Treatment for carbapenem-resistant Enterobacterales infections: recent advances and future directions

Carbapenem-resistant Enterobacterales (CRE) are a growing threat to human health worldwide. CRE often carry multiple resistance genes that limit treatment options and require longer durations of therapy, are more costly to treat, and necessitate therapies with increased toxicities when compared with carbapenem-susceptible strains. Here, we provide an overview of the mechanisms of resistance in CRE, the epidemiology of CRE infections worldwide, and available treatment options for CRE. We review recentlyapproved agents for the treatment of CRE, including ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol, and novel aminoglycosides and tetracyclines. We also discuss recent advances in phage therapy and antibiotics that are currently in development targeted to CRE. The potential for the development of resistance to these therapies remains high, and enhanced antimicrobial stewardship is imperative both to reduce the spread of CRE worldwide and to ensure continued access to efficacious treatment options

Antimicrobial Resistance in Enterobacterales and Its Contribution to Sepsis in Sub-saharan Africa

Antibiotic resistant Enterobacterales (formerly Enterobactereaceae) are a growing threat to Sub-Saharan Africa. Genes causing antibiotic resistance are easily spread between the environment and humans and infections due to drug resistant organisms contribute to sepsis mortality via delayed time to appropriate antimicrobial therapy. Additionally, second or third-line antibiotics are often not available or are prohibitively expensive in resource-constrained settings leading to limited treatment options. Lack of access to water and sanitation facilities, unregulated use of antibiotics, and malnutrition are contributors to high rates of antibiotic resistance in the region. Improvements in the monitoring of drug resistant infections and antibiotic stewardship are needed to preserve the efficacy of antibiotics for the future

A high-resolution radio survey of the Vela supernova remnant

This paper presents a high-resolution radio continuum (843 MHz) survey of the Vela supernova remnant. The contrast between the structures in the central pulsar-powered nebula of the remnant and the synchrotron radiation shell allows the remnant to be identified morphologically as a member of the composite class. The data are the first of a composite remnant at spatial scales comparable with those available for the Cygnus Loop and the Crab Nebula, and make possible a comparison of radio, optical and soft X-ray emission from the resolved shell filaments. The survey, made with the Molonglo Observatory Synthesis Telescope, covers an area of 50 square degrees at a resolution of 43'' x 60'', while imaging structures on scales up to 30'.Comment: 18 pages, 7 jpg figures (version with ps figures at http://astro.berkeley.edu/~dbock/papers/); AJ, in pres

Supernova Remnants in the Magellanic Clouds. IV. X-Ray Emission from the Largest SNR in the LMC

We present the first X-ray detection of SNR 0450-70.9 the largest known supernova remnant (SNR) in the Large Magellanic Cloud. To study the physical conditions of this SNR, we have obtained XMM-Newton X-ray observations, optical images and high-dispersion spectra, and radio continuum maps. Optical images of SNR 0450-70.9 show a large, irregular elliptical shell with bright filaments along the eastern and western rims and within the shell interior. The interior filaments have higher [S II]/Halpha ratios and form an apparent inner shell morphology. The X-ray emission region is smaller than the full extent of the optical shell, with the brightest X-ray emission found within the small interior shell and on the western rim of the large shell. The expansion velocity of the small shell is ~220 km/s, while the large shell is ~120 km/s. The radio image shows central brightening and a fairly flat radio spectral index over the SNR. However, no point X-ray or radio source corresponding to a pulsar is detected and the X-ray emission is predominantly thermal. Therefore, these phenomena can be most reasonably explained in terms of the advanced age of the large SNR. Using hydrodynamic models combined with a nonequilibrium ionization model for thermal X-ray emission, we derived a lower limit on the SNR age of about 45,000 yr, well into the later stages of SNR evolution. Despite this, the temperature and density derived from spectral fits to the X-ray emission indicate that the remnant is still overpressured, and thus that the development is largely driven by hot gas in the SNR interior.Comment: Accepted for publication in The Astrophysical Journa

Melting of Partially Fluorinated Graphene: From Detachment of Fluorine Atoms to Large Defects and Random Coils

The melting of fluorographene is very unusual and depends strongly on the degree of fluorination. For temperatures below 1000 K, fully fluorinated graphene (FFG) is thermo-mechanically more stable than graphene but at T$_m\approx$2800 K FFG transits to random coils which is almost twice lower than the melting temperature of graphene, i.e. 5300 K. For fluorinated graphene (PFG) up to 30 % ripples causes detachment of individual F-atoms around 2000 K while for 40-60 % fluorination, large defects are formed beyond 1500 K and beyond 60% of fluorination F-atoms remain bonded to graphene until melting. The results agree with recent experiments on the dependence of the reversibility of the fluorination process on the percentage of fluorination.Comment: 16 pages, 6 figure

On the origin of the quantum-critical transition in the bilayer Heisenberg model

The bilayer Heisenberg antiferromagnet is known to exhibit a quantum-critical transition at a particular value of the inter-layer coupling. Using a new type of coherent state, appropriate to the special order parameter structure of the bilayer, we map the problem onto the quantum non-linear sigma model. It is found that the bare coupling constant diverges at the classical transition of Chubukov and Morr, so that in any finite dimension the actual transition occurs inside the ordered phase of the classical theory.Comment: 9 pages Revtex, no figures, submitted to Phys. Rev. Let

Nonthermal Emission from a Supernova Remnant in a Molecular Cloud

In evolved supernova remnants (SNRs) interacting with molecular clouds, such as IC 443, W44, and 3C391, a highly inhomogeneous structure consisting of a forward shock of moderate Mach number, a cooling layer, a dense radiative shell and an interior region filled with hot tenuous plasma is expected. We present a kinetic model of nonthermal electron injection, acceleration and propagation in that environment and find that these SNRs are efficient electron accelerators and sources of hard X- and gamma-ray emission. The energy spectrum of the nonthermal electrons is shaped by the joint action of first and second order Fermi acceleration in a turbulent plasma with substantial Coulomb losses. Bremsstrahlung, synchrotron, and inverse Compton radiation of the nonthermal electrons produce multiwavelength photon spectra in quantitative agreement with the radio and the hard emission observed by ASCA and EGRET from IC 443. We distinguish interclump shock wave emission from molecular clump shock wave emission accounting for a complex structure of molecular cloud. Spatially resolved X- and gamma- ray spectra from the supernova remnants IC 443, W44, and 3C391 as might be observed with BeppoSAX, Chandra XRO, XMM, INTEGRAL and GLAST would distinguish the contribution of the energetic lepton component to the gamma-rays observed by EGRET.Comment: 14 pages, 4 figure, Astrophysical Journal, v.538, 2000 (in press