develop a system which provides transparent access to marine data sets and data products from 36 countries in and around Europe. The European context of SeaDataNet requires that the developed system complies with European Directive INSPIRE. In order to assure the required conformity a GI-cat based solution is proposed. GI-cat is a broker service able to mediate from different metadata sources and publish them through a consistent and unified interface. In this case GI-cat is used as a front end to the SeaDataNet portal publishing the original data, based on CDI v.1 XML schema, through an ISO 19139 application profile catalog interface (OGC CSW AP ISO). The choice of ISO 19139 is supported and driven by INSPIRE Implementing Rules, that have been used as a reference through the whole development process. A mapping from the CDI data model to the ISO 19139 was hence to be implemented in GI-cat and a first draft quickly developed, as both CDI v.1 and ISO 19139 happen to be XML implementations based on the same abstract data model (standard ISO 19115 - metadata about geographic information). This first draft mapping pointed out the CDI metadata model differences with respect to ISO 19115, as it was not possible to accommodate all the information contained in CDI v.1 into ISO 19139. Moreover some modifications were needed in order to reach INSPIRE compliance. The consequent work consisted in the definition of the CDI metadata model as a profile of ISO 19115. This included checking of all the metadata elements present in CDI and their cardinality. A comparison was made with respect to ISO 19115 and possible extensions were individuated. ISO 19139 was then chosen as a natural XML implementation of this new CDI metadata profile. The mapping and the profile definition processes were iteratively refined leading up to a complete mapping from the CDI data model to ISO 19139. Several issues were faced during the definition process. Among these: dynamic lists and vocabularies used by SeaDataNet could not be easily accommodated in ISO 19139, time resolution information from CDI v.1 was also difficult to accommodate, ambiguities both in the ISO 19139 specification and in the INSPIRE regulations (e.g. regarding to the bounding polygon, the language and the role of the responsible party). Another outcome of this process is the set up of conventions regarding the protocol formats to be used for a useful machine to machine data access. Changes to the original ISO 19139 schema were at the maximum extent avoided because of practical reasons within SeaDataNet: additional constraint required by the profile have been defined and will be checked by the use of Schematron or other validation mechanisms. The achieved mapping was finally ready to be integrated in GI-cat by implementation of a new accessor component for CDI. These type of components play the role of data model mediators within GI-cat framework. The new defined profile and its implementation will also be used within SeaDataNet as a replacement of the current data model implementation (CDI v.1).

Implementation of Global Strategies to Prevent Hospital-Onset Clostridium difficile Infection: Targeting Proton Pump Inhibitors and Probiotics.

PubMed

Lewis, Paul O; Lundberg, Timothy S; Tharp, Jennifer L; Runnels, Clay W

2017-10-01

Proton pump inhibitors (PPIs) have been identified as a significant risk factor for the development of Clostridium difficile infection (CDI). Probiotics given concurrently with antibiotics have been shown to have a moderate impact on preventing CDI. To evaluate the effectiveness of hospital-wide interventions designed to reduce PPI use and increase probiotics and whether these interventions were associated with a change in the incidence of hospital onset (HO)-CDI. This retrospective cohort study compared 2 fiscal years: July 2013 to June 2014 (FY14) and July 2014 to June 2015 (FY15). In July of FY15, global educational initiatives were launched targeting PPIs. Additionally, a HO-CDI prevention bundle was added to antibiotic-containing order sets targeting probiotics. Overall PPI use, probiotic use, and incidence of HO-CDI were recorded and compared for each cohort. Charts were also reviewed for patients who developed HO-CDI for the presence and appropriateness of a PPI and presence of probiotics. The interventions resulted in a decrease in PPI use by 14% or 96 doses/1000 patient days (TPD; P = 0.0002) and a reduction in IV PPI use by 31% or 71 doses/TPD ( P = 0.0008). Probiotic use increased by 130% or 126 doses/TPD ( P = 0.0006). The incidence of HO-CDI decreased by 20% or 0.1 cases/TPD ( P = 0.04). A collaborative, multifaceted educational initiative directed at highlighting the risks associated with PPI use was effective in reducing PPI prescribing. The implementation of a probiotic bundle added to antibiotic order sets was effective in increasing probiotic use. These interventions were associated with a decrease in incidence of HO-CDI.

Cost-effectiveness of Competing Strategies for Management of Recurrent Clostridium difficile Infection: A Decision Analysis

PubMed Central

Konijeti, Gauree G.; Sauk, Jenny; Shrime, Mark G.; Gupta, Meera; Ananthakrishnan, Ashwin N.

2014-01-01

Background. Clostridium difficile infection (CDI) is an important cause of morbidity and healthcare costs, and is characterized by high rates of disease recurrence. The cost-effectiveness of newer treatments for recurrent CDI has not been examined, yet would be important to inform clinical practice. The aim of this study was to analyze the cost effectiveness of competing strategies for recurrent CDI. Methods. We constructed a decision-analytic model comparing 4 treatment strategies for first-line treatment of recurrent CDI in a population with a median age of 65 years: metronidazole, vancomycin, fidaxomicin, and fecal microbiota transplant (FMT). We modeled up to 2 additional recurrences following the initial recurrence. We assumed FMT delivery via colonoscopy as our base case, but conducted sensitivity analyses based on different modes of delivery. Willingness-to-pay threshold was set at $50 000 per quality-adjusted life-year. Results. At our base case estimates, initial treatment of recurrent CDI using FMT colonoscopy was the most cost-effective strategy, with an incremental cost-effectiveness ratio of $17 016 relative to oral vancomycin. Fidaxomicin and metronidazole were both dominated by FMT colonoscopy. On sensitivity analysis, FMT colonoscopy remained the most cost-effective strategy at cure rates >88.4% and CDI recurrence rates <14.9%. Fidaxomicin required a cost <$1359 to meet our cost-effectiveness threshold. In clinical settings where FMT is not available or applicable, the preferred strategy appears to be initial treatment with oral vancomycin. Conclusions. In this decision analysis examining treatment strategies for recurrent CDI, we demonstrate that FMT colonoscopy is the most cost-effective initial strategy for management of recurrent CDI. PMID:24692533

Clinical and economic burden of Clostridium difficile infection in Europe: a systematic review of healthcare-facility-acquired infection.

PubMed

Wiegand, P N; Nathwani, D; Wilcox, M H; Stephens, J; Shelbaya, A; Haider, S

2012-05-01

PubMed, EMBASE and conference abstracts were reviewed systematically to determine the clinical and economic burden associated with Clostridium difficile infection (CDI) acquired and treated in European healthcare facilities. Inclusion criteria were: published in the English language between 2000 and 2010, and study population of at least 20 patients with documented CDI acquired/treated in European healthcare facilities. Data collection was completed by three unblinded reviewers using the Cochrane Handbook and PRISMA statement. The primary outcomes were mortality, recurrence, length of hospital stay (LOS) and cost related to CDI. In total, 1138 primary articles and conference abstracts were identified, and this was narrowed to 39 and 30 studies, respectively. Data were available from 14 countries, with 47% of studies from UK institutions. CDI mortality at 30 days ranged from 2% (France) to 42% (UK). Mortality rates more than doubled from 1999 to 2004, and continued to rise until 2007 when reductions were noted in the UK. Recurrent CDI varied from 1% (France) to 36% (Ireland); however, recurrence definitions varied between studies. Median LOS ranged from eight days (Belgium) to 27 days (UK). The incremental cost of CDI was £4577 in Ireland and £8843 in Germany, after standardization to 2010 prices. Country-specific estimates, weighted by sample size, ranged from 2.8% to 29.8% for 30-day mortality and from 16 to 37 days for LOS. CDI burden in Europe was most commonly described using 30-day mortality, recurrence, LOS and cost data. The continued spread of CDI and resultant healthcare burden underscores the need for judicious use of antibiotics. Copyright © 2012 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Economic evaluation of laboratory testing strategies for hospital-associated Clostridium difficile infection.

PubMed

Schroeder, Lee F; Robilotti, Elizabeth; Peterson, Lance R; Banaei, Niaz; Dowdy, David W

2014-02-01

Clostridium difficile infection (CDI) is the most common cause of infectious diarrhea in health care settings, and for patients presumed to have CDI, their isolation while awaiting laboratory results is costly. Newer rapid tests for CDI may reduce this burden, but the economic consequences of different testing algorithms remain unexplored. We used decision analysis from the hospital perspective to compare multiple CDI testing algorithms for adult inpatients with suspected CDI, assuming patient management according to laboratory results. CDI testing strategies included combinations of on-demand PCR (odPCR), batch PCR, lateral-flow diagnostics, plate-reader enzyme immunoassay, and direct tissue culture cytotoxicity. In the reference scenario, algorithms incorporating rapid testing were cost-effective relative to nonrapid algorithms. For every 10,000 symptomatic adults, relative to a strategy of treating nobody, lateral-flow glutamate dehydrogenase (GDH)/odPCR generated 831 true-positive results and cost $1,600 per additional true-positive case treated. Stand-alone odPCR was more effective and more expensive, identifying 174 additional true-positive cases at $6,900 per additional case treated. All other testing strategies were dominated by (i.e., more costly and less effective than) stand-alone odPCR or odPCR preceded by lateral-flow screening. A cost-benefit analysis (including estimated costs of missed cases) favored stand-alone odPCR in most settings but favored odPCR preceded by lateral-flow testing if a missed CDI case resulted in less than $5,000 of extended hospital stay costs and <2 transmissions, if lateral-flow GDH diagnostic sensitivity was >93%, or if the symptomatic carrier proportion among the toxigenic culture-positive cases was >80%. These results can aid guideline developers and laboratory directors who are considering rapid testing algorithms for diagnosing CDI.

Increased hospital length of stay attributable to Clostridium difficile infection in patients with four co-morbidities: an analysis of hospital episode statistics in four European countries.

PubMed

Eckmann, Christian; Wasserman, Matthew; Latif, Faisal; Roberts, Graeme; Beriot-Mathiot, Axelle

2013-10-01

Hospital-onset Clostridium difficile infection (CDI) places a significant burden on health care systems throughout Europe, estimated at around €3 billion per annum. This burden is shared between national payers and hospitals that support additional bed days for patients diagnosed with CDI while in hospital or patients re-admitted from a previous hospitalisation. This study was performed to quantify additional hospital stay attributable to CDI in four countries, England, Germany, Spain, and The Netherlands, by analysing nationwide hospital-episode data. We focused upon patients at increased risk of CDI: with chronic obstructive pulmonary disease, heart failure, diabetes, or chronic kidney disease, and aged 50 years or over. Multivariate regression and propensity score matching models were developed to investigate the impact of CDI on additional length of hospital stay, controlling for confounding factors such as underlying disease severity. Patients in England had the longest additional hospital stay attributable to CDI at 16.09 days, followed by Germany at 15.47 days, Spain at 13.56 days, and The Netherlands at 12.58 days, derived using regression analysis. Propensity score matching indicated a higher attributable length of stay of 32.42 days in England, 15.31 days in Spain, and 18.64 days in The Netherlands. Outputs from this study consistently demonstrate that in European countries, for patients whose hospitalisation is complicated by CDI, the infection causes a statistically significant increase in hospital length of stay. This has implications for optimising resource allocation and budget setting at both the national and hospital level to ensure that levels of CDI-complicated hospitalisations are minimised.

Cost-effectiveness analysis of fidaxomicin versus vancomycin in Clostridium difficile infection

PubMed Central

Nathwani, Dilip; Cornely, Oliver A.; Van Engen, Anke K.; Odufowora-Sita, Olatunji; Retsa, Peny; Odeyemi, Isaac A. O.

2014-01-01

Objectives Fidaxomicin was non-inferior to vancomycin with respect to clinical cure rates in the treatment of Clostridium difficile infections (CDIs) in two Phase III trials, but was associated with significantly fewer recurrences than vancomycin. This economic analysis investigated the cost-effectiveness of fidaxomicin compared with vancomycin in patients with severe CDI and in patients with their first CDI recurrence. Methods A 1 year time horizon Markov model with seven health states was developed from the perspective of Scottish public healthcare providers. Model inputs for effectiveness, resource use, direct costs and utilities were obtained from published sources and a Scottish expert panel. The main model outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY), for fidaxomicin versus vancomycin; ICERs were interpreted using willingness-to-pay thresholds of £20 000/QALY and £30 000/QALY. One-way and probabilistic sensitivity analyses were performed. Results Total costs were similar with fidaxomicin and vancomycin in patients with severe CDI (£14 515 and £14 344, respectively) and in patients with a first recurrence (£16 535 and £16 926, respectively). Improvements in clinical outcomes with fidaxomicin resulted in small QALY gains versus vancomycin (severe CDI, +0.010; patients with first recurrence, +0.019). Fidaxomicin was cost-effective in severe CDI (ICER £16 529/QALY) and dominant (i.e. more effective and less costly) in patients with a first recurrence. The probability that fidaxomicin was cost-effective at a willingness-to-pay threshold of £30 000/QALY was 60% for severe CDI and 68% in a first recurrence. Conclusions Fidaxomicin is cost-effective in patients with severe CDI and in patients with a first CDI recurrence versus vancomycin. PMID:25096079

A Systematic Literature Review of Economic Evaluations of Antibiotic Treatments for Clostridium difficile Infection.

PubMed

Burton, Hannah E; Mitchell, Stephen A; Watt, Maureen

2017-11-01

Clostridium difficile infection (CDI) is associated with high management costs, particularly in recurrent cases. Fidaxomicin treatment results in lower recurrence rates than vancomycin and metronidazole, but has higher acquisition costs in Europe and the USA. This systematic literature review summarises economic evaluations (EEs) of fidaxomicin, vancomycin and metronidazole for treatment of CDI. Electronic databases (MEDLINE ® , Embase, Cochrane Library) and conference proceedings (ISPOR, ECCMID, ICAAC and IDWeek) were searched for publications reporting EEs of fidaxomicin, vancomycin and/or metronidazole in the treatment of CDI. Reference bibliographies of identified manuscripts were also reviewed. Cost-effectiveness was evaluated according to the overall population of patients with CDI, as well as in subgroups with severe CDI or recurrent CDI, or those at higher risk of recurrence or mortality. Overall, 27 relevant EEs, conducted from the perspective of 12 different countries, were identified. Fidaxomicin was cost-effective versus vancomycin and/or metronidazole in 14 of 24 EEs (58.3%), vancomycin was cost-effective versus fidaxomicin and/or metronidazole in five of 27 EEs (18.5%) and metronidazole was cost-effective versus fidaxomicin and/or vancomycin in two of 13 EEs (15.4%). Fidaxomicin was cost-effective versus vancomycin in most of the EEs evaluating specific patient subgroups. Key cost-effectiveness drivers were cure rate, recurrence rate, time horizon, drug costs and length and cost of hospitalisation. In most EEs, fidaxomicin was demonstrated to be cost-effective versus metronidazole and vancomycin in patients with CDI. These results have relevance to clinical practice, given the high budgetary impact of managing CDI and increasing restrictions on healthcare budgets. This analysis was initiated and funded by Astellas Pharma Inc.

A mathematical model of Clostridium difficile transmission in medical wards and a cost-effectiveness analysis comparing different strategies for laboratory diagnosis and patient isolation.

PubMed

Schechner, Vered; Carmeli, Yehuda; Leshno, Moshe

2017-01-01

Clostridium difficile infection (CDI) is a common and potentially fatal healthcare-associated infection. Improving diagnostic tests and infection control measures may prevent transmission. We aimed to determine, in resource-limited settings, whether it is more effective and cost-effective to allocate resources to isolation or to diagnostics. We constructed a mathematical model of CDI transmission based on hospital data (9 medical wards, 350 beds) between March 2010 and February 2013. The model consisted of three compartments: susceptible patients, asymptomatic carriers and CDI patients. We used our model results to perform a cost-effectiveness analysis, comparing four strategies that were different combinations of 2 test methods (the two-step test and uniform PCR) and 2 infection control measures (contact isolation in multiple-bed rooms or single-bed rooms/cohorting). For each strategy, we calculated the annual cost (of CDI diagnosis and isolation) for a decrease of 1 in the average daily number of CDI patients; the strategy of the two-step test and contact isolation in multiple-bed rooms was the reference strategy. Our model showed that the average number of CDI patients increased exponentially as the transmission rate increased. Improving diagnosis by adopting uniform PCR assay reduced the average number of CDI cases per day per 350 beds from 9.4 to 8.5, while improving isolation by using single-bed rooms reduced the number to about 1; the latter was cost saving. CDI can be decreased by better isolation and more sensitive laboratory methods. From the hospital perspective, improving isolation is more cost-effective than improving diagnostics.

Economic burden of Clostridium difficile in five hospitals of the Florence health care system in Italy.

PubMed

Poli, Anna; Di Matteo, Sergio; Bruno, Giacomo M; Fornai, Enrica; Valentino, Maria Chiara; Colombo, Giorgio L

2015-01-01

Despite the awareness about the increasing rates of Clostridium difficile infection (CDI) and the economic burden arising from its management (prolonged hospitalization, laboratory tests, visits, surgical treatment, environmental sanitation), few studies are available in Italy on the economic costs directly attributable to the CDI. The Florence health care system has designed a study with the aim of describing the costs attributable to the CDI and defines the incremental economic burden associated with the management of this complication. We conducted a retrospective study in five hospitals of the Florence health care system. The enrolled population included all patients who were hospitalized during the year 2013 with a diagnosis of CDI. Of the 187 total cases reported in 2013, 69 patients were enrolled, for whom the main cause of hospitalization was directly attributable to CDI. We enrolled 69 patients (19 males and 50 females), with a mean age of 82.16 years (minimum 46 to maximum 98). The total number of hospitalization days observed was 886 (12.8 per patient on average). The data from this study show that the mean total incremental cost for a patient with CDI was €3,270.52 per year. The hospital stay length is the most significant cost parameter, having the largest influence on the overall costs, with an impact of 87% on the total cost. The results confirm the costs for the management of CDI in five hospitals of the Florence health care system are in line with data from the international literature. The economic impact of CDI is most evident in the extension of the duration of hospitalization and emergency recurrences requiring new therapeutic options with the need to develop and implement new diagnostic and therapeutic algorithms in clinical practice.

Clinical and economic benefits of fidaxomicin compared to vancomycin for Clostridium difficile infection.

PubMed

Gallagher, Jason C; Reilly, Joseph P; Navalkele, Bhagyashri; Downham, Gemma; Haynes, Kevin; Trivedi, Manish

2015-11-01

We studied the clinical and economic impact of a protocol encouraging the use of fidaxomicin as a first-line drug for treatment of Clostridium difficile infection (CDI) in patients hospitalized during a 2-year period. This study evaluated patients who received oral vancomycin or fidaxomicin for the treatment of CDI during a 2-year period. All included patients were eligible for administration of fidaxomicin via a protocol that encouraged its use for selected patients. The primary clinical endpoint was 90-day readmission with a diagnosis of CDI. Hospital charges and insurance reimbursements for readmissions were calculated along with the cost of CDI therapy to estimate the financial impact of the choice of therapy. Recurrences were seen in 10/49 (20.4%) fidaxomicin patients and 19/46 (41.3%) vancomycin patients (P = 0.027). In a multivariate analysis that included determinations of severity of CDI, serum creatinine increases, and concomitant antibiotic use, only fidaxomicin was significantly associated with decreased recurrence (adjusted odds ratio [aOR], 0.33; 95% confidence interval [CI], 0.12 to 0.93). The total lengths of stay of readmitted patients were 183 days for vancomycin and 87 days for fidaxomicin, with costs of $454,800 and $196,200, respectively. Readmissions for CDI were reimbursed on the basis of the severity of CDI, totaling $151,136 for vancomycin and $107,176 for fidaxomicin. Fidaxomicin drug costs totaled $62,112, and vancomycin drug costs were $6,646. We calculated that the hospital lost an average of $3,286 per fidaxomicin-treated patient and $6,333 per vancomycin-treated patient, thus saving $3,047 per patient with fidaxomicin. Fidaxomicin use for CDI treatment prevented readmission and decreased hospital costs compared to use of oral vancomycin. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Molecular characteristics of Clostridium difficile strains from patients with a first recurrence more than 8 weeks after the primary infection.

PubMed

Chen, Yijian; Rashid, Mamun Ur; Huang, Haihui; Fang, Hong; Nord, Carl Erik; Wang, Minggui; Weintraub, Andrej

2017-08-01

Nearly all published studies of recurrent Clostridium difficile infections (CDI) report recurrent CDI within 8 weeks after the primary infection. This study explored the molecular characteristics of C. difficile isolates from the first recurrent CDI more than 8 weeks after the primary infection. Consecutive hospitalized patients with a recurrent CDI more than 8 weeks after a primary infection were enrolled prospectively from January 2008 to February 2011. All C. difficile isolates of the primary and recurrent infections were collected and subjected to polymerase chain reaction ribotyping and antimicrobial susceptibility testing. There were 62 cases of CDI in this study, which included 32 cases (51.6%) of recurrence due to the same ribotype of C. difficile, 26 (41.9%) cases due to a different ribotype, and four (6.5%) cases with 2-4 recurrences due to the same or different strains. One hundred and forty C. difficile isolates were obtained, which included 62 primary CDI isolates and 78 recurrent isolates. Ribotype 020 was the most common C. difficile strain in primary and recurrent infections. Ribotype 001 accounted for 15.4% (10/78) of recurrent infections and 3.2% (2/62) of primary infections (p = 0.0447). The minimum inhibitory concentration at 90% (MIC 90 ) values of linezolid, moxifloxacin, and clindamycin against type 001 strains were much higher, compared to the three other common ribotypes. Recurrent CDI more than 8 weeks after a primary infection can be caused by the same or different C. difficile ribotype at similar percentages. Ribotype 001 C. difficile strains, which have a lower susceptibility to antimicrobials, were isolated more frequently in patients with a recurrent CDI. Copyright © 2015. Published by Elsevier B.V.

Economic burden of Clostridium difficile in five hospitals of the Florence health care system in Italy

PubMed Central

Poli, Anna; Di Matteo, Sergio; Bruno, Giacomo M; Fornai, Enrica; Valentino, Maria Chiara; Colombo, Giorgio L

2015-01-01

Introduction Despite the awareness about the increasing rates of Clostridium difficile infection (CDI) and the economic burden arising from its management (prolonged hospitalization, laboratory tests, visits, surgical treatment, environmental sanitation), few studies are available in Italy on the economic costs directly attributable to the CDI. The Florence health care system has designed a study with the aim of describing the costs attributable to the CDI and defines the incremental economic burden associated with the management of this complication. Methods We conducted a retrospective study in five hospitals of the Florence health care system. The enrolled population included all patients who were hospitalized during the year 2013 with a diagnosis of CDI. Of the 187 total cases reported in 2013, 69 patients were enrolled, for whom the main cause of hospitalization was directly attributable to CDI. Results We enrolled 69 patients (19 males and 50 females), with a mean age of 82.16 years (minimum 46 to maximum 98). The total number of hospitalization days observed was 886 (12.8 per patient on average). The data from this study show that the mean total incremental cost for a patient with CDI was €3,270.52 per year. The hospital stay length is the most significant cost parameter, having the largest influence on the overall costs, with an impact of 87% on the total cost. The results confirm the costs for the management of CDI in five hospitals of the Florence health care system are in line with data from the international literature. Conclusion The economic impact of CDI is most evident in the extension of the duration of hospitalization and emergency recurrences requiring new therapeutic options with the need to develop and implement new diagnostic and therapeutic algorithms in clinical practice. PMID:26604846

A mathematical model of Clostridium difficile transmission in medical wards and a cost-effectiveness analysis comparing different strategies for laboratory diagnosis and patient isolation

PubMed Central

Carmeli, Yehuda; Leshno, Moshe

2017-01-01

Background Clostridium difficile infection (CDI) is a common and potentially fatal healthcare-associated infection. Improving diagnostic tests and infection control measures may prevent transmission. We aimed to determine, in resource-limited settings, whether it is more effective and cost-effective to allocate resources to isolation or to diagnostics. Methods We constructed a mathematical model of CDI transmission based on hospital data (9 medical wards, 350 beds) between March 2010 and February 2013. The model consisted of three compartments: susceptible patients, asymptomatic carriers and CDI patients. We used our model results to perform a cost-effectiveness analysis, comparing four strategies that were different combinations of 2 test methods (the two-step test and uniform PCR) and 2 infection control measures (contact isolation in multiple-bed rooms or single-bed rooms/cohorting). For each strategy, we calculated the annual cost (of CDI diagnosis and isolation) for a decrease of 1 in the average daily number of CDI patients; the strategy of the two-step test and contact isolation in multiple-bed rooms was the reference strategy. Results Our model showed that the average number of CDI patients increased exponentially as the transmission rate increased. Improving diagnosis by adopting uniform PCR assay reduced the average number of CDI cases per day per 350 beds from 9.4 to 8.5, while improving isolation by using single-bed rooms reduced the number to about 1; the latter was cost saving. Conclusions CDI can be decreased by better isolation and more sensitive laboratory methods. From the hospital perspective, improving isolation is more cost-effective than improving diagnostics. PMID:28187144

Economic Evaluation of Laboratory Testing Strategies for Hospital-Associated Clostridium difficile Infection

PubMed Central

Robilotti, Elizabeth; Peterson, Lance R.; Banaei, Niaz; Dowdy, David W.

2014-01-01

Clostridium difficile infection (CDI) is the most common cause of infectious diarrhea in health care settings, and for patients presumed to have CDI, their isolation while awaiting laboratory results is costly. Newer rapid tests for CDI may reduce this burden, but the economic consequences of different testing algorithms remain unexplored. We used decision analysis from the hospital perspective to compare multiple CDI testing algorithms for adult inpatients with suspected CDI, assuming patient management according to laboratory results. CDI testing strategies included combinations of on-demand PCR (odPCR), batch PCR, lateral-flow diagnostics, plate-reader enzyme immunoassay, and direct tissue culture cytotoxicity. In the reference scenario, algorithms incorporating rapid testing were cost-effective relative to nonrapid algorithms. For every 10,000 symptomatic adults, relative to a strategy of treating nobody, lateral-flow glutamate dehydrogenase (GDH)/odPCR generated 831 true-positive results and cost $1,600 per additional true-positive case treated. Stand-alone odPCR was more effective and more expensive, identifying 174 additional true-positive cases at $6,900 per additional case treated. All other testing strategies were dominated by (i.e., more costly and less effective than) stand-alone odPCR or odPCR preceded by lateral-flow screening. A cost-benefit analysis (including estimated costs of missed cases) favored stand-alone odPCR in most settings but favored odPCR preceded by lateral-flow testing if a missed CDI case resulted in less than $5,000 of extended hospital stay costs and <2 transmissions, if lateral-flow GDH diagnostic sensitivity was >93%, or if the symptomatic carrier proportion among the toxigenic culture-positive cases was >80%. These results can aid guideline developers and laboratory directors who are considering rapid testing algorithms for diagnosing CDI. PMID:24478478

Binary toxin and its clinical importance in Clostridium difficile infection, Belgium.

PubMed

Pilate, T; Verhaegen, J; Van Ranst, M; Saegeman, V

2016-11-01

Binary toxin-producing Clostridium difficile strains such as ribotypes 027 and 078 have been associated with increased Clostridium difficile infection (CDI) severity. Our objective was to investigate the association between presence of the binary toxin gene and CDI severity and recurrence. We performed a laboratory-based retrospective study including patients between January 2013 and March 2015 whose fecal samples were analyzed by polymerase chain reaction (PCR) for the presence of the genes for toxin B and binary toxin and a deletion in the tcdC gene, specific for ribotype 027. Clinical and epidemiological characteristics were compared between 33 binary toxin-positive CDI patients and 33 binary toxin-negative CDI patients. Subsequently, the characteristics of 66 CDI patients were compared to those of 66 diarrhea patients who were carriers of non-toxigenic C. difficile strains. Fifty-nine of 1034 (5.7 %) fecal samples analyzed by PCR were binary toxin-positive, belonging to 33 different patients. No samples were positive for ribotype 027. Binary toxin-positive CDI patients did not differ from binary toxin-negative CDI patients in terms of disease recurrence, morbidity, or mortality, except for a higher peripheral leukocytosis in the binary toxin-positive group (16.30 × 10 9 /L vs. 11.65 × 10 9 /L; p = 0.02). The second part of our study showed that CDI patients had more severe disease, but not a higher 30-day mortality rate than diarrhea patients with a non-toxicogenic C. difficile strain. In our setting with a low prevalence of ribotype 027, the presence of the binary toxin gene is not associated with poor outcome.

The Usefulness of M-B CDI-K Short Form as Screening Test in Children With Language Developmental Delay.

PubMed

Kim, Seong Woo; Jeon, Ha Ra; Park, Eun Ji; Kim, Hyo In; Jung, Da Wa; Woo, Mee Ryung

2014-06-01

To investigate the usefulness of MacArthur-Bates Communicative Development Inventories-Korean (M-B CDI-K) short form as a screening test in children with language developmental delay. From April 2010 to May 2012, a total of 87 patients visited the department of physical medicine and rehabilitation of National Health Insurance Service Ilsan Hospital with the complaint of language developmental delay and were enrolled in this study. All patients took M-B CDI-K short form and Sequenced Language Scale for Infants (SELSI) or Preschool Receptive-Expressive Language Scale (PRES) according to their age. The study group consisted of 58 male patients and 29 female patients and the mean age was 25.9 months. The diagnosis are global developmental delay in 26 patients, selective language impairment in 31 patients, articulation disorder in 7 patients, cerebral palsy in 8 patients, autism spectrum disorder in 4 patients, motor developmental delay in 4 patients, and others in 7 patients. Seventy-one patients are diagnosed with language developmental delay in SELSI or PRES and of them showed 69 patients a high risk in the M-B CDI-K short form. Sixteen patients are normal in SELSI or PRES and of them showed 14 patients non-high risk in the M-B CDI-K short form. The M-B CDI-K short form has 97.2% sensitivity, 87.5% specificity, a positive predictive value of 0.97, and a negative predictive value of 0.88. The M-B CDI-K short form has a high sensitivity and specificity so it is considered as an useful screening tool in children with language developmental delay. Additional researches targeting normal children will be continued to supply the specificity of the M-B CDI-K short form.

Faecal lactoferrin and calprotectin in patients with Clostridium difficile infection: a case-control study.

PubMed

Barbut, F; Gouot, C; Lapidus, N; Suzon, L; Syed-Zaidi, R; Lalande, V; Eckert, C

2017-12-01

Calprotectin and lactoferrin are released by the gastrointestinal tract in response to infection and mucosal inflammation. Our objective was to assess the usefulness of quantifying faecal lactoferrin and calprotectin concentrations in Clostridium difficile infection (CDI) patients with or without free toxins in the stools. We conducted a single-centre 22-month case-control study. Patients with a positive CDI diagnosis were compared to two control groups: group 1 = diarrhoeic patients negative for C. difficile and matched (1:1) to CDI cases on the ward location and age, and group 2 = diarrhoeic patients colonised with a non-toxigenic strain of C. difficile. Faecal lactoferrin and calprotectin concentrations in faeces were determined for patients with CDI and controls. Of 135 patients with CDI, 87 (64.4%) had a positive stool cytotoxicity assay (free toxin) and 48 (35.6%) had a positive toxigenic culture without detectable toxins in the stools. The median lactoferrin values were 26.8 μg/g, 8.0 μg/g and 15.8 μg/g in CDI patients and groups 1 and 2, respectively. The median calprotectin values were 218.0 μg/g, 111.5 μg/g and 111.3 μg/g, respectively. Among patients with CDI, faecal lactoferrin and calprotectin levels were higher in those with free toxins in their stools (39.2 vs. 10.2 μg/g, p = 0.003 and 274.0 vs. 166.0 μg/g, p = 0.051, respectively). Both faecal calprotectin and lactoferrin were higher in patients with CDI, especially in those with detectable toxin in faeces, suggesting a correlation between intestinal inflammation and toxins in stools.

European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection.

PubMed

Debast, S B; Bauer, M P; Kuijper, E J

2014-03-01

In 2009 the first European Society of Clinical Microbiology and Infection (ESCMID) treatment guidance document for Clostridium difficile infection (CDI) was published. The guideline has been applied widely in clinical practice. In this document an update and review on the comparative effectiveness of the currently available treatment modalities of CDI is given, thereby providing evidence-based recommendations on this issue. A computerized literature search was carried out to investigate randomized and non-randomized trials investigating the effect of an intervention on the clinical outcome of CDI. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) system was used to grade the strength of our recommendations and the quality of the evidence. The ESCMID and an international team of experts from 11 European countries supported the process. To improve clinical guidance in the treatment of CDI, recommendations are specified for various patient groups, e.g. initial non-severe disease, severe CDI, first recurrence or risk for recurrent disease, multiple recurrences and treatment of CDI when oral administration is not possible. Treatment options that are reviewed include: antibiotics, toxin-binding resins and polymers, immunotherapy, probiotics, and faecal or bacterial intestinal transplantation. Except for very mild CDI that is clearly induced by antibiotic usage antibiotic treatment is advised. The main antibiotics that are recommended are metronidazole, vancomycin and fidaxomicin. Faecal transplantation is strongly recommended for multiple recurrent CDI. In case of perforation of the colon and/or systemic inflammation and deteriorating clinical condition despite antibiotic therapy, total abdominal colectomy or diverting loop ileostomy combined with colonic lavage is recommended. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

Update of treatment algorithms for Clostridium difficile infection.

