A probabilistic model for estimating ocean-spray distribution in extreme tropical cyclone winds

ABSTRACT. Serious gaps in knowledge about ocean spray at wind speeds over 28 m/s remain difficult to fill by observation or experiment; yet refined study of the thermodynamics of Tropical Cyclones (including typhoons and hurricanes) requires assessment of the hypothesis that ‘spray cooling’ at extreme wind speeds may act to reduce (i) the initial temperature of saturated air rising in the eyewall and so also (ii) the input of mechanical energy into the airflow as a whole. Such progressive reductions at higher speeds could, for example, make any possible influence, of future global warming on Tropical Cyclone intensification largely se1f-limiting. In order to help in extrapolation of knowledge on ocean spray to extreme wind speeds, a probabilistic analysis is introduced which allows for the effects of gusts, gravity and evaporation on droplet distributions yet all other respect is as simple as possible. Preliminary indications from this simplified analysis appear to confirm the potential importance of spray cooling.

Oxidation of Gaseous Elemental Mercury in Acidified Water: Evaluation of Possible Sinking Pathway of Atmospheric Gaseous Mercury in Acid Cloud, Fog, and Rain Droplets

This is the first report investigating the transformation of gaseous elemental mercury (GEM), the major form of airborne mercury, into oxidized mercury in bulk liquid, a possible sinking pathway of atmospheric GEM in clouds, fog, rain droplets and ocean spray. A 100–150 ng m−3 GEM standard gas, a 50–150 times higher concentration than the typical atmospheric concentration, was introduced into a 2.5 L rectangular glass vessel, at the bottom of which a 0.5 L uptake solution of pure water (pH 6–7), weakly acidified pure water with sulfuric or nitric acid (pH 3.2–3.6) or seawater (pH 8) was resting. The standard gas was introduced into the space above the solution in the vessel at the rate of 0.82 L min−1 and exited from the opposite end of the vessel, which was open to the room’s pressure. After exposing the solution to the gas for 0.5–4 h, a portion of the uptake solution was sampled, and the dissolved elemental mercury (Hg0aq) and dissolved oxidized mercury (Hg2+aq) in the solution were analyzed by the conventional trapping method, followed by cold vapor atomic fluorescent spectrometer measurements. The results showed that the quantities of total dissolved mercury (THgaq = Hg0aq + Hg2+aq) in the pure water and seawater were compatible, but those were slightly lower than the equilibrated Hg0aq concentrations estimated from Henry’s law, suggesting non-equilibrium throughout the whole solution. In contrast, the quantity of Hg2+aq and THgaq in the acidified pure water with sulfuric acid was significantly enhanced. Over the 4 h exposure, the THgaq concentrations were two times higher than the equilibrated Hg0aq concentration. This was due to the slow oxidation reaction of Hg0aq by the sulfuric acid in the bulk phase. Using the collision rate of GEM with the surface of the solution and the observed uptake, the estimated uptake coefficient of GEM by this uptake was (5.5 ± 1.6) × 10−6. Under the typical atmospheric concentration, this magnitude results in an atmospheric lifetime of 4970 years, negligibly small compared with other atmospheric oxidation processes.

847. Trends in Stenotrophomonas maltophilia Antibiotic Resistance Rates

Background Studies from the 1990’s and 2000’s identified increasing rates of Stenotrophomonas maltophilia, particularly among respiratory isolates and in intensive care populations. Additionally, resistance in S. maltophilia was found to be worsening. We aimed to quantify recent trends in prevalence and resistance of S. maltophilia in the national Veterans Affairs (VA) Healthcare system. Methods We identified positive S. maltophilia clinical cultures among VA adult patients from 2010 to 2018, collected in either VA medical centers (VAMCs), community living centers (CLCs), or the outpatient (Outpt) setting. Multidrug resistance (MDR) was defined as resistance to sulfamethoxazole/trimethoprim (SMX/TMP) and minocycline or levofloxacin. Time trends were assessed with regression analyses to estimate annual average percent changes (AAPC) with 95% confidence intervals using Joinpoint Software. Results Over the 9-year study period, we identified 18,285 S. maltophilia cultures (57% VAMCs, 3% CLCs, 40% Outpt). S. maltophilia cultures made up 0.4% of all positive cultures in the VA. In VAMCs and CLCs, the number of S. maltophilia cultures decreased 5.1% and 8.5% per year, respectively. Alternatively, of all positive cultures in VAMCs, the proportion that were S. maltophilia increased significantly by 2.6% per year. SMX/TMP resistance decreased significantly by 8.5% (2010, 15%; 2018, 6%) per year in VAMCs, and decreased non-significantly by 8.7% (2010, 13%, 2018, 6%) per year in CLCs and 6.0% (2010, 12%; 2018, 7%) in the outpatient setting. No other significant changes in resistance were observed over the study period. MDR increased non-significantly by 1.2% per year. Conclusion While previous studies found increasing rates of S. maltophilia, the number of positive S. maltophilia cultures decreased in the national VA Healthcare System between 2010 and 2018. However, S. maltophilia is making up a greater proportion of positive culture over time. During the study period, resistance to SMX/TMP decreased and now more closely reflects previously reported resistance rates worldwide (0-10%). Disclosures Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi (Research Grant or Support) Haley J. Appaneal, Pharm.D, Shionogi, Inc. (Research Grant or Support) Kerry LaPlante, PharmD, Merck (Advisor or Review Panel member, Research Grant or Support)Ocean Spray Cranberries, Inc. (Research Grant or Support)Pfizer Pharmaceuticals (Research Grant or Support)Shionogi, Inc. (Research Grant or Support)

