Presumed Source Research Articles

Preserving the antimicrobial arsenal: exploring alternatives to carbapenems in ESBL battles within the southeast of Ireland.

Introduction. Carbapenems are usually employed as first-line antimicrobials against bacteria harbouring extended-spectrum beta-lactamases (ESBLs). These enzymes confer resistance often to multiple classes of antimicrobials.Hypothesis/Gap Statement. This indiscriminate use of carbapenems and the inevitable development of carbapenem resistance have prompted the need for carbapenem-sparing strategies.Methodology. The non-carbapenem antimicrobial susceptibility patterns of 60 ESBL-producing Enterobacterales (ESBL-PE) isolates responsible for bloodstream infections, in 2022-2023 inclusive, processed at our institution were reviewed.Results. The non-carbapenem antimicrobial susceptibility patterns of 60 ESBL-PE isolates from bloodstream infections during the study period were determined. Escherichia coli was the most common species isolated (87%, n=52), with the majority of cases (73.3%, n=44) originating from a presumed urinary source. Temocillin (TMC), mecillinam (MEC), cefiderocol (FDC), amikacin and fosfomycin (FOS) displayed excellent activity against all ESBL-PE isolates tested, with susceptibility rates of≥85%. Ciprofloxacin and amoxicillin-clavulanic acid were the least efficacious agents, with susceptibility rates≤20%.Conclusions. TMC, MEC, FDC and FOS offer promising alternatives to carbapenems, demonstrating efficacy against ESBL-PE. The use of these agents not only broadens the therapeutic arsenal against ESBL-PE but also mitigates the potential for escalating carbapenem resistance, especially in regions where the incidence of carbapenem resistance is increasing.

P-1516. Addition of Single-Dose Aminoglycosides to Empiric Beta-Lactam Therapy in Septic Shock in a Setting with High Antimicrobial Resistance Rates

Abstract Background At the Detroit Medical Center (DMC), the addition of an aminoglycoside (AMG) to β-lactam therapy is recommended in patients with septic shock due to high resistance rates; however, studies assessing the benefit of such combinations have yielded conflicting results. The objective of this study is to compare the outcomes of patients with septic shock who receive empiric β-lactam therapy with and without an AMG.Figure 1.Mortality Outcomes Methods This is a retrospective cohort study from 5/2021 to 7/2023. Patients were included if they met the following: 2 of 4 SIRS criteria, received vasopressors, serum lactate > 2 mmol/L, and appropriate empiric antimicrobial therapy within 24 hrs of admission . Patients who received an AMG within 24 hrs of admission were included in the AMG cohort, and those who did not were included in the control group. Key exclusion criteria were COVID-19, burn injury, and transfer to hospice care within 4 days of admission. The primary outcome was all-cause mortality at 7 days ; secondary outcomes included 30-day mortality, vasopressor-free days by day 7, ventilator-free days by day 28, and nephrotoxicity by day 7.Table 1.Patient and treatment characteristics Results Seventy-six patients were included (AMG=38; Control=38). The most common source of infection in AMG and control groups was pulmonary (44% vs. 31%, p=0.18). More AMG patients had a presumed SSTI source (17% vs. 0.0%, p=0.0049) patients, positive blood culture (79% vs. 26%, p< 0.0001), prior history of MDRO pathogen (22% vs. 0.0%, p=0.003), and received meropenem as initial empiric therapy (40% vs. 3%, p< 0.0001). APACHE II scores were similar (30 vs. 28, p=0.09). Time to appropriate antibiotic therapy was 4.8 hrs in the AMG group vs. 6.4 hrs in the control group, p=0.81. There were no differences in 7-day mortality (47% vs. 40%, p=0.49), 30-day mortality (63% vs. 53%, p=0.3527), vasopressor-free days by day 7 (2 vs. 2, p=0.08), or ventilator-free days by day 28 (2.5 vs. 8.5, p=0.31). There were also no differences in nephrotoxicity by day 7 (50% vs. 67%, p=0.23).Table 1.Patient and treatment characteristics, continued Conclusion Further evaluations should be conducted to determine whether an AMG in combination with β-lactams should be used in patients with septic shock.Table 2.Other clinical outcomes Disclosures All Authors: No reported disclosures

P-1661. Characteristics and Outcomes Associated with Treatment of Asymptomatic Bacteriuria Among Patients with Neurogenic Bladder in a Statewide Hospital Database

