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Nursing home residents are often colonized with antibiotic-resistant bacteria. In this trial involving 28 nursing homes, decolonization with chlorhexidine and povidone–iodine reduced the risk of hospitalization for infection.

Background: More than half of nursing home (NH) residents harbor a multidrug-resistant organism (MDRO), and MDRO contamination of the environment is common. Whether NH decolonization of residents reduces MDRO contamination remains unclear. The PROTECT trial was a cluster-randomized trial of decolonization versus routine care in 28 California NHs from April 2017 through December 2018. Decolonization involved chlorhexidine bathing plus nasal iodophor (Monday–Friday, every other week), and it reduced resident nares and skin MDRO colonization by 36%. Methods: We swabbed high-touch objects in resident rooms and common areas for MDROs before and after the 3-month decolonization phase-in (April–July 2017). Five high-touch objects (bedrail, call button and TV remote, doorknob, light switch, and bathroom handles) were swabbed in 3 resident rooms per NH based on care needs (Alzheimer’s disease and related dementias (ADRD), ie, total care; ADRD, ambulatory care; and short stay). Five high-touch objects were also swabbed in the common area (nursing station, table, chair, railing, and drinking fountain). Swabs were processed for methicillin-resistant S. aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae , and carbapenem-resistant Enterobacteriaceae (CRE). We used generalized linear mixed models to assess the impact of decolonization on MDRO environmental contamination when clustering by NH and room and adjusting for room type and object because unclustered and unadjusted results are likely to be inaccurate. Results: A high proportion of rooms were contaminated with any MDRO in control NHs: 43 of 56 (77%) in the baseline period and 46 of 56 (82%) in the intervention period. In contrast, decolonization NHs had similar baseline contamination (45 of 56, 80%) but lower intervention MDRO contamination (29 of 48, 60%). When evaluating the intervention impact using multivariable models, decolonization was associated with significantly less room contamination for any MDRO (OR, 0.25; 95% CI, 0.06–0.96; P = .04) and MRSA (OR, 0.16; 95% CI, 0.05–0.55; P = .004) but nonsignificant reductions in VRE contamination (OR, 0.86; 95% CI, 0.23–3.13) and ESBL contamination (OR, 0.13; 95% CI, 0.01–1.62). CRE was not modeled due to rare counts (2 rooms total). In addition, room type was important, with common areas associated with 5-fold, 9-fold, and 3-fold higher contamination with any MDRO, MRSA, and VRE, respectively, compared with short-stay rooms. Conclusions: The high burden of MDROs in NHs calls for universal prevention strategies that can protect all residents. Although decolonization was associated with an 84% reduction in odds of MRSA contamination of inanimate room objects, significant reductions in VRE or ESBL contamination were not seen, possibly due to the lower proportion of baseline contamination due to these organisms. Multimodal strategies are needed to address high levels of MDRO contamination in NHs. Funding: None Disclosures: Gabrielle Gussin: Stryker (Sage Products): Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes. Clorox: Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes. Medline: Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes. Xttrium: Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes.

