Biomarkers of seafood intake during pregnancy - Pollutants versus fatty acids and micronutrients.

Intake of fish and seafood during pregnancy may have certain beneficial effects on fetal development, but measurement of intake using questionnaires is unreliable. Here, we assessed several candidate biomarkers of seafood intake, including long-chain omega 3 fatty acids (n-3 LCPUFA), selenium, iodine, methylmercury, and different arsenic compounds, in 549 pregnant women (gestational week 29) in the prospective birth cohort NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment). Proportions of the fatty acids eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) in erythrocytes were measured using gas chromatography with flame ionization detector. Selenium was measured in blood plasma and erythrocytes, mercury and arsenic in erythrocytes, and iodine and several arsenic compounds in urine, using inductively coupled plasma mass spectrometry, arsenic compounds after first being separated by ion exchange high-performance liquid chromatography (HPLC). Each biomarker was related to intake of total seafood and to intake of fatty and lean fish, and shellfish in third trimester, estimated from a semi-quantitative food frequency questionnaire filled out in gestational week 34. The pregnant women reported a median total seafood intake of 184 g/week (5th-95th percentiles: 34-465 g/week). This intake correlated most strongly with erythrocyte mercury concentrations (rho = 0.49, p < 0.001), consisting essentially of methylmercury, followed by total arsenic in erythrocytes (rho = 0.34, p < 0.001), and arsenobetaine in urine (rho = 0.33, p < 0.001), the main form of urinary arsenic. These biomarkers correlated well with intake of both fatty fish, lean fish, and shellfish. Erythrocyte DHA and plasma selenium correlated, although weakly, mainly with fatty fish (rho = 0.25 and 0.22, respectively, both p < 0.001). In conclusion, elevated concentrations of erythrocyte mercury and urinary arsenobetaine can be useful indicators of seafood intake, more so than the n-3 LCPUFAs. However, the relative importance of the biomarkers may differ depending on the type and amount of seafood consumed.

Serum metal levels in a population of Spanish pregnant women / Niveles de metales en suero en una población de mujeres embarazadas españolas

Objective: To describe serum levels of calcium, copper, selenium, magnesium, iron and zinc and evaluate their relationship with maternal socio-demographic characteristics and dietary variables in women in the first trimester of pregnancy. Method: Cross-sectional study with 1279 participants from the INMA cohorts. Results: The concentrations of the elements analyzed were within the normal range. Associations with higher levels of these metals were found for calcium with white meat intake (p = 0.026), for copper with excess body weight (p < 0.01), low social class (p = 0.03) and being multipara (p < 0.01), for magnesium with being over 35 years old (p = 0.001), high social class (p = 0.044), primiparous status (p = 0.002) and low daily intake of bread (p = 0.009) and legumes (p = 0.020); for zinc with university education (p = 0.039) and residence in Gipuzkoa (p < 0.01), and for selenium with residence in Valencia (p < 0.01), university education (p = 0.001), vitamin B6 supplementation (p = 0.006), fish intake (> 71 g/day) (p = 0.014) and having been born in Spain (p = 0.001). Further, lower iron levels were associated with being overweight (p = 0.021) or obese (p < 0.001) and vitamin B12 supplementation (p = 0.006). Conclusions: Our results suggest that trace elements in the analyzed cohorts are adequate for this stage of pregnancy. The variability in these elements is mainly linked to socio-demographic and anthropometric variables. (AU)