846. Trends in Acinetobacter baumanii Antibiotic Resistance Rates

Background Carbapenem-resistant Acinetobacter baumannii is described as an urgent threat by the Centers for Disease Control and Prevention and several older studies have indicated increasing resistance in Acinetobacter. We sought to describe these trends in the national Veterans Affairs (VA) Healthcare System. Methods We assessed A. baumannii positive clinical cultures collected from VA patients (> 18 years) from 2010 to 2018. We categorized cultures based on location at the time of collection: VA medical center (VAMC), community living center (CLC), or outpatient (Outpt). Multidrug resistance (MDR) and extensive drug resistance (XDR) were defined as resistance to > 1 drug in > 3 or all of the following categories, respectively: extended-spectrum cephalosporins (es-CS), fluoroquinolones (FQ), aminoglycosides (AMG), carbapenems (CARB), piperacillin/tazobactam (PIP/TAZ), and ampicillin/sulbactam (AMP/SUL). Joinpoint Software was used for regression analyses of trends over time and to estimate annual average percent changes (AAPC) with 95% confidence intervals. Results We identified 19,376 A. baumannii positive cultures over the study period (53% VAMCs, 4% CLCs, 43% Outpts), which represented 0.5% of all positive cultures in the VA. In VAMCs, the number of A. baumannii cultures decreased significantly by 12.5% per year. Of all positive cultures in VAMCs, the proportion that were A. baumannii decreased significantly by 5.4% per year. Similar trends were observed in CLCs, while Outpt cultures remained stable. Over the 9-year study period, resistance decreased significantly, with MDR decreasing by 10.2% per year and XDR decreasing by 9.4%. Carbapenem resistance decreased significantly by 4.9% per year in VAMCs (2010, 39%; 2018 28%) and 11.3% in Outpts (2010, 12%; 2018, 6%). Similar annual significant decreases were observed with AMG (9.4%), es-CS (1.4%), and FQ (7.4%) in VAMCs; es-CS (2.7%) and FQ (5.6%) in CLCs; and AMG (9.5%) and FQ (8.2%) in Outpts. Conclusion In the national VA Healthcare System, the prevalence of A. baumannii is decreasing, as is the resistance previously observed with this organism. MDR A. baumannii still made up one-third of cultures in VAMCs and CLCs in 2018, and thus remains a treatment challenge. Disclosures Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi (Research Grant or Support) Haley J. Appaneal, Pharm.D, Shionogi, Inc. (Research Grant or Support) Kerry LaPlante, PharmD, Merck (Advisor or Review Panel member, Research Grant or Support)Ocean Spray Cranberries, Inc. (Research Grant or Support)Pfizer Pharmaceuticals (Research Grant or Support)Shionogi, Inc. (Research Grant or Support)

Moderate to Severe Ulcerative Colitis Results in Differential Metabolism of Cranberry Polyphenols by the Colon Microbiome Ex Vivo