Background The prevalence of MDROs in nursing homes (NH) is much higher than that of hospitals. Decolonization to reduce the reservoir of MDRO carriage in NH residents may be a strategy to address MDRO spread within and among healthcare facilities. Methods PROTECT is an 18-month cluster randomized trial of 1:1 universal decolonization vs. routine care in 28 NHs in California. Decolonization consists of chlorhexidine (CHG) bathing plus twice daily nasal iodophor on admission and Monday–Friday biweekly. We assessed pre- vs. post-intervention MDRO prevalence by sampling 50 randomly selected residents at each NH as an outcome unrelated to the trial’s primary intent (infection, hospitalization reduction). NH residents had nasal swabs cultured for methicillin-resistant S. aureus (MRSA), and skin (axilla/groin) swabs taken for MRSA, vancomycin-resistant Enterococcus (VRE), extended-spectrum β-lactamase producers (ESBL), and carbapenem-resistant Enterobacteriaceae (CRE). Generalized linear mixed models (GLM) assessed the difference in differences of MDRO prevalence using an arm by period interaction term, clustering by NH. Results Four NHs dropped from the trial. Among the 24 NHs that remained, MDRO colonization at baseline was 49.4% and 47.5% of residents in control (N = 650) vs. decolonization (N = 550) NHs, with no difference in MRSA, VRE, ESBL, and CRE (Table 1). Among remaining NHs, decolonization was associated with 28.8% raw decrease in MDRO prevalence in decolonization sites (GLM OR = 0.51, P < 0.001), 24.3% raw decrease in MRSA (OR = 0.66, P = 0.03), 61.0% raw decrease in VRE (OR = 0.17, P < 0.001), and 51.9% raw decrease in ESBL (OR = 0.40, P < 0.001). CRE increased, but numbers were small (Control arm: 10 in baseline, 4 in intervention; intervention arm: 1 in baseline, 2 in intervention, P = NS). Conclusion Universal NH decolonization with CHG bathing and nasal iodophor resulted in a marked decrease in Gram-positive and Gram-negative MDRO prevalence. This decrease may lower MDRO acquisition, infection, and antibiotic use within NHs, as well as regional MDRO spread to other healthcare facilities. Disclosures All Authors: No reported Disclosures.

Abstract Background Early appropriate antibiotic selection is life saving in sepsis. Facility-level antibiograms inform antibiotic selection after pathogen identification and before susceptibility results are available, but only if ≥ 30 isolates from a given species are tested in the prior year. Stenotrophomonas maltophilia (SM) has a complex resistance profile and is associated with an 8-fold mortality increase. We hypothesized that a regional antibiogram may help inform clinical decision-making for severe SM infections. Methods To generate a regional SM antibiogram, we conducted a cross-sectional, voluntary survey of 2015 cumulative facility-level antibiograms from all hospitals in LA county. Non-respondents were contacted to improve response rates. Isolates from sterile sources were pooled. Susceptibility was aggregated and percent susceptible was calculated only when all isolates were tested, i.e. not reflex testing. To identify optimal combination empiric therapy for SM infections, we generated a combination antibiogram using broth microdilution results from a single tertiary care facility in LA. Results Antibiograms were submitted by 85/100 (85%); 50 hospitals (59%) reported SM (n = 1719 isolates, Table 1). Hospitals commonly (25/50) reported data for <30 isolates. The combination antibiogram for SM is presented in Table 2. Four hospitals reported susceptible results for antibiotics to which SM is intrinsically resistant (ceftriaxone, meropenem, aminoglycosides). After SXT, the most active antibiotics against SM were not routinely tested by the majority of laboratories (minocycline, colistin) (Table 2). Conclusion The LAC regional antibiogram represents one of the largest reports of SM susceptibility presented to date. Hospitals rarely tested sufficient numbers of SM isolates to provide reliable estimates for resistance and failed to report on clinically valuable treatment options. Regional antibiograms may help hospitals with low pathogen prevalence improve antibiotic selection and reduce mortality for uncommon but potentially deadly pathogens. Disclosures L. G. Miller, Sage Products: Study coordination, Conducting studies in healthcare facilities that are receiving contributed product. Xttrium: Study coordination, Conducting studies in healthcare facilities that are receiving contributed product. Clorox: Study coordination, Conducting studies in healthcare facilities that are receiving contributed product. 3M: Study coordination, Conducting studies in healthcare facilities that are receiving contributed product. J. A. McKinnell, Allergan: Research Contractor, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research support and Speaker honorarium. Achaogen: Research Contractor, Scientific Advisor and Shareholder, Research support. Cempra: Research Contractor and Scientific Advisor, Research support. Theravance: Research Contractor, Research support. Science 37: Research Contractor, Salary. Expert Stewardship, LLC: Board Member and Employee, Salary. Thermo Fisher: Scientific Advisor, Salary