Objetivo: Describir las concentraciones de calcio, cobre, selenio, magnesio, hierro y zinc en muestras de suero de gestantes en el primer trimestre y evaluar la relación con las características sociodemográficas maternas y las variables de dieta. Método: Estudio transversal con 1279 participantes de las cohortes INMA. Resultados: Las concentraciones de los elementos analizados estuvieron dentro de los límites de referencia. El calcio se asoció con el consumo de carne blanca (p = 0,026). Los valores elevados de cobre se asociaron con tener exceso de peso (p < 0,01), clase social baja (p = 0.03) y ser multípara (p < 0,01). Los valores más elevados de magnesio se asociaron con tener más de 35 años (p = 0,001), clase social alta (p = 0,044), ser primípara (p = 0,002) y bajo consumo diario de pan (p = 0,009) y legumbres (p = 0,020). El zinc se asoció con tener estudios universitarios (p = 0,039) y con la cohorte de Gipuzkoa (p < 0,01). Los valores más altos de selenio se asociaron con la cohorte de Valencia (p < 0,01), tener estudios universitarios (p = 0,001), tomar suplementos de vitamina B6 (p = 0,006), consumo de pescado >71 g/día (p = 0,014) y ser española (p = 0,001). Los valores más bajos de hierro se asociaron con tener exceso de peso (p = 0,021) u obesidad (p < 0,001) y con tomar suplementos de vitamina B12 (p = 0,006). Conclusiones: Nuestros resultados sugieren que los oligoelementos en las cohortes analizadas son adecuados para esta etapa del embarazo. La variabilidad de estos elementos está asociada principalmente a las variables sociodemográficas y antropométricas. (AU)

Association of maternal urinary fluoride concentrations during pregnancy with size at birth and the potential mediation effect by maternal thyroid hormones: The Swedish NICE birth cohort.

BACKGROUND: Observational studies have indicated that elevated maternal fluoride exposure during pregnancy may impair child neurodevelopment but a potential impact on birth outcomes is understudied. OBJECTIVES: To evaluate the impact of gestational fluoride exposure on birth outcomes (birth size and gestational age at birth) and to assess the potential mediating role of maternal thyroid hormones. METHODS: We studied 583 mother-child dyads in the NICE cohort in northern Sweden. Maternal fluoride exposure was assessed by measuring urinary concentrations at late pregnancy (median: 29th gestational week) using an ion selective electrode. Plasma levels of free and total thyroxine (fT4, tT4) and triiodothyronine (fT3, tT3), and thyroid stimulating hormone (TSH) were measured with electrochemiluminescence immunoassays. The infant's weight, length, head circumference, and gestational age at birth were extracted from hospital records. RESULTS: Median urinary fluoride concentration was 0.71 mg/L (5th-95th percentile 0.31-1.9 mg/L; specific gravity adjusted). In multivariable-adjusted regression models, every 1 mg/L increase of maternal urinary fluoride was associated with a mean increase in birth weight by 84 g (95%CI: 30, 138), length by 0.41 cm (95%CI: 0.18, 0.65), head circumference by 0.3 cm (95%CI: 0.1, 0.4), and with increased odds of being born large for gestational age (OR = 1.39, 95%CI: 1.03, 1.89). Every 1 mg/L increase of maternal urinary fluoride was also associated with a mean increase of the plasma fT3:fT4 ratio (B = 0.007, 95%CI: 0.000, 0.014), but not with the hormones or TSH. In mediation analyses, the maternal fT3:fT4 ratio did not explain the urinary fluoride-birth size relationships. DISCUSSION: Gestational urinary fluoride concentrations were associated with increased size at birth and even with increased odds of being born large for gestational age. The fluoride-related associations with increased size at birth were not explained by changes in maternal thyroid hormone levels.

Impact of a Rapid Molecular Test for Klebsiella pneumoniae Carbapenemase and Ceftazidime-Avibactam Use on Outcomes After Bacteremia Caused by Carbapenem-Resistant Enterobacterales.

BACKGROUND: Patients with bacteremia due to carbapenem-resistant Enterobacterales (CRE) experience delays until appropriate therapy and high mortality rates. Rapid molecular diagnostics for carbapenemases and new ß-lactam/ß-lactamase inhibitors may improve outcomes. METHODS: We conducted an observational study of patients with CRE bacteremia from 2016 to 2018 at 8 New York and New Jersey medical centers and assessed center-specific clinical microbiology practices. We compared time to receipt of active antimicrobial therapy and mortality between patients whose positive blood cultures underwent rapid molecular testing for the Klebsiella pneumoniae carbapenemase (KPC) gene (blaKPC) and patients whose cultures did not undergo this test. CRE isolates underwent antimicrobial susceptibility testing by broth microdilution and carbapenemase profiling by whole-genome sequencing. We also assessed outcomes when ceftazidime-avibactam and polymyxins were used as targeted therapies. RESULTS: Of 137 patients with CRE bacteremia, 89 (65%) had a KPC-producing organism. Patients whose blood cultures underwent blaKPC PCR testing (n = 51) had shorter time until receipt of active therapy (median: 24 vs 50 hours; P = .009) compared with other patients (n = 86) and decreased 14-day (16% vs 37%; P = .007) and 30-day (24% vs 47%; P = .007) mortality. blaKPC PCR testing was associated with decreased 30-day mortality (adjusted odds ratio: .37; 95% CI: .16-.84) in an adjusted model. The 30-day mortality rate was 10% with ceftazidime-avibactam monotherapy and 31% with polymyxin monotherapy (P = .08). CONCLUSIONS: In a KPC-endemic area, blaKPC PCR testing of positive blood cultures was associated with decreased time until appropriate therapy and decreased mortality for CRE bacteremia, and ceftazidime-avibactam is a reasonable first-line therapy for these infections.

