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Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker and methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history, and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing the diagnosis of B12 deficiency. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency, and the treatment goals govern decisions regarding the route and dose of B12 therapy. [ABSTRACT FROM AUTHOR]

Background: The association between markers of vitamin B12 status and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD), which precede cognitive impairment, has been investigated by only a few small studies and results have been inconsistent. Aim: The aim of this study was to investigate the associations of vitamin B12‐related markers with CSF biomarkers of AD and cognitive performance. Methods: Data included 462 patients aged 40 to 94 years referred to the Memory Clinic of the Ulm University Hospital, Ulm, Germany. Vitamin B12, holotranscobalamin (HoloTC), homocysteine (tHcy), and methylmalonic acid (MMA) have been measured. CSF values of amyloid β42 (Aβ42) and total‐tau have been assessed in 227 participants. CERAD battery was administered to examine the cognitive status, and different domains were derived. Regression models were used to investigate the associations. Results: In the multi‐adjusted model, higher levels of MMA were associated with raised CSF total‐tau values: the odds ratios (ORs) 95% confidence intervals (CIs) were 3.25 (95% CI = 1.35–7.76) for the highest quartile of MMA compared to the lowest. Furthermore, moderately increased MMA were related to lower Aβ42 levels: the ORs and 95% CIs were 3.06 (95% CI = 1.22–7.67) for the third quartile of MMA compared to the lowest. All B12 indicators except B12 itself were related to several cognitive domains, such as episodic memory and executive functioning. Conclusions: Markers of vitamin B12 may be independent predictors of CSF biomarkers of AD and cognitive functioning, with MMA showing the most consistent effects. Randomized controlled trials are needed to determine the importance of vitamin B12 supplementation on slowing structural brain changes and cognitive decline. ANN NEUROL 2023;94:223–231 [ABSTRACT FROM AUTHOR]

We aimed to investigate the association between baseline levels of total serum glutathione (tGSH) and rate of chronic disease accumulation over time. The study population (n = 2,596) was derived from a population-based longitudinal study on ≥60-year-olds living in Stockholm. Participants were clinically assessed at baseline, 3- and 6-year follow-ups. Multimorbidity was measured as the number of chronic conditions from a previously built list of 60 diseases. Linear mixed models were applied to analyze the association between baseline tGSH levels and the rate of multimorbidity development over 6 years. We found that at baseline, participants with ≥4 diseases had lower tGSH levels than participants with no chronic conditions (3.3 vs 3.6 µmol/L; p < .001). At follow-up, baseline levels of tGSH were inversely associated with the rate of multimorbidity development (β * time: -0.044, p < .001) after adjusting for age, sex, education, levels of serum creatinine, C-reactive protein, albumin, body mass index, smoking, and time of dropout or death. In conclusion, serum levels of tGSH are inversely associated with multimorbidity development; the association exists above and beyond the link between tGSH and specific chronic conditions. Our findings support the hypothesis that tGSH is a biomarker of multisystem dysregulation that eventually leads to multimorbidity. [ABSTRACT FROM AUTHOR]

Importance: Impairment of methylation status (ie, methionine to homocysteine ratio) may be a modifiable risk factor for structural brain changes and incident dementia.Objective: To investigate the association of serum markers of methylation status and sulfur amino acids with risk of incident dementia, Alzheimer disease (AD), and the rate of total brain tissue volume loss during 6 years.Design, Setting, and Participants: This population-based longitudinal study was performed from March 21, 2001, to October 10, 2010, in a sample of 2570 individuals aged 60 to 102 years from the Swedish Study on Aging and Care in Kungsholmen who were dementia free at baseline and underwent comprehensive examinations and structural brain magnetic resonance imaging (MRI) on 2 to 3 occasions during 6 years. Data analysis was performed from March 1, 2018, to October 1, 2018.Main Outcomes and Measures: Incident dementia, AD, and the rate of total brain volume