Abstract Background Inappropriate treatment of asymptomatic bacteriuria (ASB) among hospitalized patients leads to longer length of stay (LOS) without improving outcomes. ASB is common in individuals with neurogenic bladder (NB); however, little is known about the epidemiology, treatment, and outcomes of inpatients with NB and ASB. Methods Between 1/1/2017-12/31/2023, abstractors collected deidentified data—including signs/symptoms of urinary tract infections (UTI) and 30-day outcomes—from inpatients with a positive urine culture (UC) at 46 hospitals. Due to poor documentation of NB, we defined NB using surrogates (Table 1). Patients without signs or symptoms of UTI were classified as ASB. Characteristics of patients a) with vs. without NB and b) with NB and ASB who were treated vs. untreated were compared using t or chi-squared tests. Finally, we compared 30-day outcomes of patients with NB and ASB treated vs. untreated using general estimating equation models adjusting for variables known to be associated with the outcomes via inverse probability of treatment weighting. Results Of 45,800 inpatients with a positive UC, 6% (2,769) had NB (Table 2). Compared to patients without NB, patients with NB were more often male (59% vs. 29% p< 0.001), younger (median age 69 vs. 76 p< 0.001), less likely to be white (64.6% vs. 77% p< 0.001) and more likely to use a catheter (76% vs. 17% p< 0.001). While ASB rates (25.7% vs. 25.2%, p=0.62) were similar, bacteremia from a presumed urinary source (4.6% vs. 7.2%, p< 0.001) was less common in patients with NB. 85.1% (605/711) of patients with NB with ASB received antibiotic therapy. Similar to patients without NB, altered mental status (AMS) was the main predictor of ASB treatment (23.8% vs. 13.3% p=0.017; Table 3). LOS after UC was longer among those with NB and ASB who were treated vs. untreated (4 vs. 3 days, aIRR: 1.538, 95% CI: 1.33-1.77 p< 0.001; Table 4). Conclusion Among inpatients with NB in a statewide dataset, ASB was common, more frequently treated with antibiotics, and treatment was associated with longer LOS. AMS was the main predictor of ASB treatment. Bacteremia was lower among patients with NB, suggesting UC overuse. Disclosures Barbara Trautner, MD, PhD, Abbott Laboratories: Stocks/Bonds (Public Company)|AbbVie: Stocks/Bonds (Public Company)|Bristol Myers Squibb: Stocks/Bonds (Public Company)|Pfizer: Stocks/Bonds (Public Company)|Phiogen Pharma: Advisor/Consultant Elizabeth McLaughlin, MS, RN, Blue Cross Blue Shield of Michigan: Salary Support

Outbreak of Norovirus Infection in the Hematology Department of a Children's Multidisciplinary Hospital

Relevance. Noroviruses are currently considered the most common cause of sporadic cases and community-acquired outbreaks of acute gastroenteritis (AGE) worldwide [1]. However, outbreaks of healthcare-associated infections (HAI) are also often caused by norovirus etiology [2], including in the Russian Federation [3].Aim. Analysis of key aspects of prevention and anti-epidemic measures against norovirus infection (NVI) in the hematology department.Materials and methods. The following epidemiological research methods were used: descriptive (intensity, dynamics, spatial characteristics of the NVI outbreak); analytical – longitudinal cohort study of the epidemic process of HAI – assessment of hypotheses about the causes and conditions, risk factors and routes of transmission of norovirus among patients and caregivers in the oncohematology department of the children's multidisciplinary hospital.Results and discussion. An outbreak of acute norovirus gastroenteritis of an imported nature was identified in the oncohematology department of a children's multidisciplinary hospital in February 2023, an analysis of the spread of NVI was carried out: the presumed source and mechanism of transmission of norovirus infection was established; the chronology of the spread of norovirus among patients and their caregivers is shown, a list of anti-epidemic measures taken to stop the outbreak is presented, and the difficulties of verifying the epidemiological diagnosis of HAI are reflected (based on the efficiency of laboratory testing of material from patients).Conclusion. Based on the results of the activities carried out, recommendations were proposed for improving preventive and anti-epidemic measures for acute gastroenteritis (AGE) in children's oncohematology departments.

Symmetric Non-Monochromatic Light as Reference in Fourier Transform Spectrometers.