Abstract Background The majority of healthcare-associated infections due to MDROs occur in the post-discharge setting. Understanding MDRO spread and containment in NHs can help identify infection prevention activities needed to care for vulnerable patients in a medical home setting. Methods We conducted a baseline point prevalence study of MDRO colonization in residents of 28 Southern California NHs participating in a decolonization trial. In Fall 2016, residents were randomly sampled to obtain a set of 50 nares and skin (axilla/groin) swabs from each NH. Nasal swabs were processed for MRSA and skin swabs were processed for MRSA, VRE, ESBL, and CRE. In addition, environmental swabs were collected from high touch objects in resident rooms (bedrail, call button/TV remote, door knobs, light switch, bathroom) and common areas (nursing station, table, chair, railing, and drinking fountain). Results A total of 2,797 body swabs were obtained from 1400 residents. Overall, 48.6% (N = 680) of residents harbored MDROs. MRSA was found in 37% of residents (29.5% nares, 24.4% skin), followed by ESBL in 16% (Table 1). Resident MDRO status was only known for 11% of MRSA (59/518), 18% ESBL (40/228), 4% VRE (4/99), and none of the CRE (0/13) carriers. Colonization did not differ between long stay (48.8%, 534/1094) vs. post-acute (47.7%, 146/306) residents (P = NS), but bedbound residents were more likely to be MDRO colonized (58.7%, 182/310) vs. ambulatory residents (45.7%, 497/1088, P < 0.001). A total of 560 environmental swabs were obtained with 93% of common areas and 74% of resident rooms having an MDRO+ object with an average of 2.5 and 1.9 objects found to be contaminated (Table 2). Conclusion One in two NH residents are colonized with MDROs, which is largely unknown to the facility. MDRO carriage is associated with total care needs, but not long stay status. Environmental contamination in resident rooms and common areas is common. The burden of MDRO colonization and contamination is sufficiently high that universal strategies to reduce colonization and transmission are warranted. Disclosures J. A. McKinnell, Allergan: Research Contractor, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research support and Speaker honorarium; Achaogen: Research Contractor, Scientific Advisor and Shareholder, Research support; Cempra: Research Contractor and Scientific Advisor, Research support; Theravance: Research Contractor, Research support; Science 37: Research Contractor, Salary; Expert Stewardship, LLC: Board Member and Employee, Salary; Thermo Fisher: Scientific Advisor, Salary; 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium Laboratories: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; L. Miller, 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium Laboratories: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; R. D. Singh, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium Laboratories: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; J. Mendez, Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium Laboratories: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; R. Franco, Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium Laboratories: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; G. Gussin, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium Laboratories: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; L’Oreal: Consultant, Consulting fee; J. Chang, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium Laboratories: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; T. D. Dutciuc, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; R. Saavedra, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium Laboratories: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; K. Kleinman, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium Laboratories: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Molnlycke: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; E. M. Peterson, Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium Laboratories: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; L. Heim, Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; A. Miner, Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium Laboratories: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; M. Estevez, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; 3M: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; H. Custodio, Xttrium Laboratories: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Clorox: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; S. Yamaguchi, Sage Products: Receipt of contributed product, Conducting studies in healthcare facilities that are receiving contributed product; Xttrium Laboratories: Receipt of contributed product, Conducting studies in healthcare facil

Photonic integrated circuits provide a compact and stable platform for quantum photonics. Here we demonstrate a silicon photonics quantum key distribution (QKD) encoder in the first high-speed polarization-based QKD field tests. The systems reach composable secret key rates of 1.039 Mbps in a local test (on a 103.6-m fiber with a total emulated loss of 9.2 dB) and 157 kbps in an intercity metropolitan test (on a 43-km fiber with 16.4 dB loss). Our results represent the highest secret key generation rate for polarization-based QKD experiments at a standard telecom wavelength and demonstrate photonic integrated circuits as a promising, scalable resource for future formation of metropolitan quantum-secure communications networks.