loss.Results: This study included 2570 individuals (mean [SD] age, 73.1 [10.4] years; 1331 [56.5%] female). The methionine to homocysteine ratio was higher in individuals who consumed vitamin supplements (median, 1.9; interquartile range [IQR], 1.5-2.6) compared with those who did not (median, 1.8; IQR, 1.3-2.3; P < .001) and increased per each quartile increase of vitamin B12 or folate. In the multiadjusted model, an elevated baseline serum total homocysteine level was associated with an increased risk of dementia and AD during 6 years: for the highest homocysteine quartile compared with the lowest, the hazard ratios (HRs) were 1.60 (95% CI, 1.01-2.55) for dementia and 2.33 (95% CI, 1.26-4.30) for AD. In contrast, elevated concentrations of methionine were associated with a decreased risk of dementia (HR, 0.54; 95% CI, 0.36-0.81) for the highest quartile compared with the lowest. Higher values of the methionine to homocysteine ratio were significantly associated with lower risk of dementia and AD: for the fourth methionine-homocysteine quartile compared with the first quartile, the HR was 0.44 (95% CI, 0.27-0.71) for incident dementia and 0.43 (95% CI, 0.23-0.80) for AD. In the multiadjusted linear mixed models, a higher methionine to homocysteine ratio was associated with a decreased rate of total brain tissue volume loss during the study period (β [SE] per 1-SD increase, 0.038 [0.014]; P = .007).Conclusions and Relevance: The methionine to homocysteine status was associated with dementia development and structural brain changes during the 6-year study period, suggesting that a higher methionine to homocysteine ratio may be important in reducing the rate of brain atrophy and decreasing the risk of dementia in older adults. [ABSTRACT FROM AUTHOR]

Introduction Fusobacterium nucleatum is a Gram-negative, obligate anaerobic bacterium which predominantly resides within the oral cavity and causes acute abscesses and venous thrombosis, primarily in the head and neck region, but could have unique clinical presentations in different anatomical regions of body. Case report We present a case of subacute liver abscesses extending to the lung. The histopathological examination showed extensive necrosis and fibrosis. The chronic course, extensive fibrosis and extension across the anatomic barriers were suggestive of actinomycosis. two sets of blood cultures grew Fusobacterium nucleatum , only 16s rRNA analysis of the liver tissue and pleural fluid revealed F. nucleatum DNA without other organisms. The clinical and pathological features of our case illustrate that F. nucleatum may mimic actinomycosis. Conclusions This case illustrates that F. nucleatum should be considered in patients with subacute infections with extensive fibrosis that crosses anatomic barriers, mimicking actinomycosis. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the impact of Apolipoprotein ε4 (APOEε4) on the possible relationship between high sensitive serum CRP (hsCRP) and risk of incident dementia, Alzheimer's disease (AD), and cognitive impairment over seven years in a longitudinal, population based study of community dwelling older adults. Method: Serum hsCRP was measured at baseline in 304 dementia‐free individuals aged 65‐79 years derived from the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study. Participants were re‐examined seven years later, and global cognition, episodic memory, executive functioning, verbal expression, and psychomotor speed were assessed both at baseline and at follow‐up. Incident dementia was diagnosed using DSM‐IV criteria. Multiple linear regression and logistic‐regression models were used to investigate the association of serum hsCRP and its interaction with APOEε4 status on cognitive performance and incident dementia at follow‐up, after adjusting for several potential confounders, including common vascular risk factors. Result: After adjustment for age, sex, education, duration of follow‐up, systolic blood pressure, diastolic blood pressure, body mass index, prevalent stroke, and smoking status, odds ratio (95% confidence intervals (CI)) was 3.02 (1.18 – 7.73) for those who had at least one alle of APOEε4 compared to those who did not. The odds ratio (95%CI) for incident dementia was 1.00 (0.96 – 1.04) oer unit increase in hsCRP. No associations between hsCRP and cognitive impairment seven years later was detected. However, raised hsCRP values were related to worse performance in episodic memory seven years later in participants who had at least one allele of APOEε4 (β (standard error): ‐0.005 (0.002); p = 0.025). Conclusion: Raised values of hsCRP is associated with higher risk of cognitive impairment seven years later among individuals who carry at least one allele of APOEε4. Randomized controlled trials are needed to determine this issue. [ABSTRACT FROM AUTHOR]