Fourier transform spectrometers typically use a presumed monochromatic reference source to track and correct errors in optical path difference changes. This paper will conduct a theoretical analysis to show that non-monochromatic light sources with symmetric spectral profiles can also be used as reference sources without adding errors. An experiment was carried out using a symmetric broadband superluminescent diode (SLED) as reference light to measure the spectrum of some other SLED light sources to experimentally demonstrate this finding.

Bioconcentration of pharmaceuticals by aquatic flora in an Australian river system

Pharmaceuticals are emerging contaminants in the environment and are a ubiquitous presence in rivers downstream of wastewater treatment plant outfalls. Questions remain about the persistence of pharmaceuticals in rivers, and the uptake and bioconcentration of pharmaceuticals by aquatic plants. Our study took place in the Yarrowee/Leigh/Barwon River system in southeastern Australia. We quantified the concentrations of five pharmaceuticals (carbamazepine, primidone, propranolol, tramadol, and venlafaxine) in surface water at five sites along a 144-km stretch of river, downstream of the presumed primary point source (a wastewater treatment plant outfall). We quantified pharmaceuticals in the leaves of two aquatic plant species (Phragmites australis and Vallisneria australis) sampled at each site, and calculated bioconcentration factors. All five pharmaceuticals were detected in surface waters, and the highest detected concentration exceeded 500 ng.L−1 (tramadol). Four of the pharmaceuticals (all except tramadol) were detected and quantified at all sites, including the furthest site from the outfall (144 km). Carbamazepine showed less attenuation with distance from the outfall than the other pharmaceuticals. Carbamazepine and venlafaxine were quantified in the leaves of both aquatic plant species (range: 10–31 ng.g−1), and there was evidence that bioconcentration factors increased with decreasing surface water concentrations. The study demonstrates the potential long-distance persistence of pharmaceuticals in river systems, and the bioconcentration of pharmaceuticals by aquatic plants in natural ecosystems. These phenomena deserve greater attention as aquatic plants are a potential point of transfer of pharmaceuticals from aquatic ecosystems to terrestrial food webs.

Periodontal inflammation as a potential driver of HIV low level viremia.

HIV can be successfully suppressed to undetectable levels by antiretroviral therapy (ART) in most people with HIV (PWH). However, a small proportion continues to have persistent low-level viremia (LLV) during ART. A presumed source of LLV is production or replication from viral reservoirs, which are maintained in the presence of ART. It is unknown whether the oral cavity can be considered an HIV reservoir. As periodontal inflammation is a common problem in PWH, we hypothesize that periodontal inflammation in the oral cavity activates (latently) infected cells and thus might be associated with LLV. We included 11 individuals with HIV LLV, and compared HIV-RNA levels in saliva and plasma at baseline and at week 24 after switch of ART. We compared the LLV-group at baseline with 11 age-matched controls with suppressed viremia. To investigate the severity of periodontitis we used Periodontal Inflamed Surface Areas (PISA) by measuring probing depth, gingival recession, bleeding on probing and clinical attachment level. Severity of periodontitis was classified according to the CDC-AAP case definition. Additional insights in periodontal inflammation were obtained by comparing immune activation markers and the presence of periodontal pathogens. In four individuals of the LLV group, residual levels of HIV-RNA were detected in saliva at baseline (N = 1) or at week 24 (N = 2) or both (N = 1). Of the four individuals with LLV, three had residual levels of HIV-RNA in saliva. All 22 individuals had moderate to severe periodontitis. PISA was not significantly different between cases with LLV and controls. Similarly, periodontal pathogens were frequently observed in both groups. Total activated HLA-DR+CD38+ CD4+ cells and CD8+ cells were significantly higher in the LLV group than in the control group (p = <0.01). No immune markers were associated with LLV. In conclusion, periodontal inflammation is an unlikely driver of HIV LLV compared to HIV suppressed individuals.

Niche conservatism and spread explain introgression between native and invasive fish.