Objectives The microbiome plays a major role in polyphenol metabolism, producing metabolites that are bioavailable and potentially more bioactive than the polyphenol compounds from which they are derived. A consequence of ulcerative colitis (UC) is a ‘dysbiotic’ microbiome characterized by decreased species diversity, which may impact an individual's capability to metabolize polyphenols into bioavailable metabolites. The objective was to compare the microbial metabolism of cranberry polyphenols between fecal donors that were healthy or had moderate to severe UC to determine if dysbiosis effects polyphenol metabolism. Methods Fecal samples were donated by volunteers with or without moderate to severe UC (n = 9). Fecal samples were cultured anaerobically within 2 hours of defecation in the presence of A and B type proanthocyanidins, flavonols and anthocyanins extracted from cranberry powder. Aliquots were taken at 5 different time points over a 48-hour period and the resulting polyphenol metabolites were quantified via LC-ESI-MS/MS using SRM and authentic standards. 16S rRNA metagenomics analysis was also utilized to assess changes in the composition of the fecal microbiota. Results After 6 hours, healthy individuals produced 2.50, 20.1 and 5.25-fold higher (P < 0.05) concentrations of 3-(3-hydroxyphenyl)propionic acid, 3,4-dihydroxyphenylacetic acid and 3’,4’-dihydroxyphenyl-gamma-valerolactone, respectively. Healthy individuals continued to have significantly higher concentrations of these metabolites over the 48-hour period. UC microbiomes did not produce 3-hydroxyphenylacetic until after 48 hours, suggesting that the microbiome of those with UC may have significantly lower de-hydroxylase activity. Healthy microbiomes contained higher (P < 0.05) proportions of Ruminococcaceae, which could explain their ability to produce higher concentrations of cranberry polyphenol metabolites. Conclusions The microbiome of individuals with UC produces significantly lower cranberry polyphenol metabolites than healthy microbiomes. These results suggest that efficiency of polyphenol metabolism is dependent on health status of the colon and polyphenols could be potential biomarkers of colon health. Funding Sources Ocean Spray Cranberries, Inc, Middleborough, MA.

Changes of Human Gut Microbiome Correlated with Metabolomics After Cranberry Juice Consumption in a Double-Blinded, Placebo Controlled, Crossover Study

Objectives 1) To investigate the changes of gut microbiome after 3 days and 21 days of cranberry juice consumption; 2) to correlate changes of microbiome with metabolome. Methods A double blinded, placebo-controlled, cross-over intervention study were conducted in 17 healthy young women aged 18–29 with normal BMI. Fecal, urine, and plasma samples were collected at baseline, after 3 days, and after 21 days consumption of double strength cranberry juice or a placebo juice. DNA was extracted from fecal samples and 16s rRNA was sequenced. Discriminant metabolites in urine and plasma was analyzed by UHPLC-Q-Orbitrap-HRMS and 0 identified using OPLS-DA models. Results 21-days but not 3 days of cranberry juice consumption significantly increased alpha diversity of colon microbiome compared to baseline. Significant increase in the abundance of Firmicutes, Ruminococcaceae, Faecalibacterium, and F/B (Firmicutes to Bacteroidetes) ratios were found after 21-days of cranberry juice intake. This was accompanied by decreases in Bacteroidetes, Proteobacteria, Clostridia, Enterobacteriaceae, Veillonellaceae, Bacteroides, Parabacteroides, and Enterobacter. Gut microbial composition before and after 21-days of cranberry juice consumption was significantly per Bray-Curtis dissimilarity analysis. However, cranberry consumption did not alter fecal content of short chain fatty acids, ammonia, or mucin. Spearman's correlation analysis showed significant positive or negative correlations between selected strains of bacteria and discriminant metabolites. 4-O-methylgallic acid was a discriminant metabolite in urine after 21-days of cranberry juice consumption. Its content positively correlated with Parabacteroides but negatively correlated with Faecalibacterium (P < 0.05). 3-(Hydroxyphenyl) propionic acid was a discriminant metabolite in plasma after cranberry juice consumption. Its content negatively correlated with Enterobacteriaceae (P < 0.05). Conclusions 21-days but not 3 days of cranberry juice consumption significantly altered colon microbiome. Correlation between gut bacteria and plasma, urine metabolites suggested interaction between gut microbiome and serum and urine metabolome. Funding Sources This research is funded in part by Ocean Spray Cranberries, inc.

Cranberry-Derived Proanthocyanidin and Its Gut Microbial Metabolites Affect the Intestinal miRNome in a Distinct Manner In Vitro