Background: Growing evidence associates long‐term exposure to air pollution with dementia. The biological mechanisms behind this association are yet unclear. We aimed to investigate the role played by homocysteine and methionine in the association between air pollution and dementia. Method: Data from 2512 dementia‐free individuals were derived from the ongoing Swedish National study on Aging and Care in Kungsholmen (SNAC‐K). Two major air pollutants (particulate matter ≤2.5µm, PM2.5 and nitrogen oxides, NOX) were assessed yearly from 1990, using dispersion models for outdoor levels at residential addresses. The hazard of dementia was estimated using Cox models. The potential mediating or modifying effects of homocysteine and methionine were analysed through the counterfactual approach. Result: Over a mean follow‐up time of 5.18 years (SD: 2.96), 376 incident dementia cases were identified. We observed an up to 70% increased hazard of dementia per unit increase in PM2.5 levels during the previous five years (HR: 1.71; 95%CI: 1.33‐2.09). We found that approximately 50% (95%CI: 8.9‐97.7) of the total effect of PM2.5 on dementia was due to mediation (7.5%; 95%CI:1.8%‐13.3%) and/or interaction (50%; 95%CI: 5.0%‐ 94.9%) with homocysteine. Higher levels of methionine reduced the dementia risk linked to PM2.5 exposure by 31% (HR: 0.69; 95% CI: 0.56 – 0.85). No statistically significant mediation effect was found through methionine in the association between PM2.5 and dementia. Similar but attenuated results have been obtained for NOx. Conclusion: High levels of homocysteine enhanced the dementia risk associated with air pollution exposure, whereas high methionine reduced such a risk. [ABSTRACT FROM AUTHOR]

Background: The association between markers of vitamin B12 status and cerebrospinal fluid (CSF) biomarkers of Alzheimer's type dementia which precede cognitive impairment has been investigated by only a few small studies and the results have been inconsistent. Method: Data included 462 patients aged 40‐94 years referred to the Memory Clinic at the Ulm University Hospital, Ulm, Germany between December 2009 and August 2015. Vitamin B12 and HoloTC were measured via chemiluminescence microparticle immunoassay, tHcy via chemiluminescence immunoassay and MMA via liquid chromatography mass specterometry. High performance liquid chromatography with fluorescence detection was used for measuring vitamin B1 and vitamin B6 whereas electrochemiluminescence immunoassay was used tomeasure folate. CSF Aβ42 and total tau were measured using conventional methods. CERAD battery was used to examine the cognitive status, and different domains were derived. Regression models were used to investigate the associations. Result: After adjusting for age, sex, creatinine levels and APOEε4 status, higher values of vitamin B12 and lower values of MMA were associated with lower concentrations of CSF total‐tau: the odds ratios (ORs) (95% confidence intervals (CI)) in a binary logistic regression analysis investigating the associations with total tau cut‐off of 400 pg/ml were 0.39 (0.15 ‐ 0.99) and 5.60 (1.93 ‐ 16.26) for the highest quartile of B12 and MMA compared to the lowest, respectively. In addition, vitamin B1 was significantly associated with t‐tau status. Furthermore, HoloTC, MMA, tHcy, vitamin B1, and vitamin B6 were associated with several cognitive domains such as episodic memory and executive functioning. No relationships were found with Aβ42. Conclusion: Vitamin B12 and vitamin B1 may be independent predictors of CSF biomarkers of Alzheimer's disease and cognitive status. Randomized controlled trials are needed to determine the importance of supplementing with these vitamins on slowing structural brain changes and cognitive decline in older adults. [ABSTRACT FROM AUTHOR]