Hybridisation can be an important driver of evolutionary change, but hybridisation with invasive species can have adverse effects on native biodiversity. While hybridisation has been documented across taxa, there is limited understanding of ecological factors promoting patterns of hybridisation and the spatial distribution of hybrid individuals. We combined the results of ecological niche modelling (ENM) and restriction site-associated DNA sequencing to test theories of niche conservatism and biotic resistance on the success of invasion, admixture, and extent of introgression between native and non-native fishes. We related Maxent predictions of habitat suitability based on the native ranges of invasive Eastern Banded Killifish (Fundulus diaphanus diaphanus Lesueur 1817) and native Western Banded Killifish (Fundulus diaphanus menona Jordan and Copeland 1877) to admixture indices of individual Banded Killifish. We found that Eastern Banded Killifish predominated at sites predicted as suitable from their ENM, consistent with niche conservatism. Admixed individuals were more common as Eastern Banded Killifish habitat suitability declined. We also found that Eastern Banded Killifish were most common at sites closest to the presumed source of this invasion, whereas the proportion of admixed individuals increased with distance from the source of invasion. Lastly, we found little evidence that habitat suitability for Western Banded Killifish provides biotic resistance from either displacement by, or admixture with, invasive Eastern Banded Killifish. Our study demonstrates that ENMs can inform conservation-relevant outcomes between native and invasive taxa while emphasising the importance of protecting isolated Western Banded Killifish populations from invasive conspecifics.

Per- and Polyfluoroalkyl Substance Exposure Risks in US Carceral Facilities, 2022.

Objectives. To assess the US incarcerated population's risk of exposure to per- and polyfluoroalkyl substances (PFASs). Methods. We assessed how many of the 6118 US carceral facilities were located in the same hydrologic unit code watershed boundaries as known or likely locations of PFAS contamination. We conducted geospatial analyses on data aggregated from Environmental Protection Agency databases and a PFAS site tracker in 2022 to model the hydrologically feasible known and presumptive PFAS contamination sites for nearly 2 million incarcerated people. Results. Findings indicate that 5% (∼310) of US carceral facilities have at least 1 known source of PFAS contamination in the same watershed boundary and that it is at a higher elevation than the facility; also 47% (∼2285) have at least 1 presumptive source. A minimum of 990 000 people are incarcerated in these facilities, including at least 12 800 juveniles. Exposure risks faced by incarcerated youths are disproportionately underassessed. Conclusions. The long-term impacts from potential exposures to PFAS are preventable and exacerbate health inequities among incarcerated populations. Widespread public attention to PFASs can be parlayed into broader environmental monitoring for imprisoned people. (Am J Public Health. 2024;114(5):501-510. https://doi.org/10.2105/AJPH.2024.307571).

Bacteremia From a Presumed Urinary Source in Hospitalized Adults With Asymptomatic Bacteriuria

Guidelines recommend withholding antibiotics in asymptomatic bacteriuria (ASB), including among patients with altered mental status (AMS) and no systemic signs of infection. However, ASB treatment remains common. To determine prevalence and factors associated with bacteremia from a presumed urinary source in inpatients with ASB with or without AMS and estimate antibiotics avoided if a 2% risk of bacteremia were used as a threshold to prompt empiric antibiotic treatment of ASB. This cohort study assessed patients hospitalized to nonintensive care with ASB (no immune compromise or concomitant infections) in 68 Michigan hospitals from July 1, 2017, to June 30, 2022. Data were analyzed from August 2022 to January 2023. The primary outcome was prevalence of bacteremia from a presumed urinary source (ie, positive blood culture with matching organisms within 3 days of urine culture). To determine factors associated with bacteremia, we used multivariable logistic regression models. We estimated each patient's risk of bacteremia and determined what percentage of patients empirically treated with antibiotics had less than 2% estimated risk of bacteremia. Of 11 590 hospitalized patients with ASB (median [IQR] age, 78.2 [67.7-86.6] years; 8595 female patients [74.2%]; 2235 African American or Black patients [19.3%], 184 Hispanic patients [1.6%], and 8897 White patients [76.8%]), 8364 (72.2%) received antimicrobial treatment for UTI, and 161 (1.4%) had bacteremia from a presumed urinary source. Only 17 of 2126 patients with AMS but no systemic signs of infection (0.7%) developed bacteremia. On multivariable analysis, male sex (adjusted odds ratio [aOR], 1.45; 95% CI, 1.02-2.05), hypotension (aOR, 1.86; 95% CI, 1.18-2.93), 2 or more systemic inflammatory response criteria (aOR, 1.72; 95% CI, 1.21-2.46), urinary retention (aOR, 1.87; 95% CI, 1.18-2.96), fatigue (aOR, 1.53; 95% CI, 1.08-2.17), log of serum leukocytosis (aOR, 3.38; 95% CI, 2.48-4.61), and pyuria (aOR, 3.31; 95% CI, 2.10-5.21) were associated with bacteremia. No single factor was associated with more than 2% risk of bacteremia. If 2% or higher risk of bacteremia were used as a cutoff for empiric antibiotics, antibiotic exposure would have been avoided in 78.4% (6323 of 8064) of empirically treated patients with low risk of bacteremia. In patients with ASB, bacteremia from a presumed urinary source was rare, occurring in less than 1% of patients with AMS. A personalized, risk-based approach to empiric therapy could decrease unnecessary ASB treatment.