Objectives Polyphenols are emerging as novel prebiotic compounds. Cranberries are a rich source of polyphenols, such as proanthocyanidin (PAC), which has known benefits including anti-cancer properties. In the colon, PACs are catabolized by the gut microbiota into 3,4-dihydroxyphenylacetic acid (DHPAA) and 3-(4-hydroxyphenyl) propionic acid (HPPA), which may mediate prebiotic effects. Mechanisms are unknown but may involve host microRNA (miRNA). The objective of this study was to investigate the effects of nutritionally relevant doses of cranberry PAC, DHPAA, and HPPA on the human intestinal miRNome. Methods Differentiated Caco-2BBe1 colonic epithelial cells, a morphologically homogenous subclone of Caco-2 cells, were treated with cranberry extract containing 94% PAC (Ocean Spray Cranberries, 50 μg/ml), DHPAA, HPPA (5 μg/ml) or control vehicle (Dulbecco's Modified Eagle Medium) for 24 hours. Experiments were repeated 3 times. Cell viability was assessed by fluorescence microscopy. Cell RNA was extracted and used for miRNA profiling via NanoString Technology. Data were processed and normalized in nSolverTM 4.0, statistics and hierarchical clustering were done with R and ClustVis. Gene targets were predicted with miRNet and pathway enrichment analysis was done in PathDIP. Results The treatments had no effect on cell viability. Of the 829 miRNAs assessed, 248 were expressed. Five miRNAs were differentially expressed among groups (ANOVA, P < 0.01; FDR < 5%). Unsupervised hierarchical clustering with these miRNAs revealed perfect separation based on treatment. These miRNAs were found to target 686 genes, enriched in 116 KEGG pathways including “miRNAs in cancer” and “pathways in cancer”. Treatment-specific responses included increased miR-2116-5p, miR-6721-5p, and miR-1290 for PAC, DHPAA, and HPPA, respectively. Pathways in glucagon signaling and central carbon metabolism in cancer were enriched in response to DHPPA only. Conclusions Cranberry PAC and polyphenol metabolites at concentrations representing dietary intakes elicit different miRNA signatures in colonic cells, providing a novel mechanism to explain their effects on intestinal health. Cranberry-mediated miRNA modulation may represent a potential strategy for preventing chronic disease. Funding Sources NSERC, Ocean Spray Cranberries, Inc., NSERC Graduate Scholarship.

1067. Comparative Effectiveness of Nafcillin or Oxacillin, Cefazolin, and Piperacillin/Tazobactam in Methicillin-Sensitive Staphylococcus aureus Bacteremia

Background β-Lactam antibiotics are recommended as first line for treatment of methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia. The objective of this study was to compare effectiveness among β-lactam therapies in MSSA bacteremia patients that were exclusively treated with one antibiotic. Methods This was a retrospective cohort study of patients hospitalized at Veterans Affairs (VA) medical centers with MSSA bacteremia from January 1, 2002 to October 1, 2015. Patients were included if they were treated exclusively with nafcillin, oxacillin, cefazolin, or piperacillin/tazobactam (i.e., monotherapy with no changes in therapy). The primary outcome was 30-day mortality, and secondary outcomes were time to discharge, inpatient mortality, 30-day readmission, and 30-day S. aureus reinfection. Hazard ratios (HRs) and 95% confidence intervals (CI) were calculated using unadjusted, quintile adjusted, and propensity-score (PS) matched (nearest neighbor, 0.05 caliper) Cox proportional hazards regression. Results A total of 326 patients were included in the final analysis. When comparing nafcillin (n = 75)/oxacillin (n = 30) with cefazolin (n = 108), 30-day mortality was similar between groups (PS matched n = 40, HR 4.0, 95% CI 0.45–35.79), as were rates of the other outcomes assessed. When combining nafcillin/oxacillin with cefazolin, and comparing to piperacillin/tazobactam (n = 113), 30-day mortality was significantly lower in the nafcillin/oxacillin/cefazolin group (PS matched n = 66, HR 0.29, 95% CI 0.09–0.87). Inpatient mortality and 30-day mortality were significantly lower with nafcillin/oxacillin/cefazolin in PS-adjusted analyses (HR 0.29, 95% CI 0.11–0.73 and HR 0.23, 95% CI 0.10–0.50, respectively). Conclusion In hospitalized patients with MSSA bacteremia, no difference in mortality was observed between nafcillin/oxacillin and cefazolin in patients that were exclusively treated with these monotherapies. However, higher mortality was observed with piperacillin/tazobactam as compared with nafcillin/oxacillin/cefazolin, suggesting that it may not be as effective as other monotherapies for MSSA bacteremia. Disclosures K. LaPlante, Merck: Grant Investigator, Research grant. Pfizer Pharmaceuticals: Grant Investigator, Research grant. Allergan: Scientific Advisor, Honorarium. Ocean Spray Cranberries, Inc.: Grant Investigator and Scientific Advisor, Honorarium and Research grant. Achaogen, Inc.: Scientific Advisor, Honorarium. Zavante Therapeutics, Inc.: Scientific Advisor, Honorarium. A. Caffrey, Merck: Grant Investigator, Research grant. The Medicine’s Company: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant.