Carbapenem-resistant Enterobacterales in patients with bacteraemia at tertiary academic hospitals in South Africa, 2019 - 2020: An update

Background. The emergence of carbapenem-resistant Enterobacterales (CRE) has become a serious and significant public health threat worldwide, owing to the limited antimicrobial therapy options, and the elevated mortality rates associated with these infections. Objectives. To present an update on the epidemiology of CRE bloodstream infections among hospitalised patients reported under the Group for Enteric, Respiratory and Meningeal Diseases Surveillance in South Africa (GERMS-SA) between January 2019 and December 2020. Methods. Patients of all ages with CRE bacteraemia were included and isolates, when available, were sent to the reference laboratory for confirmatory testing and molecular characterisation. Multivariable logistic regression analysis was performed to assess factors associated with in-hospital mortality. Results. We included 2 144 patients with CRE bacteraemia with a median age of 33 (interquartile range 1 - 51) years, of whom 1 145 (54.2%) were male. Klebsiella pneumoniae accounted for 79.8% of infections (n=863/1 082), of which 89.5% (n=611/683) were healthcare associated (HA). The most common carbapenemase genes were carbapenem-hydrolysing oxacillinase-48 (blaOXA-48-like) (76.8%; n=761/991), New Delhi metallo-β-lactamase (blaNDM) (21.1%; n=209/991) and Verona integron-encoded metallo-β-lactamase (blaVIM) (1.3%; n=13/991). None of the screened isolates with a colistin minimum inhibitory concentration >2 μg/mL harboured the mobilised colistin resistance (mcr)-1 to mcr-5 genes. The crude in-hospital mortality rate was 36.6% (n=377/1 029). Patients aged ≥60 years (v. 1.6 - 9 years) (adjusted odds ratio (aOR) 4.53; 95% confidence interval (CI) 2.21 - 9.28), those with comorbidities (diabetes, malignancy, renal and/or cardiovascular failure) (aOR 1.72; 95% CI 1.17 - 2.52), those with altered mental state (aOR 5.36; 95% CI 3.21 - 8.92) and those with previous antimicrobial use (aOR 1.88; 95% CI 1.27 - 2.77) had increased odds of in-hospital mortality. Conclusion. The epidemiology of CRE bloodstream infections remained similar compared with the previous surveillance report. Most infections were HA and caused by OXA-48-like carbapenemase-producing K. pneumoniae with no plasmid-mediated colistin resistance. Standard infection control measures should be strengthened

Differentiation between temporary and real non-clearability of biotinylated IgG antibody by avidin in mice

Although an increasing number of antibody conjugates are being used in the clinic, there remain many unmet needs in antibody targeting. Normal tissue background is one of the key issues that limits the therapeutic efficacy and the detection sensitivity. Background reduction coupled with dose increase may provide the required target accumulation of the label or toxin at an acceptable normal tissue background. However, the knowledge about the in vivo interaction between antibody and a clearing agent is currently inadequate for designing a rational clearance regimen or system. The current investigation focuses on the clearability of antibody for background reduction, an important topic to antibody targeting in general. The investigation employs pretargeting as a research tool and avidin as a model clearing agent. By comparing the effects of natural clearance at a longer post-injection time and avidin clearance, we demonstrated that avidin clearance is much more effective. By directly attaching avidin to a biotinylated antibody prior to injection, we found that the biotinylated antibody in blood, once bound to the clearing agent, can be removed from the circulation immediately and completely, while the real non-clearable antibody without biotin stays. The study of multiple avidin injections confirmed that the presence of clearable biotinylated antibodies after an avidin injection is due to their temporary inaccessibility and subsequent return from tissue compartments. The collective clearance efficiency of 91% by three avidin injections indicates a continuous IV infusion would be recommended to remove all of the biotinylated IgG molecules. In conclusion, the use of antibody pretargeting as a tool in this study has improved understanding of the incomplete clearance by avidin and can aid in overcoming this obstacle

First science results from SOFIA/FORCAST: The mid-infrared view of the compact HII region W3A