Serum metal levels in a population of Spanish pregnant women.

OBJECTIVE: To describe serum levels of calcium, copper, selenium, magnesium, iron and zinc and evaluate their relationship with maternal socio-demographic characteristics and dietary variables in women in the first trimester of pregnancy. METHOD: Cross-sectional study with 1279 participants from the INMA cohorts. RESULTS: The concentrations of the elements analyzed were within the normal range. Associations with higher levels of these metals were found for calcium with white meat intake (p=0.026), for copper with excess body weight (p <0.01), low social class (p=0.03) and being multipara (p <0.01), for magnesium with being over 35 years old (p=0.001), high social class (p=0.044), primiparous status (p=0.002) and low daily intake of bread (p=0.009) and legumes (p=0.020); for zinc with university education (p=0.039) and residence in Gipuzkoa (p <0.01), and for selenium with residence in Valencia (p <0.01), university education (p=0.001), vitamin B6 supplementation (p=0.006), fish intake (> 71g/day) (p=0.014) and having been born in Spain (p=0.001). Further, lower iron levels were associated with being overweight (p=0.021) or obese (p <0.001) and vitamin B12 supplementation (p=0.006). CONCLUSIONS: Our results suggest that trace elements in the analyzed cohorts are adequate for this stage of pregnancy. The variability in these elements is mainly linked to socio-demographic and anthropometric variables.

Blood Metal Levels and Amyotrophic Lateral Sclerosis Risk: A Prospective Cohort.

OBJECTIVE: Metals have been suggested as a risk factor for amyotrophic lateral sclerosis (ALS), but only retrospective studies are available to date. We compared metal levels in prospectively collected blood samples from ALS patients and controls, to explore whether metals are associated with ALS mortality. METHODS: A nested ALS case-control study was conducted within the prospective EPIC (European Prospective Investigation into Cancer and Nutrition) cohort. Cases were identified through death certificates. We analyzed metal levels in erythrocyte samples obtained at recruitment, as a biomarker for metal exposure from any source. Arsenic, cadmium, copper, lead, manganese, mercury, selenium, and zinc concentrations were measured by inductively coupled plasma-mass spectrometry. To estimate ALS risk, we applied conditional logistic regression models. RESULTS: The study population comprised 107 cases (65% female) and 319 controls matched for age, sex, and study center. Median time between blood collection and ALS death was 8 years (range = 1-15). Comparing the highest with the lowest tertile, cadmium (odds ratio [OR] = 2.04, 95% confidence interval [CI] = 1.08-3.87) and lead (OR = 1.89, 95% CI = 0.97-3.67) concentrations suggest associations with increased ALS risk. Zinc was associated with a decreased risk (OR = 0.50, 95% CI = 0.27-0.94). Associations for cadmium and lead remained when limiting analyses to noncurrent smokers. INTERPRETATION: This is the first study to compare metal levels before disease onset, minimizing reverse causation. The observed associations suggest that cadmium, lead, and zinc may play a role in ALS etiology. Cadmium and lead possibly act as intermediates on the pathway from smoking to ALS. ANN NEUROL 20209999:n/a-n/a.

Making sense of professional enablers' involvement in laundering organized crime proceeds and of their regulation.