Floating marine debris in two pelagic ecosystems of the southwestern Atlantic off Argentina

In 2012 and 2013, observational surveys from seismic vessels were conducted to evaluate the abundance and composition of floating marine debris (FMD) in the east of Tierra del Fuego (TDF), Argentina, and the Brazil/Malvinas Confluence zone (BMC), respectively. The mean abundance of FMD varied significantly between sampled ecosystems, with higher loads in TDF (mean abundance = 6.15 ± 8.84 items) when compared to BMC (3.31 ± 6.83 items). Plastics dominated the composition of FMD at both ecosystems (&gt; 80%), followed by foamed plastics. Within the plastic category, bags were the most abundant item, followed by wrappers, and bottles, among others. According to its color, white/clear, and multicolor debris were the most abundant. The main presumed source of FMD was domestic activities, followed by fisheries-related, and construction. This is the first study demonstrating the utility of using seismic vessels as a platform for monitoring FMD in waters within the Argentine continental shelf and adjacent waters.

Retrospective evaluation and review of approaches for nonspecific lameness in dogs presented to an emergency service (2013-2014): 134 cases.

This retrospective study aimed to characterize and evaluate the emergency approach, diagnosis, management, treatment, and follow-up of nonspecific canine lameness cases. Retrospective case series from September 25, 2013 to September 25, 2014. The study was conducted at an urban university teaching hospital. A consecutive sample of dogs presenting to the emergency service with nonspecific lameness in the designated timeframe was used to identify 134 cases. Owners were contacted to participate in the follow-up survey; dogs that died prior to data collection were excluded from the survey. Medical records were reviewed for lameness localization, etiology of lameness, diagnostics obtained, medications prescribed, and owner recommendations. Based on review of the medical records, the lameness localization, presumptive source of lameness (joint, soft tissue, neurological, or bone), diagnostics obtained, medications prescribed, and owner recommendations were recorded. Survey data included duration of lameness, perceived response to treatment, and activity level. Definitive diagnoses were not assigned in 88.8% of lameness cases. A presumptive diagnosis of soft tissue injury was assigned in 45.3% of cases. Single limb lameness was more prevalent than multiple limb lameness. Owners whose dogs were treated with medication were significantly more likely to report that the lameness resolved (P=0.049). Dogs with injury localized to ≥1 of the joints were significantly less likely to have resolution of lameness (P=0.037). Treatment recommendations were predominantly pain control and activity restriction. Nonspecific lameness represents approximately 4% of canine urban emergency cases. Highlighting the points of clinical care considerations in understanding the etiology of lameness in dogs represents an opportunity for improved patient care and growth in emergency referral and follow-up.

Distribution of select per- and polyfluoroalkyl substances at a chemical manufacturing plant

Per- and polyfluoroalkyl substances (PFAS) are used in various industrial products; however, they pose serious health risks. In this study, soil, soil gas, and groundwater samples were collected at a PFAS manufacturing facility in New Jersey, USA, to determine the presence and distribution of PFASs from the soil surface to groundwater and at various distances from the presumed source. Fluorotelomer alcohols (FTOHs) were detected in soil (< 0.26–36.15 ng/g) and soil gas (160–12,000 E µg/m3), while perfluorinated carboxylic acids (PFCAs) were found in soil (4.3–810 ng/g), soil gas (<0.10–180 µg/m3), and groundwater (37–49 µg/L). FTOH and PFCA concentrations decreased as the distance from the presumed source increased, suggesting that PFCAs are likely to migrate in groundwater, whereas FTOHs primarily move in the vapor phase. The presence of PFAS in the groundwater, soil, and soil gas samples indicate its potential for vapor intrusion; thus, some PFAS may contribute to indoor air inhalation exposure. To the best of our knowledge, this is the first report on the quantification of volatile PFAS in soil gas at a PFAS manufacturing facility.