PubMed

Ooijevaar, R E; van Beurden, Y H; Terveer, E M; Goorhuis, A; Bauer, M P; Keller, J J; Mulder, C J J; Kuijper, E J

2018-05-01

Clostridium difficile is the leading cause of antibiotic-associated diarrhoea, both in healthcare facilities and in the community. The recurrence rate of C. difficile infection (CDI) remains high, up to 20%. Since the publication of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidance document on CDI treatment in 2014, new therapeutic approaches have been developed and tested to achieve higher sustained clinical cure in CDI. To review novel treatments and approaches for CDI, except probiotics and vaccines. We focused on new antibiotics, antibiotic inactivators, monoclonal antibodies and gut microbiota modulating therapies. A literature review was performed for clinical trials published in PubMed, Embase or Cochrane Library between January 2013 and November 2017. We analysed 28 clinical trials and identified 14 novel agents. Completed phase 2 studies were found for cadazolid, LFF571, ridinilazole and nontoxigenic C. difficile strains. Four phase 3 active comparator studies comparing vancomycin with bezlotoxumab, surotomycin (n = 2) and rifaximin have been published. Seven clinical trials for treatment of multiple recurrent CDI with faecal microbiota transplantation were analysed, describing faecal microbiota transplantation by upper or lower gastrointestinal route (n = 5) or by capsules (n = 2). Metronidazole is mentioned in the ESCMID guideline as first-line therapy, but we propose that oral vancomycin will become the first choice when antibiotic treatment for CDI is necessary. Fidaxomicin is a good alternative, especially in patients at risk of relapse. Vancomycin combined with faecal microbiota transplantation remains the primary therapy for multiple recurrent CDI. We anticipate that new medication that protects the gut microbiota will be further developed and tested to prevent CDI during antibiotic therapy. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Quality of life in the patients with central diabetes insipidus assessed by Nagasaki Diabetes Insipidus Questionnaire.

PubMed

Nozaki, Aya; Ando, Takao; Akazawa, Satoru; Satoh, Tsuyoshi; Sagara, Ikuko; Horie, Ichiro; Imaizumi, Misa; Usa, Toshiro; Yanagisawa, Robert T; Kawakami, Atsushi

2016-01-01

Central diabetes insipidus (CDI) is characterized by polyuria and polydipsia due to a deficiency of vasopressin. Currently, the treatment goal for CDI is improvement of quality of life (QOL) by desmopressin (DDAVP) without developing hyponatremia. However, there is no reliable measure for QOL in CDI patients. We evaluate our original questionnaire for QOL, consisting of 12 questions focusing on polyuria, polydipsia, and DDAVP treatment, in CDI patients who underwent a switch from nasal spray to oral disintegrating tablets of DDAVP. Twenty-five CDI patients under nasal DDAVP treatment, six with newly developed CDI, and 18 healthy individuals without known polyuric/polydipsic disorders as control subjects were enrolled. QOL scores were determined by our questionnaire at the enrollment and 3 months after the start of oral DDAVP treatment and were examined by the Wilcoxon signed-rank test. Eleven questions detected improvement in QOL. The sum of the QOL scores of the eleven questions increased from 29.2 ± 5.6 under nasal to 36.8 ± 4.5 under oral DDAVP (p < 0.001). There were no clinically relevant changes in serum levels of Na. After eliminating two questions about DDAVP treatment, the sum of QOL scores was 15.3 ± 6.5 in untreated CDI patients, 24.4 ± 5.2 in those with nasal treatment, 28.9 ± 4.9 in those with oral DDAVP, and 29.5 ± 3.6 in healthy controls. The difference among groups was significant (p < 0.05 in Steel-Dwass test) except between patients treated with oral DDAVP and healthy controls. Our questionnaire can be used to accurately assess QOL in CDI patients.

Clostridium Difficile Infection in Acute Care Hospitals: Systematic Review and Best Practices for Prevention.

PubMed

Louh, Irene K; Greendyke, William G; Hermann, Emilia A; Davidson, Karina W; Falzon, Louise; Vawdrey, David K; Shaffer, Jonathan A; Calfee, David P; Furuya, E Yoko; Ting, Henry H

2017-04-01

OBJECTIVE Prevention of Clostridium difficile infection (CDI) in acute-care hospitals is a priority for hospitals and clinicians. We performed a qualitative systematic review to update the evidence on interventions to prevent CDI published since 2009. DESIGN We searched Ovid, MEDLINE, EMBASE, The Cochrane Library, CINAHL, the ISI Web of Knowledge, and grey literature databases from January 1, 2009 to August 1, 2015. SETTING We included studies performed in acute-care hospitals. PATIENTS OR PARTICIPANTS We included studies conducted on hospitalized patients that investigated the impact of specific interventions on CDI rates. INTERVENTIONS We used the QI-Minimum Quality Criteria Set (QI-MQCS) to assess the quality of included studies. Interventions were grouped thematically: environmental disinfection, antimicrobial stewardship, hand hygiene, chlorhexidine bathing, probiotics, bundled approaches, and others. A meta-analysis was performed when possible. RESULTS Of 3,236 articles screened, 261 met the criteria for full-text review and 46 studies were ultimately included. The average quality rating was 82% according to the QI-MQCS. The most effective interventions, resulting in a 45% to 85% reduction in CDI, included daily to twice daily disinfection of high-touch surfaces (including bed rails) and terminal cleaning of patient rooms with chlorine-based products. Bundled interventions and antimicrobial stewardship showed promise for reducing CDI rates. Chlorhexidine bathing and intensified hand-hygiene practices were not effective for reducing CDI rates. CONCLUSIONS Daily and terminal cleaning of patient rooms using chlorine-based products were most effective in reducing CDI rates in hospitals. Further studies are needed to identify the components of bundled interventions that reduce CDI rates. Infect Control Hosp Epidemiol 2017;38:476-482.

Berberine blocks the relapse of Clostridium difficile infection in C57BL/6 mice after standard vancomycin treatment.

PubMed

Lv, Zhi; Peng, Guoli; Liu, Weihua; Xu, Hufeng; Su, JianRong

2015-07-01

Vancomycin is a preferred antibiotic for treating Clostridium difficile infection (CDI) and has been associated with a rate of recurrence of CDI of as high as 20% in treated patients. Recent studies have suggested that berberine, an alternative medical therapy for gastroenteritis and diarrhea, exhibits several beneficial effects, including induction of anti-inflammatory responses and restoration of the intestinal barrier function. This study investigated the therapeutic effects of berberine on preventing CDI relapse and restoring the gut microbiota in a mouse model. Berberine was administered through gavage to C57BL/6 mice with established CDI-induced intestinal injury and colitis. The disease activity index (DAI), mean relative weight, histopathology scores, and levels of toxins A and B in fecal samples were measured. An Illumina sequencing-based analysis of 16S rRNA genes was used to determine the overall structural change in the microbiota in the mouse ileocecum. Berberine administration significantly promoted the restoration of the intestinal microbiota by inhibiting the expansion of members of the family Enterobacteriaceae and counteracting the side effects of vancomycin treatment. Therapy consisting of vancomycin and berberine combined prevented weight loss, improved the DAI and the histopathology scores, and effectively decreased the mortality rate. Berberine prevented CDIs from relapsing and significantly improved survival in the mouse model of CDI. Our data indicate that a combination of berberine and vancomycin is more effective than vancomycin alone for treating CDI. One of the possible mechanisms by which berberine prevents a CDI relapse is through modulation of the gut microbiota. Although this conclusion was generated in the case of the mouse model, use of the combination of vancomycin and berberine and represent a novel therapeutic approach targeting CDI. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Creativity and diabetes education: Essentiality, impact and way forward.

PubMed

Sarda, Archana

2015-04-01

The changing diabetes in children (CDiC) program is a unique program aimed at children suffering from type 1 diabetes. The whole focus of CDiC is to provide comprehensive care including diabetes education. Various innovative and creative diabetes educational materials have been developed, which makes learning fun. Lot of diabetes camps are held at CDiC, focusing on diabetes education, experience sharing and fun activities. CDiC faces many challenges in an effort to cater to the needs of most deserving children with type 1 diabetes mellitus (T1DM) throughout the country, to provide comprehensive care including self-sufficiency, to serve children for as long as possible and to ultimately have better outcomes for all children with T1DM. The CDiC program aims to make the child more positive, secure and hopeful and initiate and strive for comprehensive diabetes care for the economically underprivileged children with T1DM.

Cecal Perforation Associated with Clostridium difficile Infection: A Case Report.

PubMed

Luthe, Sarah Kyuragi; Sato, Ryota

2017-04-01

Various complications are reported with Clostridium difficile infection (CDI), including fulminant CDI. Fulminant CDI is an underappreciated life-threatening condition associated with complications such as toxic megacolon and bowel perforation. A 79-year-old woman presented to the Emergency Department with altered mental status. She was admitted and conservatively treated for a left thalamic hemorrhage. While hospitalized, she developed watery diarrhea due to Clostridium difficile. Although metronidazole was initiated, she developed altered mental status and septic shock. Abdominal x-ray study and computed tomography revealed a significantly dilatated colon and a massive pneumoperitoneum. She underwent subtotal colectomy with a 14-day course of intravenous meropenem. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case suggests that we must be aware of the complications that CDI may present and adequately consider surgical management because early diagnosis and surgical treatment is critical to reduce the mortality of fulminant CDI. Copyright © 2016 Elsevier Inc. All rights reserved.

Optimizing the diagnostic testing of Clostridium difficile infection.

PubMed

Bouza, Emilio; Alcalá, Luis; Reigadas, Elena

2016-09-01

Clostridium difficile infection (CDI) is the leading cause of hospital-acquired diarrhea and is associated with a considerable health and cost burden. However, there is still not a clear consensus on the best laboratory diagnosis approach and a wide variation of testing methods and strategies can be encountered. We aim to review the most practical aspects of CDI diagnosis providing our own view on how to optimize CDI diagnosis. Expert commentary: Laboratory diagnosis in search of C. difficile toxins should be applied to all fecal diarrheic samples reaching the microbiology laboratory in patients > 2 years old, with or without classic risk factors for CDI. Detection of toxins either directly in the fecal sample or in the bacteria isolated in culture confirm CDI in the proper clinical setting. Nuclear Acid Assay techniques (NAAT) allow to speed up the process with epidemiological and therapeutic consequences.

Permanent Central Diabetes Insipidus as a Complication of S. pneumoniae Meningitis in the Pediatric Population.

PubMed

Statz, Hannah; Hsu, Benson S

2016-05-01

Diabetes insipidus is a rare but recognized complication of meningitis. The occurrence of diabetes insidipus has been previously attributed to Streptococcus pneumoniae (S. pneumoniae) in a handful of patients and only once within the pediatric subpopulation. We present the clinical course of a previously healthy 2-year, 8-month-old male child ultimately diagnosed with central diabetes insipidus (CDI) secondary to S. pneumoniae meningitis. Permanent CDI following S. pneumoniae meningitis is unique to our case and has not been previously described. Following the case presentation, we describe the etiology, pathophysiology, diagnosis, and treatment of CDI. The mechanism proposed for this clinical outcome is cerebral herniation for a sufficient duration and subsequent ischemia leading to the development of permanent CDI. Providers should be aware of CDI resulting from S. pneumoniae meningitis as prompt diagnosis and management may decrease the risk of permanent hypothalamo-pituitary axis damage. Copyright© South Dakota State Medical Association.

Friendship Interactions in Children with and without Depressive Symptoms: Observation of Emotion during Game-Playing Interactions and Post-Game Evaluations

ERIC Educational Resources Information Center

Rockhill, Carol M.; Fan, Ming-Yu; Katon, Wayne J.; McCauley, Elizabeth; Crick, Nicki R.; Pleck, Joseph H.

2007-01-01

This observational study supplements the strong and consistent link found between childhood depression and deficits in interpersonal functioning by examining the relationship between a high versus low score on the Children's Depression Inventory (CDI) and children's emotions when interacting with their best friends. High-CDI and low-CDI target…

A Long-Term Predictive Validity Study: Can the CDI Short Form be Used to Predict Language and Early Literacy Skills Four Years Later?

ERIC Educational Resources Information Center

Can, Dilara Deniz; Ginsburg-Block, Marika; Golinkoff, Roberta Michnick; Hirsh-Pasek, Kathryn

2013-01-01

This longitudinal study examined the predictive validity of the MacArthur Communicative Developmental Inventories-Short Form (CDI-SF), a parent report questionnaire about children's language development (Fenson, Pethick, Renda, Cox, Dale & Reznick, 2000). Data were first gathered from parents on the CDI-SF vocabulary scores for seventy-six…

The potential value of Clostridium difficile vaccine: an economic computer simulation model.

PubMed

Lee, Bruce Y; Popovich, Michael J; Tian, Ye; Bailey, Rachel R; Ufberg, Paul J; Wiringa, Ann E; Muder, Robert R

2010-07-19

Efforts are currently underway to develop a vaccine against Clostridium difficile infection (CDI). We developed two decision analytic Monte Carlo computer simulation models: (1) an Initial Prevention Model depicting the decision whether to administer C. difficile vaccine to patients at-risk for CDI and (2) a Recurrence Prevention Model depicting the decision whether to administer C. difficile vaccine to prevent CDI recurrence. Our results suggest that a C. difficile vaccine could be cost-effective over a wide range of C. difficile risk, vaccine costs, and vaccine efficacies especially, when being used post-CDI treatment to prevent recurrent disease. (c) 2010 Elsevier Ltd. All rights reserved.

The Potential Value of Clostridium difficile Vaccine: An Economic Computer Simulation Model

PubMed Central

Lee, Bruce Y.; Popovich, Michael J.; Tian, Ye; Bailey, Rachel R.; Ufberg, Paul J.; Wiringa, Ann E.; Muder, Robert R.

2010-01-01

Efforts are currently underway to develop a vaccine against Clostridium difficile infection (CDI). We developed two decision analytic Monte Carlo computer simulation models: (1) an Initial Prevention Model depicting the decision whether to administer C. difficile vaccine to patients at-risk for CDI and (2) a Recurrence Prevention Model depicting the decision whether to administer C. difficile vaccine to prevent CDI recurrence. Our results suggest that a C. difficile vaccine could be cost-effective over a wide range of C. difficile risk, vaccine costs, and vaccine efficacies especially when being used post-CDI treatment to prevent recurrent disease. PMID:20541582

Treatment of pediatric Clostridium difficile infection: a review on treatment efficacy and economic value

PubMed Central

D’Ostroph, Amanda R; So, Tsz-Yin

2017-01-01

The incidence of Clostridium difficile infection (CDI) in pediatric patients continues to rise. Most of the pediatric recommendations for CDI treatment are extrapolated from the literature and guidelines for adults. The American Academy of Pediatrics recommends oral metronidazole as the first-line treatment option for an initial CDI and the first recurrence if they are mild to moderate in severity. Oral vancomycin is recommended to be used for severe CDI and the second recurrent infection. Additional pulsed regimen of oral vancomycin, which is tapered, may increase efficacy in refractory patients. However, there is lack of large studies evaluating the use of fidaxomicin in pediatrics to know whether it could be a safe and effective treatment option for difficult-to-treat patients. Fidaxomicin is associated with higher total drug costs compared to metronidazole and vancomycin, but the literature supports its use due to a lower rate of CDI recurrence, which may result in cost savings. Further studies are warranted to evaluate the use of fidaxomicin in patients <18 years old and to understand its role in the standard of care for pediatric patients with CDI. PMID:29089778

Prevention of hospital-onset Clostridium difficile infection in the New York metropolitan region using a collaborative intervention model.

PubMed

Koll, Brian S; Ruiz, Rafael E; Calfee, David P; Jalon, Hillary S; Stricof, Rachel L; Adams, Audrey; Smith, Barbara A; Shin, Gina; Gase, Kathleen; Woods, Maria K; Sirtalan, Ismail

2014-01-01

The incidence, severity, and associated costs of Clostridium difficile (C. difficile) infection (CDI) have dramatically increased in hospitals over the past decade, indicating an urgent need for strategies to prevent transmission of C. difficile. This article describes a multifaceted collaborative approach to reduce hospital-onset CDI rates in 35 acute care hospitals in the New York metropolitan region. Hospitals participated in a comprehensive CDI reduction intervention and formed interdisciplinary teams to coordinate their efforts. Standardized clinical infection prevention and environmental cleaning protocols were implemented and monitored using checklists. Monthly data reports were provided to hospitals for facility-specific performance evaluation and comparison to aggregate data from all participants. Hospitals also participated in monthly teleconferences to review data and highlight successes, challenges, and strategies to reduce CDI. Incidence of hospital-onset CDI per 10,000 patient days was the primary outcome measure. Additionally, the incidence of nonhospital-associated, community-onset, hospital-associated, and recurrent CDIs were measured. The use of a collaborative model to implement a multifaceted infection prevention strategy was temporally associated with a significant reduction in hospital-onset CDI rates in participating New York metropolitan regional hospitals. © 2013 National Association for Healthcare Quality.

Surface functional groups in capacitive deionization with porous carbon electrodes

NASA Astrophysics Data System (ADS)

Hemmatifar, Ali; Oyarzun, Diego I.; Palko, James W.; Hawks, Steven A.; Stadermann, Michael; Santiago, Juan G.; Stanford Microfluidics Lab Team; Lawrence Livermore National Lab Team

2017-11-01

Capacitive deionization (CDI) is a promising technology for removal of toxic ions and salt from water. In CDI, an applied potential of about 1 V to pairs of porous electrodes (e.g. activated carbon) induces ion electromigration and electrostatic adsorption at electrode surfaces. Immobile surface functional groups play a critical role in the type and capacity of ion adsorption, and this can dramatically change desalination performance. We here use models and experiments to study weak electrolyte surface groups which protonate and/or depropotante based on their acid/base dissociation constants and local pore pH. Net chemical surface charge and differential capacitance can thus vary during CDI operation. In this work, we present a CDI model based on weak electrolyte acid/base equilibria theory. Our model incorporates preferential cation (anion) adsorption for activated carbon with acidic (basic) surface groups. We validated our model with experiments on custom built CDI cells with a variety of functionalizations. To this end, we varied electrolyte pH and measured adsorption of individual anionic and cationic ions using inductively coupled plasma mass spectrometry (ICP-MS) and ion chromatography (IC) techniques. Our model shows good agreement with experiments and provides a framework useful in the design of CDI control schemes.

An in silico evaluation of treatment regimens for recurrent Clostridium difficile infection

PubMed Central

Blanco, Natalia; Foxman, Betsy; Malani, Anurag N.; Zhang, Min; Walk, Seth; Rickard, Alexander H.

2017-01-01

Background Clostridium difficile infection (CDI) is a significant nosocomial infection worldwide, that recurs in as many as 35% of infections. Risk of CDI recurrence varies by ribotype, which also vary in sporulation and germination rates. Whether sporulation/germination mediate risk of recurrence and effectiveness of treatment of recurring CDI remains unclear. We aim to assess the role of sporulation/germination patterns on risk of recurrence, and the relative effectiveness of the recommended tapered/pulsing regimens using an in silico model. Methods We created a compartmental in-host mathematical model of CDI, composed of vegetative cells, toxins, and spores, to explore whether sporulation and germination have an impact on recurrence rates. We also simulated the effectiveness of three tapered/pulsed vancomycin regimens by ribotype. Results Simulations underscored the importance of sporulation/germination patterns in determining pathogenicity and transmission. All recommended regimens for recurring CDI tested were effective in reducing risk of an additional recurrence. Most modified regimens were still effective even after reducing the duration or dosage of vancomycin. However, the effectiveness of treatment varied by ribotype. Conclusion Current CDI vancomycin regimen for treating recurrent cases should be studied further to better balance associated risks and benefits. PMID:28800598

Faecal microbiota transplantation in patients with Clostridium difficile and significant comorbidities as well as in patients with new indications: A case series.

PubMed

Lahtinen, Perttu; Mattila, Eero; Anttila, Veli-Jukka; Tillonen, Jyrki; Teittinen, Matti; Nevalainen, Pasi; Salminen, Seppo; Satokari, Reetta; Arkkila, Perttu

2017-10-21

Fecal microbiota transplantation (FMT) is effective in recurrent Clostridium difficile infection (rCDI). Knowledge of the safety and efficacy of FMT treatment in immune deficient patients is scarce. FMT has been suggested as a potential method for an increasing number of new indications besides rCDI. Among our FMT-treated rCDI patients, we reviewed those with major comorbidities: two human immunodeficiency virus patients, six haemodialysis patients, two kidney transplant patients, two liver transplant patients and a patient with chronic lymphatic leukaemia. We also reviewed those treated with FMT for indications other than rCDI: Salmonella carriage (two patients), trimethylaminuria (two patients), small intestinal bacterial overgrowth (SIBO; one patient), and lymphocytic colitis (one patient), as well as a common variable immunodeficiency patient with chronic norovirus infection and ESBL-producing Escherichia coli ( E. coli ) carriage. Of the thirteen rCDI patients treated with FMT, eleven cleared the CDI. The observed adverse events were not directly attributable to FMT. Concerning the special indications, both Salmonellas and ESBL-producing E. coli were eradicated. One trimethylaminuria patient and one SIBO-patient reported a reduction of symptoms. Three patients did not experience a benefit from FMT: chronic norovirus, lymphocytic colitis and the other fish malodour syndrome. There were no reported side effects in this group. FMT appeared to be safe and effective for immunocompromised patients with rCDI. FMT showed promise for the eradication of antibiotic-resistant bacteria, but further research is warranted.

The Present Status of Fecal Microbiota Transplantation and Its Value in the Elderly.

PubMed

Cheng, Yao-Wen; Fischer, Monika

2017-09-01

PURPOSE OF REVIEW: This article will review current literature describing fecal microbiota transplantation (FMT) in the treatment of various diseases, and its potential role in elderly patients (age ≥ 65 years). Research on FMT has blossomed in the last decade and its pivotal role in the treatment of recurrent Clostridium difficile infection (CDI) has been recognized by the American College of Gastroenterology in the latest guidelines. There is also emerging evidence that FMT may be beneficial in the treatment of severe and/or complicated CDI refractory to medical therapy, resulting in decreased rates of colectomy and mortality. In the elderly, CDI is associated with markedly higher rates of mortality and colectomy; outcomes are even worse when patients have underlying inflammatory bowel disease (IBD). While the majority of patients who receive FMT for CDI are older, only a handful of studies focused specifically on FMT treatment outcomes and safety in this age group. Current data corroborate the efficacy and safety profile of FMT, while also supporting its use for recurrent, severe, and/or complicated CDI in the elderly population. FMT is recommended for the treatment of recurrent, severe, and/or complicated CDI in patients older than 65 years of age. It may be prudent to offer FMT earlier in the disease course, possibly after just the second recurrence and for the first episode of severe CDI to avert complications including colectomy and end-organ failure that elderly patients are more prone to developing.

Fecal microbiota transplantation for management of Clostridium difficile infection.

PubMed

Vaishnavi, Chetana

2014-07-01

The widespread use of antibiotics has led Clostridium difficile infection (CDI) to become a common problem with pronounced medical and economic effects. The recurrence of CDI after treatment with standard antibiotics is becoming more common with the emergence of more resistant strains of C. difficile. As CDI is an antibiotic-associated disease, further treatment with antibiotic is best avoided. As the gut flora is severely disturbed in CDI, approaches that restore the gut microbiota may become good alternative modes of CDI therapies. Fecal microbiota transplantation (FMT) is the procedure of transplantation of fecal bacteria from a healthy donor individual into a patient for restoration of the normal colonic flora. Thus, FMT helps in the eradication of C. difficile and resolution of clinical symptoms such as diarrhea, cramping, and urgency. Though this approach to treatment is not new, presently, it has become an alternative and promising way of combating infections. The procedure is not in regular use because of the time required to identify a suitable donor, the risk of introducing opportunistic pathogens, and a general patient aversion to the transplant. However, FMT is gaining popularity because of its success rate as a panacea for recurrent attacks of CDI and is being increasingly used in clinical practice. This review describes the rationale, the indications, the results, the techniques, the potential donors, the benefits as well as the complications of fecal microbiota instillation to CDI patients in order to restore the normal gut flora.

Is fidaxomicin worth the cost? An economic analysis.

PubMed

Bartsch, Sarah M; Umscheid, Craig A; Fishman, Neil; Lee, Bruce Y

2013-08-01

In May 2011, the Food and Drug Administration approved fidaxomicin for the treatment of Clostridium difficile infection (CDI). It has been found to be noninferior to vancomycin; however, its cost-effectiveness for the treatment of CDI remains undetermined. We developed a decision analytic simulation model to determine the economic value of fidaxomicin for CDI treatment from the third-party payer perspective. We looked at CDI treatment in these 3 cases: (1) no fidaxomicin, (2) only fidaxomicin, and (3) fidaxomicin based on strain typing results. The incremental cost-effectiveness ratio for fidaxomicin based on screening given current conditions was >$43.7 million per quality-adjusted life-year and using only fidaxomicin was dominated (ie, more costly and less effective) by the other 2 treatment strategies explored. The fidaxomicin strategy tended to remain dominated, even at lower costs. With approximately 50% of CDI due to the NAP1/BI/027 strain, a course of fidaxomicin would need to cost ≤$150 to be cost-effective in the treatment of all CDI cases and between $160 and $400 to be cost-effective for those with a non-NAP1/BI/027 strain (ie, treatment based on strain typing). Given the current cost and NAP1/BI/027 accounting for approximately 50% of isolates, using fidaxomicin as a first-line treatment for CDI is not cost-effective. However, typing and treatment with fidaxomicin based on strain may be more promising depending on the costs of fidaxomicin.

A microbial fuel cell driven capacitive deionization technology for removal of low level dissolved ions.

PubMed

Feng, Cuijie; Hou, Chia-Hung; Chen, Shaohua; Yu, Chang-Ping

2013-04-01

The microbial fuel cell (MFC) is an emerging technology, which uses exoelectrogenic microorganisms to oxidize organic matter in the wastewater to produce electricity. However, the low energy output limits its application in practice. Capacitive deionization (CDI), an electrochemically controlled method for deionization by the adsorption of ions in the electrical double layer region at an electrode-solution interface, requires a low external power supply. Therefore, in this study, we investigated the MFC driven CDI (MFC-CDI) technology to integrate deionization with wastewater treatment and electricity production. Taking advantage of the low potential requirement of CDI, voltage generated from a continuous flow MFC could be used to drive the CDI to achieve removal of the electrolyte to a stable status. The results indicated that among the three connection types of MFCs including single-, series-, and parallel-configuration, the parallel connection of two MFCs resulted in the highest potential (0.63V) applied to CDI and the conductivity removal of NaCl solution was more than 60%. The electrosorption capacities under different electrolyte concentrations of 50, 100 and 150 mg L(-1) were 150, 346 and 295 μg g(-1), respectively. These results suggest that the new MFC-CDI technology, which utilizes energy recovery from the wastewater, has great potential to be an energy saving technology to remove low level dissolved ions from aqueous solutions for the water and wastewater treatment processes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bloom and bust: intestinal microbiota dynamics in response to hospital exposures and Clostridium difficile colonization or infection.

PubMed

Vincent, Caroline; Miller, Mark A; Edens, Thaddeus J; Mehrotra, Sudeep; Dewar, Ken; Manges, Amee R

2016-03-14

Clostridium difficile infection (CDI) is the leading infectious cause of nosocomial diarrhea. Hospitalized patients are at increased risk of developing CDI because they are exposed to C. difficile spores through contact with the hospital environment and often receive antibiotics and other medications that can disrupt the integrity of the indigenous intestinal microbiota and impair colonization resistance. Using whole metagenome shotgun sequencing, we examined the diversity and composition of the fecal microbiota in a prospective cohort study of 98 hospitalized patients. Four patients had asymptomatic C. difficile colonization, and four patients developed CDI. We observed dramatic shifts in the structure of the gut microbiota during hospitalization. In contrast to CDI cases, asymptomatic patients exhibited elevated relative abundance of potentially protective bacterial taxa in their gut at the onset of C. difficile colonization. Use of laxatives was associated with significant reductions in the relative abundance of Clostridium and Eubacterium; species within these genera have previously been shown to enhance resistance to CDI via the production of secondary bile acids. Cephalosporin and fluoroquinolone exposure decreased the frequency of Clostridiales Family XI Incertae Sedis, a bacterial family that has been previously associated with decreased CDI risk. This study underscores the detrimental impact of antibiotics as well as other medications, particularly laxatives, on the intestinal microbiota and suggests that co-colonization with key bacterial taxa may prevent C. difficile overgrowth or the transition from asymptomatic C. difficile colonization to CDI.

Clostridium difficile Infection: Associations with Chemotherapy, Radiation Therapy, and Targeting Therapy Treatments.

PubMed

Peretz, Avi; Shlomo, Izhar Ben; Nitzan, Orna; Bonavina, Luigi; Schaffer, Pmela M; Schaffer, Moshe

2016-01-01

Although mucositis, diarrhea, and constipation as well as immunosuppression are well recognized side-effects of cancer treatment, the underlying mechanisms including changes in the composition of gut microbiota and Clostridium difficile infection have not yet been thoroughly reviewed. We herein set out to review the literature regarding the relations between cancer chemotherapy, radiation treatment, and Clostridium difficile-associated colitis. Review of the English language literature published from 2008 to 2015 on the association between cancer chemotherapy, radiation treatment, and C. difficile-associated colitis. Certain chemotherapeutic combinations, mainly those containing paclitaxel, are more likely to be followed by C. difficile infection (CDI), while some tumor types are more likely to be complicated by CDI following chemotherapy. CDI following irradiation occurs mostly in patients who were treated for cancer in the head and neck area. Risk factors found were proton pump inhibitors, antibiotics, cytostatic agents, and tube feeding. The drug of choice for an initial episode of mild-to-moderate CDI is metronidazole, whereas vancomycin is reserved for an initial episode of severe CDI. Fidaxomycin is another option for treatment of severe CDI, with fewer recurrences. The influence of CDI on the treatment of oncological patients is not fully acknowledged. Infection with C. difficile is more frequent in those patients treated by antibiotics simultaneously with chemotherapy. Aggressive supportive care with intravenous hydration, antibiotics, and close surgical monitoring for selective intervention can significantly decrease the morbidity and life-threatening complications associated with this infection.

Is Fidaxomicin Worth the Cost? An Economic Analysis

PubMed Central

Bartsch, Sarah M.; Umscheid, Craig A.; Fishman, Neil; Lee, Bruce Y.

2013-01-01

Background. In May 2011, the Food and Drug Administration approved fidaxomicin for the treatment of Clostridium difficile infection (CDI). It has been found to be noninferior to vancomycin; however, its cost-effectiveness for the treatment of CDI remains undetermined. Methods. We developed a decision analytic simulation model to determine the economic value of fidaxomicin for CDI treatment from the third-party payer perspective. We looked at CDI treatment in these 3 cases: (1) no fidaxomicin, (2) only fidaxomicin, and (3) fidaxomicin based on strain typing results. Results. The incremental cost-effectiveness ratio for fidaxomicin based on screening given current conditions was >$43.7 million per quality-adjusted life-year and using only fidaxomicin was dominated (ie, more costly and less effective) by the other 2 treatment strategies explored. The fidaxomicin strategy tended to remain dominated, even at lower costs. With approximately 50% of CDI due to the NAP1/BI/027 strain, a course of fidaxomicin would need to cost ≤$150 to be cost-effective in the treatment of all CDI cases and between $160 and $400 to be cost-effective for those with a non-NAP1/BI/027 strain (ie, treatment based on strain typing). Conclusions. Given the current cost and NAP1/BI/027 accounting for approximately 50% of isolates, using fidaxomicin as a first-line treatment for CDI is not cost-effective. However, typing and treatment with fidaxomicin based on strain may be more promising depending on the costs of fidaxomicin. PMID:23704121

All-cause mortality in hospitalized patients with infectious diarrhea: Clostridium difficile versus other enteric pathogens in Austria from 2008 to 2010.

PubMed

Schmid, D; Kuo, H W; Simons, E; Kanitz, E E; Wenisch, J; Allerberger, F; Wenisch, C

2014-01-01

Clostridium difficile infection is the leading cause of gastroenteritis-associated deaths in the industrialized world, followed by infection with norovirus. Using a cohort study design, we compared 90 inpatients with diarrhea due to C. difficile infection (CDI) with 180 inpatients with diarrhea due to other infectious agents (including 55% with norovirus infection) with respect to complications and all-cause mortality. The effects of age, severity of underlying diseases and additional infections were assessed by stratified analyses. Diarrhea recurrence occurred 8.9 (95%CI: 2.9-27.3) times more often in CDI independent of age and severity of comorbidities. The all-cause mortality in CDI patients pre-discharge and at 30 and 180 days, respectively, was 20.0%, 17.0% and 42.3% versus 7.2%, 6.7% and 22.5% in non-CDI diarrhea patients. Among those patients with low comorbidities, who were younger than 65 years and without additional infections, the all-cause pre-discharge, 30-day and 180-day mortality risks were significantly higher for the CDI diarrhea patients than the non-CDI diarrhea patients. This association was not observed among patients with an older age, more severe comorbidities or additional infections. CDI results in higher all-cause mortality than diarrhea due to other infectious agents in younger patients with low comorbidities. Copyright © 2013 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

The Effect of Lactobacillus plantarum 299v on the Incidence of Clostridium difficile Infection in High Risk Patients Treated with Antibiotics

PubMed Central

Kujawa-Szewieczek, Agata; Adamczak, Marcin; Kwiecień, Katarzyna; Dudzicz, Sylwia; Gazda, Magdalena; Więcek, Andrzej

2015-01-01

Background: Lactobacillus plantarum 299v (LP299v) has been used in order to reduce gastrointestinal symptoms during antibiotic exposure. However, it remains controversial whether or not probiotics are effective in the prevention of Clostridium difficile infections (CDI) among patients receiving antibiotics. The aim of this study was to analyze the CDI among patients receiving antibiotics and hospitalized in the period before and after starting routine use of LP299v as a prevention of this infection. Methods: Among 3533 patients hospitalized in the nephrology and transplantation ward during a two-year period, 23 patients with CDI were diagnosed and enrolled in this retrospective study. Since November 2013, prevention of CDI with oral use of LP299v was performed in all patients treated with antibiotics and who were at a high risk of developing CDI. The observation period was divided into two twelve-month intervals before and after initiation of the use of LP299v as a prophylactic against CDI. Results: A significant (p = 0.0001) reduction of the number of cases of CDI was found after routinely using LP299v (n = 2; 0.11% of all hospitalized patients) compared with the previous twelve-month period of observation (n = 21; 1.21% of all hospitalized patients). Conclusions: Routine use of LP299v during treatment with antibiotics may prevent C. difficile infection in the nephrology and transplantation ward. PMID:26690209

Norms and Screening Utility of the Dutch Version of the Children's Depression Inventory in Clinical and Nonclinical Youths

ERIC Educational Resources Information Center

Roelofs, Jeffrey; Braet, Caroline; Rood, Lea; Timbremont, Benedikte; van Vlierberghe, Leen; Goossens, Lien; van Breukelen, Gerard

2010-01-01

This study aimed to (a) assess relationships between the Children's Depression Inventory (CDI) and "DSM"-oriented depression and anxiety scales of the Youth Self Report, (b) develop reliable norms for the CDI, and (c) determine CDI cutoff scores for selecting youngsters at risk for depression and anxiety. A total of 3,073 nonclinical and…

Test Review: Kovacs, M. "Children's Depression Inventory 2 (CDI 2)" (2nd ed.). North Tonawanda, NY: Multi-Health Systems Inc, 2011

ERIC Educational Resources Information Center

Bae, Yunhee

2012-01-01

This article presents a review of the Children's Depression Inventory 2 (CDI 2), published by Multi-Health Systems (MHS) to assess depressive symptoms in 7- to 17-year-old children and adolescents. Given the importance of early diagnosis and treatment (Kovacs & Devlin, 1998), the CDI 2 can assist professionals to pinpoint critical depressive…

Experiences and perspectives of community health workers from implementing treatment for schistosomiasis using the community directed intervention strategy in an informal settlement in Kisumu City, western Kenya.

PubMed

Odhiambo, Gladys O; Musuva, Rosemary M; Odiere, Maurice R; Mwinzi, Pauline N

2016-09-15

The Community Directed Intervention (CDI) strategy has been used to conduct various health interventions in Africa, including control of Neglected Tropical Diseases (NTDs). Although the CDI approach has shown good results in the control of onchocerciasis and lymphatic filariasis with respect to treatment coverage using community drug distributors, its utility in the control of schistosomiasis among urban poor is yet to be established. Using a longitudinal qualitative study, we explored the experiences, opportunities, challenges as well as recommendations of Community Health Workers (CHWs) after participation in annual mass drug administration (MDA) activities for schistosomiasis using the CDI approach in an urban setting. Unstructured open-ended group discussions were conducted with CHWs after completion of annual MDA activities. Narratives were obtained from CHWs using a digital audio recorder during the group discussions, transcribed verbatim and translated into English where applicable. Thematic decomposition of data was done using ATLAS.ti. software, and themes explored using the principle of interpretative phenomenological analysis (IPA). From the perspective of the CHWs, opportunities for implementing CDI in urban settings, included the presence of CHWs, their supervisory structures and their knowledge of intervention areas, and opportunity to integrate MDA with other health interventions. Several challenges were mentioned with regards to implementing MDA using the CDI strategy among them lack of incentives, fear of side effects, misconceptions regarding treatment and mistrust, difficulties working in unsanitary environmental conditions, insecurity, and insufficient time. A key recommendation in promoting more effective MDA using the CDI approach was allocation of more time to the exercise. Findings from this study support the feasibility of using CDI for implementing MDA for schistosomiasis in informal settlements of urban areas. Extensive community sensitization and provision of incentives may help address the aforementioned challenges associated with implementing MDA using the CDI strategy. Opportunities highlighted in this study may be of value to other programmes that may be considering the adoption of the CDI strategy for rolling out interventions in the urban setting.

Quantitative assessment of image motion blur in diffraction images of moving biological cells

NASA Astrophysics Data System (ADS)

Wang, He; Jin, Changrong; Feng, Yuanming; Qi, Dandan; Sa, Yu; Hu, Xin-Hua

2016-02-01

Motion blur (MB) presents a significant challenge for obtaining high-contrast image data from biological cells with a polarization diffraction imaging flow cytometry (p-DIFC) method. A new p-DIFC experimental system has been developed to evaluate the MB and its effect on image analysis using a time-delay-integration (TDI) CCD camera. Diffraction images of MCF-7 and K562 cells have been acquired with different speed-mismatch ratios and compared to characterize MB quantitatively. Frequency analysis of the diffraction images shows that the degree of MB can be quantified by bandwidth variations of the diffraction images along the motion direction. The analytical results were confirmed by the p-DIFC image data acquired at different speed-mismatch ratios and used to validate a method of numerical simulation of MB on blur-free diffraction images, which provides a useful tool to examine the blurring effect on diffraction images acquired from the same cell. These results provide insights on the dependence of diffraction image on MB and allow significant improvement on rapid biological cell assay with the p-DIFC method.

The role of local and systemic cytokines in patients infected with Clostridium difficile.

PubMed

Czepiel, J; Biesiada, G; Brzozowski, T; Ptak-Belowska, A; Perucki, W; Birczynska, M; Jurczyszyn, A; Strzalka, M; Targosz, A; Garlicki, A

2014-10-01

It is widely accepted that the pathogenesis of Clostridium difficile infection (CDI) is multifactorial, dependent on pathogen virulence factors produced by the organism as well as disorders of the gastrointestinal tract, the alteration in intestinal flora and the immune response of the host. In particular, the immune response in the course of CDI and the involvement of cytokines in the pathogenesis of CDI is not fully understood. The aim of our study was to evaluate the relationship between proinflammatory and anti-inflammatory cytokines and the course of CDI in vivo. We prospectively studied 80 patients. Our study group included 40 patients aged 30-87 years (mean age 66.9 years) with CDI hospitalized at Infectious Diseases Department and Gastroenterology and Hepatology Clinic, University Hospital in Cracow, and 40 healthy volunteers aged 24-62 years (mean age 51.1 years). The serum concentrations of cytokines IL-1β, IL-6, IL-8, IL-10, tumor necrosis factor (TNF-α), myeloperoxidase (MPO), and prostaglandin E2 (PGE2) were measured using ELISA assays. Additionally, the routine biochemical parameters were assessed including the following: white blood cells with differential leukocyte count, platelets counts, and blood plasma levels of creatinine, alanine transaminase, and C-reactive protein were determined. We noted a significant increase in the concentration of the following cytokines in the CDI group when compared to the control group: IL-1b (4.7 vs. 3.6 pg/ml), IL-6 (21.0 vs. 0.04 pg/ml), IL-10 (8.5 vs. 0.5 pg/ml), TNF-α (7.1 vs. 0.09 pg/ml). In addition the serum concentration of MPO (1056.0 vs. 498.0 pg/ml), and PGE2 (2036.7 vs. 1492.0 pg/ml) showed a significant increase in CDI patients as compared with control subjects. Most CDI patients did not show any increase in the concentration of IL-8. We did observe a direct relationship between TNF-α and creatinine. The course of CDI is characterized by an initial local inflammatory process followed by a systemic inflammatory response, which manifests clinically as fever, and includes leukocytosis, an increase in the level of neutrophils in the blood, and an increase in the serum concentrations of TNF-α, IL-1β, IL-6, IL-10, MPO and PGE2. Despite the leading role of IL-8 in the local inflammatory process, we postulate TNF-α and IL-6 play a key role in the systemic inflammatory response in CDI, and the plasma TNF-α level seems to act as a major factor of poor prognosis in patients with CDI.

Clostridium difficile Infection and Fecal Microbiota Transplant

PubMed Central

Liubakka, Alyssa; Vaughn, Byron P.

2017-01-01

Clostridium difficile infection (CDI) is a major source of morbidity and mortality for hospitalized patients. Although most patients have a clinical response to existing antimicrobial therapies, recurrent infection develops in up to 30% of patients. Fecal microbiota transplant is a novel approach to this complex problem, with an efficacy rate of nearly 90% in the setting of multiple recurrent CDI. This review covers the current epidemiology of CDI (including toxigenic and nontoxigenic strains, risk factors for infection, and recurrent infection), methods of diagnosis, existing first-line therapies in CDI, the role of fecal microbiota transplant for multiple recurrent CDIs, and the potential use of fecal microbial transplant for patients with severe or refractory infection. PMID:27959316

Advances in the Microbiome: Applications to Clostridium difficile Infection

PubMed Central

Culligan, Eamonn P.; Sleator, Roy D.

2016-01-01

Clostridium difficile is a major cause of morbidity and mortality worldwide, causing over 400,000 infections and approximately 29,000 deaths in the United States alone each year. C. difficile is the most common cause of nosocomial diarrhoea in the developed world, and, in recent years, the emergence of hyper-virulent (mainly ribotypes 027 and 078, sometimes characterised by increased toxin production), epidemic strains and an increase in the number of community-acquired infections has caused further concern. Antibiotic therapy with metronidazole, vancomycin or fidaxomicin is the primary treatment for C. difficile infection (CDI). However, CDI is unique, in that, antibiotic use is also a major risk factor for acquiring CDI or recurrent CDI due to disruption of the normal gut microbiota. Therefore, there is an urgent need for alternative, non-antibiotic therapeutics to treat or prevent CDI. Here, we review a number of such potential treatments which have emerged from advances in the field of microbiome research. PMID:27657145

Children's Depression Inventory (CDI) and the Children's Depression Rating Scale-Revised (CDRS-R): reliability of the Hebrew version.

PubMed

Zalsman, Gil; Misgav, Sagit; Sommerfeld, Eliane; Kohn, Yoav; Brunstein-Klomek, Anat; Diller, Robyne; Sher, Leo; Schwartz, Joseph; Shoval, Gal; Ben-Dor, David H; Wolovik, Luisa; Oquendo, Maria A

2005-01-01

The Children's Depression Inventory (CDI) and Children's Depression Rating Scale-Revised (CDRS-R) are two widely used instruments, which measure depression in children and adolescents. This pilot study assessed the reliability of the Hebrew versions of these two instruments. Both CDRS-R and CDI were translated from English into Hebrew and then back translated. Seventeen healthy Israeli bilingual children volunteers were interviewed with both scales with a one day intermission between the interviews. Non-parametric correlations were used to compare scores in the two versions for each item. Results showed high agreement between the two versions for almost all items of the CDI and moderate to high for the CDRS-R. When CDRS-R summary scores for each item were compared, the agreement was high for this instrument as well. It is concluded that both CDI and CDRS-R Hebrew versions are reliable and can be used for studies of depression in the Israeli pediatric population.

Community for Data Integration 2015 annual report

USGS Publications Warehouse

Langseth, Madison L.; Chang, Michelle Y.; Carlino, Jennifer; Bellmore, J. Ryan; Birch, Daniella D.; Bradley, Joshua; Bristol, R. Sky; Buscombe, Daniel D.; Duda, Jeffrey J.; Everette, Anthony L.; Graves, Tabitha A.; Greenwood, Michelle M.; Govoni, David L.; Henkel, Heather S.; Hutchison, Vivian B.; Jones, Brenda K.; Kern, Tim; Lacey, Jennifer; Lamb, Rynn M.; Lightsom, Frances L.; Long, John L.; Saleh, Ra'ad A.; Smith, Stan W.; Soulard, Christopher E.; Viger, Roland J.; Warrick, Jonathan A.; Wesenberg, Katherine E.; Wieferich, Daniel J.; Winslow, Luke A.

2016-10-28

The Community for Data Integration (CDI) continued to experience success in fiscal year 2015. The CDI community members have been sharing, learning, and collaborating through monthly forums, workshops, working groups, and funded projects. In fiscal year 2015, CDI coordinated 10 monthly forums with 16 different speakers from the U.S. Geological Survey and external partners; funded 11 collaborative projects; and hosted an in-person, four-day workshop, which attracted 168 (134 in-person and 34 remote) data practitioners, data providers, and data consumers from across the USGS, academia, industry, and other government agencies. The Citizen Science, Connected Devices, Data Management, Semantic Web, and Tech Stack Working Groups continued to accomplish great things in fiscal year 2015. These working groups were major stakeholders in planning the 2015 CDI Workshop; they continued developing solutions to pressing challenges, and they brought in speakers throughout the year for more focused presentations and discussions. Additionally, a new working group formed during the 2015 CDI Workshop—the Earth-Science Themes Working Group.

A long-term predictive validity study: can the CDI Short Form be used to predict language and early literacy skills four years later?

PubMed

Can, Dilara Deniz; Ginsburg-Block, Marika; Golinkoff, Roberta Michnick; Hirsh-Pasek, Kathryn

2013-09-01

This longitudinal study examined the predictive validity of the MacArthur Communicative Developmental Inventories-Short Form (CDI-SF), a parent report questionnaire about children's language development (Fenson, Pethick, Renda, Cox, Dale & Reznick, 2000). Data were first gathered from parents on the CDI-SF vocabulary scores for seventy-six children (mean age=1 ; 10). Four years later (mean age=6 ; 1), children were assessed on language outcomes (expressive vocabulary, syntax, semantics and pragmatics) and code-related skills, including phonemic awareness, word recognition and decoding skills. Hierarchical regression analyses revealed that early expressive vocabulary accounted for 17% of the variance in picture vocabulary, 11% of the variance in syntax, and 7% of the variance in semantics, while not accounting for any variance in pragmatics in kindergarten. CDI-SF scores did not predict code-related skills in kindergarten. The importance of early vocabulary skills for later language development and CDI-SF as a valuable research tool are discussed.

Fidaxomicin - the new drug for Clostridium difficile infection

PubMed Central

Vaishnavi, Chetana

2015-01-01

Clostridium difficile is one of the many aetiological agents of antibiotic associated diarrhoea and is implicated in 15-25 per cent of the cases. The organism is also involved in the exacearbation of inflammatory bowel disease and extracolonic manifestations. Due to increase in the incidence of C. difficile infection (CDI), emergence of hypervirulent strains, and increased frequency of recurrence, the clinical management of the disease has become important. The management of CDI is based on disease severity, and current antibiotic treatment options are limited to vancomycin or metronidazole in the developing countries. this review article briefly describes important aspects of CDI, and the new drug, fidaxomicin, for its treatment. Fidaxomicin is particularly active against C. difficile and acts by inhibition of RNA synthesis. Clinical trials done to compare the efficacy and safety of fidaxomicin with that of vancomycin in treating CDI concluded that fidaxomicin was non-inferior to vancomycin for treatment of CDI and that there was a significant reduction in recurrences. The bactericidal properties of fidaxomicin make it an ideal alternative for CDI treatment. However, fidaxomicin use should be considered taking into account the potential benefits of the drug, along with the medical requirements of the patient, the risks of treatment and the high cost of fidaxomicin compared to other treatment regimens. PMID:26112840

Control of Clostridium difficile infection by defined microbial communities

PubMed Central

Collins, James

2017-01-01

Summary Each year in the United States, billions of dollars are spent combating almost half a million Clostridium difficile infections (CDI) and trying to reduce the ~29,000 patient deaths where C. difficile has an attributed role (1). In Europe, disease prevalence varies by country and level of surveillance, though yearly costs are estimated at €3 billion (2). One factor contributing to the significant healthcare burden of C. difficile is the relatively high frequency of recurrent C. difficile infections(3). Recurrent C. difficile infection (rCDI), i.e., a second episode of symptomatic CDI occurring within eight weeks of successful initial CDI treatment, occurs in ~25% of patients with 35-65% of these patients experiencing multiple episodes of recurrent disease(4, 5). Using microbial communities to treat rCDI, either as whole fecal transplants or as defined consortia of bacterial isolates have shown great success (in the case of fecal transplants) or potential promise (in the case of defined consortia of isolates). This review will briefly summarize the epidemiology and physiology of C. difficile infection, describe our current understanding of how fecal microbiota transplants treat recurrent CDI, and outline potential ways through which that knowledge can be used to rationally-design and test alternative microbe-based therapeutics. PMID:28936948

Management of Clostridium difficile Infection

PubMed Central

Al-Jashaami, Layth S.

2016-01-01

Since the discovery of Clostridium difficile infection (CDI) in the 1970s, there has been an increase in the incidence, severity, and recurrence rate of the disease. We reviewed the recent CDI literature in PubMed published before February 28, 2016 that focused on advances in therapy. Despite a large number of studies describing methods for diagnosing the disease, there is currently no definitive test that identifies this infection with certainty, which complicates therapy. Recommended therapy for CDI includes oral metronidazole for mild cases and oral vancomycin or fidaxomicin for moderate to severe cases, each given for 10 to 14 days. For infection with spore-forming C difficile, this length of treatment may be insufficient to lead to cure; however, continuing antibiotics for longer periods of time may unfavorably alter the microbiome, preventing recovery. Treatment with metronidazole has been associated with an increasing failure rate, and the only clear recommended form of metronidazole for treatment of CDI is the intravenous formulation for patients unable to take oral medications. For vancomycin or fidaxomicin treatment of first CDI recurrences, the drug used in the initial bout can be repeated. For second or future recurrences, vancomycin can be given in pulsed or tapered doses. New modalities of treatment, such as bacteriotherapy and immunotherapy, show promise for the treatment of recurrent CDI. PMID:27917075

Fidaxomicin versus vancomycin for Clostridium difficile infection: meta-analysis of pivotal randomized controlled trials.

PubMed

Crook, Derrick W; Walker, A Sarah; Kean, Yin; Weiss, Karl; Cornely, Oliver A; Miller, Mark A; Esposito, Roberto; Louie, Thomas J; Stoesser, Nicole E; Young, Bernadette C; Angus, Brian J; Gorbach, Sherwood L; Peto, Timothy E A

2012-08-01

Two recently completed phase 3 trials (003 and 004) showed fidaxomicin to be noninferior to vancomycin for curing Clostridium difficile infection (CDI) and superior for reducing CDI recurrences. In both studies, adults with active CDI were randomized to receive blinded fidaxomicin 200 mg twice daily or vancomycin 125 mg 4 times a day for 10 days. Post hoc exploratory intent-to-treat (ITT) time-to-event analyses were undertaken on the combined study 003 and 004 data, using fixed-effects meta-analysis and Cox regression models. ITT analysis of the combined 003/004 data for 1164 patients showed that fidaxomicin reduced persistent diarrhea, recurrence, or death by 40% (95% confidence interval [CI], 26%-51%; P < .0001) compared with vancomycin through day 40. A 37% (95% CI, 2%-60%; P = .037) reduction in persistent diarrhea or death was evident through day 12 (heterogeneity P = .50 vs 13-40 days), driven by 7 (1.2%) fidaxomicin versus 17 (2.9%) vancomycin deaths at <12 days. Low albumin level, low eosinophil count, and CDI treatment preenrollment were risk factors for persistent diarrhea or death at 12 days, and CDI in the previous 3 months was a risk factor for recurrence (all P < .01). Fidaxomicin has the potential to substantially improve outcomes from CDI.

Evaluation of NVB302 versus vancomycin activity in an in vitro human gut model of Clostridium difficile infection.

PubMed

Crowther, Grace S; Baines, Simon D; Todhunter, Sharie L; Freeman, Jane; Chilton, Caroline H; Wilcox, Mark H

2013-01-01

First-line treatment options for Clostridium difficile infection (CDI) are limited. NVB302 is a novel type B lantibiotic under evaluation for the treatment of CDI. We compared the responses to NVB302 and vancomycin when used to treat simulated CDI in an in vitro gut model. We used ceftriaxone to elicit simulated CDI in an in vitro gut model primed with human faeces. Vancomycin and NVB302 were instilled into separate gut models and the indigenous gut microbiota and C. difficile total viable counts, spores and toxin levels were monitored throughout. Ceftriaxone instillation promoted C. difficile germination and high-level toxin production. Commencement of NVB302 and vancomycin instillation reduced C. difficile total viable counts rapidly with only C. difficile spores remaining within 3 and 4 days, respectively. Cytotoxin was reduced to undetectable levels 5 and 7 days after vancomycin and NVB302 instillation commenced in vessel 2 and 3, respectively, and remained undetectable for the remainder of the experiments. C. difficile spores were unaffected by the presence of vancomycin or NVB302. NVB302 treatment was associated with faster resolution of Bacteroides fragilis group. Both NVB302 and vancomycin were effective in treating simulated CDI in an in vitro gut model. C. difficile spore recrudescence was not observed following successful treatment with either NVB302 or vancomycin. NVB302 displayed non-inferiority to vancomycin in the treatment of simulated CDI, and had less deleterious effects against B. fragilis group. NVB302 warrants further clinical investigation as a potentially novel antimicrobial agent for the treatment of CDI.

An antimicrobial stewardship program's real-world experience with fidaxomicin for treatment of Clostridium difficile infection: a case series.

PubMed

Vargo, Craig A; Bauer, Karri A; Mangino, Julie E; Johnston, Jessica E W; Goff, Debra A

2014-09-01

To evaluate real-world clinical and economic outcomes in patients with Clostridium difficile infection (CDI) treated with fidaxomicin. Retrospective case series. Academic medical center. A total of 61 patients with CDI who were treated with fidaxomicin monotherapy or combination therapy from September 2011 to December 2012. Data on demographics, infection characteristics, and clinical and economic outcomes were evaluated. Clinical cure was defined as resolution of diarrhea (less than or equal to three unformed stools for at least 2 consecutive days) maintained for the duration of therapy with no further requirement for CDI therapy and was achieved in 44 (72.1%) patients. Clinical cure was significantly higher for patients receiving fidaxomicin monotherapy compared with fidaxomicin combination therapy (25/29 [86.2%] patients vs 19/32 [59.4%] patients, p=0.04). Clinical cure was similar in patients with a first or prior CDI episode (65.5% vs 78.1%, p=0.27) and in patients with severe versus nonsevere disease (68.4% vs 73.8%, p=0.66). Recurrence occurred in 6 (13.6%) of the 44 patients who achieved clinical cure. Mortality attributable to CDI was 11.5%, and 30-day readmission rate was 4.9%. Median cost accrued during CDI was $19,483/patient. Our real-world experience with fidaxomicin significantly differs from the findings of phase III clinical trials. Fidaxomicin is also associated with substantial costs. Multicenter studies are needed to determine the optimal role of fidaxomicin in the treatment of CDI. © 2014 Pharmacotherapy Publications, Inc.

Factors Associated With Health Care Utilization of Recurrent Clostridium difficile Infection in New York State.

PubMed

Mathews, Steven N; Lamm, Ryan; Yang, Jie; Park, Jihye; Tzimas, Demetrios; Buscaglia, Jonathan M; Pryor, Aurora; Talamini, Mark; Telem, Dana; Bucobo, Juan C

2018-03-21

The incidence of infection due to Clostridium difficile infection (CDI) and subsequent economic burden are substantial. The impact of changing practice patterns on demographics at risk and utilization of health care resources for recurrence of CDI remains unclear. A total of 291,163 patients hospitalized for CDI were identified from 1995 to 2014 from the New York SPARCS database. The χ test, the Welch t test, and multivariable logistic regression analysis were performed to evaluate factors related to readmission. Hospital admissions and readmissions for CDI peaked in 2008 at 20,487 and 13,795, respectively, and have since decreased (linear trend, 0.9706 and 0.9464, respectively; P<0.0001). In total, 60,077 (21%) patients required ≥2 admissions. Risk factors for readmission included: age 55 to 74, government insurance, hypertension, diabetes, anemia, hypothyroidism, chronic pulmonary disease, rheumatoid arthritis, renal failure, peripheral vascular disease, and depression (all P<0.05). Trends in surgery showed a similar peak in 2008 at 165 and have since decreased (linear trend, 0.8660; P<0.0001). A total of 1830 (0.63%) patients with CDI underwent surgery, with emergent being more common than elective (71% vs. 29%). Hospital admissions and readmissions for CDI peaked in 2008 and have since been steadily declining. These trends may be secondary to improved diagnostic capabilities and evolving antibiotic regimens. More than 1 in 5 hospitalized patients had at least 1 readmission. Numerous risk factors for these patients have been identified. Although <1% of all patients with CDI undergo surgery, these rates have also been declining.

Cost-effectiveness analysis on the use of fidaxomicin and vancomycin to treat Clostridium difficile infection in France.

PubMed

Watt, Maureen; Dinh, Aurélien; Le Monnier, Alban; Tilleul, Patrick

2017-07-01

Fidaxomicin is a macrocyclic antibiotic with proven efficacy against Clostridium difficile infection (CDI) in adults. It was licensed in France in 2012, but, due to higher acquisition costs compared with existing treatments, healthcare providers require information on its cost/benefit profile. To compare healthcare costs and health outcomes of fidaxomicin and vancomycin, as reference treatment for CDI. A Markov model was used to simulate the treatment pathway, over 1 year, of adult patients with CDI receiving fidaxomicin or vancomycin. Several patient sub-groups (severe CDI; recurrent CDI; concomitant antibiotics; cancer; renal failure; elderly) were evaluated. Cost-effectiveness was analyzed based on cure and recurrence rates derived from published randomized clinical trials comparing fidaxomicin and vancomycin, and costs calculated from the payer perspective using French hospitalization data and drug cost databases. Model outputs included costs in euros (reference year 2014) and health outcomes (recurrence; sustained cure rates). Alternative scenario and sensitivity analyses were performed using data from other clinical trials in CDI, including one conducted in real-life clinical practice in France. Drug acquisition costs were €1,692 higher in fidaxomicin-treated patients, but this was offset by the lower hospitalization costs with fidaxomicin, which were reduced by €1,722. The reduction in the cost of hospitalization was driven by the significantly lower number of recurrences in fidaxomicin-treated patients, offsetting the acquisition cost of fidaxomicin in all sub-groups except recurrent CDI and concomitant antibiotics. This study demonstrated that, despite higher acquisition costs, the lower recurrence rate with fidaxomicin resulted in cost savings or low incremental costs compared with vancomycin.

Acute kidney injury impact on inpatient mortality in Clostridium difficile infection: A national propensity-matched study.

PubMed

Charilaou, Paris; Devani, Kalpit; John, Febin; Kanna, Sowjanya; Ahlawat, Sushil; Young, Mark; Khanna, Sahil; Reddy, Chakradhar

2018-06-01

Acute kidney injury (AKI) is used as a marker of severity in Clostridium difficile infection (CDI) patients. We estimated the true effect of AKI in inpatient mortality of CDI patients, as there are no large-scale, population-based, propensity-matched studies evaluating AKI's effect in this patient cohort. A retrospective observational study utilizing the National Inpatient Sample from years 2003 to 2012, including all adults with CDI, excluding cases missing data on age, inpatient mortality or gender. Trends and CDI-related complications as mortality predictors were assessed using survey-weighted multivariable regression. We estimated AKI's independent effect by propensity-matching, post-stratifying by chronic kidney disease status, allowing for multiple comorbidity adjustment. A total of 2 859 599 patients with CDI were included, of which 896 122 (31.3%) had principal diagnosis of CDI. AKI prevalence was 22%. Mortality rate was 8.4%, while among AKI patients was higher (18.2%). In multivariable regression, AKI was associated with higher mortality (odds ratio [OR] = 3.16, 95% confidence interval [CI]: 3.02-3.30; P < 0.001), while after propensity matching, AKI increased mortality by 86% (OR = 1.86, 95% CI: 1.79-1.94; P < 0.001). CDI incidence increased by 1.8, together with the rate of AKI (12.6% in 2003 to 28.8% in 2012, P-trend < 0.001). Despite increasing hospitalizations, mortality over the study period decreased to 7.2% (2012) from 9.0% (2003); P-trend < 0.001. Hospital admissions of patients with CDI and concomitant AKI are increasing, but their inpatient mortality has improved over the study period. AKI is a significant contributor to mortality, independently of other comorbidities, complications, and hospital characteristics, emphasizing the need for early diagnosis and aggressive management in such patients. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Agent-based model of fecal microbial transplant effect on bile acid metabolism on suppressing Clostridium difficile infection: an example of agent-based modeling of intestinal bacterial infection.

PubMed

Peer, Xavier; An, Gary

2014-10-01

Agent-based modeling is a computational modeling method that represents system-level behavior as arising from multiple interactions between the multiple components that make up a system. Biological systems are thus readily described using agent-based models (ABMs), as multi-cellular organisms can be viewed as populations of interacting cells, and microbial systems manifest as colonies of individual microbes. Intersections between these two domains underlie an increasing number of pathophysiological processes, and the intestinal tract represents one of the most significant locations for these inter-domain interactions, so much so that it can be considered an internal ecology of varying robustness and function. Intestinal infections represent significant disturbances of this internal ecology, and one of the most clinically relevant intestinal infections is Clostridium difficile infection (CDI). CDI is precipitated by the use of broad-spectrum antibiotics, involves the depletion of commensal microbiota, and alterations in bile acid composition in the intestinal lumen. We present an example ABM of CDI (the C. difficile Infection ABM, or CDIABM) to examine fundamental dynamics of the pathogenesis of CDI and its response to treatment with anti-CDI antibiotics and a newer treatment therapy, fecal microbial transplant. The CDIABM focuses on one specific mechanism of potential CDI suppression: commensal modulation of bile acid composition. Even given its abstraction, the CDIABM reproduces essential dynamics of CDI and its response to therapy, and identifies a paradoxical zone of behavior that provides insight into the role of intestinal nutritional status and the efficacy of anti-CDI therapies. It is hoped that this use case example of the CDIABM can demonstrate the usefulness of both agent-based modeling and the application of abstract functional representation as the biomedical community seeks to address the challenges of increasingly complex diseases with the goal of personalized medicine.

Agent-based model of Fecal Microbial Transplant effect on Bile Acid Metabolism on suppressing Clostridium difficile infection: an example of agent-based modeling of intestinal bacterial infection

PubMed Central

Peer, Xavier; An, Gary

2014-01-01

Agent-based modeling is a computational modeling method that represents system-level behavior as arising from multiple interactions between the multiple components that make up a system. Biological systems are thus readily described using agent-based models (ABMs), as multi-cellular organisms can be viewed as populations of interacting cells, and microbial systems manifest as colonies of individual microbes. Intersections between these two domains underlie an increasing number of pathophysiological processes, and the intestinal tract represents one of the most significant locations for these inter-domain interactions, so much so that it can be considered an internal ecology of varying robustness and function. Intestinal infections represent significant disturbances of this internal ecology, and one of the most clinically relevant intestinal infections is Clostridium difficile infection (CDI). CDI is precipitated by the use of broad-spectrum antibiotics, involves the depletion of commensal microbiota, and alterations in bile acid composition in the intestinal lumen. We present an example ABM of CDI (the Clostridium difficile Infection ABM, or CDIABM) to examine fundamental dynamics of the pathogenesis of CDI and its response to treatment with anti-CDI antibiotics and a newer treatment therapy, Fecal Microbial Transplant (FMT). The CDIABM focuses on one specific mechanism of potential CDI suppression: commensal modulation of bile acid composition. Even given its abstraction, the CDIABM reproduces essential dynamics of CDI and its response to therapy, and identifies a paradoxical zone of behavior that provides insight into the role of intestinal nutritional status and the efficacy of anti-CDI therapies. It is hoped that this use case example of the CDIABM can demonstrate the usefulness of both agent-based modeling and the application of abstract functional representation as the biomedical community seeks to address the challenges of increasingly complex diseases with the goal of personalized medicine. PMID:25168489

Clinical and economic impact of the introduction of a nucleic acid amplification assay for Clostridium difficile.

PubMed

Guinta, Margaret M; Bunnell, Kristen; Harrington, Amanda; Bleasdale, Susan; Danziger, Larry; Wenzler, Eric

2017-12-04

The clinical outcomes and cost implications of a diagnostic shift from an EIA- to PCR-based assay for Clostridium difficile infection (CDI) have not been completely described in the literature. The impact of the PCR-based assay on the incidence and duration of CDI therapy was compared to the EIA assay for patients with a negative CDI diagnostic result. Secondary clinical and economic outcomes were also evaluated. Independent predictors of receipt of antibiotic therapy were assessed via logistic regression. 141 EIA and 140 PCR patients were included. Significantly more patients were started or continued on anti-CDI antibiotic therapy after a known negative assay result in the EIA group (26 patients vs. 8 patients, P = 0.002). Duration of antibiotic therapy after a known negative result was significantly shorter in the PCR group (1 vs. 4 days, P = 0.029) and a 23% reduction in the number of tests obtained per patient was observed (1.41 ± 0.86 vs. 1.82 ± 1.35, P = 0.007). The over fourfold difference in per-test cost of the EIA assay ($8.33 vs. $42.86, P < 0.0001) was offset by the overall medication costs required for the increased treatment in the EIA group ($546.60 vs. $188.96, P = 0.191). Utilization of the EIA-based CDI assay was associated with increased odds of CDI treatment after a negative test (aOR 4.71, 95% CI 1.93-11.46, P = 0.001). The transition from an EIA to PCR-based assay for diagnosing CDI resulted in a significant decrease in the number of patients treated and the duration of treatment in response to a negative test result. This significant decrease in treatment resulted in decreased costs offsetting the utilization of a more expensive molecular test for patients with a negative CDI diagnostic result.

Cost-effectiveness analysis of fidaxomicin versus vancomycin in Clostridium difficile infection.

PubMed

Nathwani, Dilip; Cornely, Oliver A; Van Engen, Anke K; Odufowora-Sita, Olatunji; Retsa, Peny; Odeyemi, Isaac A O

2014-11-01

Fidaxomicin was non-inferior to vancomycin with respect to clinical cure rates in the treatment of Clostridium difficile infections (CDIs) in two Phase III trials, but was associated with significantly fewer recurrences than vancomycin. This economic analysis investigated the cost-effectiveness of fidaxomicin compared with vancomycin in patients with severe CDI and in patients with their first CDI recurrence. A 1 year time horizon Markov model with seven health states was developed from the perspective of Scottish public healthcare providers. Model inputs for effectiveness, resource use, direct costs and utilities were obtained from published sources and a Scottish expert panel. The main model outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY), for fidaxomicin versus vancomycin; ICERs were interpreted using willingness-to-pay thresholds of £20,000/QALY and £30,000/QALY. One-way and probabilistic sensitivity analyses were performed. Total costs were similar with fidaxomicin and vancomycin in patients with severe CDI (£14,515 and £14,344, respectively) and in patients with a first recurrence (£16,535 and £16,926, respectively). Improvements in clinical outcomes with fidaxomicin resulted in small QALY gains versus vancomycin (severe CDI, +0.010; patients with first recurrence, +0.019). Fidaxomicin was cost-effective in severe CDI (ICER £16,529/QALY) and dominant (i.e. more effective and less costly) in patients with a first recurrence. The probability that fidaxomicin was cost-effective at a willingness-to-pay threshold of £30,000/QALY was 60% for severe CDI and 68% in a first recurrence. Fidaxomicin is cost-effective in patients with severe CDI and in patients with a first CDI recurrence versus vancomycin. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

Inflammatory Bowel Disease Affects the Outcome of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection

PubMed Central

Khoruts, Alexander; Rank, Kevin M.; Newman, Krista M.; Viskocil, Kimberly; Vaughn, Byron P.; Hamilton, Matthew J.; Sadowsky, Michael J.

2017-01-01

BACKGROUND & AIMS A significant fraction of patients with recurrent Clostridium difficile infections (CDI) have inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) can break the cycle of CDI recurrence and can be performed without evaluation of the colon. We evaluated the efficacy of colonoscopic FMT in patients with and without IBD, and whether we could identify IBD in patients during this procedure. METHODS We collected clinical meta-data and colonoscopy results from 272 consecutive patients that underwent FMT for recurrent CDI at the University of Minnesota from 2008 through 2015. Patients had at least 2 spontaneous relapses of CDI following their initial episode and did not clear the infection after 1 extended antibiotic regimen. We collected random mucosal biopsies from patients’ right colons to identify lymphocytic or collagenous colitis during the FMT procedure. Failure or success in clearing CDI was determined within or at 2 months after the FMT. RESULTS Of patients undergoing FMT, 15% had established IBD and 2.6% were found to have IBD during the FMT procedure. A single colonoscopic FMT cleared CDI from 74.4% of patients with IBD and 92.1% of patients without IBD (P = .0018). Patients had similar responses to FMT regardless of immunosuppressive therapy. More than one-quarter of patients with IBD (25.6%) had a clinically significant flare of IBD after FMT. Lymphocytic colitis was documented in 7.4% of patients with endoscopically normal colon mucosa; only 3 of these patients (20%) required additional treatment for colitis after clearance of CDI. CONCLUSIONS Based on an analysis of 272 patients, FMT is somewhat less effective in clearing recurrent CDI from patients with IBD, compared with patients without IBD, regardless of immunosuppressive therapy. More than 25% of patients with IBD have a disease flare following FMT. Lymphocytic colitis did not affect the outcome of FMT, but a small fraction of these patients required pharmacologic treatment after the procedure. PMID:26905904

The projected effectiveness of Clostridium difficile vaccination as part of an integrated infection control strategy.

PubMed

van Kleef, Esther; Deeny, Sarah R; Jit, Mark; Cookson, Barry; Goldenberg, Simon D; Edmunds, W John; Robotham, Julie V

2016-11-04

Early clinical trials of a Clostridium difficile toxoid vaccine show efficacy in preventing C. difficile infection (CDI). The optimal patient group to target for vaccination programmes remains unexplored. This study performed a model-based evaluation of the effectiveness of different CDI vaccination strategies, within the context of existing infection prevention and control strategies such as antimicrobial stewardship. An individual-based transmission model of CDI in a high-risk hospital setting was developed. The model incorporated data on patient movements between the hospital, and catchment populations from the community and long-term care facilities (LTCF), using English national and local level data for model-parameterisation. We evaluated vaccination of: (1) discharged patients who had an CDI-occurrence in the ward; (2) LTCF-residents; (3) Planned elective surgical admissions and (4) All three strategies combined. Without vaccination, 10.9 [Interquartile range: 10.0-11.8] patients per 1000 ward admissions developed CDI, of which 31% were ward-acquired. Immunising all three patient groups resulted in a 43% [42-44], reduction of ward-onset CDI on average. Among the strategies restricting vaccination to one target group, vaccinating elective surgical patients proved most effective (35% [34-36] reduction), but least efficient, requiring 146 [133-162] courses to prevent one ICU-onset case. Immunising LTCF residents was most efficient, requiring just 13 [11-16] courses to prevent one case, but considering this only comprised a small group of our hospital population, it only reduced ICU-onset CDI by 9% [8-11]. Vaccination proved most efficient when ward-based transmission rates and antimicrobial consumption were high. Strategy success depends on the interaction between hospital and catchment populations, and importantly, consideration of importations of CDI from outside the hospital which we found to substantially impact hospital dynamics. Vaccination may be most desirable in settings or patient groups where levels of broad-spectrum antimicrobial use are high and difficult to reduce. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Python Interface for the Dakota Iterative Systems Analysis Toolkit

NASA Astrophysics Data System (ADS)

Piper, M.; Hutton, E.; Syvitski, J. P.

2016-12-01

Uncertainty quantification is required to improve the accuracy, reliability, and accountability of Earth science models. Dakota is a software toolkit, developed at Sandia National Laboratories, that provides an interface between models and a library of analysis methods, including support for sensitivity analysis, uncertainty quantification, optimization, and calibration techniques. Dakota is a powerful tool, but its learning curve is steep: the user not only must understand the structure and syntax of the Dakota input file, but also must develop intermediate code, called an analysis driver, that allows Dakota to run a model. The CSDMS Dakota interface (CDI) is a Python package that wraps and extends Dakota's user interface. It simplifies the process of configuring and running a Dakota experiment. A user can program to the CDI, allowing a Dakota experiment to be scripted. The CDI creates Dakota input files and provides a generic analysis driver. Any model written in Python that exposes a Basic Model Interface (BMI), as well as any model componentized in the CSDMS modeling framework, automatically works with the CDI. The CDI has a plugin architecture, so models written in other languages, or those that don't expose a BMI, can be accessed by the CDI by programmatically extending a template; an example is provided in the CDI distribution. Currently, six Dakota analysis methods have been implemented for examples from the much larger Dakota library. To demonstrate the CDI, we performed an uncertainty quantification experiment with the HydroTrend hydrological water balance and transport model. In the experiment, we evaluated the response of long-term suspended sediment load at the river mouth (Qs) to uncertainty in two input parameters, annual mean temperature (T) and precipitation (P), over a series of 100-year runs, using the polynomial chaos method. Through Dakota, we calculated moments, local and global (Sobol') sensitivity indices, and probability density and cumulative distribution functions for the response.

Statin use and the risk of Clostridium difficile infection: a systematic review with meta-analysis.

PubMed

Tariq, Raseen; Mukhija, Dhruvika; Gupta, Arjun; Singh, Siddharth; Pardi, Darrell S; Khanna, Sahil

2018-01-01

Statins have pleiotropic effects beyond cholesterol lowering by immune modulation. The association of statins with primary Clostridium difficile infection (CDI) is unclear as studies have reported conflicting findings. We performed a systematic review and meta-analysis to evaluate the association between statin use and CDI. We searched MEDLINE, Embase, and Web of Science from January 1978 to December 2016 for studies assessing the association between statin use and CDI. The Newcastle-Ottawa Scale was used to assess the methodologic quality of included studies. Weighted summary estimates were calculated using generalized inverse variance with random-effects model. Eight studies (6 case-control and 2 cohort) were included in the meta-analysis, which comprised 156,722 patients exposed to statins and 356,185 controls, with 34,849 total cases of CDI available in 7 studies. The rate of CDI in patients with statin use was 4.3%, compared with 7.8% in patients without statin use. An overall meta-analysis of 8 studies using the random-effects model demonstrated that statins may be associated with a decreased risk of CDI (maximally adjusted odds ratio [OR], 0.80; 95% CI, 0.66-0.97; P =0.02). There was significant heterogeneity among the studies, with an I 2 of 79%. No publication bias was seen. Meta-analysis of studies that adjusted for confounders revealed no protective effect of statins (adjusted OR, 0.84; 95% CI, 0.70-1.01; P =0.06, I 2 =75%). However, a meta-analysis of only full-text studies using the random-effects model demonstrated a decreased risk of CDI with the use of statins (OR 0.77; 95% CI, 0.61-0.99; P =0.04, I 2 =85%). Meta-analyses of existing studies suggest that patients prescribed a statin may be at decreased risk for CDI. The results must be interpreted with caution given the significant heterogeneity and lack of benefit on analysis of studies that adjusted for confounders.

Effect of Detecting and Isolating Clostridium difficile Carriers at Hospital Admission on the Incidence of C difficile Infections: A Quasi-Experimental Controlled Study.

PubMed

Longtin, Yves; Paquet-Bolduc, Bianka; Gilca, Rodica; Garenc, Christophe; Fortin, Elise; Longtin, Jean; Trottier, Sylvie; Gervais, Philippe; Roussy, Jean-François; Lévesque, Simon; Ben-David, Debby; Cloutier, Isabelle; Loo, Vivian G

2016-06-01

Clostridium difficile infection (CDI) is a major cause of health care-associated infection worldwide, and new preventive strategies are urgently needed. Current control measures do not target asymptomatic carriers, despite evidence that they can contaminate the hospital environment and health care workers' hands and potentially transmit C difficile to other patients. To investigate the effect of detecting and isolating C difficile asymptomatic carriers at hospital admission on the incidence of health care-associated CDI (HA-CDI). We performed a controlled quasi-experimental study between November 19, 2013, and March 7, 2015, in a Canadian acute care facility. Admission screening was conducted by detecting the tcdB gene by polymerase chain reaction on a rectal swab. Carriers were placed under contact isolation precautions during their hospitalization. Changes in HA-CDI incidence level and trend during the intervention period (17 periods of 4 weeks each) were compared with the preintervention control period (120 periods of 4 weeks each) by segmented regression analysis and autoregressive integrated moving average (ARIMA) modeling. Concomitant changes in the aggregated HA-CDI incidence at other institutions in Québec City, Québec (n = 6) and the province of Québec (n = 94) were also examined. Overall, 7599 of 8218 (92.5%) eligible patients were screened, among whom 368 (4.8%) were identified as C difficile carriers. During the intervention, 38 patients (3.0 per 10 000 patient-days) developed an HA-CDI compared with 416 patients (6.9 per 10 000 patient-days) during the preintervention control period (P < .001). There was no immediate change in the level of HA-CDIs on implementation (P = .92), but there was a significant decrease in trend over time of 7% per 4-week period (rate ratio, 0.93; 95% CI, 0.87-0.99 per period; P = .02). ARIMA modeling also detected a significant effect of the intervention, represented by a gradual progressive decrease in the HA-CDI time series by an overall magnitude of 7.2 HA-CDIs per 10 000 patient-days. We estimated that the intervention had prevented 63 of the 101 (62.4%) expected cases. By contrast, no significant decrease in HA-CDI rates occurred in the control groups. Detecting and isolating C difficile carriers was associated with a significant decrease in the incidence of HA-CDI. If confirmed in subsequent studies, this strategy could help prevent HA-CDI.

A new scheme for velocity analysis and imaging of diffractions

NASA Astrophysics Data System (ADS)

Lin, Peng; Peng, Suping; Zhao, Jingtao; Cui, Xiaoqin; Du, Wenfeng

2018-06-01

Seismic diffractions are the responses of small-scale inhomogeneities or discontinuous geological features, which play a vital role in the exploitation and development of oil and gas reservoirs. However, diffractions are generally ignored and considered as interference noise in conventional data processing. In this paper, a new scheme for velocity analysis and imaging of seismic diffractions is proposed. Two steps compose of this scheme in our application. First, the plane-wave destruction method is used to separate diffractions from specular reflections in the prestack domain. Second, in order to accurately estimate migration velocity of the diffractions, the time-domain dip-angle gathers are derived from a Kirchhoff-based angle prestack time migration using separated diffractions. Diffraction events appear flat in the dip-angle gathers when imaged above the diffraction point with selected accurate migration velocity for diffractions. The selected migration velocity helps to produce the desired prestack imaging of diffractions. Synthetic and field examples are applied to test the validity of the new scheme. The diffraction imaging results indicate that the proposed scheme for velocity analysis and imaging of diffractions can provide more detailed information about small-scale geologic features for seismic interpretation.

Administration of Probiotic Kefir to Mice with Clostridium difficile Infection Exacerbates Disease

PubMed Central

Spinler, Jennifer K.; Brown, Aaron; Ross, Caná L.; Boonma, Prapaporn; Conner, Margaret E.; Savidge, Tor C.

2016-01-01

Lifeway® kefir, a fermented milk product containing 12 probiotic organisms, is reported to show promise as an alternative to fecal microbiota transplantation for recurrent Clostridium difficile infection (CDI). We employed a murine CDI model to study the probiotic protective mechanisms and unexpectedly determined that kefir drastically increased disease severity. Our results emphasize the need for further independent clinical testing of kefir as alternative therapy in recurrent CDI. PMID:27180007

Challenges and opportunities in the management of Clostridium difficile infection.

PubMed

DuPont, Herbert L

2014-11-01

Clostridium difficile infection (CDI) is increasing in all regions of the world where sought. There is no gold standard for diagnosis of CDI, with available tests having limitations. Prevention of CDI will be seen with antibiotic stewardship, improved disinfection of hospitals and nursing homes, chemo- and immuno-prophylaxis and next generation probiotics. The important therapeutic agents are oral vancomycin and fidaxomicin with metronidazole being used only in mild cases or when oral therapy cannot be given. Current therapy of CDI for 10 days is associated with high rate of recurrence that may be prevented by prolonging initial therapy. Future treatment strategies will focus on drugs that inhibit C. difficile, reduce toxin activity and inflammation in the gut, and improve colonic flora diversity.

Toward an Understanding of Changes in Diversity Associated with Fecal Microbiome Transplantation Based on 16S rRNA Gene Deep Sequencing

PubMed Central

Shahinas, Dea; Silverman, Michael; Sittler, Taylor; Chiu, Charles; Kim, Peter; Allen-Vercoe, Emma; Weese, Scott; Wong, Andrew; Low, Donald E.; Pillai, Dylan R.

2012-01-01

ABSTRACT Fecal microbiome transplantation by low-volume enema is an effective, safe, and inexpensive alternative to antibiotic therapy for patients with chronic relapsing Clostridium difficile infection (CDI). We explored the microbial diversity of pre- and posttransplant stool specimens from CDI patients (n = 6) using deep sequencing of the 16S rRNA gene. While interindividual variability in microbiota change occurs with fecal transplantation and vancomycin exposure, in this pilot study we note that clinical cure of CDI is associated with an increase in diversity and richness. Genus- and species-level analysis may reveal a cocktail of microorganisms or products thereof that will ultimately be used as a probiotic to treat CDI. PMID:23093385

Image degradation characteristics and restoration based on regularization for diffractive imaging

NASA Astrophysics Data System (ADS)

Zhi, Xiyang; Jiang, Shikai; Zhang, Wei; Wang, Dawei; Li, Yun

2017-11-01

The diffractive membrane optical imaging system is an important development trend of ultra large aperture and lightweight space camera. However, related investigations on physics-based diffractive imaging degradation characteristics and corresponding image restoration methods are less studied. In this paper, the model of image quality degradation for the diffraction imaging system is first deduced mathematically based on diffraction theory and then the degradation characteristics are analyzed. On this basis, a novel regularization model of image restoration that contains multiple prior constraints is established. After that, the solving approach of the equation with the multi-norm coexistence and multi-regularization parameters (prior's parameters) is presented. Subsequently, the space-variant PSF image restoration method for large aperture diffractive imaging system is proposed combined with block idea of isoplanatic region. Experimentally, the proposed algorithm demonstrates its capacity to achieve multi-objective improvement including MTF enhancing, dispersion correcting, noise and artifact suppressing as well as image's detail preserving, and produce satisfactory visual quality. This can provide scientific basis for applications and possesses potential application prospects on future space applications of diffractive membrane imaging technology.

Effect of multiple circular holes Fraunhofer diffraction for the infrared optical imaging

NASA Astrophysics Data System (ADS)

Lu, Chunlian; Lv, He; Cao, Yang; Cai, Zhisong; Tan, Xiaojun

2014-11-01

With the development of infrared optics, infrared optical imaging systems play an increasingly important role in modern optical imaging systems. Infrared optical imaging is used in industry, agriculture, medical, military and transportation. But in terms of infrared optical imaging systems which are exposed for a long time, some contaminations will affect the infrared optical imaging. When the contamination contaminate on the lens surface of the optical system, it would affect diffraction. The lens can be seen as complementary multiple circular holes screen happen Fraunhofer diffraction. According to Babinet principle, you can get the diffraction of the imaging system. Therefore, by studying the multiple circular holes Fraunhofer diffraction, conclusions can be drawn about the effect of infrared imaging. This paper mainly studies the effect of multiple circular holes Fraunhofer diffraction for the optical imaging. Firstly, we introduce the theory of Fraunhofer diffraction and Point Spread Function. Point Spread Function is a basic tool to evaluate the image quality of the optical system. Fraunhofer diffraction will affect Point Spread Function. Then, the results of multiple circular holes Fraunhofer diffraction are given for different hole size and hole spacing. We choose the hole size from 0.1mm to 1mm and hole spacing from 0.3mm to 0.8mm. The infrared wavebands of optical imaging are chosen from 1μm to 5μm. We use the MATLAB to simulate light intensity distribution of multiple circular holes Fraunhofer diffraction. Finally, three-dimensional diffraction maps of light intensity are given to contrast.

Depression and quality of life in children with sickle cell disease: the effect of social support.

PubMed

Sehlo, Mohammad Gamal; Kamfar, Hayat Zakaria

2015-04-11

The majority of available studies have shown that children with sickle cell disease (SCD) have a higher risk of depressive symptoms than those without. The present study aimed to: assess the prevalence of depression in a sample of children with SCD; evaluate the association between disease severity, social support and depression, and the combined and/or singular effect on health-related quality of life (HRQL) in children with SCD; and show the predictive value of social support and disease severity on depression. A total of 120 children were included in the study, 60 (group I) with SCD and 60 matched, healthy control children (group II). Depression was assessed in both groups using the Children's Depression Inventory (CDI) and the Children's Depression Inventory-Parent (CDI-P). Children with CDI and CDI-P scores of more than 12 were interviewed for further assessment of depression using the Diagnostic Interview Schedule for Children Version IV (DISC-IV). The Pediatric Quality of Life Inventory Version 4.0 Generic Core Scales (PedsQL 4.0) was used to assess HRQL in both groups, and social support was measured with the Child and Adolescent Social Support Scale (CASSS). Eight (13%) of the 60 children with SCD had CDI and CDI-P scores of more than 12 (CDI mean score 14.50 ± 1.19, CDI-P mean score 14.13 ± 1.12), and were diagnosed as having clinical depression using the diagnostic interview DISC-IV. For group I, HRQL was poor across all PedsQL 4.0 domains in both self- and parent-reports (P < 0.001) compared with group II. A higher level of parent support was a significantly associated with decreased depressive symptoms, demonstrated by lower CDI scores. Better quality of life was shown by the associated higher total PedsQL 4.0 self-scores of children with SCD (B = -1.79, P = 0.01 and B = 1.89, P = 0.02 respectively). The present study demonstrates that higher levels of parent support were significantly associated with decreased depressive symptoms and better quality of life in children with SCD. Interventions focused on increasing parent support may be an important part of treatment for depression in children with SCD.

Interventions to Reduce the Incidence of Hospital-Onset Clostridium difficile Infection: An Agent-Based Modeling Approach to Evaluate Clinical Effectiveness in Adult Acute Care Hospitals.

PubMed

Barker, Anna K; Alagoz, Oguzhan; Safdar, Nasia

2018-04-03

Despite intensified efforts to reduce hospital-onset Clostridium difficile infection (HO-CDI), its clinical and economic impacts continue to worsen. Many institutions have adopted bundled interventions that vary considerably in composition, strength of evidence, and effectiveness. Considerable gaps remain in our knowledge of intervention effectiveness and disease transmission, which hinders HO-CDI prevention. We developed an agent-based model of C. difficile transmission in a 200-bed adult hospital using studies from the literature, supplemented with primary data collection. The model includes an environmental component and 4 distinct agent types: patients, visitors, nurses, and physicians. We used the model to evaluate the comparative clinical effectiveness of 9 single interventions and 8 multiple-intervention bundles at reducing HO-CDI and asymptomatic C. difficile colonization. Daily cleaning with sporicidal disinfectant and C. difficile screening at admission were the most effective single-intervention strategies, reducing HO-CDI by 68.9% and 35.7%, respectively (both P < .001). Combining these interventions into a 2-intervention bundle reduced HO-CDI by 82.3% and asymptomatic hospital-onset colonization by 90.6% (both, P < .001). Adding patient hand hygiene to healthcare worker hand hygiene reduced HO-CDI rates an additional 7.9%. Visitor hand hygiene and contact precaution interventions did not reduce HO-CDI, compared with baseline. Excluding those strategies, healthcare worker contact precautions were the least effective intervention at reducing hospital-onset colonization and infection. Identifying and managing the vast hospital reservoir of asymptomatic C. difficile by screening and daily cleaning with sporicidal disinfectant are high-yield strategies. These findings provide much-needed data regarding which interventions to prioritize for optimal C. difficile control.

Cardiac Implantable Electronic Device-Related Infection and Extraction Trends in the U.S.

PubMed

Sridhar, Arun Raghav Mahankali; Lavu, Madhav; Yarlagadda, Vivek; Reddy, Madhu; Gunda, Sampath; Afzal, Rizwan; Atkins, Donita; Gopinathanair, Rakesh; Dawn, Buddhadeb; Lakkireddy, Dhanunjaya R

2017-03-01

Implantation of cardiac implanted electronic device (CIED) has surged lately. This resulted in a rise in cardiac device-related infections (CDI) and inevitably, lead extractions. We examined the recent national trend in the incidence of CIED infections and lead extractions in hospitalized patients and associated mortality. Using the Nationwide Inpatient Sample for the years 2003-2011 we identified patients diagnosed with a CDI-associated infection as determined by discharge ICD-9 diagnostic codes. We examined the trend of device-related infections overall and in different subgroups. We studied mortality associated with device infections, lead extractions, associated costs, and length of stay. There is a significant increase in the number of hospitalizations due to CDI from 5,308 in the year 2003 to 9,948 in 2011. Males (68%), Caucasians (77%), and age group 65-84 years (56.4%) accounted for majority of CDI. The mortality associated with CDI was 4.5 %, and was worse in higher age groups (2.5% in 18-44 years compared to 5.3% in 85+ years, P < 0.001). Average length of stay was unchanged over the years remaining at 13.6 days; however, mean hospitalization charges increased from $91,348 in 2003 to $173,211 in 2011 (P < 0.001). Among all lead extraction procedures, the percentage of patients undergoing lead extraction secondary to CDI also increased from 2003 (59.1%) to 2011 (76.7%), P-value < 0.001. Healthcare burden associated with CDI infections and associated lead extractions has significantly increased in the recent years. Despite an increase in cost associated with CIED infections, mortality remains the same, and is higher in older patients. © 2017 Wiley Periodicals, Inc.

Economic assessment of fidaxomicin for the treatment of Clostridium difficile infection (CDI) in special populations (patients with cancer, concomitant antibiotic treatment or renal impairment) in Spain.

PubMed

Rubio-Terrés, C; Cobo Reinoso, J; Grau Cerrato, S; Mensa Pueyo, J; Salavert Lletí, M; Toledo, A; Anguita, P; Rubio-Rodríguez, D; Watt, M; Gani, R

2015-11-01

The objective of this paper was to assess the cost-utility of fidaxomicin versus vancomycin in the treatment of Clostridium difficile infection (CDI) in three specific CDI patient subgroups: those with cancer, treated with concomitant antibiotic therapy or with renal impairment. A Markov model with six health states was developed to assess the cost-utility of fidaxomicin versus vancomycin in the patient subgroups over a period of 1 year from initial infection. Cost and outcome data used to parameterise the model were taken from Spanish sources and published literature. The costs were from the Spanish hospital perspective, in Euros (€) and for 2013. For CDI patients with cancer, fidaxomicin was dominant versus vancomycin [gain of 0.016 quality-adjusted life-years (QALYs) and savings of €2,397 per patient]. At a cost-effectiveness threshold of €30,000 per QALY gained, the probability that fidaxomicin was cost-effective was 96 %. For CDI patients treated with concomitant antibiotic therapy, fidaxomicin was the dominant treatment versus vancomycin (gain of 0.014 QALYs and savings of €1,452 per patient), with a probability that fidaxomicin was cost-effective of 94 %. For CDI patients with renal impairment, fidaxomicin was also dominant versus vancomycin (gain of 0.013 QALYs and savings of €1,432 per patient), with a probability that fidaxomicin was cost-effective of 96 %. Over a 1-year time horizon, when fidaxomicin is compared to vancomycin in CDI patients with cancer, treated with concomitant antibiotic therapy or with renal impairment, the use of fidaxomicin would be expected to result in increased QALYs for patients and reduced overall costs.

Clostridium difficile colonization and disease in patients undergoing hematopoietic stem cell transplantation.

PubMed

Bruminhent, Jackrapong; Wang, Zi-Xuan; Hu, Carol; Wagner, John; Sunday, Richard; Bobik, Brent; Hegarty, Sarah; Keith, Scott; Alpdogan, Seyfettin; Carabasi, Matthew; Filicko-O'Hara, Joanne; Flomenberg, Neal; Kasner, Margaret; Outschoorn, Ubaldo Martinez; Weiss, Mark; Flomenberg, Phyllis

2014-09-01

There was an increase in the Clostridium difficile infection (CDI) rate in our bone marrow transplantation unit. To evaluate the role of unit-based transmission, C. difficile screening was performed on adult patients admitted for hematopoietic stem cell transplantation (HSCT) over a 2-year period, and C. difficile isolates were typed. C. difficile testing was performed using a 2-step C. difficile glutamate dehydrogenase antigen plus toxin A/B enzyme immunoassay (EIA) and cytotoxin assay (or molecular toxin assay). Multilocus sequence typing (MLST) was performed on toxin-positive whole stool samples. A retrospective chart review was performed on all patients with a positive toxin assay. Sixteen of 150 patients (10.7%) had toxigenic C. difficile colonization (CDC) on admission. The overall incidence of CDI within 100 days after HSCT was 24.7% (37 of 150). The median time to diagnosis of CDI was 3.5 days after HSCT. In an adjusted logistic regression model, CDC on admission was a significant risk factor for CDI (odds ratio, 68.5; 95% confidence interval, 11.4 to 416.2). MLST on 22 unit patient toxin-positive stool specimens revealed 15 distinct strain types. Further analysis identified at least 1 potential cross-transmission event; some events may have been missed because of incomplete typing from other specimens. Despite aggressive infection control interventions, there was no decline in the number of CDI cases during the study period. These data suggest that prior CDC plays a major role in CDI rates in this high-risk patient population. It remains unclear if CDI was cross-transmitted in the unit. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Severity and frequency of community-onset Clostridium difficile infection on an Australian tertiary referral hospital campus.

PubMed

Clohessy, Penny; Merif, Juan; Post, Jeffrey John

2014-12-01

Clostridium difficile infection (CDI) is increasingly being found in populations without traditional risk factors. We compared the relative frequency, risk factors, severity, and outcomes of community-onset CDI with hospital-acquired infection. This was a retrospective, observational study of CDI at a tertiary hospital campus in Sydney, Australia. Patients aged 15 years and older with a first episode of CDI from January 1 to December 31, 2011 were included. CDI was defined as the presence of diarrhoea with a positive enzyme immunoassay in conjunction with a positive cell cytotoxicity assay, toxin culture, or organism culture. Main outcome measures were onset of infection (hospital or community), risk factors, markers of severity, and outcomes for the two groups. One hundred and twenty-nine cases of CDI infection were identified, of which 38 (29%) were community-onset. The community-onset infection group were less likely to have a recent history of antibiotic use (66% vs. 98%; p<0.001) or proton pump inhibitor use (38% vs. 69%; p=0.03) than the hospital-acquired infection group. Markers of severity and outcomes were similar in the two groups, with an overall mortality of 9%. Community-onset CDI accounts for a large proportion of C. difficile infections and has a similar potential for severe disease as hospital-acquired infection. Using a history of previous antibiotic use, proton pump inhibitor use, or recent hospitalization to predict cases is unreliable. We recommend that patients with diarrhoea being investigated in emergency departments and community practice are tested for Clostridium difficile infection. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Risks factors and outcomes of Clostridium difficile infection in patients with cancer: a matched case-control study.

PubMed

Hebbard, Andrew I T; Slavin, Monica A; Reed, Caroline; Trubiano, Jason A; Teh, Benjamin W; Haeusler, Gabrielle M; Thursky, Karin A; Worth, Leon J

2017-06-01

Clostridium difficile infection (CDI) is the leading cause of diarrhoea in hospitalised patients. Cancer populations are at high-risk for infection, but comprehensive evaluation in the current era of cancer care has not been performed. The objective of this study was to describe characteristics, risk factors, and outcomes of CDI in cancer patients. Fifty consecutive patients with CDI at a large Australian cancer centre (2013-2015) were identified from the hospital pathology database. Each case was matched by ward and hospital admission date to three controls without toxigenic CDI. Treatment and outcomes of infection were evaluated and potential risk factors were analysed using conditional logistic regression. Patients with CDI had a mean age of 59.7 years and 74% had an underlying solid tumour. Healthcare-associated infection comprised 80% of cases. Recurrence occurred in 10, and 12% of cases were admitted to ICU within 30 days. Severe or severe-complicated infection was observed in 32%. Independent risk factors for infection included chemotherapy (odds ratio (OR) 3.82, 95% CI 1.67-8.75; p = 0.002), gastro-intestinal/abdominal surgery (OR 4.64, 95% CI 1.20-17.91; p = 0.03), proton pump inhibitor (PPI) therapy (OR 2.47, 95% CI 1.05-5.80; p = 0.04), and days of antibiotic therapy (OR 1.04, 95% CI 1.01-1.08; p = 0.02). Severe or complicated infections are frequent in patients with cancer who develop CDI. Receipt of chemotherapy, gastro-intestinal/abdominal surgery, PPI therapy, and antibiotic exposure contribute to infection risk. More effective CDI therapy for cancer patients is required and dedicated antibiotic stewardship programs in high-risk cancer populations are needed to ameliorate infection risk.