IMPORTANCE Vitamin B12, folate, and sulfur amino acids may be modifiable risk factors for structural brain changes that precede clinical dementia. OBJECTIVE To investigate the association of circulating levels of vitamin B12, red blood cell folate, and sulfur amino acids with the rate of total brain volume loss and the change in white matter hyperintensity volume as measured by fluid-attenuated inversion recovery in older adults. DESIGN, SETTING, AND PARTICIPANTS Themagnetic resonance imaging subsample of the Swedish National Study on Aging and Care in Kungsholmen, a population-based longitudinal study in Stockholm, Sweden, was conducted in 501 participants aged 60 years or older who were free of dementia at baseline. A total of 299 participants underwent repeated structural brain magnetic resonance imaging scans from September 17, 2001, to December 17, 2009. MAIN OUTCOMES AND MEASURES The rate of brain tissue volume loss and the progression of total white matter hyperintensity volume. RESULTS In the multi-adjusted linear mixed models, among 501 participants (300 women [59.9%]; mean [SD] age, 70.9 [9.1] years), higher baseline vitamin B12 and holotranscobalamin levels were associated with a decreased rate of total brain volume loss during the study period: for each increase of 1 SD, β (SE) was 0.048 (0.013) for vitamin B12 (P < .001) and 0.040 (0.013) for holotranscobalamin (P = .002). Increased total homocysteine levels were associated with faster rates of total brain volume loss in the whole sample (β [SE] per 1-SD increase, -0.035 [0.015]; P = .02) and with the progression of white matter hyperintensity among participants with systolic blood pressure greater than 140mmHg (β [SE] per 1-SD increase, 0.000019 [0.00001]; P = .047). No longitudinal associations were found for red blood cell folate and other sulfur amino acids. CONCLUSIONS AND RELEVANCE This study suggests that both vitamin B12 and total homocysteine concentrations may be related to accelerated aging of the brain. Randomized clinical trials are needed to determine the importance of vitamin B12 supplementation on slowing brain aging in older adults. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate brain tissue volumes, grey matter (GM) distribution, and cognitive performance for cognitively impaired subjects using cerebrospinal fluid (CSF) biomarker cut-offs as grouping criteria. 41 subjects attending the Memory Clinic, Karolinska University Hospital, Huddinge, Sweden, were divided into groups based on normal or abnormal CSF levels of Aβ1-42, t-tau, and p-tau181. SIENAX algorithms were employed for brain tissue volumes estimation and voxel-based morphometry (VBM) for mapping the differences in GM patterns. VBM revealed significant lower GM volumes in temporo-parietal, occipital, and prefrontal cortices for those subjects belonging to abnormal CSF t-tau and p-tau181 groups. No differences were found between groups according to CSF Aβ1-42 cut-offs. Patients with abnormal CSF p-tau181 showed lower cognitive performance compared to those with normal levels. Patients with abnormal levels of CSF tau (but not Aβ1-42) showed an Alzheimer's disease-like pattern for both GM distribution and cognitive profile, compared to those with normal levels. These results support the hypothesis that CSF t-tau or p-tau181 levels may be of direct value for the evaluation of disease severity. [ABSTRACT FROM AUTHOR]

Background: Impairment of methylation status and raised values of homocysteine and cysteine may be modifiable risk factors for cognitive decline. We aimed to investigate the association of vitamin B12, folate, and sulfur amino‐acids with cognitive decline in a large sample of community dwelling older adults. Method: From the Swedish National Study of Aging and Care in Kungsholmen (SNAC‐K), 2900 dementia‐free individuals at baseline aged 60‐102 years with comprehensive assessments and Mini‐mental state examination (MMSE) were recruited. A total of 2202 participants underwent repeated MMSE assessments up to 5 occasions over 15 years. The association of baseline vitamin B12, holotranscobalamin, folate, homocysteine, methionine, cystathionine, cysteine, glutathione, and methylation status (defined as serum methionine/homocysteine ratio) with rate of cognitive decline was examined using linear mixed models, adjusted for several potential confounders, including common vascular risk factors. Result: After adjusting for age, sex, education, creatinine, albumin, smoking status, systolic blood pressure, and APOEε4 status, raised baseline serum total homocysteine and cysteine values were associated with faster rate of cognitive decline: for the highest quartile compared with the lowest, β coefficient and standard error (SE) were ‐0.0058 (0.002) for homocysteine (p=0.004) and ‐0.0051 (0.002) for cysteine (p=0.014) In contrast, a better methylation status was associated with less MMSE decline over 15 years: β (SE) was 0.0058 (0.002) for the highest quartile compared with the lowest (p=0.004). Furthermore, elevated methionine values tended to slow rate of cognitive decline (p=0.079). No relationships were found for other sulfur amino acids, vitamin B12 or folate. Conclusion: Markers of methylation status and raised cysteine values were related to more rapid cognitive decline over 15 years, suggesting that optimizing homocysteine, cysteine, and methionine values may be important in reducing the risk of cognitive decline in older adults. [ABSTRACT FROM AUTHOR]