Money laundering has ascended the enforcement and criminological agenda in the course of this century, and has been accompanied by an increased focus on legal professionals as 'enablers' of crime. This article explores the dynamics of this enforcement, media and political agenda, and how the legal profession has responded in the UK and elsewhere, within the context of ignoring the difficulties of judging the effectiveness of anti money laundering. It concludes that legal responses are a function of their lobbying power, the determination of governments to clamp down on the toxic impacts of legal structures, and different legal cultures. However, it remains unclear what the effects on the levels and organization of serious crimes for gain are of controls on the professions.

Total mercury in hair as biomarker for methylmercury exposure among women in central Sweden- a 23 year long temporal trend study.

Exposure to methylmercury (MeHg) through fish is a global public health problem. Exposure monitoring is essential for health risk assessment, especially in pregnant women and children due to the documented neurotoxicity. Herein, we evaluate a time series of MeHg exposure via fish in primiparous Swedish women, covering a time period of 23 years (1996-2019). The 655 included mothers were part of the POPUP study (Persistent Organic Pollutants in Uppsala Primiparas) conducted by the Swedish Food Agency (SFA). MeHg exposure was assessed via measurements of total mercury (Hg) in hair using either cold vapor atomic fluorescence spectrophotometry or inductively coupled plasma mass spectrometry, showing very good linear agreement (R2 = 0.97). Maternal characteristics and fish consumption were obtained via questionnaires. The median concentration of total Hg in hair was 0.38 mg/kg (range 0.17-1.5) in 1996 and 0.25 mg/kg (range 0.03-1.1) in 2019. On average the women consumed 11 ± 8.2 meals of fish per month, and fish consumption was positively correlated with total Hg in hair (Spearman correlation: 0.39; p < 0.001). In multiple regression analyses, the geometric mean annual decrease of total Hg in hair was -2.5% (95% CI: -3.2, -1.8%). Total fish consumption increased up to 2011 (B: 0.32 times/month per year; 95% CI 0.17, 0.46) after which it started to decline (B: -0.66 times/month per year; 95% CI -0.92, -0.40). Moreover, both total Hg in hair and fish consumption was positively associated with maternal age and education, and inversely associated with pre-pregnancy BMI. In conclusion, the exposure to MeHg via fish appears to be slowly declining among Swedish pregnant women.

Arsenic Exposure and Cancer-Related Proteins in Urine of Indigenous Bolivian Women.

Indigenous people living in the Bolivian Andes are exposed through their drinking water to inorganic arsenic, a potent carcinogen. However, the health consequences of arsenic exposure in this region are unknown. The aim of this study was to evaluate associations between arsenic exposure and changes in cancer-related proteins in indigenous women (n = 176) from communities around the Andean Lake Poopó, Bolivia. Arsenic exposure was assessed in whole blood (B-As) and urine (as the sum of arsenic metabolites, U-As) by inductively coupled plasma-mass spectrometry (ICP-MS). Cancer-related proteins (N = 92) were measured in urine using the proximity extension assay. The median B-As concentration was 2.1 (range 0.60-9.1) ng/g, and U-As concentration was 67 (12-399) µg/L. Using linear regression models adjusted for age, urinary osmolality, and urinary leukocytes, we identified associations between B-As and four putative cancer-related proteins: FASLG, SEZ6L, LYPD3, and TFPI2. Increasing B-As concentrations were associated with lower protein expression of SEZ6L, LYPD3, and TFPI2, and with higher expression of FASLG in urine (no association was statistically significant after correcting for multiple comparisons). The associations were similar across groups with different arsenic metabolism efficiency, a susceptibility factor for arsenic toxicity. In conclusion, arsenic exposure in this region was associated with changes in the expression of some cancer-related proteins in urine. Future research is warranted to understand if these proteins could serve as valid biomarkers for arsenic-related toxicity.

Predicted AS3MT Proteins Methylate Arsenic and Support Two Major Phylogenetic AS3MT Groups.