A multi-institutional cohort study confirming the risks of Clostridium difficile infection associated with prolonged antibiotic prophylaxis.

PubMed

Kirkwood, Katherine A; Gulack, Brian C; Iribarne, Alexander; Bowdish, Michael E; Greco, Giampaolo; Mayer, Mary Lou; O'Sullivan, Karen; Gelijns, Annetine C; Fumakia, Nishit; Ghanta, Ravi K; Raiten, Jesse M; Lala, Anuradha; Ladowski, Joseph S; Blackstone, Eugene H; Parides, Michael K; Moskowitz, Alan J; Horvath, Keith A

2018-02-01

The incidence and severity of Clostridium difficile infection (CDI) have increased rapidly over the past 2 decades, particularly in elderly patients with multiple comorbidities. This study sought to characterize the incidence and risks of these infections in cardiac surgery patients. A total of 5158 patients at 10 Cardiothoracic Surgical Trials Network sites in the US and Canada participated in a prospective study of major infections after cardiac surgery. Patients were followed for infection, readmission, reoperation, or death up to 65 days after surgery. We compared clinical and demographic characteristics, surgical data, management practices, and outcomes for patients with CDI and without CDI. C difficile was the third most common infection observed (0.97%) and was more common in patients with preoperative comorbidities and complex operations. Antibiotic prophylaxis for >2 days, intensive care unit stay >2 days, and postoperative hyperglycemia were associated with increased risk of CDI. The median time to onset was 17 days; 48% of infections occurred after discharge. The additional length of stay due to infection was 12 days. The readmission and mortality rates were 3-fold and 5-fold higher, respectively, in patients with CDI compared with uninfected patients. In this large multicenter prospective study of major infections following cardiac surgery, CDI was encountered in nearly 1% of patients, was frequently diagnosed postdischarge, and was associated with extended length of stay and substantially increased mortality. Patients with comorbidities, longer surgery time, extended antibiotic exposure, and/or hyperglycemic episodes were at increased risk for CDI. Copyright © 2017 The American Association for Thoracic Surgery. All rights reserved.

[Thickening of the pituitary stalk in children and adolescents with central diabetes insipidus: Causes and consequences].

PubMed

Corredor Andrés, Beatriz; Muñoz Calvo, María Teresa; López Pino, Miguel Ángel; Márquez Rivera, María; Travieso Suárez, Lourdes; Pozo Román, Jesús; Argente, Jesús

2018-06-09

Central diabetes insipidus (CDI) is a rare disorder in children. The aetiology of CDI in childhood is heterogeneous. The aim of this study is to illustrate the importance of a careful clinical and neuro-radiological follow-up of the pituitary and hypothalamus region in order to identify the aetiology and the development of associated hormonal deficiencies. Clinical and auxological variables of 15 children diagnosed with CDI were retrospectively analysed in a paediatric hospital. Evaluations of adenohypophyseal function and cranial MRI were performed periodically. The mean age at diagnosis of CDI was 9.6 years (range: 1.32-15.9). The aetiological diagnosis could be established initially in 9 of the 15 patients, as 7 with a germinoma and 2 with a histiocytosis. After a mean follow-up of 5.5 years (range: 1.6-11.8), the number of idiopathic cases was reduced by half. At the end of the follow-up, the aetiological diagnoses were: 9 germinoma (60%), 3 histiocytosis (20%), and 3 idiopathic CDI (20%). There is a statistically significant association between stalk thickening and tumour aetiology. At least one adenohypophyseal hormonal deficiency was found in 67% of cases, with the majority developing in the first two years of follow-up. Growth hormone deficiency (60%) was the most prevalent. The follow-up of CDI should include hormone evaluation with special attention, due to its frequency, to GH deficiency. In addition, a biannual MRI in an idiopathic CDI should be performed, at least during the first 2-3 years after diagnosis, as 50% of them were diagnosed with a germinoma or histiocytosis during this period. Copyright © 2018. Publicado por Elsevier España, S.L.U.

Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection.

PubMed

Brown, Kevin A; Khanafer, Nagham; Daneman, Nick; Fisman, David N

2013-05-01

The rising incidence of Clostridium difficile infection (CDI) could be reduced by lowering exposure to high-risk antibiotics. The objective of this study was to determine the association between antibiotic class and the risk of CDI in the community setting. The EMBASE and PubMed databases were queried without restriction to time period or language. Comparative observational studies and randomized controlled trials (RCTs) considering the impact of exposure to antibiotics on CDI risk among nonhospitalized populations were considered. We estimated pooled odds ratios (OR) for antibiotic classes using random-effect meta-analysis. Our search criteria identified 465 articles, of which 7 met inclusion criteria; all were observational studies. Five studies considered antibiotic risk relative to no antibiotic exposure: clindamycin (OR = 16.80; 95% confidence interval [95% CI], 7.48 to 37.76), fluoroquinolones (OR = 5.50; 95% CI, 4.26 to 7.11), and cephalosporins, monobactams, and carbapenems (CMCs) (OR = 5.68; 95% CI, 2.12 to 15.23) had the largest effects, while macrolides (OR = 2.65; 95% CI, 1.92 to 3.64), sulfonamides and trimethoprim (OR = 1.81; 95% CI, 1.34 to 2.43), and penicillins (OR = 2.71; 95% CI, 1.75 to 4.21) had lower associations with CDI. We noted no effect of tetracyclines on CDI risk (OR = 0.92; 95% CI, 0.61 to 1.40). In the community setting, there is substantial variation in the risk of CDI associated with different antimicrobial classes. Avoidance of high-risk antibiotics (such as clindamycin, CMCs, and fluoroquinolones) in favor of lower-risk antibiotics (such as penicillins, macrolides, and tetracyclines) may help reduce the incidence of CDI.

Risk of Clostridium difficile Infection in Patients With Celiac Disease: A Population-Based Study.

PubMed

Lebwohl, Benjamin; Nobel, Yael R; Green, Peter H R; Blaser, Martin J; Ludvigsson, Jonas F

2017-12-01

Patients with celiac disease are at increased risk for infections such as tuberculosis, influenza, and pneumococcal pneumonia. However, little is known about the incidence of Clostridium difficile infection (CDI) in patients with celiac disease. We identified patients with celiac disease based on intestinal biopsies submitted to all pathology departments in Sweden over a 39-year period (from July 1969 through February 2008). We compared risk of CDI (based on stratified Cox proportional hazards models) among patients with celiac disease vs. without celiac disease (controls) matched by age, sex, and calendar period. We identified 28,339 patients with celiac disease and 141,588 controls; neither group had a history of CDI. The incidence of CDI was 56/100,000 person-years among patients with celiac disease and 26/100,000 person-years among controls, yielding an overall hazard ratio (HR) of 2.01 (95% confidence interval (CI), 1.64-2.47; P<0.0001). The risk of CDI was highest in the first 12 months after diagnosis of celiac disease (HR, 5.20; 95% CI, 2.81-9.62; P<0.0001), but remained high, compared to that of controls, 1-5 years after diagnosis (HR, 1.85; 95% CI, 1.22-2.81; P=0.004). Among 493 patients with CDI, antibiotic data were available for 251; there were no significant differences in prior exposures to antibiotics between patients with celiac disease and controls. In a large population-based cohort study, patients with celiac disease had significantly higher incidence of CDI than controls. This finding is consistent with prior findings of higher rates of other infections in patients with celiac disease, and suggests the possibility of altered gut immunity and/or microbial composition in patients with celiac disease.

[The efficacy of desmopressin in the treatment of central diabetes insipidus after resection of chiasmo-sellar region tumors].

PubMed

Astaf'eva, L I

Central diabetes insipidus (CDI) is a neuroendocrine disease, the pathogenesis of which is associated with abnormal secretion of the antidiuretic hormone. One of the specific causes of CDI is neurosurgical resection of chiasmatic-sellar region tumors. to study the efficacy and safety of desmopressin in CDI patients after resection of chiasmatic-sellar region (CSR) tumors. Examination and treatment of patients were performed at a hospital for 7-14 days after surgery and then were continued after discharge. During treatment, the following tests were performed: a daily fluid intake and excretion volume, serum levels of sodium, potassium, and glucose twice a day, morning urine specific gravity, and Zimnitsky's test. Twenty-three patients with CSR tumors (11 craniopharyngiomas, 10 pituitary adenomas, 1 skull base chordoma, and 1 CSR meningioma) and CDI after neurosurgical treatment received desmopressin. On treatment, a thirst decrease, a reduced rate of diuresis, a reduced amount of excreted urine, and normalization of the sodium level were observed in all patients. In 12 patients (with pituitary adenoma, skull base chordoma, and meningioma) with transient CDI, desmopressin therapy was discontinued upon regression of symptoms 7-30 days after surgery. Eleven patients with permanent CDI continued to receive the drug at a dose of 1 to 4 doses per day. All patients well tolerated the drug without significant adverse effects. Therapy with desmopressin in the form of a nasal spray (vazomirin) in patients with transient and permanent CDI after resection CSR tumors of various histological nature (craniopharyngiomas, pituitary adenomas, meningiomas, and chordomas) was effective and safe in the early postoperative and long-term postoperative periods.

Clostridium difficile Associated Risk of Death Score (CARDS): A novel severity score to predict mortality among hospitalized patients with Clostridium difficile infection

PubMed Central

Kassam, Zain; Fabersunne, Camila Cribb; Smith, Mark B.; Alm, Eric J.; Kaplan, Gilaad G.; Nguyen, Geoffrey C.; Ananthakrishnan, Ashwin N.

2016-01-01

Background Clostridium difficile infection (CDI) is public health threat and associated with significant mortality. However, there is a paucity of objectively derived CDI severity scoring systems to predict mortality. Aims To develop a novel CDI risk score to predict mortality entitled: Clostridium difficile Associated Risk of Death Score (CARDS). Methods We obtained data from the United States 2011 Nationwide Inpatient Sample (NIS) database. All CDI-associated hospitalizations were identified using discharge codes (ICD-9-CM, 008.45). Multivariate logistic regression was utilized to identify independent predictors of mortality. CARDS was calculated by assigning a numeric weight to each parameter based on their odds ratio in the final logistic model. Predictive properties of model discrimination were assessed using the c-statistic and validated in an independent sample using the 2010 NIS database. Results We identified 77,776 hospitalizations, yielding an estimate of 374,747 cases with an associated diagnosis of CDI in the United States, 8% of whom died in the hospital. The 8 severity score predictors were identified on multivariate analysis: age, cardiopulmonary disease, malignancy, diabetes, inflammatory bowel disease, acute renal failure, liver disease and ICU admission, with weights ranging from −1 (for diabetes) to 5 (for ICU admission). The overall risk score in the cohort ranged from 0 to 18. Mortality increased significantly as CARDS increased. CDI-associated mortality was 1.2% with a CARDS of 0 compared to 100% with CARDS of 18. The model performed equally well in our validation cohort. Conclusion CARDS is a promising simple severity score to predict mortality among those hospitalized with CDI. PMID:26849527

Variability in testing policies and impact on reported Clostridium difficile infection rates: results from the pilot Longitudinal European Clostridium difficile Infection Diagnosis surveillance study (LuCID).

PubMed

Davies, K; Davis, G; Barbut, F; Eckert, C; Petrosillo, N; Wilcox, M H

2016-12-01

Lack of standardised Clostridium difficile testing is a potential confounder when comparing infection rates. We used an observational, systematic, prospective large-scale sampling approach to investigate variability in C. difficile sampling to understand C. difficile infection (CDI) incidence rates. In-patient and institutional data were gathered from 60 European hospitals (across three countries). Testing methodology, testing/CDI rates and case profiles were compared between countries and institution types. The mean annual CDI rate per hospital was lowest in the UK and highest in Italy (1.5 vs. 4.7 cases/10,000 patient bed days [pbds], p < 0.001). The testing rate was highest in the UK compared with Italy and France (50.7/10,000 pbds vs. 31.5 and 30.3, respectively, p < 0.001). Only 58.4 % of diarrhoeal samples were tested for CDI across all countries. Overall, only 64 % of hospitals used recommended testing algorithms for laboratory testing. Small hospitals were significantly more likely to use standalone toxin tests (SATTs). There was an inverse correlation between hospital size and CDI testing rate. Hospitals using SATT or assays not detecting toxin reported significantly higher CDI rates than those using recommended methods, despite testing similar testing frequencies. These data are consistent with higher false-positive rates in such (non-recommended) testing scenarios. Cases in Italy and those diagnosed by SATT or methods NOT detecting toxin were significantly older. Testing occurred significantly earlier in the UK. Assessment of testing practice is paramount to the accurate interpretation and comparison of CDI rates.

WSES guidelines for management of Clostridium difficile infection in surgical patients.

PubMed

Sartelli, Massimo; Malangoni, Mark A; Abu-Zidan, Fikri M; Griffiths, Ewen A; Di Bella, Stefano; McFarland, Lynne V; Eltringham, Ian; Shelat, Vishal G; Velmahos, George C; Kelly, Ciarán P; Khanna, Sahil; Abdelsattar, Zaid M; Alrahmani, Layan; Ansaloni, Luca; Augustin, Goran; Bala, Miklosh; Barbut, Frédéric; Ben-Ishay, Offir; Bhangu, Aneel; Biffl, Walter L; Brecher, Stephen M; Camacho-Ortiz, Adrián; Caínzos, Miguel A; Canterbury, Laura A; Catena, Fausto; Chan, Shirley; Cherry-Bukowiec, Jill R; Clanton, Jesse; Coccolini, Federico; Cocuz, Maria Elena; Coimbra, Raul; Cook, Charles H; Cui, Yunfeng; Czepiel, Jacek; Das, Koray; Demetrashvili, Zaza; Di Carlo, Isidoro; Di Saverio, Salomone; Dumitru, Irina Magdalena; Eckert, Catherine; Eckmann, Christian; Eiland, Edward H; Enani, Mushira Abdulaziz; Faro, Mario; Ferrada, Paula; Forrester, Joseph Derek; Fraga, Gustavo P; Frossard, Jean Louis; Galeiras, Rita; Ghnnam, Wagih; Gomes, Carlos Augusto; Gorrepati, Venkata; Ahmed, Mohamed Hassan; Herzog, Torsten; Humphrey, Felicia; Kim, Jae Il; Isik, Arda; Ivatury, Rao; Lee, Yeong Yeh; Juang, Paul; Furuya-Kanamori, Luis; Karamarkovic, Aleksandar; Kim, Peter K; Kluger, Yoram; Ko, Wen Chien; LaBarbera, Francis D; Lee, Jae Gil; Leppaniemi, Ari; Lohsiriwat, Varut; Marwah, Sanjay; Mazuski, John E; Metan, Gokhan; Moore, Ernest E; Moore, Frederick Alan; Nord, Carl Erik; Ordoñez, Carlos A; Júnior, Gerson Alves Pereira; Petrosillo, Nicola; Portela, Francisco; Puri, Basant K; Ray, Arnab; Raza, Mansoor; Rems, Miran; Sakakushev, Boris E; Sganga, Gabriele; Spigaglia, Patrizia; Stewart, David B; Tattevin, Pierre; Timsit, Jean Francois; To, Kathleen B; Tranà, Cristian; Uhl, Waldemar; Urbánek, Libor; van Goor, Harry; Vassallo, Angela; Zahar, Jean Ralph; Caproli, Emanuele; Viale, Pierluigi

2015-01-01

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.

The use of fidaxomicin for treatment of relapsed Clostridium difficile infections in patients with cancer.

PubMed

Esmaily-Fard, Amin; Tverdek, Frank P; Crowther, David M; Ghantoji, Shashank S; Adachi, Javier A; Chemaly, Roy F

2014-11-01

To report our experience with the use of fidaxomicin (FDX), an oral macrocyclic antibiotic, in cancer patients with Clostridium difficile infection (CDI). A single-center retrospective case series was conducted at The University of Texas MD Anderson Cancer Center. Patients with CDI treated with FDX from May 2011 to January 2013 were identified via the pharmacy database. Clinical response and recurrence after FDX initiation were evaluated. Twenty-two patients were included, most of whom were male (55%) with a mean age of 58 years (range: 20-83 yrs). The most common underlying malignancies were nine patients with lymphoma (41%), seven with leukemia (32%), and six with solid tumors (27%). Indications for FDX included recurrent CDI in 16 patients (72%) and failure of both metronidazole and oral vancomycin in 6 patients (28%). Nineteen patients (86%) were on concomitant antimicrobials during CDI treatment. Clinical response to FDX was 91%, and overall sustained clinical response was 82%. FDX was well tolerated with no major adverse events that were FDX related or discontinuations due to drug-related adverse events. In cancer patients, FDX is effective treatment for the first episode of CDI after failure of standard therapies and treatment of recurrent CDI. This was interesting given the large number of high-risk patients who continued to receive concomitant antimicrobial therapy, which is common in this immunocompromised patient population. © 2014 Pharmacotherapy Publications, Inc.

Hospital-acquired Clostridium difficile infection: determinants for severe disease.

PubMed

Wenisch, J M; Schmid, D; Kuo, H-W; Simons, E; Allerberger, F; Michl, V; Tesik, P; Tucek, G; Wenisch, C

2012-08-01

Risk factors of severity (need for surgical intervention, intensive care or fatal outcome) were analysed in hospital-acquired Clostridium difficile infection (CDI) in a 777-bed community hospital. In a prospective analytical cross-sectional study, age (≥ 65 years), sex, CDI characteristics, underlying diseases, severity of comorbidity and PCR ribotypes were tested for associations with severe CDI. In total, 133 cases of hospital-acquired CDI (mean age 74.4 years) were identified, resulting in an incidence rate of 5.7/10,000 hospital-days. A recurrent episode of diarrhoea occurred in 25 cases (18.8%) and complications including toxic megacolon, dehydration and septicaemia in 69 cases (51.9%). Four cases (3.0%) required ICU admission, one case (0.8%) surgical intervention and 22 cases (16.5%) died within the 30-day follow-up period. Variables identified to be independently associated with severe CDI were severe diarrhoea (odds ratio [OR] 3.64, 95% confidence interval [CI] 1.19-11.11, p=0.02), chronic pulmonary disease (OR 3.0, 95% CI 1.08-8.40, p=0.04), chronic renal disease (OR 2.9, 95% CI 1.07-7.81, p=0.04) and diabetes mellitus (OR 4.30, 95% CI 1.57-11.76, p=0.004). The case fatality of 16.5% underlines the importance of increased efforts in CDI prevention, in particular for patients with underlying diseases.

Highlighting clinical needs in Clostridium difficile infection: the views of European healthcare professionals at the front line.

PubMed

Aguado, J M; Anttila, V J; Galperine, T; Goldenberg, S D; Gwynn, S; Jenkins, D; Norén, T; Petrosillo, N; Seifert, H; Stallmach, A; Warren, T; Wenisch, C

2015-06-01

Clostridium difficile infection (CDI) is the leading cause of infectious nosocomial diarrhoea in Europe. Despite increased focus, its incidence and severity are increasing in many European countries. We developed a series of consensus statements to identify unmet clinical needs in the recognition and management of CDI. A consortium of European experts prepared a series of 29 statements representing their collective views on the diagnosis and management of CDI in Europe. The statements were grouped into the following six broad themes: diagnosis; definitions of severity; treatment failure, recurrence and its consequences; infection prevention and control interventions; education and antimicrobial stewardship; and National CDI clinical guidance and policy. These statements were reviewed using questionnaires by 1047 clinicians involved in managing CDI, who indicated their level of agreement with each statement. Levels of agreement exceeded the 66% threshold for consensus for 27 out of 29 statements (93.1%), indicating strong support. Variance between countries and specialties was analysed and showed strong alignment with the overall consensus scores. Based on the consensus scores of the respondent group, recommendations are suggested for the further development of CDI services in order to reduce transmission and recurrence and to ensure that appropriate diagnosis and treatment strategies are applied across all healthcare settings. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Fidaxomicin Versus Vancomycin for Clostridium difficile Infection: Meta-analysis of Pivotal Randomized Controlled Trials

PubMed Central

Crook, Derrick W.; Walker, A. Sarah; Kean, Yin; Weiss, Karl; Cornely, Oliver A.; Miller, Mark A.; Esposito, Roberto; Louie, Thomas J.; Stoesser, Nicole E.; Young, Bernadette C.; Angus, Brian J.; Gorbach, Sherwood L.; Peto, Timothy E. A.

2012-01-01

Two recently completed phase 3 trials (003 and 004) showed fidaxomicin to be noninferior to vancomycin for curing Clostridium difficile infection (CDI) and superior for reducing CDI recurrences. In both studies, adults with active CDI were randomized to receive blinded fidaxomicin 200 mg twice daily or vancomycin 125 mg 4 times a day for 10 days. Post hoc exploratory intent-to-treat (ITT) time-to-event analyses were undertaken on the combined study 003 and 004 data, using fixed-effects meta-analysis and Cox regression models. ITT analysis of the combined 003/004 data for 1164 patients showed that fidaxomicin reduced persistent diarrhea, recurrence, or death by 40% (95% confidence interval [CI], 26%–51%; P < .0001) compared with vancomycin through day 40. A 37% (95% CI, 2%–60%; P = .037) reduction in persistent diarrhea or death was evident through day 12 (heterogeneity P = .50 vs 13–40 days), driven by 7 (1.2%) fidaxomicin versus 17 (2.9%) vancomycin deaths at <12 days. Low albumin level, low eosinophil count, and CDI treatment preenrollment were risk factors for persistent diarrhea or death at 12 days, and CDI in the previous 3 months was a risk factor for recurrence (all P < .01). Fidaxomicin has the potential to substantially improve outcomes from CDI. PMID:22752871

Infection prevention and control practices related to Clostridium difficile infection in Canadian acute and long-term care institutions.

PubMed

Wilkinson, Krista; Gravel, Denise; Taylor, Geoffrey; McGeer, Allison; Simor, Andrew; Suh, Kathryn; Moore, Dorothy; Kelly, Sharon; Boyd, David; Mulvey, Michael; Mounchili, Aboubakar; Miller, Mark

2011-04-01

Clostridium difficile is an important pathogen in Canadian health care facilities, and infection prevention and control (IPC) practices are crucial to reducing C difficile infections (CDIs). We performed a cross-sectional study to identify CDI-related IPC practices in Canadian health care facilities. A survey assessing facility characteristics, CDI testing strategies, CDI contact precautions, and antimicrobial stewardship programs was sent to Canadian health care facilities in February 2005. Responses were received from 943 (33%) facilities. Acute care facilities were more likely than long-term care (P < .001) and mixed care facilities (P = .03) to submit liquid stools from all patients for CDI testing. Physician orders were required before testing for CDI in 394 long-term care facilities (66%)-significantly higher than the proportions in acute care (41%; P < .001) and mixed care sites (49%; P < .001). A total of 841 sites (93%) had an infection control manual, 639 (76%) of which contained CDI-specific guidelines. Antimicrobial stewardship programs were reported by 40 (29%) acute care facilities; 19 (54%) of these sites reported full enforcement of the program. Canadian health care facilities have widely varying C difficile IPC practices. Opportunities exist for facilities to take a more active role in IPC policy development and implementation, as well as antimicrobial stewardship. Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

Structural basis of toxicity and immunity in contact-dependent growth inhibition (CDI) systems.

PubMed

Morse, Robert P; Nikolakakis, Kiel C; Willett, Julia L E; Gerrick, Elias; Low, David A; Hayes, Christopher S; Goulding, Celia W

2012-12-26

Contact-dependent growth inhibition (CDI) systems encode polymorphic toxin/immunity proteins that mediate competition between neighboring bacterial cells. We present crystal structures of CDI toxin/immunity complexes from Escherichia coli EC869 and Burkholderia pseudomallei 1026b. Despite sharing little sequence identity, the toxin domains are structurally similar and have homology to endonucleases. The EC869 toxin is a Zn(2+)-dependent DNase capable of completely degrading the genomes of target cells, whereas the Bp1026b toxin cleaves the aminoacyl acceptor stems of tRNA molecules. Each immunity protein binds and inactivates its cognate toxin in a unique manner. The EC869 toxin/immunity complex is stabilized through an unusual β-augmentation interaction. In contrast, the Bp1026b immunity protein exploits shape and charge complementarity to occlude the toxin active site. These structures represent the initial glimpse into the CDI toxin/immunity network, illustrating how sequence-diverse toxins adopt convergent folds yet retain distinct binding interactions with cognate immunity proteins. Moreover, we present visual demonstration of CDI toxin delivery into a target cell.

Current Trends in the Epidemiology and Outcomes of Clostridium difficile Infection.

PubMed

Evans, Charlesnika T; Safdar, Nasia

2015-05-15

Clostridium difficile is the most frequently identified cause of nosocomial diarrhea and has been associated with epidemics of diarrhea in hospitals and long-term care facilities. The continued increase in C. difficile infection (CDI) suggests that it has surpassed other pathogens in causing healthcare-associated infections. The Centers for Disease Control and Prevention recently identified CDI as an "urgent threat" in its recent report on antibiotic resistance threats in the United States, highlighting the need for urgent and aggressive action to prevent this infection. The impact of antibiotics as a risk factor for new-onset CDI is well established; however, recognizing classes of antibiotics with the highest risks and reducing unnecessary antibiotic use are important strategies for prevention of CDI and subsequent recurrence. In addition, the recognition of the community as an important setting for onset of CDI presents a challenge and is an area for future research. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Overdiagnosis of Clostridium difficile Infection in the Molecular Test Era.

PubMed

Polage, Christopher R; Gyorke, Clare E; Kennedy, Michael A; Leslie, Jhansi L; Chin, David L; Wang, Susan; Nguyen, Hien H; Huang, Bin; Tang, Yi-Wei; Lee, Lenora W; Kim, Kyoungmi; Taylor, Sandra; Romano, Patrick S; Panacek, Edward A; Goodell, Parker B; Solnick, Jay V; Cohen, Stuart H

2015-11-01

Clostridium difficile is a major cause of health care-associated infection, but disagreement between diagnostic tests is an ongoing barrier to clinical decision making and public health reporting. Molecular tests are increasingly used to diagnose C difficile infection (CDI), but many molecular test-positive patients lack toxins that historically defined disease, making it unclear if they need treatment. To determine the natural history and need for treatment of patients who are toxin immunoassay negative and polymerase chain reaction (PCR) positive (Tox-/PCR+) for CDI. Prospective observational cohort study at a single academic medical center among 1416 hospitalized adults tested for C difficile toxins 72 hours or longer after admission between December 1, 2010, and October 20, 2012. The analysis was conducted in stages with revisions from April 27, 2013, to January 13, 2015. Patients undergoing C difficile testing were grouped by US Food and Drug Administration-approved toxin and PCR tests as Tox+/PCR+, Tox-/PCR+, or Tox-/PCR-. Toxin results were reported clinically. Polymerase chain reaction results were not reported. The main study outcomes were duration of diarrhea during up to 14 days of treatment, rate of CDI-related complications (ie, colectomy, megacolon, or intensive care unit care) and CDI-related death within 30 days. Twenty-one percent (293 of 1416) of hospitalized adults tested for C difficile were positive by PCR, but 44.7% (131 of 293) had toxins detected by the clinical toxin test. At baseline, Tox-/PCR+ patients had lower C difficile bacterial load and less antibiotic exposure, fecal inflammation, and diarrhea than Tox+/PCR+ patients (P < .001 for all). The median duration of diarrhea was shorter in Tox-/PCR+ patients (2 days; interquartile range, 1-4 days) than in Tox+/PCR+ patients (3 days; interquartile range, 1-6 days) (P = .003) and was similar to that in Tox-/PCR- patients (2 days; interquartile range, 1-3 days), despite minimal empirical treatment of Tox-/PCR+ patients. No CDI-related complications occurred in Tox-/PCR+ patients vs 10 complications in Tox+/PCR+ patients (0% vs 7.6%, P < .001). One Tox-/PCR+ patient had recurrent CDI as a contributing factor to death within 30 days vs 11 CDI-related deaths in Tox+/PCR+ patients (0.6% vs 8.4%, P = .001). Among hospitalized adults with suspected CDI, virtually all CDI-related complications and deaths occurred in patients with positive toxin immunoassay test results. Patients with a positive molecular test result and a negative toxin immunoassay test result had outcomes that were comparable to patients without C difficile by either method. Exclusive reliance on molecular tests for CDI diagnosis without tests for toxins or host response is likely to result in overdiagnosis, overtreatment, and increased health care costs.

Administration of probiotic kefir to mice with Clostridium difficile infection exacerbates disease.

PubMed

Spinler, Jennifer K; Brown, Aaron; Ross, Caná L; Boonma, Prapaporn; Conner, Margaret E; Savidge, Tor C

2016-08-01

Lifeway(®) kefir, a fermented milk product containing 12 probiotic organisms, is reported to show promise as an alternative to fecal microbiota transplantation for recurrent Clostridium difficile infection (CDI). We employed a murine CDI model to study the probiotic protective mechanisms and unexpectedly determined that kefir drastically increased disease severity. Our results emphasize the need for further independent clinical testing of kefir as alternative therapy in recurrent CDI. Copyright © 2016 Elsevier Ltd. All rights reserved.

Broadband diffractive lens or imaging element

DOEpatents

Ceglio, Natale M.; Hawryluk, Andrew M.; London, Richard A.; Seppala, Lynn G.

1991-01-01

A broadband diffractive lens or imaging element produces a sharp focus and/or a high resolution image with broad bandwidth illuminating radiation. The diffractive lens is sectored or segmented into regions, each of which focuses or images a distinct narrowband of radiation but all of which have a common focal length. Alternatively, a serial stack of minus filters, each with a diffraction pattern which focuses or images a distinct narrowband of radiation but all of which have a common focal length, is used. The two approaches can be combined. Multifocal broadband diffractive elements can also be formed.

Accurate determination of segmented X-ray detector geometry

DOE PAGES

Yefanov, Oleksandr; Mariani, Valerio; Gati, Cornelius; ...

2015-10-22

Recent advances in X-ray detector technology have resulted in the introduction of segmented detectors composed of many small detector modules tiled together to cover a large detection area. Due to mechanical tolerances and the desire to be able to change the module layout to suit the needs of different experiments, the pixels on each module might not align perfectly on a regular grid. Several detectors are designed to permit detector sub-regions (or modules) to be moved relative to each other for different experiments. Accurate determination of the location of detector elements relative to the beam-sample interaction point is critical formore » many types of experiment, including X-ray crystallography, coherent diffractive imaging (CDI), small angle X-ray scattering (SAXS) and spectroscopy. For detectors with moveable modules, the relative positions of pixels are no longer fixed, necessitating the development of a simple procedure to calibrate detector geometry after reconfiguration. We describe a simple and robust method for determining the geometry of segmented X-ray detectors using measurements obtained by serial crystallography. By comparing the location of observed Bragg peaks to the spot locations predicted from the crystal indexing procedure, the position, rotation and distance of each module relative to the interaction region can be refined. Furthermore, we show that the refined detector geometry greatly improves the results of experiments.« less

75 FR 20383 - Amended Certification Regarding Eligibility To Apply for Worker Adjustment Assistance and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-19

... Personnel Services Corporation, CDI Corporation, Finesse Personnel Associates (W.C. Barlow & Associates... Services Corporation, CDI Corporation, Finesse Personnel Associates (W.C. Barlow & Associates), Hightower...

Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: A Systematic Review With Meta-Regression Analysis.

PubMed

Shen, Nicole T; Maw, Anna; Tmanova, Lyubov L; Pino, Alejandro; Ancy, Kayley; Crawford, Carl V; Simon, Matthew S; Evans, Arthur T

2017-06-01

Systematic reviews have provided evidence for the efficacy of probiotics in preventing Clostridium difficile infection (CDI), but guidelines do not recommend probiotic use for prevention of CDI. We performed an updated systematic review to help guide clinical practice. We searched MEDLINE, EMBASE, International Journal of Probiotics and Prebiotics, and The Cochrane Library databases for randomized controlled trials evaluating use of probiotics and CDI in hospitalized adults taking antibiotics. Two reviewers independently extracted data and assessed risk of bias and overall quality of the evidence. Primary and secondary outcomes were incidence of CDI and adverse events, respectively. Secondary analyses examined the effects of probiotic species, dose, timing, formulation, duration, and study quality. We analyzed data from 19 published studies, comprising 6261 subjects. The incidence of CDI in the probiotic cohort, 1.6% (54 of 3277), was lower than of controls, 3.9% (115 of 2984) (P < .001). The pooled relative risk of CDI in probiotic users was 0.42 (95% confidence interval, 0.30-0.57; I 2  = 0.0%). Meta-regression analysis demonstrated that probiotics were significantly more effective if given closer to the first antibiotic dose, with a decrement in efficacy for every day of delay in starting probiotics (P = .04); probiotics given within 2 days of antibiotic initiation produced a greater reduction of risk for CDI (relative risk, 0.32; 95% confidence interval, 0.22-0.48; I 2  = 0%) than later administration (relative risk, 0.70; 95% confidence interval, 0.40-1.23; I 2  = 0%) (P = .02). There was no increased risk for adverse events among patients given probiotics. The overall quality of the evidence was high. In a systematic review with meta-regression analysis, we found evidence that administration of probiotics closer to the first dose of antibiotic reduces the risk of CDI by >50% in hospitalized adults. Future research should focus on optimal probiotic dose, species, and formulation. Systematic Review Registration: PROSPERO CRD42015016395. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Fidaxomicin: the newest addition to the armamentarium against Clostridium difficile infections.