Background Enterobacter prosthetic joint infections (PJIs) are rare, occurring mainly in elderly people usually with complex medical and surgical history, and their treatment is usually challenging. Aim of this study is to assess the characteristics and outcomes of Enterobacter PJIs. Methods A retrospective multi-centric cohort was studied at three hospitals from January 2012 to December 2018. Patients with PJIs were identified using ICD codes. Enterobacter PJIs were then identified through reviewing patients' electronic medical records. Results 13 enterobacter PJIs were identified. 9 (69%) were polymicrobial. Mean age of the patients was 61.7 years, and mean BMI was 34.6 kg/m2. 8 patients (62%) were females, and 8 patients (62%) were Caucasians. Infected sites were: Hip in 5 patients (38%%), knee in 5 patients (38%) and ankle in 3 patients (23%) patients. 9 patients (69%) had osteoarthritis, 3 patients (23%) had diabetes mellitus, and 1 patient (8%) had connective tissue diseases requiring steroids. Most patients (11 out of 13) (85%) presented within 1 week of symptoms onset. Presenting clinical features were pain in 9 patients (69%), drainage in 10 patients (77%), purulence in 7 patients (54%), and fever in 5 patients (38%). 11 patients (85%) were managed with debridement, antibiotics and implant retention (DAIR), and 2 patients (15%) with antibiotics alone. Antibiotics used while managing were as follows: Cefepime n = 6, quinolones n = 2, carbapenems n = 4 and aminoglycosides n = 1. Outcome: 4 patients (31%) developed deep surgical site infections (and two of them required implant removal), 5 patients had no events in 12 months of follow-up, 3 patients (23%) had less than 6 months of follow-up, and one patient died in the hospital due to cardiac failure. Conclusion In our study, most cases of Enterobacter PJIs were polymicrobial. The success rate in monomicrobial infections was 75% while overall it was noted to be 38%. DAIR was associated with high readmission rates and deep surgical site infections (36%). 18% cases managed with DAIR required implant removal. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Polymicrobial prosthetic joint infections (PMPJIs) are rare but treatment is usually challenging. Published studies described the PMPJIs without differentiating the component pathogens. We assessed clinical features and treatment outcome among Gram-negative polymicrobial (GNPM), Gram-positive polymicrobial (GPPM) and mixed polymicrobial (MPM) PJIs. Methods A retrospective cohort was studied at three Ascension hospitals in Detroit from January 2012 to December 2018. Cases were identified using the International Classification of Diseases, 9th and 10th Revision code specific for PJIs. Patient's electronic medical records were reviewed. Results 38 patients with PMPJI with a mean age of 67 years. were identified. 71% patients were female and caucasians. Nineteen (50%) patients had MPM, 16 (42%) had GPPM and 3 had GNPM. Among MPM PJIs, 14 (74%) involved hips, 4 (21%) knee and 1 (5%) ankle joint. Among GPPM PJIs, 7 (44%) involved hips, 8 (50%) knee and 1 (6%) shoulder joints. Among GNPM PJIs, 1 (33%) involved hip and 2 (67%) involved knee joints. 4 (21%), 1 (6%), and 1 (33%) patients had diabetes among MPM, GPPM and GNPM, respectively. Symptom onset of less than a week was noted in 13 (68%), 5 (31%), 3(100%) and of more than 3 weeks in 3 (16%), 7 (43%) and in 0 among MPM, GPPM and GNPM, respectively. 18 (95%), 12 (75%) and 2 (67%) patients presented with pain; 16 (84%), 6 (38%) and 3 (100%) patients had drainage among MPM, GPPM and GNPM, respectively. Among MPM PJIs, 12 (63%) underwent debridement, antibiotics and implant retention (DAIR), 2 (11%) for two stage exchange, 4 (21%) for chronic suppressive therapy and 1 (5%) had an amputation. 6 (58%) were readmitted within 6 months; 3 (50%) required prosthesis removal, 1 (4%) each died, was made hospice and was lost to follow-up. Among GPPM PJIs, 12 (75%) underwent DAIR and 4 (25%) went for two stage exchange. 