Inorganic arsenic is one of the most toxic and carcinogenic substances in the environment, but many organisms, including humans, methylate inorganic arsenic to mono-, di-, and trimethylated arsenic metabolites, which the organism can excrete. In humans and other eukaryotic organisms, the arsenite methyltransferase (AS3MT) protein methylates arsenite. AS3MT sequences from eukaryotic organisms group phylogenetically with predicted eubacterial AS3MT sequences, which has led to the suggestion that AS3MT was acquired from eubacteria by multiple events of horizontal gene transfer. In this study, we evaluated whether 55 (out of which 47 were predicted based on protein sequence similarity) sequences encoding putative AS3MT orthologues in 47 species from different kingdoms can indeed methylate arsenic. Fifty-three of the proteins showed arsenic methylating capacity. For example, the predicted AS3MT of the human gut bacterium Faecalibacterium prausnitzii methylated arsenic efficiently. We performed a kinetic analysis of 14 AS3MT proteins representing two phylogenetically distinct clades (Group 1 and 2) that each contain both eubacterial and eukaryotic sequences. We found that animal and bacterial AS3MTs in Group 1 rarely produce trimethylated arsenic, whereas Hydra vulgaris and the bacterium Rhodopseudomonas palustris in Group 2 produce trimethylated arsenic metabolites. These findings suggest that animals during evolution have acquired different arsenic methylating phenotypes from different bacteria. Further, it shows that humans carry two bacterial systems for arsenic methylation: one bacterium-derived AS3MT from Group 1 incorporated in the human genome and one from Group 2 in F. prausnitzii present in the gut microbiome.

Evaluating the Control of Money Laundering and Its Underlying Offences: the Search for Meaningful Data.

This article examines the political and criminological history of anti-money controls, including the involvement of Asian countries and the varied motivations and interests engaged. It goes on to review where empirical evidence has been used and can be used in fighting the financial components of underlying crimes, examining the denotation of the problem(s) we are supposed to be fighting-money laundering as an evil in itself and/or the underlying crimes which give rise to it; estimates of the size and harmfulness of the problems and identifies any improvements/emerging problems in the assessment of money laundering. It concludes with some reflections on assessing policy effectiveness and the need for greater engagement by criminologists and other social scientists in this process.

Low-level maternal exposure to cadmium, lead, and mercury and birth outcomes in a Swedish prospective birth-cohort.

Observational studies have indicated that low-to-moderate exposure to cadmium (Cd), lead (Pb), and mercury (Hg) adversely affects birth anthropometry, but results are inconclusive. The aim of this study was to elucidate potential impact on birth anthropometry of exposure to Cd, Pb, and Hg in pregnant women, and to identify the main dietary sources. In the NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment) birth-cohort in northern Sweden, blood and urine were collected from pregnant women in early third trimester. Cd, Pb and Hg were measured in erythrocytes (n = 584), and Cd also in urine (n = 581), by inductively coupled plasma mass spectrometry. Dietary data were collected through a semi-quantitative food frequency questionnaire administered in mid-third trimester. Birth anthropometry data were extracted from hospital records. In multivariable-adjusted spline regression models, a doubling of maternal erythrocyte Cd (median: 0.29 µg/kg) above the spline knot of 0.50 µg/kg was associated with reduced birth weight (B: -191 g; 95% CI: -315, -68) and length (-0.67 cm; -1.2, -0.14). The association with birth weight remained when the analysis was restricted to never-smokers. Likewise, a doubling of erythrocyte Hg (median 1.5 µg/kg, mainly MeHg) above 1.0 µg/kg, was associated with decreased birth weight (-59 g; -115, -3.0), and length (-0.29 cm; -0.54, -0.047). Maternal Pb (median 11 µg/kg) was unrelated to birth weight and length. Erythrocyte Cd was primarily associated with intake of plant derived foods, Pb with game meat, tea and coffee, and Hg with fish. The results indicated that low-level maternal Cd and Hg exposure were associated with poorer birth anthropometry. Further prospective studies in low-level exposed populations are warranted.

Prenatal and childhood arsenic exposure through drinking water and food and cognitive abilities at 10 years of age: A prospective cohort study.