PubMed

Lancaster, Jason W; Matthews, S James

2012-01-01

Fidaxomicin, a macrolide antibiotic, was the first medication for the management of Clostridium difficile infections (CDI) to be approved by the US Food and Drug Administration in more than 20 years. This article reviews published literature on fidaxomicin for management of CDI, including its chemistry, spectrum of activity, pharmacokinetic properties, pharmacodynamics, therapeutic efficacy, adverse events, dosing, administration, and pharmacoeconomic considerations. Pertinent English-language literature was reviewed through searches of MEDLINE, EMBASE, and BIOSIS from 1975 through September 2011. Reference lists of identified publications and published abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy meetings were also reviewed. Search terms included, but were not limited to, fidaxomicin, difimicin, lipiarmycin, tiacumicin B, OPT-80, Clostridium spp, and diarrhea. A total of 79 publications were identified and 10 were excluded; 6 review articles and 4 abstracts that were later published as articles. Fidaxomicin's in vitro profile is favorable compared with oral metronidazole and vancomycin, with minimum inhibitory concentrations against C difficile that are 2 dilutions lower. From the 2 published Phase III trials, fidaxomicin was deemed to be noninferior in the treatment of mild to moderate CDI compared with oral vancomycin. Recurrence rates for all strains of CDI were lower with fidaxomicin than vancomycin. Adverse events associated with fidaxomicin were similar to placebo, with nausea and vomiting being the most common. Although no pharmacoeconomic studies have compared fidaxomicin with metronidazole or vancomycin, the current price exceeds $2500 (US) per treatment course. Reports suggest that fidaxomicin is noninferior to oral vancomycin in the treatment of mild or moderate CDI, although no published comparisons with metronidazole exist to date. Additionally, fidaxomicin improved outcomes compared with oral vancomycin in terms of rates of relapse and recurrent CDI, and in patients who might require concomitant antibiotics. Prospective, randomized studies comparing fidaxomicin with metronidazole in the treatment of mild or moderate CDI, as well as against vancomycin for severe CDI, should be undertaken to clarify the exact role of fidaxomicin in clinical practice. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Molecular Epidemiology of Clostridium difficile Infection in Hospitalized Patients in Eastern China.

PubMed

Jin, Dazhi; Luo, Yun; Huang, Chen; Cai, Jian; Ye, Julian; Zheng, Yi; Wang, Liqian; Zhao, Peng; Liu, Anbing; Fang, Weijia; Wang, Xianjun; Xia, Shichang; Jiang, Jianmin; Tang, Yi-Wei

2017-03-01

Few studies on risk factors for and transmission of Clostridium difficile infection (CDI) in China have been reported. A cross-sectional study was conducted for 3 years in eastern China. Consecutive stool specimens from hospitalized patients with diarrhea were cultured for C. difficile. C. difficile isolates from these patients then were analyzed for toxin genes, genotypes, and antimicrobial resistance. A severity score for the CDI in each patient was determined by a blinded review of the medical record, and these scores ranged from 1 to 6. A total of 397 out of 3,953 patients (10.0%) with diarrhea were found to have CDI. Severity of CDI was mild to moderate, and the average (± standard deviation) severity score was 2.61 ± 1.01. C. difficile was isolated from stool specimens in 432 (10.9%) of all the patients who had diarrhea. C. difficile genotypes were determined by multilocus sequence analysis and PCR ribotyping; sequence type 37 (ST37)/ribotype 017 (RT017) ( n = 68, 16.5%) was the dominant genotype. Eleven patients (16.2%) with this genotype had a CDI severity score of 5. Overall, three RTs and four STs were predominant; these genotypes were associated with significantly different antimicrobial resistance patterns in comparison to all genotypes (χ 2 = 79.56 to 97.76; P < 0.001). Independent risk factors associated with CDI included age greater than 55 years (odds ratio [95% confidence interval], 26.80 [18.76 to 38.29]), previous hospitalization (12.42 [8.85 to 17.43]), previous antimicrobial treatment within 8 weeks (150.56 [73.11 to 310.06]), hospital stay more than 3 days before sampling (2.34 [1.71 to 3.22]), undergoing chemotherapy (3.31 [2.22 to 4.92]), and undergoing abdominal surgery (4.82 [3.54 to 6.55]). CDI is clearly a problem in eastern China and has a prevalence of 10.0% in hospitalized patients. Among risk factors for CDI, the advanced age threshold was younger for Chinese patients than that reported for patients in developed countries. Copyright © 2017 American Society for Microbiology.

Improved Resolution Optical Time Stretch Imaging Based on High Efficiency In-Fiber Diffraction.

PubMed

Wang, Guoqing; Yan, Zhijun; Yang, Lei; Zhang, Lin; Wang, Chao

2018-01-12

Most overlooked challenges in ultrafast optical time stretch imaging (OTSI) are sacrificed spatial resolution and higher optical loss. These challenges are originated from optical diffraction devices used in OTSI, which encode image into spectra of ultrashort optical pulses. Conventional free-space diffraction gratings, as widely used in existing OTSI systems, suffer from several inherent drawbacks: limited diffraction efficiency in a non-Littrow configuration due to inherent zeroth-order reflection, high coupling loss between free-space gratings and optical fibers, bulky footprint, and more importantly, sacrificed imaging resolution due to non-full-aperture illumination for individual wavelengths. Here we report resolution-improved and diffraction-efficient OTSI using in-fiber diffraction for the first time to our knowledge. The key to overcome the existing challenges is a 45° tilted fiber grating (TFG), which serves as a compact in-fiber diffraction device offering improved diffraction efficiency (up to 97%), inherent compatibility with optical fibers, and improved imaging resolution owning to almost full-aperture illumination for all illumination wavelengths. 50 million frames per second imaging of fast moving object at 46 m/s with improved imaging resolution has been demonstrated. This conceptually new in-fiber diffraction design opens the way towards cost-effective, compact and high-resolution OTSI systems for image-based high-throughput detection and measurement.

Resolving power of diffraction imaging with an objective: a numerical study.

PubMed

Wang, Wenjin; Liu, Jing; Lu, Jun Qing; Ding, Junhua; Hu, Xin-Hua

2017-05-01

Diffraction imaging in the far-field can detect 3D morphological features of an object for its coherent nature. We describe methods for accurate calculation and analysis of diffraction images of scatterers of single and double spheres by an imaging unit based on microscope objective at non-conjugate positions. A quantitative study of the calculated diffraction imaging in spectral domain has been performed to assess the resolving power of diffraction imaging. It has been shown numerically that with coherent illumination of 532 nm in wavelength the imaging unit can resolve single spheres of 2 μm or larger in diameters and double spheres separated by less than 300 nm between their centers.

Development of a diffraction imaging flow cytometer

PubMed Central

Jacobs, Kenneth M.; Lu, Jun Q.

2013-01-01

Diffraction images record angle-resolved distribution of scattered light from a particle excited by coherent light and can correlate highly with the 3D morphology of a particle. We present a jet-in-fluid design of flow chamber for acquisition of clear diffraction images in a laminar flow. Diffraction images of polystyrene spheres of different diameters were acquired and found to correlate highly with the calculated ones based on the Mie theory. Fast Fourier transform analysis indicated that the measured images can be used to extract sphere diameter values. These results demonstrate the significant potentials of high-throughput diffraction imaging flow cytometry for extracting 3D morphological features of cells. PMID:19794790

Study on High Resolution Membrane-Based Diffractive Optical Imaging on Geostationary Orbit

NASA Astrophysics Data System (ADS)

Jiao, J.; Wang, B.; Wang, C.; Zhang, Y.; Jin, J.; Liu, Z.; Su, Y.; Ruan, N.

2017-05-01

Diffractive optical imaging technology provides a new way to realize high resolution earth observation on geostationary orbit. There are a lot of benefits to use the membrane-based diffractive optical element in ultra-large aperture optical imaging system, including loose tolerance, light weight, easy folding and unfolding, which make it easy to realize high resolution earth observation on geostationary orbit. The implementation of this technology also faces some challenges, including the configuration of the diffractive primary lens, the development of high diffraction efficiency membrane-based diffractive optical elements, and the correction of the chromatic aberration of the diffractive optical elements. Aiming at the configuration of the diffractive primary lens, the "6+1" petal-type unfold scheme is proposed, which consider the compression ratio, the blocking rate and the development complexity. For high diffraction efficiency membrane-based diffractive optical element, a self-collimating method is proposed. The diffraction efficiency is more than 90 % of the theoretical value. For the chromatic aberration correction problem, an optimization method based on schupmann is proposed to make the imaging spectral bandwidth in visible light band reach 100 nm. The above conclusions have reference significance for the development of ultra-large aperture diffractive optical imaging system.

Stray light characteristics of the diffractive telescope system

NASA Astrophysics Data System (ADS)

Liu, Dun; Wang, Lihua; Yang, Wei; Wu, Shibin; Fan, Bin; Wu, Fan

2018-02-01

Diffractive telescope technology is an innovation solution in construction of large light-weight space telescope. However, the nondesign orders of diffractive optical elements (DOEs) may affect the imaging performance as stray light. To study the stray light characteristics of a diffractive telescope, a prototype was developed and its stray light analysis model was established. The stray light characteristics including ghost, point source transmittance, and veiling glare index (VGI) were analyzed. During the star imaging test of the prototype, the ghost images appeared around the star image as the exposure time of the charge-coupled device improving, consistent with the simulation results. The test result of VGI was 67.11%, slightly higher than the calculated value 57.88%. The study shows that the same order diffraction of the diffractive primary lens and correcting DOE is the main factor that causes ghost images. The stray light sources outside the field of view can illuminate the image plane through nondesign orders diffraction of the primary lens and contributes to more than 90% of the stray light flux on the image plane. In summary, it is expected that these works will provide some guidance for optimizing the imaging performance of diffractive telescopes.

Clostridium difficile

PubMed Central

Curry, Scott R.

2017-01-01

SYNOPSIS Clostridium difficile infections (CDI) have emerged as one of the principal threats to the health of hospitalized and immunocompromised patients. Nucleic acid testing for C. difficile toxin genes has eclipsed traditional clinical diagnostics for CDI in sensitivity and is now widespread in clinical use, but preliminary evidence suggests that this may have come at a cost of substantially reduced positive predictive value. The importance of C. difficile colonization is increasingly recognized not only as a source for false positive clinical testing but also as a source of new infections within hospitals and other healthcare environments. In the last five years, several new treatment strategies that capitalize on the increasing understanding of the altered microbiome and host defenses in CDI patients have completed clinical trials, including fecal microbiota transplantation (FMT). This article highlights the changing epidemiology, laboratory diagnostics, pathogenesis, and treatment of CDI. PMID:20513554

SULI Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clevenger, E.

2018-02-02

This project looks at alternative water sources, specifically in the field of desalination and selective ion removal through capacitive deionization (CDI). It project aims to both scale up the desalination capabilities of CDI cells as well as determine the selectivity of CDI for particular ions. My task is to design and build cells that have reproducible performance and characterize the materials for building these cells. The scientific methods I’ve learned through my work in CDI and the data mining and analysis tools I’ve become familiar with through CAES will be important catalysts in my future success in a graduate program.more » The purpose of this presentation is to give a standard of practice for my current method of building of capacitive deionization cells. Parts 1 and 2 will be discussed in which the electrodes are prepared, and the cell is built.« less

Central diabetes insipidus following cardiopulmonary arrest in a dog.

PubMed

Bellis, Tara; Daly, Meredith; Davidson, Benjamin

2015-01-01

To describe a clinical case of transient central diabetes insipidus (CDI) occurring post cardiopulmonary arrest (CPA) in a dog. An 8-week-old dog presented for intensive care after successful resuscitation following CPA. The patient exhibited neurologic deficits at initial presentation and over the following days developed marked polyuria, isosthenuria, and low urine osmolality. Treatment with synthetic vasopressin resulted in a reduction in urine output, increase in urine specific gravity (>50%), and increase in urine osmolality, suggesting a diagnosis of partial CDI. Clinical signs resolved over the following weeks and treatment was discontinued. CPA has been described as a cause of ischemic injury to the pituitary gland resulting in CDI in people. To the authors' knowledge, this is the first report of a dog developing transient partial CDI following CPA and successful resuscitation. © Veterinary Emergency and Critical Care Society 2015.

Effect of metronidazole use on tacrolimus concentrations in transplant patients treated for Clostridium difficile.

PubMed

Early, C R; Park, J M; Dorsch, M P; Pogue, K T; Hanigan, S M

2016-10-01

Two case reports suggest that metronidazole treatment for Clostridium difficile infections (CDI) increases tacrolimus (TAC) trough levels. The primary objective of this study was to determine the clinical significance of this potential interaction in transplant patients receiving CDI treatment. Currently, no robust literature exists to estimate a magnitude of pharmacokinetic interaction between metronidazole and TAC. In this retrospective study, the effects of CDI and metronidazole treatment on TAC levels in 52 adult solid organ transplant patients were investigated. The primary outcome was to determine the difference in dose-normalized TAC levels between baseline and symptom resolution in patients treated with metronidazole or vancomycin. The secondary outcome was to determine the difference in dose-normalized TAC levels at baseline and CDI diagnosis. The average change in log-transformed dose-normalized TAC levels from baseline to symptom resolution was 0.99 for metronidazole (n = 35) and 1.04 for vancomycin (n = 17) treatment. The mean difference between the groups was 0.96 (95% confidence interval: 0.74-1.24). No significant difference was found between dose-normalized TAC levels at CDI diagnosis and baseline (P = 0.37). CDI treatment with metronidazole was not associated with a >30% increase in TAC levels compared with vancomycin. Both treatment groups required TAC dose adjustments to maintain goal TAC levels and those treated with metronidazole did not require a significantly greater dose adjustment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of incidence of hyponatremia between intranasal and oral desmopressin in patients with central diabetes insipidus.

PubMed

Kataoka, Yuko; Nishida, Sachi; Hirakawa, Akihiro; Oiso, Yutaka; Arima, Hiroshi

2015-01-01

Central diabetes insipidus (CDI), which is characterized by polyuria and polydipsia, is caused by a deficiency of the antidiuretic hormone arginine vasopressin (AVP). While CDI is treated with desmopressin, an analogue of AVP, the intranasal formulation is inconvenient and CDI patients reportedly prefer the oral formulation to the intranasal one. In Japan, intranasal desmopressin had been the only formulation for the treatment of CDI until 2012, when the desmopressin orally disintegrating tablet (ODT) was approved for treatment. In this study we analyzed 26 patients with CDI in whom intranasal desmopressin was switched to desmopressin ODT. The mean daily dose of intranasal desmopressin was 10 ± 8 μg/day, and that of desmopressin ODT was 142 ± 59 μg/day. The mean serum sodium levels were 140 ± 5 mmol/L and 140 ± 3 mmol/L with intranasal desmopressin and desmopressin ODT, respectively, and there were no significant differences between these values. The frequency of hyponatremia (<135 mmol/L) with intranasal desmopressin was 11.7% and that with desmopressin ODT was 7.6%, while the frequency of hyponatremia (<130 mmol/L) with intranasal desmopressin was 4.2% and that with desmopressin ODT was 1.3%. Statistical analyses revealed that incidence of hyponatremia was significantly decreased after the switch to desmopressin ODT. Thus, it is suggested that water balance is better controlled with desmopressin ODT than with intranasal desmopressin in patients with CDI.

Broadband diffractive lens or imaging element

DOEpatents

Ceglio, Natale M.; Hawryluk, Andrew M.; London, Richard A.; Seppala, Lynn G.

1993-01-01

A broadband diffractive lens or imaging element produces a sharp focus and/or a high resolution image with broad bandwidth illuminating radiation. The diffractive lens is sectored or segmented into regions, each of which focuses or images a distinct narrowband of radiation but all of which have a common focal length. Alternatively, a serial stack of minus filters, each with a diffraction pattern which focuses or images a distinct narrowband of radiation but all of which have a common focal length, is used. The two approaches can be combined. Multifocal broadband diffractive elements can also be formed. Thin film embodiments are described.

Broadband diffractive lens or imaging element

DOEpatents

Ceglio, N.M.; Hawryluk, A.M.; London, R.A.; Seppala, L.G.

1993-10-26

A broadband diffractive lens or imaging element produces a sharp focus and/or a high resolution image with broad bandwidth illuminating radiation. The diffractive lens is sectored or segmented into regions, each of which focuses or images a distinct narrowband of radiation but all of which have a common focal length. Alternatively, a serial stack of minus filters, each with a diffraction pattern which focuses or images a distinct narrowband of radiation but all of which have a common focal length, is used. The two approaches can be combined. Multifocal broadband diffractive elements can also be formed. Thin film embodiments are described. 21 figures.

Status of the Neutron Imaging and Diffraction Instrument IMAT

NASA Astrophysics Data System (ADS)

Kockelmann, Winfried; Burca, Genoveva; Kelleher, Joe F.; Kabra, Saurabh; Zhang, Shu-Yan; Rhodes, Nigel J.; Schooneveld, Erik M.; Sykora, Jeff; Pooley, Daniel E.; Nightingale, Jim B.; Aliotta, Francesco; Ponterio, Rosa C.; Salvato, Gabriele; Tresoldi, Dario; Vasi, Cirino; McPhate, Jason B.; Tremsin, Anton S.

A cold neutron imaging and diffraction instrument, IMAT, is currently being constructed at the ISIS second target station. IMAT will capitalize on time-of-flight transmission and diffraction techniques available at a pulsed neutron source. Analytical techniques will include neutron radiography, neutron tomography, energy-selective neutron imaging, and spatially resolved diffraction scans for residual strain and texture determination. Commissioning of the instrument will start in 2015, with time-resolving imaging detectors and two diffraction detector prototype modules. IMAT will be operated as a user facility for material science applications and will be open for developments of time-of-flight imaging methods.

Diffractive shear interferometry for extreme ultraviolet high-resolution lensless imaging

NASA Astrophysics Data System (ADS)

Jansen, G. S. M.; de Beurs, A.; Liu, X.; Eikema, K. S. E.; Witte, S.

2018-05-01

We demonstrate a novel imaging approach and associated reconstruction algorithm for far-field coherent diffractive imaging, based on the measurement of a pair of laterally sheared diffraction patterns. The differential phase profile retrieved from such a measurement leads to improved reconstruction accuracy, increased robustness against noise, and faster convergence compared to traditional coherent diffractive imaging methods. We measure laterally sheared diffraction patterns using Fourier-transform spectroscopy with two phase-locked pulse pairs from a high harmonic source. Using this approach, we demonstrate spectrally resolved imaging at extreme ultraviolet wavelengths between 28 and 35 nm.

Structured illumination multimodal 3D-resolved quantitative phase and fluorescence sub-diffraction microscopy

PubMed Central

Chowdhury, Shwetadwip; Eldridge, Will J.; Wax, Adam; Izatt, Joseph A.

2017-01-01

Sub-diffraction resolution imaging has played a pivotal role in biological research by visualizing key, but previously unresolvable, sub-cellular structures. Unfortunately, applications of far-field sub-diffraction resolution are currently divided between fluorescent and coherent-diffraction regimes, and a multimodal sub-diffraction technique that bridges this gap has not yet been demonstrated. Here we report that structured illumination (SI) allows multimodal sub-diffraction imaging of both coherent quantitative-phase (QP) and fluorescence. Due to SI’s conventionally fluorescent applications, we first demonstrate the principle of SI-enabled three-dimensional (3D) QP sub-diffraction imaging with calibration microspheres. Image analysis confirmed enhanced lateral and axial resolutions over diffraction-limited QP imaging, and established striking parallels between coherent SI and conventional optical diffraction tomography. We next introduce an optical system utilizing SI to achieve 3D sub-diffraction, multimodal QP/fluorescent visualization of A549 biological cells fluorescently tagged for F-actin. Our results suggest that SI has a unique utility in studying biological phenomena with significant molecular, biophysical, and biochemical components. PMID:28663887

Faradaic reactions in capacitive deionization (CDI) - problems and possibilities: A review.

PubMed

Zhang, Changyong; He, Di; Ma, Jinxing; Tang, Wangwang; Waite, T David

2018-01-01

Capacitive deionization (CDI) is considered to be one of the most promising technologies for the desalination of brackish water with low to medium salinity. In practical applications, Faradaic redox reactions occurring in CDI may have both negative and positive effects on CDI performance. In this review, we present an overview of the types and mechanisms of Faradaic reactions in CDI systems including anodic oxidation of carbon electrodes, cathodic reduction of oxygen and Faradaic ion storage and identify their apparent negative and positive effects on water desalination. A variety of strategies including development of novel electrode materials and use of alternative configurations and/or operational modes are proposed for the purpose of mitigation or elimination of the deterioration of electrodes and the formation of byproducts caused by undesired side Faradaic reactions. It is also recognized that Faradaic reactions facilitate a variety of exciting new applications including i) the incorporation of intercalation electrodes to enhance water desalination or to selectively separate certain ions through reversible Faradaic reactions and ii) the use of particular anodic oxidation and cathodic reduction reactions to realize functions such as water disinfection and contaminant removal. Copyright © 2017 Elsevier Ltd. All rights reserved.

Particulate-free porous silicon networks for efficient capacitive deionization water desalination

PubMed Central

Metke, Thomas; Westover, Andrew S.; Carter, Rachel; Oakes, Landon; Douglas, Anna; Pint, Cary L.

2016-01-01

Energy efficient water desalination processes employing low-cost and earth-abundant materials is a critical step to sustainably manage future human needs for clean water resources. Here we demonstrate that porous silicon – a material harnessing earth abundance, cost, and environmental/biological compatibility is a candidate material for water desalination. With appropriate surface passivation of the porous silicon material to prevent surface corrosion in aqueous environments, we show that porous silicon templates can enable salt removal in capacitive deionization (CDI) ranging from 0.36% by mass at the onset from fresh to brackish water (10 mM, or 0.06% salinity) to 0.52% in ocean water salt concentrations (500 mM, or ~0.3% salinity). This is on par with reports of most carbon nanomaterial based CDI systems based on particulate electrodes and covers the full salinity range required of a CDI system with a total ocean-to-fresh water required energy input of ~1.45 Wh/L. The use of porous silicon for CDI enables new routes to directly couple water desalination technology with microfluidic systems and photovoltaics that natively use silicon materials, while mitigating adverse effects of water contamination occurring from nanoparticulate-based CDI electrodes. PMID:27101809

Particulate-free porous silicon networks for efficient capacitive deionization water desalination.

PubMed

Metke, Thomas; Westover, Andrew S; Carter, Rachel; Oakes, Landon; Douglas, Anna; Pint, Cary L

2016-04-22

Energy efficient water desalination processes employing low-cost and earth-abundant materials is a critical step to sustainably manage future human needs for clean water resources. Here we demonstrate that porous silicon - a material harnessing earth abundance, cost, and environmental/biological compatibility is a candidate material for water desalination. With appropriate surface passivation of the porous silicon material to prevent surface corrosion in aqueous environments, we show that porous silicon templates can enable salt removal in capacitive deionization (CDI) ranging from 0.36% by mass at the onset from fresh to brackish water (10 mM, or 0.06% salinity) to 0.52% in ocean water salt concentrations (500 mM, or ~0.3% salinity). This is on par with reports of most carbon nanomaterial based CDI systems based on particulate electrodes and covers the full salinity range required of a CDI system with a total ocean-to-fresh water required energy input of ~1.45 Wh/L. The use of porous silicon for CDI enables new routes to directly couple water desalination technology with microfluidic systems and photovoltaics that natively use silicon materials, while mitigating adverse effects of water contamination occurring from nanoparticulate-based CDI electrodes.

75 FR 11916 - Chrysler Group LLC, Formerly Known as Chrysler LLC, Conner Avenue Assembly Plant, Including On...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-12

..., CDI, Syncreon and Caravan Knight Facilities Management LLC; Detriot, MI; Amended Certification... workers from Aerotek, CDI, Syncreon and Caravan Knight Facilities Management LLC, Detroit, Michigan, who...

CDI Sensitivity and Crosstrack Error on Nonprecision Approaches

DOT National Transportation Integrated Search

1991-01-01

This study was conducted to determine the influence of course deviation : indicator (CDI) sensitivity on pilot tracking error during nonprecision approaches. : Twelve pilots flew an instrumented single-engine airplane on 144 approaches at six : diffe...

Polymerization of beta-amino acids in aqueous solution

NASA Technical Reports Server (NTRS)

Liu, R.; Orgel, L. E.; Bada, J. L. (Principal Investigator)

1998-01-01

We have compared carbonyl diimidazole (CDI) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC) as activating agents for the oligomerization of negatively-charged alpha- and beta-amino acids in homogeneous aqueous solution. alpha-Amino acids can be oligomerized efficiently using CDI, but not by EDAC. beta-Amino acids can be oligomerized efficiently using EDAC, but not by CDI. Aspartic acid, an alpha- and beta-dicarboxylic acid is oligomerized efficiently by both reagents. These results are explained in terms of the mechanisms of the reactions, and their relevance to prebiotic chemistry is discussed.

Streaking images that appear only in the plane of diffraction in undoped GaAs single crystals: Diffraction imaging (topography) by monochromatic synchrotron radiation

NASA Technical Reports Server (NTRS)

Kuriyama, Masao; Steiner, Bruce; Dobbyn, Ronald C.; Laor, Uri; Larson, David; Brown, Margaret

1988-01-01

Streaking images restricted to the direction of the diffraction (scattering) vector have been observed on transmission through undoped GaAs. These disruption images (caused by the reduction of diffraction in the direction of observation) appear both in the forward and in Bragg diffracted directions in monochromatic synchrontron radiation diffraction imaging. This previously unobserved phenomenon can be explained in terms of planar defects (interfaces) or platelets which affects the absorption coefficient in anomalous transmission. Such regions of the crystal look perfect despite the presence of imperfections when the scattering vector is not perpendicular to the normal of the platelets. The observed crystallographic orientation of these interfaces strongly indicates that they are antiphase boundaries.

Comparative Effectiveness of Vancomycin and Metronidazole for the Prevention of Recurrence and Death in Patients With Clostridium difficile Infection.

PubMed

Stevens, Vanessa W; Nelson, Richard E; Schwab-Daugherty, Elyse M; Khader, Karim; Jones, Makoto M; Brown, Kevin A; Greene, Tom; Croft, Lindsay D; Neuhauser, Melinda; Glassman, Peter; Goetz, Matthew Bidwell; Samore, Matthew H; Rubin, Michael A

2017-04-01

Metronidazole hydrochloride has historically been considered first-line therapy for patients with mild to moderate Clostridium difficile infection (CDI) but is inferior to vancomycin hydrochloride for clinical cure. The choice of therapy may likewise have substantial consequences on other downstream outcomes, such as recurrence and mortality, although these secondary outcomes have been less studied. To evaluate the risk of recurrence and all-cause 30-day mortality among patients receiving metronidazole or vancomycin for the treatment of mild to moderate and severe CDI. This retrospective, propensity-matched cohort study evaluated patients treated for CDI, defined as a positive laboratory test result for the presence of C difficile toxins or toxin genes in a stool sample, in the US Department of Veterans Affairs health care system from January 1, 2005, through December 31, 2012. Data analysis was performed from February 7, 2015, through November 22, 2016. Treatment with vancomycin or metronidazole. The outcomes of interest in this study were CDI recurrence and all-cause 30-day mortality. Recurrence was defined as a second positive laboratory test result within 8 weeks of the initial CDI diagnosis. All-cause 30-day mortality was defined as death from any cause within 30 days of the initial CDI diagnosis. A total of 47 471 patients (mean [SD] age, 68.8 [13.3] years; 1947 women [4.1%] and 45 524 men [95.9%]) developed CDI, were treated with vancomycin or metronidazole, and met criteria for entry into the study. Of 47 147 eligible first treatment episodes, 2068 (4.4%) were with vancomycin. Those 2068 patients were matched to 8069 patients in the metronidazole group for a total of 10 137 included patients. Subcohorts were constructed that comprised 5452 patients with mild to moderate disease and 3130 patients with severe disease. There were no differences in the risk of recurrence between patients treated with vancomycin vs those treated with metronidazole in any of the disease severity cohorts. Among patients in the any severity cohort, those who were treated with vancomycin were less likely to die (adjusted relative risk, 0.86; 95% CI, 0.74 to 0.98; adjusted risk difference, -0.02; 95% CI, -0.03 to -0.01). No significant difference was found in the risk of mortality between treatment groups among patients with mild to moderate CDI, but vancomycin significantly reduced the risk of all-cause 30-day mortality among patients with severe CDI (adjusted relative risk, 0.79; 95% CI, 0.65 to 0.97; adjusted risk difference, -0.04; 95% CI, -0.07 to -0.01). Recurrence rates were similar among patients treated with vancomycin and metronidazole. However, the risk of 30-day mortality was significantly reduced among patients who received vancomycin. Our findings may further justify the use of vancomycin as initial therapy for severe CDI.

Epidemiology of Clostridium difficile in infants in Oxfordshire, UK: Risk factors for colonization and carriage, and genetic overlap with regional C. difficile infection strains.

PubMed

Stoesser, Nicole; Eyre, David W; Quan, T Phuong; Godwin, Heather; Pill, Gemma; Mbuvi, Emily; Vaughan, Alison; Griffiths, David; Martin, Jessica; Fawley, Warren; Dingle, Kate E; Oakley, Sarah; Wanelik, Kazimierz; Finney, John M; Kachrimanidou, Melina; Moore, Catrin E; Gorbach, Sherwood; Riley, Thomas V; Crook, Derrick W; Peto, Tim E A; Wilcox, Mark H; Walker, A Sarah

2017-01-01

Approximately 30-40% of children <1 year of age are Clostridium difficile colonized, and may represent a reservoir for adult C. difficile infections (CDI). Risk factors for colonization with toxigenic versus non-toxigenic C. difficile strains and longitudinal acquisition dynamics in infants remain incompletely characterized. Predominantly healthy infants (≤2 years) were recruited in Oxfordshire, UK, and provided ≥1 fecal samples. Independent risk factors for toxigenic/non-toxigenic C. difficile colonization and acquisition were identified using multivariable regression. Infant C. difficile isolates were whole-genome sequenced to assay genetic diversity and prevalence of toxin-associated genes, and compared with sequenced strains from Oxfordshire CDI cases. 338/365 enrolled infants provided 1332 fecal samples, representing 158 C. difficile colonization or carriage episodes (107[68%] toxigenic). Initial colonization was associated with age, and reduced with breastfeeding but increased with pet dogs. Acquisition was associated with older age, Caesarean delivery, and diarrhea. Breastfeeding and pre-existing C. difficile colonization reduced acquisition risk. Overall 13% of CDI C. difficile strains were genetically related to infant strains. 29(18%) infant C. difficile sequences were consistent with recent direct/indirect transmission to/from Oxfordshire CDI cases (≤2 single nucleotide variants [SNVs]); 79(50%) shared a common origin with an Oxfordshire CDI case within the last ~5 years (0-10 SNVs). The hypervirulent, epidemic ST1/ribotype 027 remained notably absent in infants in this large study, as did other lineages such as STs 10/44 (ribotype 015); the most common strain in infants was ST2 (ribotype 020/014)(22%). In predominantly healthy infants without significant healthcare exposure C. difficile colonization and acquisition reflect environmental exposures, with pet dogs identified as a novel risk factor. Genetic overlap between some infant strains and those isolated from CDI cases suggest common community reservoirs of these C. difficile lineages, contrasting with those lineages found only in CDI cases, and therefore more consistent with healthcare-associated spread.

Low sensitivity of fecal toxin A/B enzyme immunoassay for diagnosis of Clostridium difficile infection in immunocompromised patients.