The Aedes aegypti mosquito is the main hematophagous vector responsible for arbovirus transmission in Brazil. The disruption of A. aegypti hematophagy remains one of the most efficient and least toxic methods against these diseases and, therefore, efforts in the research of new chemical entities with repellent activity have advanced due to the elucidation of the functionality of the olfactory receptors and the behavior of mosquitoes. With the growing interest of the pharmaceutical and cosmetic industries in the development of chemical entities with repellent activity, computational studies (e.g., virtual screening and molecular modeling) are a way to prioritize potential modulators with stereoelectronic characteristics (e.g., pharmacophore models) and binding affinity to the AaegOBP1 binding site (e.g., molecular docking) at a lower computational cost. Thus, pharmacophore- and docking-based virtual screening was employed to prioritize compounds from Sigma-Aldrich® (n = 126,851) and biogenic databases (n = 8766). In addition, molecular dynamics (MD) was performed to prioritize the most potential potent compounds compared to DEET according to free binding energy calculations. Two compounds showed adequate stereoelectronic requirements (QFIT > 81.53), AaegOBP1 binding site score (Score > 42.0), volatility and non-toxic properties and better binding free energy value (∆G < −24.13 kcal/mol) compared to DEET ((N,N-diethyl-meta-toluamide)) (∆G = −24.13 kcal/mol).

Adenosine Receptor Type 2A (A2AAR) plays a role in important processes, such as anti-inflammatory ones. In this way, the present work aimed to search for compounds by pharmacophore-based virtual screening. The pharmacokinetic/toxicological profiles of the compounds, as well as a robust QSAR, predicted the binding modes via molecular docking. Finally, we used molecular dynamics to investigate the stability of interactions from ligand-A2AAR. For the search for A2AAR agonists, the UK-432097 and a set of 20 compounds available in the BindingDB database were studied. These compounds were used to generate pharmacophore models. Molecular properties were used for construction of the QSAR model by multiple linear regression for the prediction of biological activity. The best pharmacophore model was used by searching for commercial compounds in databases and the resulting compounds from the pharmacophore-based virtual screening were applied to the QSAR. Two compounds had promising activity due to their satisfactory pharmacokinetic/toxicological profiles and predictions via QSAR (Diverset 10002403 pEC50 = 7.54407; ZINC04257548 pEC50 = 7.38310). Moreover, they had satisfactory docking and molecular dynamics results compared to those obtained for Regadenoson (Lexiscan®), used as the positive control. These compounds can be used in biological assays (in vitro and in vivo) in order to confirm the potential activity agonist to A2AAR.

The ongoing COVID-19 pandemic has revealed the shortfalls in our understanding of how to treat coronavirus infections. With almost 7 million case fatalities of COVID-19 globally, the catalog of FDA-approved antiviral therapeutics is limited compared to other medications, such as antibiotics. All-trans retinoic acid (RA), or activated vitamin A, has been studied as a potential therapeutic against coronavirus infection because of its antiviral properties. Due to its impact on different signaling pathways, RA’s mechanism of action during coronavirus infection has not been thoroughly described. To determine RA’s mechanism of action, we examined its effect against a mouse coronavirus, mouse hepatitis virus strain A59 (MHV). We demonstrated that RA significantly decreased viral titers in infected mouse L929 fibroblasts and RAW 264.7 macrophages. The reduced viral titers were associated with a corresponding decrease in MHV nucleocapsid protein expression. Using interferon regulatory factor 3 (IRF3) knockout RAW 264.7 cells, we demonstrated that RA-induced suppression of MHV required IRF3 activity. RNA-seq analysis of wildtype and IRF3 knockout RAW cells showed that RA upregulated calcium/calmodulin (CaM) signaling proteins, such as CaM kinase kinase 1 (CaMKK1). When treated with a CaMKK inhibitor, RA was unable to upregulate IRF activation during MHV infection. In conclusion, our results demonstrate that RA-induced protection against coronavirus infection depends on IRF3 and CaMKK.