Modelled and observed plastic pollution on remote Scottish beaches: The importance of local marine sources

Beach-cleans conducted on the west coast of Scotland investigated the distribution of land- and marine-sourced litter and compared these with a particle tracking model representing the presumed principal land-based source. Modelled particles dispersed widely, even reaching the remote northwest coast, with ‘hotspots’ and ‘coldspots’ on windward and leeward coasts respectively. In beach sampling, however, land-sourced litter represented only 19% of items by count and 8% by weight, while marine-sourced litter represented 46% by count and 62% by weight. The source of the remainder could not be identified. Windward coasts had an average count of 1859 litter items per 100 m, and weight of 14,862 g per 100 m. Leeward coasts had an average count of 32 litter items per 100 m and weight of 738 g per 100 m. Field observations and model predictions were consistent in many respects for land-sourced litter, however marine-sourced litter is dominant on many coastlines.

Keck near-infrared detections of Mab and Perdita

We report the first near-infrared detection of Uranus’s tiny moon Mab, the presumed source of the blue and diffuse μ ring, using the NIRC2 instrument at Keck Observatory. The detection was permitted by an updated shift-and-stack procedure allowing us to integrate on Mab as it moved across the detector in 23 separate exposures taken over ∼2 h, as well as the very low (0.02∘) phase angle at the time of observation. At this phase angle, Mab has an integrated I/F of 24 ± 3 km2 at 1.6 μm and ≲37 km2 at 2.1 μm. Comparing these values with Mab’s visible reflectance as derived by HST reveals that Mab is spectrally blue; its (0.5 μm)/(1.6 μm) color is more consistent with Miranda’s value than Puck’s value. Mab is therefore more likely a ∼6-km radius body with a Miranda-like surface than a 12-km radius body with a Puck-like surface, in agreement with prior work based on infrared upper limits, but we caution that a Puck-like color is only ruled out at the 2σ level. We also report the first infrared photometry of Perdita, finding an integrated I/F of 31 ± 3 km2 at 1.6 μm.

An Overview of Angiostrongylus cantonensis (Nematoda: Angiostrongylidae), an Emerging Cause of Human Angiostrongylosis on the Indian Subcontinent.

Human angiostrongylosis is an emerging zoonosis caused by the larvae of three species of metastrongyloid nematodes of the genus Angiostrongylus, with Angiostrongylus cantonensis (Chen, 1935) being dominant across the world. Its obligatory heteroxenous life cycle includes rats as definitive hosts, mollusks as intermediate hosts, and amphibians and reptiles as paratenic hosts. In humans, the infection manifests as Angiostrongylus eosinophilic meningitis (AEM) or ocular form. Since there is no comprehensive study on the disease in the Indian subcontinent, our study aims at the growing incidence of angiostrongylosis in humans, alongside its clinical course and possible causes. A systematic literature search revealed 28 reports of 45 human cases from 1966 to 2022; eosinophilic meningitis accounted for 33 cases (75.5%), 12 cases were reported as ocular, 1 case was combined, and 1 case was unspecified. The presumed source of infection was reported in 5 cases only. Importantly, 22 AEM patients reported a history of eating raw monitor lizard (Varanus spp.) tissues in the past. As apex predators, monitor lizards accumulate high numbers of L3 responsible for acute illness in humans. For ocular cases, the source was not identified. Most cases were diagnosed based on nematode findings and clinical pathology (primarily eosinophilia in the cerebrospinal fluid). Only two cases were confirmed to be A. cantonensis, one by immunoblot and the other by q-PCR. Cases of angiostrongylosis have been reported in Delhi, Karnataka, Kerala, Maharashtra, Madhya Pradesh, Puducherry, Telangana, and West Bengal. With a population of more than 1.4 billion, India is one of the least studied areas for A. cantonensis. It is likely that many cases remain undetected/unreported. Since most cases have been reported from the state of Kerala, further research may focus on this region. Gastropods, amphibians, and reptiles are commonly consumed in India; however, typical preparation methods involve cooking, which kills the nematode larvae. In addition to studying rodent and mollusk hosts, monitor lizards can be used as effective sentinels. Sequence data are urgently needed to answer the question of the identity of Angiostrongylus-like metastrongylid nematodes isolated from all types of hosts. DNA-based diagnostic methods such as q-PCR and LAMP should be included in clinical diagnosis of suspected cases and in studies of genetic diversity and species identity of nematodes tentatively identified as A. cantonensis.

