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We present the unusual case of a 60-year-old immunocompetent woman with chronic obstructive pulmonary disease who developed a necrotising pneumonia with isolation of

Chagas disease is a neglected anthropozoonosis of global importance with significant cardiovascular-associated mortality. This review focuses on the Trypanosoma cruzi reinfections' role in chronic Chagas cardiomyopathy pathogenesis. We discuss and summarize the available data related to pathology, pathogenesis, diagnosis, and treatment of reinfections.Reinfections influence the genetic and regional diversity of T. cruzi, tissue tropism, modulation of the host's immune system response, clinical manifestations, the risk for congenital infections, differences in diagnostics performances, response to antiparasitic therapy, and the natural history of the disease. Animal models suggest that reinfections lead to worse outcomes and increased mortality, while other studies showed an association between reinfections and lower parasitemia levels and subsequent infection protection. In some regions, the human risk of reinfections is 14% at 5 years. Evidence has shown that higher anti-T. cruzi antibodies are correlated with an increased rate of cardiomyopathy and death, suggesting that a higher parasite exposure related to reinfections may lead to worse outcomes. Based on the existing literature, reinfections may play a role in developing and exacerbating chronic Chagas cardiomyopathy and are linked to worse outcomes. Control efforts should be redirected to interventions that address structural poverty for the successful and sustainable prevention of Chagas disease.

Background Gram negative bacteria (GNB) have been identified as a cause of upper extremity infections and empiric treatment directed to both gram positive and negative organisms is often recommended. Risk-based approaches to establish need for gram-negative coverage may help to minimize unnecessary drug exposure, but further information on such methods are currently lacking. The aim of this study was to identify risk factors associated with the isolation of GNB in patients with upper extremity infections. Methods We reviewed records of patients with upper extremity infections treated in two urban hospitals between March 2018 and July 2020. Prosthetic joint infections were excluded. Baseline demographic, clinical, surgical and microbiology data was collected. Multivariable logistic regression models were screened using Akaike Information Criterion to establish the best model and risk factors associated with isolation of a GNB. Results We identified 111 patients, the majority of whom were male with frequent history of IV drug use. Deep wound cultures in 30 (33.3%) individuals yielded a GNB, and 80% of these cases were polymicrobial. Among the GNB, most prevalent were Enterobacterales (10.4%), HACEK group (6.39%), and Pseudomonas spp. (4.5%) (Tables 1. and 2.). Infections were mostly limited to the soft tissue structures of the hand and the forearm, with involvements of the joint and bone being second and third most common. The final model identified the use of IV medications (OR 4.14, 95% CI 1.3 - 14.46) together with prior surgery at the site of infection within the last year (OR 5.56, 95% CI 1.06 - 30.98), and having an open wound on presentation (OR 3.03, 95% CI 1.04 - 9.47) as factors independently associated with isolation of a GNB (Table 3). AUROC of 0.702 indicates acceptable model discrimination. Table 1: Baseline characteristics Table 2: Bacterial isolates Table 3: Final model Conclusion Our logistic regression model identified significant predictors for isolation of GNB in upper extremity infections within this population. Results of this study will assist clinicians in making a better informed decision for the need of empiric gram negative coverage aimed to support the reduction of patient exposure to unnecessary antimicrobial coverage. External validation of the model is warranted prior to application to clinical care. Figure 1: AUROC Disclosures All Authors: No reported disclosures