The massive star forming region W3 was observed with the faint object infrared camera for the SOFIA telescope (FORCAST) as part of the Short Science program. The 6.4, 6.6, 7.7, 19.7, 24.2, 31.5 and 37.1 \um bandpasses were used to observe the emission of Polycyclic Aromatic Hydrocarbon (PAH) molecules, Very Small Grains and Big Grains. Optical depth and color temperature maps of W3A show that IRS2 has blown a bubble devoid of gas and dust of $\sim$0.05 pc radius. It is embedded in a dusty shell of ionized gas that contributes 40% of the total 24 \um emission of W3A. This dust component is mostly heated by far ultraviolet, rather than trapped Ly$\alpha$ photons. This shell is itself surrounded by a thin ($\sim$0.01 pc) photodissociation region where PAHs show intense emission. The infrared spectral energy distribution (SED) of three different zones located at 8, 20 and 25\arcsec from IRS2, show that the peak of the SED shifts towards longer wavelengths, when moving away from the star. Adopting the stellar radiation field for these three positions, DUSTEM model fits to these SEDs yield a dust-to-gas mass ratio in the ionized gas similar to that in the diffuse ISM. However, the ratio of the IR-to-UV opacity of the dust in the ionized shell is increased by a factor $\simeq$3 compared to the diffuse ISM.Comment: Accepted for publication in ApJ letters; 13 pages, 3 figures 1 tabl

Transcriptional profiling avian beta-defensins in chicken oviduct epithelial cells before and after infection with Salmonella enterica serovar Enteritidis

<p>Abstract</p> <p>Background</p> <p><it>Salmonella enterica </it>serovar Enteritidis (SE) colonizes the ovary and oviduct of chickens without causing overt clinical signs which can lead to SE-contamination of the content and membrane of shell-eggs as well as hatchery eggs. The organism utilizes the <it>Salmonella </it>Pathogenicity Island-2 encoded type III secretion system (T3SS-2) to promote persistence in the oviduct of laying hens. In this study, reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out to determine the expression profiles of 14 known avian beta defensins (AvBDs) in primary chicken oviduct epithelial cells (COEC) before and after infections with a wild type SE strain and T3SS mutant SE strains carrying an inactivated <it>sipA </it>or <it>pipB </it>gene.</p> <p>Results</p> <p>Based on the expression levels in uninfected COEC, AvBDs can be loosely grouped into three categories with AvBD4-5 and AvBD9-12 being constitutively expressed at high levels; AvBD1, AvBD3, and AvBD13-14 at moderate levels; and AvBD2 and AvBD6-8 at minimal levels. Infection with the wild type SE strain temporarily repressed certain highly expressed AvBDs and induced the expression of minimally expressed AvBDs. The <it>pipB </it>mutant, compared to the wild type strain, had reduced suppressive effect on the expression of highly expressed AvBDs. Moreover, the <it>pipB </it>mutant elicited significantly higher levels of the minimally expressed AvBDs than the wild type SE or the <it>sipA </it>mutant did.</p> <p>Conclusion</p> <p>Chicken oviduct epithelial cells express most of the known AvBD genes in response to SE infection. PipB, a T3SS-2 effector protein, plays a role in dampening the β-defensin arm of innate immunity during SE invasion of chicken oviduct epithelium.</p

Phage mediated horizontal transfer of the sopE1 gene increases enteropathogenicity of Salmonella enterica serotype Typhimurium for calves

Epidemiological evidence shows that the sopE1 gene is associated with Salmonella Typhimurium phage types causing epidemics in cattle. In this study we demonstrate that horizontal transfer of the sopE1 gene by lysogenic conversion with the SopEΦ increased enteropathogenicity of S. Typhimurium in the bovine ligated ileal loop model. These data support the hypothesis that phage mediated horizontal transfer of the sopE1 gene contributes to the emergence of epidemic cattle-associated S. Typhimurium clone

CO and C_2 Absorption Toward W40 IRS 1a

The H II region W40 harbors a small group of young, hot stars behind roughly 9 magnitudes of visual extinction. We have detected gaseous carbon monoxide (CO) and diatomic carbon (C_2) in absorption toward the star W40 IRS 1a. The 2-0 R0, R1, and R2 lines of 12CO at 2.3 micron were measured using the CSHELL on the NASA IR Telescope Facility (with upper limits placed on R3, R4, and R5) yielding an N_CO of (1.1 +/- 0.2) x 10^18 cm^-2. Excitation analysis indicates T_kin > 7 K. The Phillips system of C_2 transitions near 8775 Ang. was measured using the Kitt Peak 4-m telescope and echelle spectrometer. Radiative pumping models indicate a total C_2 column density of (7.0 +/- 0.4) x 10^14 cm^-2, two excitation temperatures (39 and 126 K), and a total gas density of n ~ 250 cm^-3. The CO ice band at 4.7 micron was not detected, placing an upper limit on the CO depletion of delta < 1 %. We postulate that the sightline has multiple translucent components and is associated with the W40 molecular cloud. Our data for W40 IRS 1a, coupled with other sightlines, shows that the ratio of CO/C_2 increases from diffuse through translucent environs. Finally, we show that the hydrogen to dust ratio seems to remain constant from diffuse to dense environments, while the CO to dust ratio apparently does not.Comment: To appear in The Astrophysical Journal 17 pages total, 5 figures Also available at http://casa.colorado.edu/~shuping/research/w40/w40.htm