Algal ciguatoxin identified as source of ciguatera poisoning in the Caribbean

Ciguatera poisoning (CP) is a severe seafood-borne disease, caused by the consumption of reef fish contaminated with Caribbean ciguatoxins (C-CTXs) in the Caribbean and tropical Atlantic. However, C-CTXs have not been identified from their presumed algal source, so the relationship to the CTXs in fish causing illness remains unknown. This has hindered the development of detection methods, diagnostics, monitoring programs, and limited fundamental knowledge on the environmental factors that regulate C-CTX production. In this study, in vitro and chemical techniques were applied to unambiguously identify a novel C-CTX analogue, C-CTX5, from Gambierdiscus silvae and Gambierdiscus caribaeus strains from the Caribbean. Metabolism in vitro by fish liver microsomes converted algal C-CTX5 into C-CTX1/2, the dominant CTX in ciguatoxic fish from the Caribbean. Furthermore, C-CTX5 from G. silvae was confirmed to have voltage-gated sodium-channel-specific activity. This finding is crucial for risk assessment, understanding the fate of C-CTXs in food webs, and is a prerequisite for development of effective analytical methods and monitoring programs. The identification of an algal precursor produced by two Gambierdiscus species is a major breakthrough for ciguatera research that will foster major advances in this important seafood safety issue.

Risk of tuberculosis transmission by children in Hamburg, Germany

BackgroundData from a prospective molecular-epidemiologic study (1997–2021) in Hamburg, Germany, were evaluated to assess the transmission risk of Mycobacterium tuberculosis complex (Mtbc) by children <15 years in a low-incidence setting. MethodsIsolates of Mtbc were genotyped whole genome sequencing, applying a core genome multilocus sequence typing scheme. Close contacts of culture-confirmed children were examined for latent Mtbc infections (LTBI) with particular focus on IGRA testing. ResultsOut of 3154 culture-confirmed tuberculosis (TB) cases, 79 (2.5%) were children <15 years. Of those, 52 (58%) had pulmonary TB. Genotyping revealed that 35 of the 52 children (67%) were epidemiologically confirmed secondary cluster members; all of their source cases were adults. Six immigrant children presented without a presumed source case; their TB diagnoses came on average 48 weeks (interquartile range [IQR] 71) after their arrival in Germany. Three German-born children were determined to have been infected by adult relatives while visiting their parents' home country. Of the 317 children's close contacts tested with QuantiFERON-TB Gold-In Tube for LTBI, only 21 (6.6%) were positive. Absent a history of prior exposure or immigration from a high-incidence country, none of the contacts of younger (<10 years) TB-afflicted children was latently infected, whereas 2 older children infected 12 of their contacts, children and adults. During a mean observational period of 551 weeks (IQR 735) on average, no secondary TB cases appeared. ConclusionsChildren with pulmonary TB disease, especially those aged below 10 years, rarely transmit Mtbc to their close contacts in a low-incidence setting.

913. Impact of BioFire® FilmArray® Blood Culture Identification Panels on Time to Optimal Antimicrobial Therapy

Abstract Background Bloodstream infections are associated with significant morbidity, mortality, and costs. Timely initiation of effective treatment is required for optimal outcomes. Conventional microbiological techniques require 72 hours for organism identification; however, rapid blood culture identification (BCID) polymerase chain reaction (PCR) panels have expedited this process. At Atlantic Health System, the BioFire® FilmArray® BCID panel was implemented June 2020 (BCID1), with subsequent upgrade to BCID2 March 2021. Notable features of the BCID2 panel include speciation of Enterococcus spp. and the addition of the CTX-M target. The purpose of this study is to assess time to optimal therapy (TTOT) with and without the BCID platforms for select organisms. Table 1:Select Primary and Secondary Endpoints Methods This retrospective study of hospitalized, adult patients was conducted at two community teaching hospitals from 5/2019 to 12/2021. Patients with a blood culture positive for Enterococcus faecalis, E. faecium, Proteus spp., Escherichia coli, or non-aerogenes Klebsiella spp. were included. Patients with polymicrobial or presumed polymicrobial source of bacteremia, recent positive blood cultures, PCR not performed in BCID arms, or who were deceased/comfort care at time of Gram stain were excluded. The primary endpoint was TTOT. Secondary endpoints included time to effective therapy, duration of vancomycin, therapy modification 24 hours after Gram stain result, and length of stay. All analyses compared PreBCID to either BCID1 or BCID2 arm. Results Three hundred patients (100 per arm) were included. Patient characteristics were similar across study arms. The median Pitt Bacteremia Score was 1, the most common organism identified was E. coli (65%), the most common source of bacteremia was genitourinary (65%), and 11% of isolates produced ESBL. TTOT (days) was similar in PreBCID compared to BCID1 and BCID2 [(2.48 vs. 2.65, p=0.10); (2.48 vs. 2.37 days, p=0.27)]. TTOT was significantly longer in the gram-negative subgroup of the BCID1 arm compared to PreBCID (2.62 vs 1.85 days, p=0.03). See Table 1 for full analyses. Conclusion Implementation of the BCID panels did not reduce TTOT in select organisms at our institution. Barriers to benefit may include limited education and lack of formal antimicrobial stewardship team involvement. Disclosures All Authors: No reported disclosures.

