Multicenter, prospective validation of a phenotypic algorithm to guide carbapenemase testing in carbapenem-resistant Pseudomonas aeruginosa using the ERACE-PA global surveillance program

Background: Carbapenemase-producing, carbapenem-resistant Methods: CRPA isolates were collected during the Enhancing Rational Antimicrobials for Results: A total of 807 CRPA were assessed, and 464 isolates met the algorithm criteria described above. Overall, testing was reduced by 43% compared with testing all CRPA. Carbapenemase-positive isolates missed by the algorithm were largely driven by Guiana extended spectrum (GES). Addition of the criterion of imipenem- or meropenem-resistant plus ceftolozane/tazobactam-nonsusceptible decreased the number of CP-CRPA missed by the algorithm (21 vs 40 isolates, respectively), reducing number of isolates tested by 39%. Conclusions: Application of the initial algorithm (imipenem- or meropenem-resistant plus ceftazidime-nonsusceptible plus cefepime-nonsusceptible) performed well in a global cohort, with 33% phenotypically carbapenemase-positive isolates. The addition of imipenem- or meropenem-resistant plus ceftolozane/tazobactam-nonsusceptible reduced the number of phenotypically carbapenemase-positive isolates missed and may be useful in areas with a prominence of GES

Carbapenemase-Producing \u3cem\u3ePseudomonas aeruginosa \u3c/em\u3e – an Emerging Challenge

Carbapenem-resistant Pseudomonas aeruginosa (CR-PA) is a major healthcare-associated pathogen worldwide. In the United States, 10–30% of P. aeruginosa isolates are carbapenem-resistant, while globally the percentage varies considerably. A subset of carbapenem-resistant P. aeruginosa isolates harbour carbapenemases, although due in part to limited screening for these enzymes in clinical laboratories, the actual percentage is unknown. Carbapenemase-mediated carbapenem resistance in P. aeruginosa is a significant concern as it greatly limits the choice of anti-infective strategies, although detecting carbapenemase-producing P. aeruginosa in the clinical laboratory can be challenging. Such organisms also have been associated with nosocomial spread requiring infection prevention interventions. The carbapenemases present in P. aeruginosa vary widely by region but include the Class A beta-lactamases, KPC and GES; metallo-beta-lactamases IMP, NDM, SPM, and VIM; and the Class D, OXA-48 enzymes. Rapid confirmation and differentiation among the various classes of carbapenemases is key to the initiation of early effective therapy. This may be accomplished using either molecular genotypic methods or phenotypic methods, although both have their limitations. Prompt evidence that rules out carbapenemases guides clinicians to more optimal therapeutic selections based on local phenotypic profiling of non-carbapenemase-producing, carbapenem-resistant P. aeruginosa. This article will review the testing strategies available for optimizing therapy of P. aeruginosa infections

3D magnetised jet break-out from neutron-star binary merger ejecta: afterglow emission from the jet and the ejecta

We perform three-dimensional (3D) general-relativistic magnetohydrodynamic simulations to model the jet break-out from the ejecta expected to be produced in a binary neutron-star merger. The structure of the relativistic outflow from the 3D simulation confirms our previous results from 2D simulations, namely, that a relativistic magnetized outflow breaking out from the merger ejecta exhibits a hollow core of $\theta_{\rm core}\approx4^{\circ}$, an opening angle of $\theta_{\rm jet}\gtrsim10^{\circ}$, and is accompanied by a wind of ejected matter that will contribute to the kilonova emission. We also compute the non-thermal afterglow emission of the relativistic outflow and fit it to the panchromatic afterglow from GRB170817A, together with the superluminal motion reported from VLBI observations. In this way, we deduce an observer angle of $\theta_{\rm obs}= 35.7^{\circ \,\,+1.8}_{\phantom{\circ \,\,}-2.2}$. We further compute the afterglow emission from the ejected matter and constrain the parameter space for a scenario in which the matter responsible for the thermal kilonova emission will also lead to a non-thermal emission yet to be observed.Comment: MNRAS accepted, updated versio

On the opening angle of magnetised jets from neutron-star mergers: the case of GRB170817A