PubMed

Erb, S; Frei, R; Strandén, A M; Dangel, M; Tschudin-Sutter, S; Widmer, A F

2015-11-01

The optimal approach in laboratory diagnosis of Clostridium difficile infection (CDI) is still not well defined. Toxigenic culture (TC) or alternatively fecal toxin assay by cell cytotoxicity neutralization assay are considered to be the reference standard, but these methods are time-consuming and labor intensive. In many medical centers, diagnosis of CDI is therefore still based on fecal toxin A/B enzyme immunoassay (EIA) directly from stool alone, balancing cost and speed against limited diagnostic sensitivity. The aim of the study was to assess in which patient population the additional workload of TC is justified. All consecutive stool specimens submitted for diagnosis of suspected CDI between 2004 and 2011 at a tertiary-care center were examined by toxin EIA and TC. Clinical data of patients with established diagnosis of CDI were collected in a standardized case-report form. From 12,481 stool specimens submitted to the microbiologic laboratory, 480 (3.8%) fulfilled CDI criteria; 274 (57.1%) were diagnosed by toxin EIA; and an additional 206 (42.9%) were diagnosed by TC when toxin EIA was negative. Independent predictors for negative toxin EIA but positive TC were high-dose corticosteroids (odds ratio (OR) 2.97, 95% confidence interval (CI) 1.50-5.90, p 0.002), leukocytopenia <1000/μL (OR 2.52, 95% CI 1.22-5.23, p 0.013) and nonsevere CDI (OR 2.21, 95% CI 1.39-3.50, p 0.001). There was no difference in outcomes such as in-hospital mortality and recurrence between both groups. In conclusion, negative toxin EIA does not rule out CDI in immunocompromised patients in the setting of relevant clinical symptoms. Methods with improved sensitivity such as TC or PCR should be used, particularly in this patient population. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Clostridium difficile as a cause of healthcare-associated diarrhoea among children in Auckland, New Zealand: clinical and molecular epidemiology.

PubMed

Sathyendran, V; McAuliffe, G N; Swager, T; Freeman, J T; Taylor, S L; Roberts, S A

2014-10-01

We aimed to determine the incidence of Clostridium difficile infection (CDI), the molecular epidemiology of circulating C. difficile strains and risk factors for CDI among hospitalised children in the Auckland region. A cross-sectional study was undertaken of hospitalised children <15 years of age in two hospitals investigated for healthcare-associated diarrhoea between November 2011 and June 2012. Stool specimens were analysed for the presence of C. difficile using a two-step testing algorithm including polymerase chain reaction (PCR). C. difficile was cultured and PCR ribotyping performed. Demographic data, illness characteristics and risk factors were compared between children with and without CDI. Non-duplicate stool specimens were collected from 320 children with a median age of 1.2 years (range 3 days to 15 years). Forty-six patients (14 %) tested met the definition for CDI. The overall incidence of CDI was 2.0 per 10,000 bed days. The percentage of positive tests among neonates was only 2.6 %. PCR ribotyping showed a range of strains, with ribotype 014 being the most common. Significant risk factors for CDI were treatment with proton pump inhibitors [risk ratio (RR) 1.74, 95 % confidence interval (CI) 1.09-5.59; p = 0.002], presence of underlying malignancy (RR 2.71, 95 % CI 1.65-4.62; p = 0.001), receiving chemotherapy (RR 2.70, 95 % CI 1.41-4.83; p = 0.003) and exposure to antibiotics (RR 1.17, 95 % CI 0.99-1.17; p = 0.03). C. difficile is an important cause of healthcare-associated diarrhoea in this paediatric population. The notion that neonatal populations will always have high rates of colonisation with C. difficile may not be correct. Several risk factors associated with CDI among adults were also found to be significant.

Vancomycin for the treatment of Clostridium difficile Infection: for whom is this expensive bullet really magic?

PubMed

Pepin, Jacques

2008-05-15

The epidemiology, clinical severity, and case-fatality ratio of Clostridium difficile infection (CDI) changed dramatically with the emergence of a toxin hyperproducing strain (BI/NAP1/027) in North America and Europe in 2000. For the treatment of CDI, metronidazole and vancomycin remain the 2 most commonly used drugs. The 3 randomized controlled trials published thus far, as well as the upcoming tolevamer trial, use intermediate outcomes, rather than the outcomes that now preoccupy clinicians: the frequency of complications or recurrence. The major advantage of metronidazole is its low price. The major advantage of orally administered vancomycin is its more favorable pharmacokinetics. Facilitating vancomycin-resistant enterococci colonization and/or infection is a potential drawback of both drugs. Pending the development of a prospectively validated scoring system, members of the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America expert committee will define severe CDI as present in any patient with a leukocyte count > or =15,000 cells/mm(3) or a creatinine level increased by > or =50% from baseline. For patients with mild-to-moderate CDI (defined by a leukocyte count <15000 cells/mm(3) and a creatinine level <1.5 times the baseline value), there is no evidence that treatment with vancomycin is superior to treatment with metronidazole (even for intermediate outcomes), and metronidazole therapy should be preferred. For patients with severe CDI who are not infected with BI/NAP1/027, there is reasonable evidence that the better pharmacokinetics of vancomycin translate into a lower probability of complications. For those patients who are infected with BI/NAP1/027, the superiority of vancomycin therapy remains to be proven. In practice, because it is not yet possible to rapidly type the strains, all patients with severe CDI should be treated with vancomycin. Future trials should use complicated CDI and recurrences as their primary outcomes.

Surveillance of Clostridium difficile Infections: Results from a Six-Year Retrospective Study in Nine Hospitals of a North Italian Local Health Authority

PubMed Central

Roncarati, Greta; Dallolio, Laura; Leoni, Erica; Panico, Manuela; Zanni, Angela; Farruggia, Patrizia

2017-01-01

Clostridium difficile is an emerging cause of healthcare associated infections. In nine hospitals of an Italian Local Health Authority the episodes of C. difficile infection (CDI) were identified using the data registered by the centralized Laboratory Information System, from 2010 to 2015. CDI incidence (positive patients for A and/or B toxins per patients-days) was analysed per year, hospital, and ward. A number of cases approximately equivalent to the mean of identified cases per year were studied retrospectively to highlight the risk factors associated to CDI and their severity. Nine hundred and forty-two patients affected by CDI were identified. The overall incidence was 3.7/10,000 patients-days, with a stable trend across the six years and the highest rates observed in smaller and outlying hospitals (up to 17.8/10,000), where the admitted patients were older and the wards with the highest incidences (long-term-care: 7.6/10,000, general medicine: 5.7/10,000) were more represented. The mean age of patients in each hospital was correlated with CDI rates. Of the 101 cases selected for the retrospective study, 86.1% were healthcare associated, 10.9% community acquired; 9.1% met the criteria for recurrent case and 23.8% for severe case of CDI. The overall mortality rate was 28.7%. Comorbidity conditions occurred in 91.1%, previous exposure to antibiotics in 76.2%, and proton pump inhibitors in 77.2%. Recurrent and severe cases were significantly associated with renal insufficiency and creatinine levels ≥2 mg/dL. The survey based on the centralized laboratory data was useful to study CDI epidemiology in the different centres in order to identify possible weaknesses and plan control strategies, in particular the reinforcement of staff training, mainly targeted at compliance with contact precautions and hand hygiene. PMID:28075419

Investigation to identify a resource-efficient case-control methodology for determining antibiotics associated with Clostridium difficile infection.

PubMed

Chung, Philip; Currie, Brian; Guo, Yi; Talansky, Moshe; Brown, Shakara; Ostrowsky, Belinda

2014-10-01

Antimicrobial exposure remains an important risk factor for developing Clostridium difficile infection (CDI). Efficient method to identify antibiotics associated with CDI is important for formulating strategies to curtail their use. As a prelude to a more extensive Agency for Healthcare Research and Quality-funded project (Evaluation & Research on Antimicrobial Stewardship's Effect on Clostridium difficile), we undertook an exploratory evaluation to determine a resource-efficient method for identifying antibiotic targets for antimicrobial stewardship interventions. The study compared a series of 6 focused case-control studies. Cases consisted of patients with laboratory-confirmed CDI admitted from July-October 2009. Controls were selected from patients without CDI hospitalized during the same period. Five groups of controls were matched to cases (2:1 ratio) using group-specific matching criteria, including admission date, age, type of admission, length of stay (LOS) to discharge, and/or LOS to CDI diagnosis. The final control group was selected from patients who received antibiotics during hospitalization. Data, including demographics and antibiotic usage, were compared between case and control groups. A total of 126 cases were matched to 6 groups of 252 controls. For control groups 1-5, the use of piperacillin and tazobactam, ceftriaxone or cefepime, ciprofloxacin or moxifloxacin, intravenous vancomycin, azithromycin, and antibiotics of last resort were significantly more frequent in case than control patients. For the final control group, the associations between ceftriaxone or cefepime, and ciprofloxacin or moxifloxacin use and CDI no longer persisted. This could in part be explained by differences in comorbidities between case and control patients even with stringent matching criteria. Use of a simple matching strategy to conduct case-control studies is an efficient and feasible compromise strategy, especially in resource-limited settings, to identify high-risk antibiotics associated with CDI. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Influence of seismic diffraction for high-resolution imaging: applications in offshore Malaysia

NASA Astrophysics Data System (ADS)

Bashir, Yasir; Ghosh, Deva Prasad; Sum, Chow Weng

2018-04-01

Small-scale geological discontinuities are not easy to detect and image in seismic data, as these features represent themselves as diffracted rather than reflected waves. However, the combined reflected and diffracted image contains full wave information and is of great value to an interpreter, for instance enabling the identification of faults, fractures, and surfaces in built-up carbonate. Although diffraction imaging has a resolution below the typical seismic wavelength, if the wavelength is much smaller than the width of the discontinuity then interference effects can be ignored, as they would not play a role in generating the seismic diffractions. In this paper, by means of synthetic examples and real data, the potential of diffraction separation for high-resolution seismic imaging is revealed and choosing the best method for preserving diffraction are discussed. We illustrate the accuracy of separating diffractions using the plane-wave destruction (PWD) and dip frequency filtering (DFF) techniques on data from the Sarawak Basin, a carbonate field. PWD is able to preserve the diffraction more intelligently than DFF, which is proven in the results by the model and real data. The final results illustrate the effectiveness of diffraction separation and possible imaging for high-resolution seismic data of small but significant geological features.

78 FR 61388 - TA-W-82,705, the Boeing Company Boeing Commercial Aircraft, (BCA) Including On-Site Leased...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-03

..., (BCA) Including On-Site Leased Workers From Adecco, USA, Inc., Cascade Engineering, CDI Corporation...., Cascade Engineering, CDI Corporation, Chipton Ross, Inc., Comforce Corporation, Computer Staffing Services...

Determining the cause of recurrent Clostridium difficile infection using whole genome sequencing.

PubMed

Sim, James Heng Chiak; Truong, Cynthia; Minot, Samuel S; Greenfield, Nick; Budvytiene, Indre; Lohith, Akshar; Anikst, Victoria; Pourmand, Nader; Banaei, Niaz

2017-01-01

Understanding the contribution of relapse and reinfection to recurrent Clostridium difficile infection (CDI) has implications for therapy and infection prevention, respectively. We used whole genome sequencing to determine the relation of C. difficile strains isolated from patients with recurrent CDI at an academic medical center in the United States. Thirty-five toxigenic C. difficile isolates from 16 patients with 19 recurrent CDI episodes with median time of 53.5days (range, 13-362) between episodes were whole genome sequenced on the Illumina MiSeq platform. In 84% (16) of recurrences, the cause of recurrence was relapse with prior strain of C. difficile. In 16% (3) of recurrent episodes, reinfection with a new strain of C. difficile was the cause. In conclusion, the majority of CDI recurrences at our institution were due to infection with the same strain rather than infection with a new strain. Copyright © 2016 Elsevier Inc. All rights reserved.

Invasive listeriosis in a patient with several episodes of antibiotic associated colitis presumably due to Clostridium difficile.

PubMed

Carannante, Novella; Pagliano, Pasquale; Rossi, Marco; Attanasio, Vittorio; Rescigno, Carolina; Corte, Laura; Tascini, Carlo; Cardinali, Gianluigi

2017-06-01

A 62-year-old man developed a blood stream infection and meningitis due to Listeria monocytogenes, 20 days after an episode of pseudo-membranous colitis. The patient, hospitalized for the first time for transurethral prostatectomy, was readmitted 20 days later with watery diarrhea. Pseudo-membranous colitis was diagnosed and treated successfully, without testing for Clostridium difficile infection (CDI). After 15 more days, the patient developed again diarrhea, fever and confusion. Hospitalized again, blood and cerebrospinal fluid cultures resulted positive for L. monocytogenes. The patient was treated successfully and a diagnosis of recurrent CDI was confirmed following culture and nucleic acid amplification assays both positive for C. difficile. This is the first report of an invasive listeriosis after CDI underlines the importance of taking greater awareness in complicated blood stream infections that may arise after CDI.

Capacitive deionization coupled with microbial fuel cells to desalinate low-concentration salt water.

PubMed

Yuan, Lulu; Yang, Xufei; Liang, Peng; Wang, Lei; Huang, Zheng-Hong; Wei, Jincheng; Huang, Xia

2012-04-01

A new technology (CDI-MFC) that combined capacitive deionization (CDI) and microbial fuel cell (MFC) was developed to treat low-concentration salt water with NaCl concentration of 60mg/L. The water desalination rate was 35.6mg/(Lh), meanwhile the charge efficiency was 21.8%. Two desorption modes were investigated: discharging (DC) mode and short circuit (SC) mode. The desalination rate in the DC mode was 200.6±3.1mg/(Lh), 47.8% higher than that in the SC mode [135.7±15.3mg/(Lh)]. The average current in the DC mode was also much higher than that of the SC mode. The energy stored in the CDI cell has been reused to enhance the electron production of MFC by the discharging desorption mode (DC mode), which offers an approach to recover the electrostatic energy in the CDI cell. Copyright © 2012 Elsevier Ltd. All rights reserved.

Autoimmune central diabetes insipidus in a patient with ureaplasma urealyticum infection and review on new triggers of immune response.

PubMed

Murdaca, Giuseppe; Russo, Rodolfo; Spanò, Francesca; Ferone, Diego; Albertelli, Manuela; Schenone, Angelo; Contatore, Miriam; Guastalla, Andrea; De Bellis, Annamaria; Garibotto, Giacomo; Puppo, Francesco

2015-12-01

Diabetes insipidus is a disease in which large volumes of dilute urine (polyuria) are excreted due to vasopressin (AVP) deficiency [central diabetes insipidus (CDI)] or to AVP resistance (nephrogenic diabetes insipidus). In the majority of patients, the occurrence of CDI is related to the destruction or degeneration of neurons of the hypothalamic supraoptic and paraventricular nuclei. The most common and well recognized causes include local inflammatory or autoimmune diseases, vascular disorders, Langerhans cell histiocytosis (LCH), sarcoidosis, tumors such as germinoma/craniopharyngioma or metastases, traumatic brain injuries, intracranial surgery, and midline cerebral and cranial malformations. Here we have the opportunity to describe an unusual case of female patient who developed autoimmune CDI following ureaplasma urealyticum infection and to review the literature on this uncommon feature. Moreover, we also discussed the potential mechanisms by which ureaplasma urealyticum might favor the development of autoimmune CDI.

Enhancing the Value of the Federal Climate-Relevant Data Through the Climate Data Initiative

NASA Astrophysics Data System (ADS)

Meyer, D. J.; Pinheiro Privette, A. C.; Bugbee, K.

2016-12-01

The Climate Data Initiative (CDI), launched by the Obama Administration in March of 2014, is an effort to leverage the extensive open Federal data to spur innovation and private-sector entrepreneurship around climate resilience. As part of this initiative the federal agencies identified key climate-relevant datasets and made them discoverable through an online catalog at data.gov/climate. Although this was a critical and foundational step to improve the discoverability to these federal data, enhancements to its accessibility and usability require a deeper understanding of the data needs of the different user communities. More recently, the focus of the CDI project has evolved toward extended engagement with communities of resilience trough the identification of use-cases. This effort aims to guide the next steps of the CDI project to make the CDI resources more easily integrated into decision support systems

Neurosarcoidosis-associated central diabetes insipidus masked by adrenal insufficiency

PubMed Central

Non, Lemuel; Brito, Daniel; Anastasopoulou, Catherine

2015-01-01

Central diabetes insipidus (CDI) is an infrequent complication of neurosarcoidosis (NS). Its presentation may be masked by adrenal insufficiency (AI) and uncovered by subsequent steroid replacement. A 45-year-old woman with a history of NS presented 2 weeks after abrupt cessation of prednisone with nausea, vomiting, decreased oral intake and confusion. She was diagnosed with secondary AI and intravenous hydrocortisone was promptly begun. Over the next few days, however, the patient developed severe thirst and polyuria exceeding 6 L of urine per day, accompanied by hypernatraemia and hypo-osmolar urine. She was presumed to have CDI due to NS, and intranasal desmopressin was administered. This eventually normalised her urine output and serum sodium. The patient was discharged improved on intranasal desmopressin and oral prednisone. AI may mask the manifestation of CDI because low serum cortisol impairs renal-free water clearance. Steroid replacement reverses this process and unmasks an underlying CDI. PMID:25612752

Neurosarcoidosis-associated central diabetes insipidus masked by adrenal insufficiency.

PubMed

Non, Lemuel; Brito, Daniel; Anastasopoulou, Catherine

2015-01-22

Central diabetes insipidus (CDI) is an infrequent complication of neurosarcoidosis (NS). Its presentation may be masked by adrenal insufficiency (AI) and uncovered by subsequent steroid replacement. A 45-year-old woman with a history of NS presented 2 weeks after abrupt cessation of prednisone with nausea, vomiting, decreased oral intake and confusion. She was diagnosed with secondary AI and intravenous hydrocortisone was promptly begun. Over the next few days, however, the patient developed severe thirst and polyuria exceeding 6 L of urine per day, accompanied by hypernatraemia and hypo-osmolar urine. She was presumed to have CDI due to NS, and intranasal desmopressin was administered. This eventually normalised her urine output and serum sodium. The patient was discharged improved on intranasal desmopressin and oral prednisone. AI may mask the manifestation of CDI because low serum cortisol impairs renal-free water clearance. Steroid replacement reverses this process and unmasks an underlying CDI. 2015 BMJ Publishing Group Ltd.

Characterization of Resistances of a Capacitive Deionization System

DOE PAGES

Qu, Yatian; Baumann, Theodore F.; Santiago, Juan G.; ...

2015-07-27

Capacitive deionization (CDI) is a promising desalination technology, which operates at low pressure, low temperature, requires little infrastructure, and has the potential to consume less energy for brackish water desalination. However, CDI devices consume significantly more energy than the theoretical thermodynamic minimum, and this is at least partly due to resistive power dissipation. We here report our efforts to characterize electric resistances in a CDI system, with a focus on the resistance associated with the contact between current collectors and porous electrodes. We present an equivalent circuit model to describe resistive components in a CDI cell. We propose measurable figuresmore » of merit to characterize cell resistance. We also show that contact pressure between porous electrodes and current collectors can significantly reduce contact resistance. As a result, we propose and test an alternative electrical contact configuration which uses a pore-filling conductive adhesive (silver epoxy) and achieves significant reductions in contact resistance.« less

Image cloning beyond diffraction based on coherent population trapping in a hot rubidium vapor.

PubMed

Ding, Dong-Sheng; Zhou, Zhi-Yuan; Shi, Bao-Sen

2014-01-15

Following recent theoretical predictions, we report on an experimental realization of image cloning beyond usual diffraction, through the coherent population trapping (CPT) effect in a hot rubidium vapor. In our experiment, an alphabet letter image was transferred from a coupling field to a probe field, based on the CPT effect. Furthermore, we demonstrate that the cloned probe field carrying the image is transmitted without the usual diffraction. To our best knowledge, this is the first experimental report about image cloning beyond diffraction. We believe this mechanism, based on CPT, has definite and important applications in image metrology, image processing, and biomedical imaging.

Can a toxin gene NAAT be used to predict toxin EIA and the severity of Clostridium difficile infection?

PubMed

Garvey, Mark I; Bradley, Craig W; Wilkinson, Martyn A C; Holden, Elisabeth

2017-01-01

Diagnosis of C. difficile infection (CDI) is controversial because of the many laboratory methods available and their lack of ability to distinguish between carriage, mild or severe disease. Here we describe whether a low C. difficile toxin B nucleic acid amplification test (NAAT) cycle threshold (CT) can predict toxin EIA, CDI severity and mortality. A three-stage algorithm was employed for CDI testing, comprising a screening test for glutamate dehydrogenase (GDH), followed by a NAAT, then a toxin enzyme immunoassay (EIA). All diarrhoeal samples positive for GDH and NAAT between 2012 and 2016 were analysed. The performance of the NAAT CT value as a classifier of toxin EIA outcome was analysed using a ROC curve; patient mortality was compared to CTs and toxin EIA via linear regression models. A CT value ≤26 was associated with ≥72% toxin EIA positivity; applying a logistic regression model we demonstrated an association between low CT values and toxin EIA positivity. A CT value of ≤26 was significantly associated ( p  = 0.0262) with increased one month mortality, severe cases of CDI or failure of first line treatment. The ROC curve probabilities demonstrated a CT cut off value of 26.6. Here we demonstrate that a CT ≤26 indicates more severe CDI and is associated with higher mortality. Samples with a low CT value are often toxin EIA positive, questioning the need for this additional EIA test. A CT ≤26 could be used to assess the potential for severity of CDI and guide patient treatment.

Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection.

PubMed

Weingarden, Alexa R; Chen, Chi; Bobr, Aleh; Yao, Dan; Lu, Yuwei; Nelson, Valerie M; Sadowsky, Michael J; Khoruts, Alexander

2014-02-15

Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for refractory, recurrent Clostridium difficile infection (CDI), which develops following antibiotic treatments. Intestinal microbiota play a critical role in the metabolism of bile acids in the colon, which in turn have major effects on the lifecycle of C. difficile bacteria. We hypothesized that fecal bile acid composition is altered in patients with recurrent CDI and that FMT results in its normalization. General metabolomics and targeted bile acid analyses were performed on fecal extracts from patients with recurrent CDI treated with FMT and their donors. In addition, 16S rRNA gene sequencing was used to determine the bacterial composition of pre- and post-FMT fecal samples. Taxonomic bacterial composition of fecal samples from FMT recipients showed rapid change and became similar to the donor after the procedure. Pre-FMT fecal samples contained high concentrations of primary bile acids and bile salts, while secondary bile acids were nearly undetectable. In contrast, post-FMT fecal samples contained mostly secondary bile acids, as did non-CDI donor samples. Therefore, our analysis showed that FMT resulted in normalization of fecal bacterial community structure and metabolic composition. Importantly, metabolism of bile salts and primary bile acids to secondary bile acids is disrupted in patients with recurrent CDI, and FMT corrects this abnormality. Since individual bile salts and bile acids have pro-germinant and inhibitory activities, the changes suggest that correction of bile acid metabolism is likely a major mechanism by which FMT results in a cure and prevents recurrence of CDI.

Bacterial Signaling Nucleotides Inhibit Yeast Cell Growth by Impacting Mitochondrial and Other Specifically Eukaryotic Functions

PubMed Central

Vergnano, Marta; Wan, Chris

2017-01-01

ABSTRACT We have engineered Saccharomyces cerevisiae to inducibly synthesize the prokaryotic signaling nucleotides cyclic di-GMP (cdiGMP), cdiAMP, and ppGpp in order to characterize the range of effects these nucleotides exert on eukaryotic cell function during bacterial pathogenesis. Synthetic genetic array (SGA) and transcriptome analyses indicated that, while these compounds elicit some common reactions in yeast, there are also complex and distinctive responses to each of the three nucleotides. All three are capable of inhibiting eukaryotic cell growth, with the guanine nucleotides exhibiting stronger effects than cdiAMP. Mutations compromising mitochondrial function and chromatin remodeling show negative epistatic interactions with all three nucleotides. In contrast, certain mutations that cause defects in chromatin modification and ribosomal protein function show positive epistasis, alleviating growth inhibition by at least two of the three nucleotides. Uniquely, cdiGMP is lethal both to cells growing by respiration on acetate and to obligately fermentative petite mutants. cdiGMP is also synthetically lethal with the ribonucleotide reductase (RNR) inhibitor hydroxyurea. Heterologous expression of the human ppGpp hydrolase Mesh1p prevented the accumulation of ppGpp in the engineered yeast and restored cell growth. Extensive in vivo interactions between bacterial signaling molecules and eukaryotic gene function occur, resulting in outcomes ranging from growth inhibition to death. cdiGMP functions through a mechanism that must be compensated by unhindered RNR activity or by functionally competent mitochondria. Mesh1p may be required for abrogating the damaging effects of ppGpp in human cells subjected to bacterial infection. PMID:28743817

Oral Teicoplanin as an Alternative First-Line Regimen in Clostridium difficile Infection in Elderly Patients: A Case Series.

PubMed

Davido, Benjamin; Leplay, Céline; Bouchand, Frédérique; Dinh, Aurélien; Villart, Maryvonne; Le Quintrec, Jean-Laurent; Teillet, Laurent; Salomon, Jérôme; Michelon, Hugues

2017-07-01

Elderly patients are more susceptible to Clostridium difficile infections (CDIs). Despite existing guidelines, there is no specific treatment for CDI in geriatrics. Vancomycin is commonly used in the treatment of CDI. Teicoplanin is an alternative glycopeptide which recently received marketing authorization approval for CDI in Europe. Evaluate the potential interest of oral teicoplanin and assess whether such treatment could potentially become an alternative treatment in mild to severe CDIs in elderly patients. A prospective monocentric study was conducted over 10 months (from December 2015 to October 2016) in a geriatric unit (Sainte Périne, AP-HP, Paris, France). According to the remote infectious disease specialist, some hospitalized patients suffering from CDI and aged over 65 years received oral teicoplanin 200 mg twice a day (highest dose recommended). The clinical response to teicoplanin and relapses after treatment were evaluated. Patients were monitored up to 90 days after teicoplanin administration, and analyzed in non-responder imputation analysis. Eleven patients received teicoplanin among 19 CDIs during the study time period. In non-responder imputation analysis, 90.9% (n = 10) successfully responded to oral teicoplanin. The rate of relapse observed after a 90-day follow-up was 36.4%. Patients reported no drug-related adverse effects. Oral teicoplanin is a glycopeptide that could be proposed as an alternative to other recommended drugs for CDI. In our case series, teicoplanin seems to be an effective therapy as a first-line regimen for CDI in geriatrics. Such treatment has good acceptability in geriatrics, considering it can be taken orally twice a day.

Enhanced charge efficiency and reduced energy use in capacitive deionization by increasing the discharge voltage.

PubMed

Kim, T; Dykstra, J E; Porada, S; van der Wal, A; Yoon, J; Biesheuvel, P M

2015-05-15

Capacitive deionization (CDI) is an electrochemical method for water desalination using porous carbon electrodes. A key parameter in CDI is the charge efficiency, Λ, which is the ratio of salt adsorption over charge in a CDI-cycle. Values for Λ in CDI are typically around 0.5-0.8, significantly less than the theoretical maximum of unity, due to the fact that not only counterions are adsorbed into the pores of the carbon electrodes, but at the same time coions are released. To enhance Λ, ion-exchange membranes (IEMs) can be implemented. With membranes, Λ can be close to unity because the membranes only allow passage for the counterions. Enhancing the value of Λ is advantageous as this implies a lower electrical current and (at a fixed charging voltage) a reduced energy use. We demonstrate how, without the need to include IEMs, the charge efficiency can be increased to values close to the theoretical maximum of unity, by increasing the cell voltage during discharge, with only a small loss of salt adsorption capacity per cycle. In separate constant-current CDI experiments, where after some time the effluent salt concentration reaches a stable value, this value is reached earlier with increased discharge voltage. We compare the experimental results with predictions of porous electrode theory which includes an equilibrium Donnan electrical double layer model for salt adsorption in carbon micropores. Our results highlight the potential of modified operational schemes in CDI to increase charge efficiency and reduce energy use of water desalination. Copyright © 2014 Elsevier Inc. All rights reserved.

Prevalence of Clostridium difficile infection presenting to US EDs.

PubMed

Smith, Aaron M; Wuerth, Brandon A; Wiemken, Timothy L; Arnold, Forest W

2015-02-01

The objective of the study is to determine the prevalence of Clostridium difficile infection (CDI) presenting to emergency departments (EDs) in the United States. Secondary objectives included defining the burden of CDI. This is a retrospective, observational cohort study of 2006-2010 Nationwide Emergency Department Sample database of 980 US hospital EDs in 29 states. Prevalence, mortality rate, length of stay, hospital charges, and endemicity were measured. A total of 474513 patients with CDI-related ED visits were identified. From 2006 to 2010, the prevalence of CDI increased from 26.2 to 33.1 per 100,000 population (P<.001). The number of CDI-related ED cases increased 26.1% (P<.001) over the study period: 18.6% from 2006 to 2007 (P<.001), 4.3% from 2007 to 2008 (P=.46), 1.8% from 2008 to 2009 (P=.73), and 0.13% from 2009 to 2010 (P=.95). Emergency department visits occurred more frequently with individuals 85 years or older (relative risk [RR], 13.74; P<.001), females (RR, 1.77; P<.001) and in the northeast United States (RR, 1.42; P<.001). From 2009 to 2010, the mortality rate decreased 17.9% (P=.01). The prevalence of CDI presenting to EDs increased each year from 2006 to 2010; however, the rate of increase slowed from each year to the next. The mortality rate increased from 2006 to 2009 and decreased significantly from 2009 to 2010. C difficile infection visits presenting to EDs occurred more frequently with older individuals, females, and in the northeast. Copyright © 2014 Elsevier Inc. All rights reserved.

Clostridium difficile infection among children across diverse US geographic locations.

PubMed

Wendt, Joyanna M; Cohen, Jessica A; Mu, Yi; Dumyati, Ghinwa K; Dunn, John R; Holzbauer, Stacy M; Winston, Lisa G; Johnston, Helen L; Meek, James I; Farley, Monica M; Wilson, Lucy E; Phipps, Erin C; Beldavs, Zintars G; Gerding, Dale N; McDonald, L Clifford; Gould, Carolyn V; Lessa, Fernanda C

2014-04-01

Little is known about the epidemiology of Clostridium difficile infection (CDI) among children, particularly children ≤3 years of age in whom colonization is common but pathogenicity uncertain. We sought to describe pediatric CDI incidence, clinical presentation, and outcomes across age groups. Data from an active population- and laboratory-based CDI surveillance in 10 US geographic areas during 2010-2011 were used to identify cases (ie, residents with C difficile-positive stool without a positive test in the previous 8 weeks). Community-associated (CA) cases had stool collected as outpatients or ≤3 days after hospital admission and no overnight health care facility stay in the previous 12 weeks. A convenience sample of CA cases were interviewed. Demographic, exposure, and clinical data for cases aged 1 to 17 years were compared across 4 age groups: 1 year, 2 to 3 years, 4 to 9 years, and 10 to 17 years. Of 944 pediatric CDI cases identified, 71% were CA. CDI incidence per 100,000 children was highest among 1-year-old (66.3) and white (23.9) cases. The proportion of cases with documented diarrhea (72%) or severe disease (8%) was similar across age groups; no cases died. Among the 84 cases interviewed who reported diarrhea on the day of stool collection, 73% received antibiotics during the previous 12 weeks. Similar disease severity across age groups suggests an etiologic role for C difficile in the high rates of CDI observed in younger children. Prevention efforts to reduce unnecessary antimicrobial use among young children in outpatient settings should be prioritized.

Self similarities in desalination dynamics and performance using capacitive deionization.

PubMed

Ramachandran, Ashwin; Hemmatifar, Ali; Hawks, Steven A; Stadermann, Michael; Santiago, Juan G

2018-09-01

Charge transfer and mass transport are two underlying mechanisms which are coupled in desalination dynamics using capacitive deionization (CDI). We developed simple reduced-order models based on a mixed reactor volume principle which capture the coupled dynamics of CDI operation using closed-form semi-analytical and analytical solutions. We use the models to identify and explore self-similarities in the dynamics among flow rate, current, and voltage for CDI cell operation including both charging and discharging cycles. The similarity approach identifies the specific combination of cell (e.g. capacitance, resistance) and operational parameters (e.g. flow rate, current) which determine a unique effluent dynamic response. We here demonstrate self-similarity using a conventional flow between CDI (fbCDI) architecture, and we hypothesize that our similarity approach has potential application to a wide range of designs. We performed an experimental study of these dynamics and used well-controlled experiments of CDI cell operation to validate and explore limits of the model. For experiments, we used a CDI cell with five electrode pairs and a standard flow between (electrodes) architecture. Guided by the model, we performed a series of experiments that demonstrate natural response of the CDI system. We also identify cell parameters and operation conditions which lead to self-similar dynamics under a constant current forcing function and perform a series of experiments by varying flowrate, currents, and voltage thresholds to demonstrate self-similarity. Based on this study, we hypothesize that the average differential electric double layer (EDL) efficiency (a measure of ion adsorption rate to EDL charging rate) is mainly dependent on user-defined voltage thresholds, whereas flow efficiency (measure of how well desalinated water is recovered from inside the cell) depends on cell volumes flowed during charging, which is determined by flowrate, current and voltage thresholds. Results of experiments strongly support this hypothesis. Results show that cycle efficiency and salt removal for a given flowrate and current are maximum when average EDL and flow efficiencies are approximately equal. We further explored a range of CC operations with varying flowrates, currents, and voltage thresholds using our similarity variables to highlight trade-offs among salt removal, energy, and throughput performance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Central diabetes insipidus is not a common and prognostically worse type of hypernatremia in neurointensive care.