PMON123 Diagnostically Challenging Case of Cushing's Syndrome from a Pancreatic Neuroendocrine Tumor Treated with Radiofrequency Ablation

Abstract Background The delayed diagnosis of Cushing's syndrome (CS) results in advanced disease, treatment delays and poor outcomes. We present a patient with ectopic ACTH-syndrome (EAS) from a pancreatic neuroendocrine tumor (NET) whose care posed significant diagnostic and therapeutic challenges. Clinical Case 59F with classic Cushing's stigmata (including striae, plethora, supraclavicular and dorsocervical fat pads, muscle wasting), and two-year history of rapid weight gain, hypertension, T2DM, hyperlipidemia, severe osteoporosis complicated by multiple vertebral compression fractures, presented for workup and management of ACTH dependent CS. CS was confirmed (Baseline: ACTH 96 [7.2-63.3 pg/ml], serum cortisol 19.6 [4.8 - 19.5 mcg/dL]; LDSST: cortisol 18.5 [&amp;lt;1.8 mcg/dL], dexamethasone 547 [&amp;gt;200 ng/dL]; 24-hour Urine Free Cortisol: 191.60 [&amp;lt;45 mcg/d], 24-hour Cr 484 mg/day; LNSC: 436, 464 [29-101 ng/dL]; 8 mg ODST cortisol 7.2 mcg/dL). Pituitary MRI showed possible 0.5 cm left anterior pituitary lesion. Inferior petrosal sinus sampling (IPSS) to differentiate between Cushing's disease and EAS was initially planned, however, her course was complicated by an NSTEMI and acute/subacute lacunar infarcts in the left parietal and frontal lobes, and IPSS was deemed contraindicated. Additional workup was pursued including POMC 154 [&amp;lt;40 fmol/ml], Chromogranin A 538 [0-103 ng/ml] (on pantoprazole), pancreatic polypeptide 798 [0 - 435 pg/mL], 24-hour 5HIAA/Creatinine 3 [0 - 15 mg/24hr]. Chest/Abdominal/Pelvis CT showed a 1.5 cm incidental lipid rich adrenal adenoma; workup was negative for pheochromocytoma/ Conn's tumor/ adrenocortical carcinoma. Given elevated POMC and clinical suspicion for EAS, the patient underwent 68Ga-DOTATATE PET-CT scan which revealed an avid 7 mm lesion (SUVmax 14.5) in the pancreatic tail suspicious for a pancreatic NET- the presumed ectopic source of ACTH. Given the patient's poor functional status she was not a candidate for tumoral resection via distal pancreatectomy. Ketoconazole was initiated for treatment of hypercortisolism with good biochemical control, but the patient developed liver toxicity. The decision was made to pursue endoscopic ultrasound guided biopsy and radiofrequency ablation of the lesion. Pathology confirmed ACTH immunoreactive low-grade pancreatic NET. Post-procedure, morning ACTH was 8 pg/ml and cortisol was 9.1 mcg/dL, and the patient required steroids for relative adrenal insufficiency. Further follow up with repeat POMC, cortisol, ACTH levels, 24-hour UFC is required to monitor response. Conclusion IPSS is the gold standard test for differentiating Cushing's disease from EAS but is only available in select centers and for suitable candidates. This case supports the potential utility of POMC peptide measurements in the differential diagnosis of CS and the use of advanced nuclear imaging modalities for tumor localization. For patients with functional pNET who are poor surgical candidates or intolerant of pharmacotherapy, novel endoscopic ablation may offer a lower risk therapeutic option and its use should be further investigated. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.