The observations of GW170817/GRB170817A have confirmed that the coalescence of a neutron-star binary is the progenitor of a short gamma-ray burst. In the standard picture of a short gamma-ray burst, a collimated highly relativistic outflow is launched after merger and it successfully breaks out from the surrounding ejected matter. Using initial conditions inspired from numerical-relativity binary neutron-star merger simulations, we have performed general-relativistic hydrodynamic (HD) and magnetohydrodynamic (MHD) simulations in which the jet is launched and propagates self-consistently. The complete set of simulations suggests that: (i) MHD jets have an intrinsic energy and velocity polar structure with a ``hollow core'' subtending an angle $\theta_{\rm core}\approx4^{\circ}-5^{\circ}$ and an opening angle of $\theta_{\rm jet}\gtrsim10^{\circ}$; (ii) MHD jets eject significant amounts of matter and two orders of magnitude more than HD jets; (iii) the energy stratification in MHD jets naturally yields the power-law energy scaling $E(>\Gamma\beta)\propto(\Gamma\beta)^{-4.5}$; (iv) MHD jets provide fits to the afterglow data from GRB170817A that are comparatively better than those of the HD jets and without free parameters; (v) finally, both of the best-fit HD/MHD models suggest an observation angle $\theta_{\rm obs} \simeq 21^{\circ}$ for GRB170817A.Comment: 9 pages, 5 figures, submitte

Directed Carbapenemase Testing Is No Longer Just for Enterobacterales: Cost, Labor, and Workflow Assessment of Expanding Carbapenemase Testing to Carbapenem-Resistant \u3cem\u3eP. aeruginosa\u3c/em\u3e

Molecular carbapenem-resistance testing, such as for the presence of carbapenemases genes, is commonly implemented for the detection of carbapenemase-producing Enterobacterales. Carbapenemase-producing P. aeruginosa is also associated with significant morbidity and mortality, although; prevalence may be underappreciated in the United States due to a lack of carbapenemase testing. The present study sought to compare hands-on time, cost and workflow implementation of carbapenemase gene testing in Enterobacterales and P. aeruginosa isolates versus sending out isolates to a public health laboratory (PHL) for testing to assess if in-house can provide actionable results. The time to carbapenemase gene results were compared. Differences in cost for infection prevention measures were extrapolated from the time of positive carbapenemase gene detection in-house versus PHL. The median time to perform carbapenemase gene testing was 7.5 min (range 5–14) versus 10 min (range 8–22) for preparation to send isolates to the PHL. In-house testing produced same day results compared with a median of 6 days (range 3–14) to receive results from PHL. Cost of in-house testing and send outs were similar ($46.92 versus$40.53, respectively). If contact precautions for patients are implemented until carbapenemase genes are ruled out, in-house testing can save an estimated $76,836.60 annually. Extension of in-house carbapenemase testing to include P. aeruginosa provides actionable results 3–14 days earlier than PHL Standard Pathway testing, facilitating guided therapeutic decisions and infection prevention measures. Supplemental phenotypic algorithms can be implemented to curb the cost of P. aeruginosa carbapenemases testing by identifying isolates most likely to harbour carbapenemases

Evaluation of the Xpert Carba-R Nxg Assay for Detection of Carbapenemase Genes in a Global Challenge Set of \u3cem\u3ePseudomonas aeruginosa \u3c/em\u3e Isolates

The growing prevalence and diversity of carbapenemase producers among carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates warrants an expansion of detection capabilities. The purpose of this study was to evaluate the performance of the commercially available Xpert Carba-R (Carba-R) and the research-use-only Xpert Carba-R NxG (Carba-R NxG) in a global collection of P. aeruginosa. The challenge set included 123 P. aeruginosa clinical isolates from 12 countries. Isolates were previously categorized via PCR or whole-genome sequencing. Carbapenemase classes tested include VIM, IMP, NDM, SPM, KPC, and GES. Non-carbapenemase (non-CP)-harboring isolates were also tested (negative control). Isolates were tested using the Carba-R NxG and the Carba-R tests per the manufacturer’s instructions. Carba-R NxG testing was completed by Cepheid (Sunnyvale, CA), blinded to genotype. Both assays gave negative results for all non-CP isolates and positive results for all VIM, NDM, and KPC isolates. An improvement in IMP detection among isolates was observed (100% detection by Carba-R NxG versus 58% by Carba-R). All SPM and GES isolates, targets not present in commercially available Carba-R, were positive by Carba-R NxG. Two isolates harbored both VIM and GES, while a third isolate contained VIM and NDM. The Carba-R NxG identified both targets in all 3 isolates, while the Carba-R was negative for both GES-containing isolates. Overall, the Carba-R NxG successfully categorized 100% of isolates tested compared with 68% for its predecessor. The Carba-R NxG will expand the detection spectrum of the current Carba-R assay to include SPM, GES, and expanded IMP variants, increasing the global utility of the test