BACKGROUND: Our studies of children in a rural Bangladeshi area, with varying concentrations of arsenic in well-water, indicated modest impact on child verbal cognitive function at 5 years of age. OBJECTIVES: Follow-up of arsenic exposure and children's cognitive abilities at school-age. METHODS: In a nested sub-cohort of the MINIMat supplementation trial, we assessed cognitive abilities at 10 years of age (n = 1523), using Wechsler Intelligence Scale for Children (WISC-IV). Arsenic in maternal urine and erythrocytes in early pregnancy, in child urine at 5 and 10 years, and in hair at 10 years, was measured using Inductively Coupled Plasma Mass Spectrometry. RESULTS: Median urinary arsenic at 10 years was 58 µg/L (range 7.3-940 µg/L). Multivariable-adjusted regression analysis showed that, compared to the first urinary arsenic quintile at 10 years (<30 µg/L), the third and fourth quintiles (30-45 and 46-73 µg/L, respectively) had 6-7 points lower Full developmental raw scores (B: -7.23, 95% CI -11.3; -3.18, and B: -6.37, 95% CI -10.5; -2.22, respectively), corresponding to ~0.2 SD. Verbal comprehension and Perceptual reasoning seemed to be affected. Models with children's hair arsenic concentrations showed similar results. Maternal urinary arsenic in early pregnancy, but not late pregnancy, showed inverse associations with Full developmental scores (quintiles 2-4: B: -4.52, 95% CI -8.61; -0.43, B: -5.91, 95% CI -10.0; -1.77, and B: -5.98, 95%CI -10.2; -1.77, respectively, compared to first quintile), as well as with Verbal comprehension, Perceptual reasoning, and Processing speed, especially in girls (p < 0.05 for interaction of sex with Full developmental scores and Perceptual reasoning). In models with all exposure time points included, both concurrent exposure at 10 years and early prenatal exposure remained associated with cognitive abilities. CONCLUSIONS: Both early prenatal and childhood arsenic exposure, even at low levels (about 50 µg/L in urine), was inversely associated with cognitive abilities at school-age, although the estimates were modest.

Diagnostic stewardship of Clostridioides difficile polymerase chain reaction results from syndromic diarrhea panel and implications for patient outcomes.

BACKGROUND: A syndromic gastrointestinal pathogen panel (GIP) was implemented in May 2018. All positive (+) GIP and standard-of-care (SOC) C. difficile results were reviewed. METHODS: A single-center audit of adult patients with GIP results was conducted May-December 2018. We reviewed GIP(+)/SOC(+/-) and GIP(-)/SOC(-) tests (control group) for clinical outcomes. RESULTS: We reviewed 269 GIP(+) patients. Of 119 GIP(+)/SOC(+) patients, 44 (37%) were positive by toxin A/B enzyme immunoassay, and 75 (63%) by PCR only. Thirty-day mortality and re-admission were not significantly different between groups. CDI rates within 6 months were not significantly different between GIP(+)/SOC(-) and controls (p-value = 0.39). Those with initial SOC(+) tests had more true CDI events within 6 months, compared to controls (p-values < 0.001). CONCLUSIONS: Forty percent of patients with GIP(+) C. difficile were (-) by SOC test, suggesting that true CDI was not present. Additional PCR-based testing may not impact outcomes.

Multidisciplinary Tool Kit for Febrile Neutropenia: Stewardship Guidelines, Staphylococcus aureus Epidemiology, and Antibiotic Use Ratios.

PURPOSE: Inappropriate vancomycin for febrile neutropenia (FN) is an ideal antimicrobial stewardship target. To improve vancomycin prescribing, we instituted a multifaceted intervention, including an educational guideline with audit for compliance; an antibiotic use audit; and an assessment of local burden of methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection. MATERIALS AND METHODS: We conducted a quasi-experimental pre-post intervention review of vancomycin initiation for FN on a 32-bed hematology/oncology unit. A retrospective chart review was conducted from November 2015 to May 2016 (preintervention period). In January 2017, we implemented an institutional FN guideline emphasizing criteria for appropriate use. Vancomycin audit was conducted from February 2017 to October 2017 (postintervention period). The primary outcome was appropriateness of vancomycin initiation. We then compared average antibiotic use (days of therapy per 1,000 patient days) for vancomycin and cefepime before and after intervention. Finally, unit-wide MRSA screening cultures were obtained upon admission and bimonthly for 6 weeks (October 2, 2017, to November 9, 2017). Screened patients were followed for 12 months for clinical MRSA infection. RESULTS: Forty-three (49%) of 88 preintervention patients were started on empiric vancomycin appropriately, compared with 59 (66%) of 90 postintervention patients (P = .02). There was a significant decrease in vancomycin use after intervention. Six (7.1%) of 85 patients screened positive for MRSA colonization. During the 12-month follow-up, no colonized patients developed clinical MRSA infections (positive predictive value, 0.0%). Of the 79 noncolonized patients, 2 developed a clinically significant infection (negative predictive value, 97.5%). CONCLUSION: Guideline-focused education can improve vancomycin appropriateness in FN and should be bundled with education and feedback about local MRSA epidemiology and antibiotic use rates for maximal stewardship impact.