Background Accurately predicting the presence of a carbapenem resistant enterobacterales (CRE) in hospitalized patients presents itself as an opportunity that would support timely initiation of CRE active agents. The aim of this study is to determine how reliably the existing risk prediction models identify patients likely to require empiric anti-CRE treatment, preliminary results of which are presented herein. Methods A systematic search identified all existing CRE prediction models for validation in our patient population. Medical records of hospitalized patients within the Mount Sinai Health System in New York were subsequently reviewed. Data was gathered on model predictors, baseline demographics, clinical information, microbiology results, antibiotic utilization history and index infection. Besides calculating the AUROC, the main outcome of our study was to establish optimal prediction score cutoffs and false positive rates (FPR) where corresponding model performance maintains a false negative rate (FNR) of < 10%, < 20% and < 30%, respectively. Results 12 models were retained for validation. We identified 106 patients, 41 of which were treated for a CRE infection. Previous admission, organ transplantation, CKD, infection type, and carbapenem use were baseline variables that significantly differed between the groups treated for a CRE or non-CRE related infection (Table 1). The models ability to discriminate varied as evidenced by the AUROC range of 0.5 to 0.77 (Figure 1), suggesting the Seligmen et al. model as the overall best. When evaluated at the pre-specified FNR intervals of < 10%, < 20% and < 30%, the model by Lodise et al., Seligman et al., and Vazquez-Guillamet et al. produced the best FPR, respectively (Table 2). Table 1. Baseline characchteristics Table 2. Model Performance Figure 1. AUROCs Conclusion Discriminative ability of the risk prediction models showed varying performance. The model by Lodise et al. appears to be most useful when a low risk level is deemed acceptable for failure rate, while at a moderate to high risk of missing a CRE case (20% and 30% FNR), the methods by Seligman and Vazquez-Guillamet et al. are most desirable as they minimize the chance of over-treatment. Additional work to increase sample size and to evaluate the models inter-rater reliability is currently on going. Disclosures All Authors: No reported disclosures

Some racial and ethnic minorities in the United States are disproportionally affected by allergic diseases such as asthma, food allergies, anaphylaxis, and atopic dermatitis. Reasons for this are complex, involving psychosocial, environmental, and genetic factors. Possible asthma susceptibility genes have been identified in racial/ethnic minorities that are likely modified by epigenetic changes following exposure to environmental factors. Examples of these environmental factors are pollution, stress, and violence, which disproportionally affect poor and urban communities. Hispanics and African Americans in inner-city areas are more frequently exposed to air pollution, poor housing conditions, and indoor allergens compared to Whites. These effects are compounded by a lack of regular health care, language barriers, and low health literacy. African ancestry is associated with increased asthma risk and might contribute to disparities among some Hispanic patients such as Puerto Ricans who have the highest asthma burden. African Americans are especially affected by atopic dermatitis, food allergy, and anaphylaxis-related death due to any cause. In contrast, rates of allergic rhinitis are higher among Whites and Asian Americans. Overcoming these disparities in allergic diseases will require culturally competent interventions aimed at risk factors that disproportionally affect racial/ethnic minorities.

We present the unusual case of a 60-year-old immunocompetent woman with chronic obstructive pulmonary disease who developed a necrotising pneumonia with isolation of Cunninghamella bertholletiae, Aspergillus niger, Staphylococcus pseudintermedius and adenovirus. The patient recovered with antimicrobial therapy and supportive care in the intensive care unit. The current literature on diagnosis and treatment of these pathogens is reviewed.

Background Hand infections represent a major source of morbidity, which can result in hand stiffness and amputation. Early appropriate empiric antibiotic regimen may reduce the associated morbidity, hence the importance to examine local epidemiology. The aim of this study was to define the current epidemiology of adult hand infections at two urban hospitals in New York City. Methods We performed a double center, retrospective study of adult patients hospitalized from March 2018 to May 2020. Patients with positive cultures associated with the hand infections were included. Retrospectively, 100 patients were reviewed. Data on baseline demographic, clinical, surgical, microbiology, and treatment parameters were collected. Results Of the 100 patients, 76% were male, with median age of 47.5 years (35, 58.25) and average C-reactive protein (CRP) of 50.66 mg/L (± 64.64) on admission (see Table 1). Previous hospitalization within 1 year (38%), previous surgical procedures (39%) and recent IV medication use (26%) were common. 130 bacterial isolates were identified (see Table 2). The most frequent organisms were Gram-positive, with Methicillin susceptible Staphylococcus aureus (MSSA, 25.38%), Streptococcus species (20.08%), and Methicillin resistant Staphylococcus aureus (MRSA, 15.38%) being the most common. Gram-negative organisms were infrequent, with Haemophilus parainfluenzae (3.85%), Enterobacter cloacae (3.85) and Pseudomonas aeruginosa (3.08%) being the most prevalent. Of the 100 patients, 27% had polymicrobial infections, associated with trauma (6%), illicit IV use (6%) and unknown (7%) etiologies. Table 1: Baseline demographics and co-morbid conditions Table 2: Types and numbers of organisms in relation to etiologies Conclusion Within our population, the most common organisms associated with hand infections were Gram-positive, with Staphylococcus aureus and Streptococcus species being the most prevalent. Gram-negative pathogens were infrequently isolated. The results within this study can provide guidance to clinicians on assessing the appropriate empiric antibiotic regimen in patients with hand infections, and can serve as a basis for further studies identifying risk factors associated with isolation of organisms associated with hand infections. Disclosures All Authors: No reported disclosures