Obstructive hydrocephalus and intracerebral mass secondary to Epicoccum nigrum

Here we report a case of a 14-week-old girl with a history of intrauterine drug exposure and hypoxic ischemic encephalopathy secondary to cardiac arrest requiring prolonged resuscitation at birth presented with irritability and a bulging anterior fontanelle. After neurosurgical resection, pathologic examination showed fungal hyphae, an

Integrating the Combined Sagittal Index Reduces the Risk of Dislocation Following Total Hip Replacement

Background: The aims of this matched cohort study were to (1) assess differences in spinopelvic characteristics between patients who sustained a dislocation after total hip arthroplasty (THA) and a control group without a dislocation, (2) identify spinopelvic characteristics associated with the risk of dislocation, and (3) propose an algorithm including individual spinopelvic characteristics to define an optimized cup orientation target to minimize dislocation risk.Methods: Fifty patients with a history of THA dislocation (29 posterior and 21 anterior dislocations) were matched for age, sex, body mass index (BMI), index diagnosis, surgical approach, and femoral head size with 200 controls. All patients underwent detailed quasi-static radiographic evaluations of the coronal (offset, center of rotation, and cup inclination/anteversion) and sagittal (pelvic tilt [PT], sacral slope [SS], pelvic incidence [PI], lumbar lordosis [LL], pelvic-femoral angle [PFA], and cup anteinclination [AI]) reconstructions. The spinopelvic balance (PI - LL), combined sagittal index (CSI = PFA + cup AI), and Hip-User Index were determined. Parameters were compared between the control and dislocation groups (2-group analysis) and between the controls and 2 dislocation groups identified according to the direction of the dislocation (3-group analysis). Important thresholds were determined from receiver operating characteristic (ROC) curve analyses and the mean values of the control group; thresholds were expanded incrementally in conjunction with running-hypothesis tests.Results: There were no coronal differences, other than cup anteversion, between groups. However, most sagittal parameters (LL, PT, CSI, PI - LL, and Hip-User Index) differed significantly. The 3 strongest predictors of instability were PI - LL &gt; 10° (sensitivity of 70% and specificity of 65% for instability regardless of direction), CSI standingof &lt; 216° (posterior instability), and CSI standingof &gt; 244° (anterior instability). A CSI that was not between 205° and 245° on the standing radiograph (CSI standing) was associated with a significantly increased dislocation risk (odds ratio [OR]: 4.2; 95% confidence interval [CI]: 2.2 to 8.2; p &lt; 0.001). In patients with an unbalanced and/or rigid lumbar spine, a CSI standingthat was not 215° to 235° was associated with a significantly increased dislocation risk (OR: 5.1; 95% CI: 1.8 to 14.9; p = 0.001).Conclusions: Spinopelvic imbalance (PI - LL &gt; 10° ) determined from a preoperative standing lateral spinopelvic radiograph can be a useful screening tool, alerting surgeons that a patient is at increased dislocation risk. Measurement of the PFA preoperatively provides valuable information to determine the optimum cup orientation to aim for a CSI standingof 205° to 245° , which is associated with a reduced dislocation risk. For patients at increased dislocation risk due to spinopelvic imbalance (PI - LL &gt; 10° ), the range for the optimum CSI is narrower.Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.</p

Flexible transmitter employing Silicon-segmented Mach–zehnder modulator with 32-nm CMOS distributed driver

Artículo científicoWe propose a flexible optical transmitter for shortreach optical interconnects that includes a silicon photonic segmented Mach-Zehnder modulator (MZM) driven by a distributed six-channel 32nm SOI CMOS driver integrated circuit. Optical equalization is demonstrated to extend the bandwidth limitation of the transmitter with NRZ signaling at 25Gb/s. We also generate four-level pulse amplitude modulation (PAM-4) signaling using the same transmitter architecture. Transmission of 46Gb/s PAM-4 signal with bit error rate (BER) well below hard-decision forward error correction limit (BER=3.8×10-3) is experimentally demonstrated. Low driver power consumption of 130 mW at 46Gb/s PAM-4, corresponding to 2.8 pJ/bit power efficiency, is also achieved