Screening of Clostridioides difficile carriers in an urban academic medical center: Understanding implications of disease.

OBJECTIVE: Efforts to reduce Clostridioides difficile infection (CDI) have targeted transmission from patients with symptomatic C. difficile. However, many patients with the C. difficile organism are carriers without symptoms who may serve as reservoirs for spread of infection and may be at risk for progression to symptomatic C. difficile. To estimate the prevalence of C. difficile carriage and determine the risk and speed of progression to symptomatic C. difficile among carriers, we established a pilot screening program in a large urban hospital. DESIGN: Prospective cohort study. SETTING: An 800-bed, tertiary-care, academic medical center in the Bronx, New York. PARTICIPANTS: A sample of admitted adults without diarrhea, with oversampling of nursing facility patients. METHODS: Perirectal swabs were tested by polymerase chain reaction for C. difficile within 24 hours of admission, and patients were followed for progression to symptomatic C. difficile. Development of symptomatic C. difficile was compared among C. difficile carriers and noncarriers using a Cox proportional hazards model. RESULTS: Of the 220 subjects, 21 (9.6%) were C. difficile carriers, including 10.2% of the nursing facility residents and 7.7% of the community residents (P = .60). Among the 21 C. difficile carriers, 8 (38.1%) progressed to symptomatic C. difficile, but only 4 (2.0%) of the 199 noncarriers progressed to symptomatic C. difficile (hazard ratio, 23.9; 95% CI, 7.2-79.6; P < .0001). CONCLUSIONS: Asymptomatic carriage of C. difficile is prevalent among admitted patients and confers a significant risk of progression to symptomatic CDI. Screening for asymptomatic carriers may represent an opportunity to reduce CDI.

Helicobacter pylori Infections in the Bronx, New York: Surveying Antibiotic Susceptibility and Strain Lineage by Whole-Genome Sequencing.

The emergence of drug resistance in Helicobacter pylori has resulted in a greater need for susceptibility-guided treatment. While the alleles associated with resistance to clarithromycin and levofloxacin have been defined, there are limited data regarding the molecular mechanisms underlying resistance to other antimicrobials. Using H. pylori isolates from 42 clinical specimens, we compared phenotypic and whole-genome sequencing (WGS)-based detection of resistance. Phenotypic resistance correlated with the presence of alleles of 23S rRNA (A2142G/A2143G) for clarithromycin (kappa coefficient, 0.84; 95% confidence interval [CI], 0.67 to 1.0) and gyrA (N87I/N87K/D91Y/D91N/D91G/D99N) for levofloxacin (kappa coefficient, 0.90; 95% CI, 0.77 to 1.0). Phenotypic resistance to amoxicillin in three isolates correlated with mutations in pbp1, pbp2, and/or pbp3 within coding regions near known amoxicillin binding motifs. All isolates were phenotypically susceptible to tetracycline, although four bore a mutation in 16S rRNA (A926G). For metronidazole, nonsense mutations and R16H substitutions in rdxA correlated with phenotypic resistance (kappa coefficient, 0.76; 95% CI, 0.56 to 0.96). Previously identified mutations in the rpoB rifampin resistance-determining region (RRDR) were not present, but 14 novel mutations outside the RRDR were found in rifampin-resistant isolates. WGS also allowed for strain lineage determination, which may be important for future studies in associating precise MICs with specific resistance alleles. In summary, WGS allows for broad analyses of H. pylori isolates, and our findings support the use of WGS for the detection of clarithromycin and levofloxacin resistance. Additional studies are warranted to better define mutations conferring resistance to amoxicillin, tetracycline, and rifampin, but combinatorial analyses for rdxA gene truncations and R16H mutations have utility for determining metronidazole resistance.