PubMed

Spatenkova, Vera; Bradac, Ondrej; Kazda, Antonin; Suchomel, Petr

2011-01-01

Hypernatremia is a common sodium dysbalance in neurointensive care which is associated with worse outcome. It can be caused by central diabetes insipidus (cDI) or by other mechanisms, more often from osmotherapy and furosemide. The aim of this study was to determine the incidence of cDI and to analyse outcome as compared with other causes of hypernatremias found in neurointesive care. We analysed 75 hypernatremic (serum sodium, SNa+ >150 mmol/l) patients (pts) with brain diseases admitted over a period of five years to Neurologic-Neurosurgical Intensive Care Unit (NNICU). Firstly we diagnosed cDI according to measured serum and urine osmolality, eletrolyte free water clearance (EWC) and response to desmopressin acetate. The remaining hypernatremias were categorised as "non cDI". We observed Glasgow Coma Scale (GCS) on onset of hypernatremia, incidence of cerebral complications, Glasgow Outcome Scale (GOS) upon discharge from NNICU and mortality in NNICU. We found cDI in 8 pts (mean SNa+ 154.8 ± 5.4 mmol/l). Most pts (67) were classified as "non cDI" hypernatremias (mean SNa+ 154.3 ± 3.6 mmol/l). There were no differences in serum sodium (p=0.682), serum osmolality (p=0.476) between the two groups, however patients with cDI indicated low urine osmolality (p=0.001) and positive EWC (p=0.049). We did not find any differences in GCS score on onset of hypernatremia (p=0.395), incidence of cerebral complications (p=0.705), GOS score upon discharge from NNICU (p=0.61) and mortality in NNICU (p=0.638). More patients in the "non cDI" group received antiedematic therapy (p=0.028) and diuretic furosemide (p=0.026). Multivariate logistic regression analysis showed that independent predictors of NNICU mortality was the highest level of serum sodium (Odds ratio, OR 1.13, per 1 mmol/l increase in maximal hypernatremia during NNICU stay, 95% confidence interval, CI 1.01-1.26, p=0.027), and GCS on admission of less than 9 (OR 2.61, 95% CI 1.41-5.44, p=0.003). Central diabetes insipidus is not a frequent type of hypernatremia in neurointensive care. Prognosis is connected with serum sodium level, not with type of hypernatremia.

High-resolution three-dimensional partially coherent diffraction imaging.

PubMed

Clark, J N; Huang, X; Harder, R; Robinson, I K

2012-01-01

The wave properties of light, particularly its coherence, are responsible for interference effects, which can be exploited in powerful imaging applications. Coherent diffractive imaging relies heavily on coherence and has recently experienced rapid growth. Coherent diffractive imaging recovers an object from its diffraction pattern by computational phasing with the potential of wavelength-limited resolution. Diminished coherence results in reconstructions that suffer from artefacts or fail completely. Here we demonstrate ab initio phasing of partially coherent diffraction patterns in three dimensions, while simultaneously determining the coherence properties of the illuminating wavefield. Both the dramatic improvements in image interpretability and the three-dimensional evaluation of the coherence will have broad implications for quantitative imaging of nanostructures and wavefield characterization with X-rays and electrons.

Dark-field imaging based on post-processed electron backscatter diffraction patterns of bulk crystalline materials in a scanning electron microscope.

PubMed

Brodusch, Nicolas; Demers, Hendrix; Gauvin, Raynald

2015-01-01

Dark-field (DF) images were acquired in the scanning electron microscope with an offline procedure based on electron backscatter diffraction (EBSD) patterns (EBSPs). These EBSD-DF images were generated by selecting a particular reflection on the electron backscatter diffraction pattern and by reporting the intensity of one or several pixels around this point at each pixel of the EBSD-DF image. Unlike previous studies, the diffraction information of the sample is the basis of the final image contrast with a pixel scale resolution at the EBSP providing DF imaging in the scanning electron microscope. The offline facility of this technique permits the selection of any diffraction condition available in the diffraction pattern and displaying the corresponding image. The high number of diffraction-based images available allows a better monitoring of deformation structures compared to electron channeling contrast imaging (ECCI) which is generally limited to a few images of the same area. This technique was applied to steel and iron specimens and showed its high capability in describing more rigorously the deformation structures around micro-hardness indents. Due to the offline relation between the reference EBSP and the EBSD-DF images, this new technique will undoubtedly greatly improve our knowledge of deformation mechanism and help to improve our understanding of the ECCI contrast mechanisms. Copyright © 2014 Elsevier B.V. All rights reserved.

Revealing small-scale diffracting discontinuities by an optimization inversion algorithm

NASA Astrophysics Data System (ADS)

Yu, Caixia; Zhao, Jingtao; Wang, Yanfei

2017-02-01

Small-scale diffracting geologic discontinuities play a significant role in studying carbonate reservoirs. The seismic responses of them are coded in diffracted/scattered waves. However, compared with reflections, the energy of these valuable diffractions is generally one or even two orders of magnitude weaker. This means that the information of diffractions is strongly masked by reflections in the seismic images. Detecting the small-scale cavities and tiny faults from the deep carbonate reservoirs, mainly over 6 km, poses an even bigger challenge to seismic diffractions, as the signals of seismic surveyed data are weak and have a low signal-to-noise ratio (SNR). After analyzing the mechanism of the Kirchhoff migration method, the residual of prestack diffractions located in the neighborhood of the first Fresnel aperture is found to remain in the image space. Therefore, a strategy for extracting diffractions in the image space is proposed and a regularized L 2-norm model with a smooth constraint to the local slopes is suggested for predicting reflections. According to the focusing conditions of residual diffractions in the image space, two approaches are provided for extracting diffractions. Diffraction extraction can be directly accomplished by subtracting the predicted reflections from seismic imaging data if the residual diffractions are focused. Otherwise, a diffraction velocity analysis will be performed for refocusing residual diffractions. Two synthetic examples and one field application demonstrate the feasibility and efficiency of the two proposed methods in detecting the small-scale geologic scatterers, tiny faults and cavities.

Quantitative evaluation of high-resolution features in images of negatively stained Tobacco Mosaic Virus.

PubMed

Chang, C F; Williams, R C; Grano, D A; Downing, K H; Glaeser, R M

1983-01-01

This study investigates the causes of the apparent differences between the optical diffraction pattern of a micrograph of a Tobacco Mosaic Virus (TMV) particle, the optical diffraction pattern of a ten-fold photographically averaged image, and the computed diffraction pattern of the original micrograph. Peak intensities along the layer lines in the transform of the averaged image appear to be quite unlike those in the diffraction pattern of the original micrograph, and the diffraction intensities for the averaged image extend to unexpectedly high resolution. A carefully controlled, quantitative comparison reveals, however, that the optical diffraction pattern of the original micrograph and that of the ten-fold averaged image are essentially equivalent. Using computer-based image processing, we discovered that the peak intensities on the 6th layer line have values very similar in magnitude to the neighboring noise, in contrast to what was expected from the optical diffraction pattern of the original micrograph. This discrepancy was resolved by recording a series of optical diffraction patterns when the original micrograph was immersed in oil. These patterns revealed the presence of a substantial phase grating effect, which exaggerated the peak intensities on the 6th layer line, causing an erroneous impression that the high resolution features possessed a good signal-to-noise ratio. This study thus reveals some pitfalls and misleading results that can be encountered when using optical diffraction patterns to evaluate image quality.

Imaging spectrometer/camera having convex grating

NASA Technical Reports Server (NTRS)

Reininger, Francis M. (Inventor)

2000-01-01

An imaging spectrometer has fore-optics coupled to a spectral resolving system with an entrance slit extending in a first direction at an imaging location of the fore-optics for receiving the image, a convex diffraction grating for separating the image into a plurality of spectra of predetermined wavelength ranges; a spectrometer array for detecting the spectra; and at least one concave sperical mirror concentric with the diffraction grating for relaying the image from the entrance slit to the diffraction grating and from the diffraction grating to the spectrometer array. In one embodiment, the spectrometer is configured in a lateral mode in which the entrance slit and the spectrometer array are displaced laterally on opposite sides of the diffraction grating in a second direction substantially perpendicular to the first direction. In another embodiment, the spectrometer is combined with a polychromatic imaging camera array disposed adjacent said entrance slit for recording said image.

Clostridium difficile infection: Early history, diagnosis and molecular strain typing methods.

PubMed

Rodriguez, C; Van Broeck, J; Taminiau, B; Delmée, M; Daube, G

2016-08-01

Recognised as the leading cause of nosocomial antibiotic-associated diarrhoea, the incidence of Clostridium difficile infection (CDI) remains high despite efforts to improve prevention and reduce the spread of the bacterium in healthcare settings. In the last decade, many studies have focused on the epidemiology and rapid diagnosis of CDI. In addition, different typing methods have been developed for epidemiological studies. This review explores the history of C. difficile and the current scope of the infection. The variety of available laboratory tests for CDI diagnosis and strain typing methods are also examined. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Rise and Fall of Metronidazole for Clostridium difficile Infection.

PubMed

Chahine, Elias B

2018-06-01

Clostridium difficile is posing urgent health threats. Older studies have shown that metronidazole and vancomycin are equally effective in the treatment of Clostridium difficile infection (CDI). Given its inexpensive cost and low propensity to select antimicrobial resistant organisms, metronidazole became rapidly the drug of choice despite its pharmacokinetic limitations in the treatment of CDI. However, newer studies demonstrated that metronidazole is inferior to vancomycin, prompting clinicians to change their long-standing position on using metronidazole for mild to moderate infections and on reserving vancomycin for severe infections. Moving forward, metronidazole will fall out of favor in the treatment of CDI.

Clostridium difficile infection in returning travellers

PubMed Central

Stevens, A. Michal; Esposito, Douglas H.; Stoney, Rhett J.; Hamer, Davidson H.; Flores-Figueroa, Jose; Bottieau, Emmanuel; Connor, Bradley A.; Gkrania-Klotsas, Effrossyni; Goorhuis, Abraham; Hynes, Noreen A.; Libman, Michael; Lopez-Velez, Rogelio; McCarthy, Anne E.; von Sonnenburg, Frank; Schwartz, Eli; van Genderen, Perry J.J.; Benson, L. Scott; Leung, Daniel T.

2017-01-01

Background There is increasing recognition of the contribution of community-acquired cases to the global burden of Clostridium difficile infection (CDI). The epidemiology of CDI among international travellers is poorly understood, and factors associated with international travel, such as antibiotic use and changes in gut microbiota, could potentially put travellers at higher risk. Methods We summarized demographic, travel-associated and geographic characteristics of travellers with CDI in the GeoSentinel database from 1997 to 2015. We also surveyed GeoSentinel sites to compare various testing indications, approaches, and diagnostic modalities. Results We identified 260 GeoSentinel records, including 187 that satisfied criteria for analysis (confirmed cases in non-immigrant travellers aged >2 years, seen <12 weeks post-travel). CDI was reported in all age groups and in travellers to all world regions; the largest proportions of cases having destinations in Asia (31%), Central/South America or the Caribbean (30%) and Africa (24%). Our site survey revealed substantial heterogeneity of testing approaches between sites; the most commonly used test was the C. difficile toxin gene PCR. Conclusions CDI is encountered in returning international travellers, although there is considerable variability in testing practices. These data underscore the importance of awareness of C. difficile as a potential cause of travel-associated diarrhoea. PMID:28355613

First clinical and microbiological characterization of Clostridium difficile infection in a Croatian University Hospital.

PubMed

Novak, Anita; Spigaglia, Patrizia; Barbanti, Fabrizio; Goic-Barisic, Ivana; Tonkic, Marija

2014-12-01

Clinical background and molecular epidemiology of Clostridium difficile infection (CDI) in the University Hospital Centre Split were investigated from January 2010 to December 2011. In total, 54 patients with first episode of CDI were consecutively included in the study based on the positive EIA test specific for A and B toxins. Demographic and clinical data were prospectively analyzed from medical records. CDI incidence rate was 0.6 per 10,000 patient-days. Thirty six cases (70.6%) were healthcare-associated, twelve cases (23.5%) were community-associated and three (5.9%) were indeterminate. Six patients (11.7%) had suffered one or more recurrences and 37 patients (72.5%) showed severe CDI. Prior therapy with third generation cephalosporin was significantly associated with severe CDI (P<0.021). Fifty four toxigenic C. difficile strains were isolated and 50 of them were available for PCR-ribotyping. Sixteen different PCR-ribotypes were identified. The most prevalent were PCR-ribotype 001 (27.8%) and 014/020 (24.1%). Twenty three strains were resistant to at least one of the antibiotics tested. Among resistant strains, three (13.0%)--all PCR-ribotype 001--were multi-resistant. Resistance to fluoroquinolones was significantly higher in strains that caused infection after previous use of fluoroquinolones (P=0.04). Copyright © 2014 Elsevier Ltd. All rights reserved.

Fluorination effect of activated carbons on performance of asymmetric capacitive deionization

NASA Astrophysics Data System (ADS)

Jo, Hanjoo; Kim, Kyung Hoon; Jung, Min-Jung; Park, Jae Hyun; Lee, Young-Seak

2017-07-01

Activated carbons (ACs) were fluorinated and fabricated into electrodes to investigate the effect of fluorination on asymmetric capacitive deionization (CDI). Fluorine functional groups were introduced on the AC surfaces via fluorination. The specific capacitance of the fluorinated AC (Fsbnd AC) electrode increased drastically from 261 to 337 F/g compared with the untreated AC (Rsbnd AC) electrode at a scan rate of 5 mV/s, despite a decrease in the specific surface area and total pore volume after fluorination. The desalination behavior of asymmetric CDI cells assembled with an Rsbnd AC electrode as the counter electrode and an Fsbnd AC electrode as the cathode (R || F-) or anode (R || F +) was studied. For R || F-, the salt adsorption capacity and charge efficiency increased from 10.6 mg/g and 0.58-12.4 mg/g and 0.75, respectively, compared with the CDI cell assembled with identical Rsbnd AC electrodes at 1 V. This CDI cell exhibited consistently better salt adsorption capacity and charge efficiency at different applied voltages because Fsbnd AC electrodes have a cation attractive effect originating from the partially negatively charged fluorine functional groups on the AC surface. Therefore, co-ion expulsion in the Fsbnd AC electrode as the cathode is effectively diminished, leading to enhanced CDI performance.

A study of the capacitive deionisation performance under various operational conditions.

PubMed

Mossad, Mohamed; Zou, Linda

2012-04-30

Capacitive deionisation (CDI) has many advantages over other desalination technologies due to its low energy consumption, less environmental pollution and low fouling potential. The objectives of this study are to investigate the effect of operational conditions on the CDI electrosorption efficiency and energy consumption, to identify ion selectivity in multi-ionic solutions and to probe the effect of dissolved reactive silica on the treatment efficiency. A series of laboratory scale experiments were conducted using a CDI unit with activated carbon electrodes. The electrosorption removal efficiency was inversely related to solution temperature, initial total dissolved salts (TDS) concentration and the applied flow rate. CDI energy consumption (kWh/m(3)) is directly related to the TDS concentration and inversely related to the flow rate. The kinetics analysis indicated that the electrosorption followed pseudo-first-order kinetics model. Ion selectivity on activated carbon electrodes followed the order of Fe(3+)>Ca(2+)>Mg(2+)>Na(+) for cations and SO(4)(2-)>Br(-)>Cl(-)>F(-)>NO(3)(-) for anions. It was found that the dissolved silica was not removed by CDI; no silica fouling was found. The deterioration of activated carbon electrodes was not observed at any time during experiment. Copyright © 2012 Elsevier B.V. All rights reserved.

Relationship between Family Meals and Depressive Symptoms in Children.

PubMed

Kim, Young-Seok; Lee, Min-Ji; Suh, Young-Sung; Kim, Dae-Hyun

2013-05-01

Recently, importance of family meals has been emphasized at home and abroad, and several journals reported that family meals had a big impact on children's development. In this paper, we would like to report the relationship between family meals and depressive symptoms in children. This study was based on questionnaires distributed to 162 5th and 6th graders of one elementary school in the area of Daegu, Korea, in July, 2010. The questionnaire was about general characteristics, family characteristics, and quantity/quality of family meals. Family functions and depressive symptoms in children were evaluated with Smilkstein's family APGAR (adaptability, partnership, growth, affection, and resolve) score (FAS) and Kovac's Children's Depression Inventory (CDI). In one-way analyses of variance, there was no significant difference in FAS and CDI according to general and family characteristics (P > 0.05). CDI was significantly lower in the group having more frequent family meals (P < 0.05). Higher FAS and lower CDI was seen in the group having more conversation and better atmosphere during meals (P < 0.05). There were no significant differences in FAS and CDI according to the number of participants, duration, and watching television during meals (P > 0.05). The frequency of family meals, having more conversation and better atmosphere during family meals predicted less depressive symptoms in children.

Fecal Microbiota Therapy With a Focus on Clostridium difficile Infection.

PubMed

Brandt, Lawrence J

2017-10-01

There has been a paradigm shift in our view of bacteria away from their role as just pathogens. We now have a deepening appreciation of their critical influences in our health maintenance, including energy harvest, metabolism, intestinal development, cell proliferation, nervous system and immune function, as well as their role to protect against intestinal and other infections. A perturbed intestinal microbiome has been associated with an increasing number of gastrointestinal and nongastrointestinal diseases but particularly with Clostridium difficile infection (CDI). Although such association does not imply causation, it has been shown that fecal microbiota transplantation (FMT) can correct the dysbiosis that characterizes chronic and recurring CDI and that FMT can effect a seemingly safe and rapidly effective cure for most patients with CDI so treated. FMT has been used to treat a wide range of other diseases, although conclusions about efficacy in any disease other than CDI must await appropriate well-designed trials. More work needs to be conducted with FMT, especially to evaluate and ensure its long-term safety. Future studies are likely to narrow the spectrum of organisms that needs to be given to patients to cure CDI, and perhaps other diseases, and to elucidate the mechanisms whereby such therapeutic benefit occurs. FMT is but the first step in this journey.

Clostridium difficile PCR ribotypes 001 and 176 - the common denominator of C. difficile infection epidemiology in the Czech Republic, 2014.

PubMed

Krutova, Marcela; Matejkova, Jana; Kuijper, Ed J; Drevinek, Pavel; Nyc, Otakar

2016-07-21

In 2014, 18 hospitals in the Czech Republic participated in a survey of the incidence of Clostridium difficile infections (CDI) in the country. The mean CDI incidence was 6.1 (standard deviation (SD):7.2) cases per 10,000 patient bed-days and 37.8 cases (SD: 41.4) per 10,000 admissions. The mean CDI testing frequency was 39.5 tests (SD: 25.4) per 10,000 patient bed-days and 255.8 tests (SD: 164.0) per 10,000 admissions. A total of 774 C. difficile isolates were investigated, of which 225 (29%) belonged to PCR ribotype 176, and 184 isolates (24%) belonged to PCR ribotype 001. Multilocus variable-number tandem repeat analysis (MLVA) revealed 27 clonal complexes formed by 84% (190/225) of PCR ribotype 176 isolates, and 14 clonal complexes formed by 77% (141/184) of PCR ribotype 001 isolates. Clonal clusters of PCR ribotypes 176 and 001 were observed in 11 and 7 hospitals, respectively. Our data demonstrate the spread of two C. difficile PCR ribotypes within 18 hospitals in the Czech Republic, stressing the importance of standardising CDI testing protocols and implementing mandatory CDI surveillance in the country. This article is copyright of The Authors, 2016.

Utility of Satellite Remote Sensing for Land-Atmosphere Coupling and Drought Metrics

NASA Technical Reports Server (NTRS)

Roundy, Joshua K.; Santanello, Joseph A.

2017-01-01

Feedbacks between the land and the atmosphere can play an important role in the water cycle and a number of studies have quantified Land-Atmosphere (L-A) interactions and feedbacks through observations and prediction models. Due to the complex nature of L-A interactions, the observed variables are not always available at the needed temporal and spatial scales. This work derives the Coupling Drought Index (CDI) solely from satellite data and evaluates the input variables and the resultant CDI against in-situ data and reanalysis products. NASA's AQUA satellite and retrievals of soil moisture and lower tropospheric temperature and humidity properties are used as input. Overall, the AQUA-based CDI and its inputs perform well at a point, spatially, and in time (trends) compared to in-situ and reanalysis products. In addition, this work represents the first time that in-situ observations were utilized for the coupling classification and CDI. The combination of in-situ and satellite remote sensing CDI is unique and provides an observational tool for evaluating models at local and large scales. Overall, results indicate that there is sufficient information in the signal from simultaneous measurements of the land and atmosphere from satellite remote sensing to provide useful information for applications of drought monitoring and coupling metrics.

Utility of Satellite Remote Sensing for Land-Atmosphere Coupling and Drought Metrics

PubMed Central

Roundy, Joshua K.; Santanello, Joseph A.

2018-01-01

Feedbacks between the land and the atmosphere can play an important role in the water cycle and a number of studies have quantified Land-Atmosphere (L-A) interactions and feedbacks through observations and prediction models. Due to the complex nature of L-A interactions, the observed variables are not always available at the needed temporal and spatial scales. This work derives the Coupling Drought Index (CDI) solely from satellite data and evaluates the input variables and the resultant CDI against in-situ data and reanalysis products. NASA’s AQUA satellite and retrievals of soil moisture and lower tropospheric temperature and humidity properties are used as input. Overall, the AQUA-based CDI and its inputs perform well at a point, spatially, and in time (trends) compared to in-situ and reanalysis products. In addition, this work represents the first time that in-situ observations were utilized for the coupling classification and CDI. The combination of in-situ and satellite remote sensing CDI is unique and provides an observational tool for evaluating models at local and large scales. Overall, results indicate that there is sufficient information in the signal from simultaneous measurements of the land and atmosphere from satellite remote sensing to provide useful information for applications of drought monitoring and coupling metrics. PMID:29645012

Achromatic shearing phase sensor for generating images indicative of measure(s) of alignment between segments of a segmented telescope's mirrors

NASA Technical Reports Server (NTRS)

Stahl, H. Philip (Inventor); Walker, Chanda Bartlett (Inventor)

2006-01-01

An achromatic shearing phase sensor generates an image indicative of at least one measure of alignment between two segments of a segmented telescope's mirrors. An optical grating receives at least a portion of irradiance originating at the segmented telescope in the form of a collimated beam and the collimated beam into a plurality of diffraction orders. Focusing optics separate and focus the diffraction orders. Filtering optics then filter the diffraction orders to generate a resultant set of diffraction orders that are modified. Imaging optics combine portions of the resultant set of diffraction orders to generate an interference pattern that is ultimately imaged by an imager.

Separation and imaging diffractions by a sparsity-promoting model and subspace trust-region algorithm

NASA Astrophysics Data System (ADS)

Yu, Caixia; Zhao, Jingtao; Wang, Yanfei; Wang, Chengxiang; Geng, Weifeng

2017-03-01

The small-scale geologic inhomogeneities or discontinuities, such as tiny faults, cavities or fractures, generally have spatial scales comparable to or even smaller than the seismic wavelength. Therefore, the seismic responses of these objects are coded in diffractions and an attempt to high-resolution imaging can be made if we can appropriately image them. As the amplitudes of reflections can be several orders of magnitude larger than those of diffractions, one of the key problems of diffraction imaging is to suppress reflections and at the same time to preserve diffractions. A sparsity-promoting method for separating diffractions in the common-offset domain is proposed that uses the Kirchhoff integral formula to enforce the sparsity of diffractions and the linear Radon transform to formulate reflections. A subspace trust-region algorithm that can provide globally convergent solutions is employed for solving this large-scale computation problem. The method not only allows for separation of diffractions in the case of interfering events but also ensures a high fidelity of the separated diffractions. Numerical experiment and field application demonstrate the good performance of the proposed method in imaging the small-scale geological features related to the migration channel and storage spaces of carbonate reservoirs.

Environmental Contamination in Households of Patients with Recurrent Clostridium difficile Infection

PubMed Central

Bobr, Aleh; Kuskowski, Michael A.; Johnston, Brian D.; Sadowsky, Michael J.; Khoruts, Alexander

2016-01-01

Recurrent Clostridium difficile infection (R-CDI) is common and difficult to treat, potentially necessitating fecal microbiota transplantation (FMT). Although C. difficile spores persist in the hospital environment and cause infection, little is known about their potential presence or importance in the household environment. Households of R-CDI subjects in the peri-FMT period and of geographically matched and age-matched controls were analyzed for the presence of C. difficile. Household environmental surfaces and fecal samples from humans and pets in the household were examined. Households of post-FMT subjects were also examined (environmental surfaces only). Participants were surveyed regarding their personal history and household cleaning habits. Species identity and molecular characteristics of presumptive C. difficile isolates from environmental and fecal samples were determined by using the Pro kit (Remel, USA), Gram staining, PCR, toxinotyping, tcdC gene sequencing, and pulsed-field gel electrophoresis (PFGE). Environmental cultures detected C. difficile on ≥1 surface in 8/8 (100%) peri-FMT households, versus 3/8 (38%) post-FMT households and 3/8 (38%) control households (P = 0.025). The most common C. difficile-positive sites were the vacuum (11/27; 41%), toilet (8/30; 27%), and bathroom sink (5/29; 17%). C. difficile was detected in 3/36 (8%) fecal samples (two R-CDI subjects and one household member). Nine (90%) of 10 households with multiple C. difficile-positive samples had a single genotype present each. In conclusion, C. difficile was found in the household environment of R-CDI patients, but whether it was found as a cause or consequence of R-CDI is unknown. If household contamination leads to R-CDI, effective decontamination may be protective. PMID:26921425

A cost-effectiveness and budget impact analysis of first-line fidaxomicin for patients with Clostridium difficile infection (CDI) in Germany.

PubMed

Watt, Maureen; McCrea, Charles; Johal, Sukhvinder; Posnett, John; Nazir, Jameel

2016-10-01

Clostridium difficile infection (CDI) represents a significant economic healthcare burden, especially the cost of recurrent disease. Fidaxomicin produced significantly lower recurrence rates and higher sustained cure rates in clinical trials. We evaluated the cost-effectiveness and budget impact of fidaxomicin compared with vancomycin in Germany in the first-line treatment of patient subgroups with CDI at increased risk of recurrence. A semi-Markov model was used to compare the cost-effectiveness and budget impact of fidaxomicin vs. vancomycin from a payer perspective in Germany. The model cycle length was 10 days. The time horizon was 1 year. Model inputs were probability of clinical cure, 30-day probability of recurrence, and 30-day attributable mortality based on evidence from two randomized controlled trials comparing fidaxomicin and vancomycin in patients with CDI. Cost-effectiveness outcomes were cost per quality-adjusted life year gained, cost per bed-day saved, and cost per recurrence avoided. Despite higher drug acquisition costs, fidaxomicin was dominant in the cancer subgroup (less costly and more effective) and cost-effective in the other subgroups, with incremental cost-effectiveness ratios vs. vancomycin ranging from €26,900 to €44,500. Hospitalization costs of the first-line treatment of CDI with fidaxomicin vs. vancomycin were lower in every patient subgroup, resulting in budget impacts ranging from -€1325 (in patients ≥65 years) to -€2438 (in cancer patients). Reductions in the cost of treating recurrence with fidaxomicin ranged from -€574.32 per patient in those receiving concomitant antibiotics to -€1500.68 per patient in renally impaired patients. In patient subgroups with CDI at increased recurrence risk, fidaxomicin was cost-effective vs. vancomycin, and less costly and more effective in patients with cancer.

Community-directed interventions for priority health problems in Africa: results of a multicountry study.

PubMed

2010-07-01

To determine the extent to which the community-directed approach used in onchocerciasis control in Africa could effectively and efficiently provide integrated delivery of other health interventions. A three-year experimental study was undertaken in 35 health districts from 2005 to 2007 in seven research sites in Cameroon, Nigeria and Uganda. Four trial districts and one comparison district were randomly selected in each site. All districts had established ivermectin treatment programmes, and in the trial districts four other established interventions - vitamin A supplementation, use of insecticide-treated nets, home management of malaria and short-course, directly-observed treatment for tuberculosis patients - were progressively incorporated into a community-directed intervention (CDI) process. At the end of each of the three study years, we performed quantitative evaluations of intervention coverage and provider costs, as well as qualitative assessments of the CDI process. With the CDI strategy, significantly higher coverage was achieved than with other delivery approaches for all interventions except for short-course, directly-observed treatment. The coverage of malaria interventions more than doubled. The district-level costs of delivering all five interventions were lower in the CDI districts, but no cost difference was found at the first-line health facility level. Process evaluation showed that: (i) participatory processes were important; (ii) recurrent problems with the supply of intervention materials were a major constraint to implementation; (iii) the communities and community implementers were deeply committed to the CDI process; (iv) community implementers were more motivated by intangible incentives than by external financial incentives. The CDI strategy, which builds upon the core principles of primary health care, is an effective and efficient model for integrated delivery of appropriate health interventions at the community level in Africa.

Incorrect diagnosis of Clostridium difficile infection in a university hospital in Japan.

PubMed

Mori, Nobuaki; Yoshizawa, Sadako; Saga, Tomoo; Ishii, Yoshikazu; Murakami, Hinako; Iwata, Morihiro; Collins, Deirdre A; Riley, Thomas V; Tateda, Kazuhiro

2015-10-01

Physicians often fail to suspect Clostridium difficile infection (CDI) and many microbiology laboratories use suboptimal diagnostic techniques. To estimate the extent of and reasons for incorrect diagnosis of CDI in Japan, we investigated toxigenic C. difficile isolated from all stool culture samples and clinical course. Over a 12-month period in 2010, all stool culture samples (n = 975) submitted from inpatients in a university hospital in Japan were cultured for C. difficile and routine microbiological testing was conducted. In total, 177 C. difficile isolates were recovered, and 127 isolates were toxigenic. Among the toxin-A-positive/toxin-B-positive isolates, 12 were also positive for the binary toxin gene. However, clinically important ribotypes, such as 027 and 078, were not identified. A total of 58 (45.7%) cases with toxigenic C. difficile had unformed stool, and the incidence CDI was 1.6 cases per 10,000 patient-days. Of these 58 cases, 40 were not diagnosed in routine testing due to a lack of clinical suspicion (24.1%, 14/58) or a negative C. difficile toxin assay result (44.8%, 26/58). A stool toxin assay was performed in 54 patients (78.2%, 54/69) who did not have unformed stool. The present study demonstrated that a significant number of CDI cases in Japan might be overlooked or misdiagnosed in clinical practice due to a lack of clinical suspicion and limitations of microbiological testing for CDI in Japan. Providing education to promote awareness of CDI among physicians is important to improve the accuracy of diagnosis in Japan. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Containment of Clostridium difficile infection without reduction in antimicrobial use in Hong Kong.

PubMed

Cheng, V C C; Chau, P H; So, S Y C; Chen, J H K; Poon, R W S; Wong, S C Y; Hung, I F N; Lee, W M; Tai, J W M; Ho, P L; Yam, W C; Yuen, K Y

2015-07-01

Clostridium difficile ribotype 002 with hypersporulating capacity has been increasingly identified in Hong Kong. Proactive infection control measures are important to prevent the establishment of endemicity of C. difficile ribotype 002. A total of 329 patients with healthcare-associated C. difficile infection (CDI) were recruited in our healthcare network between 1 January 2008 and 30 June 2012 in this study. The incidence rates of healthcare-associated CDI per 10,000 admissions and 10,000 patient-days increased significantly by 15.3 and 17.0%, respectively, per quarter (p < 0.001) from 2008 1Q to 2010 1Q by segmented Poisson regression. With the full implementation of enhanced infection control interventions, there was an immediate significant reduction in both healthcare-associated CDI rates per 10,000 admissions and per 10,000 patient-days by 47% (p < 0.001) in 2010 2Q, followed by a further decline of CDI per 10,000 admissions and CDI per 10,000 patient-days by -19.4 and -19.8% from 2010 2Q to 2012 2Q, respectively (p < 0.001), despite a replacement of hand washing with soap and water by alcohol-based hand rub in the healthcare network. The proportion of C. difficile ribotype 002 was not statistically different (34/177, 19.2% vs. 25/152, 16.4%, p = 0.515), and the consumption of broad-spectrum antibiotics presented as divided daily dose per 1,000 acute bed-day occupancy per quarter remained unchanged (140.9 vs. 152.3) before and after infection control interventions. Our results suggested that the reduction of healthcare-associated CDI was attributable to infection control interventions instead of replacement of ribotypes or reduction in antimicrobial selective pressure.