Vaccination with attenuated Salmonella enterica Dublin expressing E coli O157:H7 outer membrane protein Intimin induces transient reduction of fecal shedding of E coli O157:H7 in cattle

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli </it>serogroup O157:H7 has emerged as an important zoonotic bacterial pathogen, causing a range of symptoms from self-limiting bloody diarrhea to severe hemorrhagic colitis and hemolytic-uremic syndrome in humans. Beef and dairy cattle are considered the most important animal reservoirs for this pathogen. One of the important virulence characteristics of <it>E. coli </it>O157:H7 is the <it>eaeA </it>gene encoding the 97 kDa surface protein intimin. Intimin is required for attachment and effacement during the interaction of enterohemorrhagic <it>E. coli </it>with human and bovine neonatal enterocytes. The present study was undertaken to test the hypothesis that an adaptive mucosal immune response directed against intimin will reduce or prevent enteric colonization and fecal shedding of <it>E. coli </it>O157:H7 in cattle.</p> <p>Results</p> <p>Cattle were orally inoculated with either milk (control), milk with live attenuated <it>Salmonella enterica </it>serovar Dublin (vector), or milk with live attenuated recombinant <it>S</it>. Dublin expressing intimin (vaccinated) on days 0, 14 and 28. On day 98, all calves were challenged orally with <it>E. coli </it>O157:H7 to evaluate whether vaccination with the recombinant <it>S</it>. Dublin expressing intimin would reduce the level of <it>E. coli </it>O157:H7 fecal shedding.</p> <p>During the first 28 days, vaccinated calves shed both the vector strain and the intimin-expressing <it>S</it>. Dublin strain at a similar level. The vector strain was shed for a significantly longer period as compared to the level of recombinant vaccine strain. Calves that received the intimin-expressed vaccine ceased shedding <it>S</it>. Dublin from day 28 to day 63. All calves were challenged with <it>E. coli </it>O157:H7 on day 98 to determine the effect on fecal shedding of <it>E. coli </it>O157:H7. The amount of <it>E. coli </it>O157:H7 in feces was measured for 30 days post-challenge. We observed a transient clearance of <it>E. coli </it>O157:H7 from the feces in the vaccinated calves. The magnitude of fecal <it>E. coli </it>O157:H7 shedding did not correlate with the presence of intimin-specific fecal IgA.</p> <p>Conclusion</p> <p>Oral vaccination with live attenuated recombinant <it>S</it>. Dublin expressing intimin reduced enteric colonization and fecal shedding of <it>E. coli </it>O157:H7. However, the transient clearance of <it>E. coli </it>O157:H7 was not associated with an enhanced IgA-mediated mucosal immune response.</p

A Multi-Epoch Study of the Radio Continuum Emission of Orion Source I: Constraints on the Disk Evolution of a Massive YSO and the Dynamical History of Orion BN/KL

We present new 7mm continuum observations of Orion BN/KL with the VLA. We resolve the emission from the protostar radio Source I and BN at several epochs. Source I is highly elongated NW-SE, and remarkably stable in flux density, position angle, and overall morphology over nearly a decade. This favors the extended emission component arising from an ionized disk rather than a jet. We have measured the proper motions of Source I and BN for the first time at 43 GHz. We confirm that both sources are moving at high speed (12 and 26 km/s, respectively) approximately in opposite directions, as previously inferred from measurements at lower frequencies. We discuss dynamical scenarios that can explain the large motions of both BN and Source I and the presence of disks around both. Our new measurements support the hypothesis that a close (~50 AU) dynamical interaction occurred around 500 years ago between Source I and BN as proposed by Gomez et al. From the dynamics of encounter we argue that Source I today is likely to be a binary with a total mass on the order of 20 Msun, and that it probably existed as a softer binary before the close encounter. This enables preservation of the original accretion disk, though truncated to its present radius of ~50 AU. N-body numerical simulations show that the dynamical interaction between a binary of 20 Msun total mass (I) and a single star of 10 Msun mass (BN) may lead to the ejection of both and binary hardening. The gravitational energy released in the process would be large enough to power the wide-angle flow traced by H2 and CO emission in the BN/KL nebula. Assuming the proposed dynamical history is correct, the smaller mass for Source I recently estimated from SiO maser dynamics (>7 Msun) by Matthews et al., suggests that non-gravitational forces (e.g. magnetic) must play an important role in the circumstellar gas dynamics.Comment: 17 pages, 7 figures, 4 tables, accepted by Ap