Brucella Exposure Risk Events in 10 Clinical Laboratories, New York City, USA, 2015 to 2017.

From 2015 to 2017, 11 confirmed brucellosis cases were reported in New York City, leading to 10 Brucella exposure risk events (Brucella events) in 7 clinical laboratories (CLs). Most patients had traveled to countries where brucellosis is endemic and presented with histories and findings consistent with brucellosis. CLs were not notified that specimens might yield a hazardous organism, as the clinicians did not consider brucellosis until they were notified that bacteremia with Brucella was suspected. In 3 Brucella events, the CLs did not suspect that slow-growing, small Gram-negative bacteria might be harmful. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), which has a limited capacity to identify biological threat agents (BTAs), was used during 4 Brucella events, which accounted for 84% of exposures. In 3 of these incidents, initial staining of liquid media showed Gram-positive rods or cocci, including some cocci in chains, suggesting streptococci. Over 200 occupational exposures occurred when the unknown isolates were manipulated and/or tested on open benches, including by procedures that could generate infectious aerosols. During 3 Brucella events, the CLs examined and/or manipulated isolates in a biological safety cabinet (BSC); in each CL, the CL had previously isolated Brucella Centers for Disease Control and Prevention recommendations to prevent laboratory-acquired brucellosis (LAB) were followed; no seroconversions or LAB cases occurred. Laboratory assessments were conducted after the Brucella events to identify facility-specific risks and mitigations. With increasing MALDI-TOF MS use, CLs are well-advised to adhere strictly to safe work practices, such as handling and manipulating all slow-growing organisms in BSCs and not using MALDI-TOF MS for identification until BTAs have been ruled out.

Increased levels of genotoxic damage in a Bolivian agricultural population exposed to mixtures of pesticides.

During the past decades, farmers in low to middle-income countries have increased their use of pesticides, and thereby the risk of being exposed to potentially genotoxic chemicals that can cause adverse health effects. Here, the aim was to investigate the correlation between exposure to pesticides and genotoxic damage in a Bolivian agricultural population. Genotoxic effects were assessed in peripheral blood samples by comet and micronucleus (MN) assays, and exposure levels by measurements of 10 urinary pesticide metabolites. Genetic susceptibility was assessed by determination of null frequency of GSTM1 and GSTT1 genotypes. The results showed higher MN frequency in women and farmers active ≥8 years compared to their counterpart (P < 0.05). In addition, age, GST genotype, alcohol consumption, and type of water source influenced levels of genotoxic damage. Individuals with high exposure to tebuconazole, 2,4-D, or cyfluthrin displayed increased levels of genotoxic damage (P < 0.05-0.001). Logistic regression was conducted to evaluate associations between pesticide exposure and risk of genotoxic damage. After adjustment for confounders, a significant increased risk of DNA strand breaks was found for high exposure to 2,4-D, odds ratio (OR) = 1.99 (P < 0.05). In contrast, high exposure to pyrethroids was associated with a reduced risk of DNA strand breaks, OR = 0.49 (P < 0.05). It was also found that high exposure to certain mixtures of pesticides (containing mainly 2,4-D or cyfluthrin) was significantly associated with increased level and risk of genotoxic damage (P < 0.05). In conclusion, our data show that high exposure levels to some pesticides is associated with an increased risk of genotoxic damage among Bolivian farmers, suggesting that their use should be better controlled or limited.

Listeria brain abscess in a patient with autoimmune hepatitis.

Listeria monocytogenes is an uncommon cause of brain abscesses. Immunocompromised hosts, pregnant women and patients at extremes of age are especially susceptible. We discuss the successful management of a woman with autoimmune hepatitis on prednisone and azathioprine therapy with a L. monocytogenes brain abscess. Previously thought to be a rare cause of central nervous system (CNS) infection, the incidence of CNS listeriosis has increased due to a rise in organ and bone marrow transplantation requiring immunosuppressive medications. L. monocytogenes brain abscesses are now more frequently described and are associated with high rates of concomitant bacteremia suggesting a hematogenous route of infection.