Background Countless diseases and medications have been implicated in the past as causing prolongation of the QT interval. Their unique role through the means of quantifying the definite magnitude of relative risk they contribute during hospitalization still requires further investigation. The aim of this study was to describe the impact of commonly used anti-infectives on the QT interval in hospitalized patients during the COVID-19 era. Methods Demographic information, medical history, laboratory data, medication administration history and ECG recording data was collected from the electronic records of adult patients admitted to two urban hospitals. A mixed effects approach with four sub-models for the QT interval comprised of: heart rate, circadian rhythm, gender, and the drug (regressed as the cumulative mg dose administered over time) and disease effects was used. Fixed and random effects with between occasion variability were estimated for the parameters with a Bayesian approach using the STAN software. Results Data from 2180 patients were used with baseline characteristics shown in Table 1. Observed vs. predicted plots based on the training (Figure 1.A) and validation data set (Figure 1.B) showed excellent fit. The parameters for QTc0, α, gender, and circadian rhythm were identified within the range previously described (Table 2.). Similarly, the model correctly identified the impact of acute or chronic diseases on the QT interval. Model coefficient estimates [mean (95% CI) of 0.010 (0.006, 0.15) and 0.0045 (0.0013, 0.01100) msec/mg cumulative dose, respectively] suggest that patients treated with conventional regimens of fluconazole and levofloxacin are most likely to present with a QT interval increase > 5 msec, the cutoff threshold of regulatory concern. Figure 1. A-B Table 1. Table 2. Conclusion The model developed accurately identified the impact baseline risk factors and concomitant medications have on the QT interval. When adjusted for these confounding variables, estimates of QT interval prolongation show that treatment with fluconazole and levofloxacin pose a considerable risk; while treatment with azithromycin or hydroxychloroquine is of moderate risk for QT interval prolongation. Disclosures All Authors: No reported disclosures

Chronic rhinosinusitis (CRS) affects 12.5% of the U.S. population. CRS can be divided into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps. Some individuals with CRSwNP do not respond to standard-of-care medical and surgical management. For these individuals, targeted biologic agents are emerging as an important therapeutic alternative. In this review, we described the most-relevant studies that addressed the use of anti-immunoglobulin E (omalizumab), anti-interleukin 5 (mepolizumab and reslizumab), and anti-interleukin 4/interleukin 13 (dupilumab) monoclonal antibodies for the treatment of CRSwNP. In addition, we discussed the importance of some of these clinical trials in identifying new CRS endotypes based on distinct inflammatory profiles.

BET proteins commonly activate cellular gene expression, yet inhibiting their recruitment paradoxically reactivates latent HIV-1 transcription. Here weidentify the short isoform of BET family member BRD4 (BRD4S) as a corepressor of HIV-1 transcription. We found that BRD4S was enriched in chromatin fractions of latently infected Tcells, and it was more rapidly displaced from chromatin upon BET inhibition than the long isoform. BET inhibition induced marked nucleosome remodeling at the latent HIV-1 promoter, which was dependent on the activity of BRG1-associated factors (BAF), an SWI/SNF chromatin-remodeling complex with known repressive functions in HIV-1 transcription. BRD4S directly bound BRG1, a catalytic subunit of BAF, via its bromodomain and extraterminal (ET) domain, and this isoform was necessary for BRG1 recruitment to latent HIV-1 chromatin. Using chromatin immunoprecipitation sequencing (ChIP-seq) combined with assay fortransposase-accessible chromatin coupled to high-throughput sequencing (ATAC-seq) data, we found that the latent HIV-1 promoter phenotypically resembles endogenous long terminal repeat (LTR) sequences, pointing to a selectrole of BRD4S-BRG1 complexes in genomic silencing of invasive retroelements.