9 (69%) patients among GPPM PJIs were readmitted in 6 months and 3 (50%) required prosthesis removal. All 3 of GNPM PJIs underwent DAIR and none were readmitted in 6 months. Conclusion Pain and drainage were common presenting symptoms. All GNPM PJIs presented within 1 week of symptoms and were treated successfully with DAIR. MPM and GPPM PJIs had high readmission rates and 6/26 (23%) managed with DAIR required prosthesis removal. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Polymicrobial (PM) prosthetic joint infections (PJIs) account for 4% to 37% of all PJIs. There is limited literature on surgical debridement, antibiotics and implant retention (DAIR) in PMPJIs. We aimed to assess clinical outcomes of PMPJIs managed with DAIR. Methods A retrospective cohort was studied at three Ascension hospitals in Detroit from January 2012 to December 2018. Cases were identified using the International Classification of Diseases, 9th and 10th Revision code specific for PJIs. Patient's electronic medical records were reviewed. Results Twenty-six PMPJIs managed with DAIR were identified. Mean age of the infected patients was 66 years. 18 (69%) patients were female and 19 (73%) were caucasians. Infected sites were hip in 15 (58%), knee in 10 (38%) and ankle in 1 (4%) patient. 22 (85%) patients had osteoarthritis, 3 (12%) had diabetes, 3 (12%) were on steroids and 1 (4%) had rheumatoid arthritis. Symptom onset of less than a week was noted in 14 (58%) and 3 or more weeks in 8 (31%) patients. Pain, swelling and drainage were present in 21 (81%), 13 (50%) and 18 (69%) cases. Fever on admission was noted in 7 (27%) patients. 11 (42%) patients were re-admitted in the following 12 months after DAIR. 2 (19%) patients developed superficial surgical site infection (SSI) while 9 (81%) had deep SSI. Implant removal was needed in 6 (55%) patients. 5 (2 superficial and 3 deep) patients required further debridement and antibiotics. 5 (19%) had good outcome with 3–6 months of antibiotics. 3 (12%) patients required long-term chronic suppressive therapy. One patient died from a cardiac event during follow-up. Conclusion In our study, PMPJIs managed with DAIR had high readmission rates and deep surgical site infections. DAIR failure, noted in 23% of our cases, required implant removal within 12 months of follow-up. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Klebsiella species (KS) bloodstream infection (BSI) is often caused by K. pneumoniae (KP). K. oxytoca (KO) is emerging and implicated in antibiotic-associated right-sided colitis. We compared the clinical and microbiological characteristics of KP and KO. Methods We reviewed blood culture (BC) results (January 1, 2010–December 31, 2017), selected patients with KS in ≥1 BC, reviewed their medical records, abstracted patient demographics, source of bacteremia, antibiotics susceptibility, and outcome. Each patient was counted once. We compared KP and KO cases. All differences were assessed by the chi-square test and regression analysis, using SPSS. Results We encountered KS in 975/14,256 (6.8%) positive BC, representing 611 BSI including 537 KP-BSI (484 patients) and 55 KO-BSI cases (54 patients); each patient was counted once. Mean age and prevalence of diabetes and most comorbidities were similar but KO was less frequent in African Americans (40.7% vs. KP [61.3%]; P = 0.005) and in patients with neurological debility (Stroke, paraplegia, multiple sclerosis; 11.1% vs. KP [24.8%]; P = 0.03). KO BSI was more frequent in IVC BSI and was absent in pneumonia-associated BSI (table). Antibiotic resistance was rare among KO isolates except for cefazolin-intermediate susceptibility (42.6% vs. 1.7%; P < 0.001). CREs were limited to KP. Logistic regression analysis confirmed KO link to IVC (OR = 3.57; 95% CI: 1.89, 6.76; P < 0.001) and Caucasian race (OR = 2.46; CI: 1.37, 4.42; P = 0.003). Mortality rate was comparable (28.1% [KP] vs. 35.2% [KO]; P = 0.3). Source and antibiotic susceptibility (%) in K. pneumoniae and K. oxytoca bacteremia   K. pneumoniae   K. oxytoca   P   Source        IVC  12.8  33.3  <0.001  UTI  34.9  24.1  0.1  Soft/tissue bone  8.7  11.1  0.6  Abdomen  21.3  14.8  0.4  Pneumonia  8.3  0  0.03  Antibiotics resistance  Cefazolin  28.6  20.4  0.1  Ceftriaxone  25.2  5.6  0.001  Ciprofloxacin  25.6  1.9  <0.001  Gentamicin  18.2  1.9  0.001  TMP/SMX  25.4  1.9  <0.001  ESBL 25.6  3.7  <0.001    CRE  4.7  0  0.1    K. pneumoniae   K. oxytoca   P   Source        IVC  12.8  33.3  <0.001  UTI  34.9  24.1  0.1  Soft/tissue bone  8.7  11.1  0.6  Abdomen  21.3  14.8  0.4  Pneumonia  8.3  0  0.03  Antibiotics resistance  Cefazolin  28.6  20.4  0.1  Ceftriaxone  25.2  5.6  0.001  Ciprofloxacin  25.6  1.9  <0.001  Gentamicin  18.2  1.9  0.001  TMP/SMX  25.4  1.9  <0.001  ESBL 25.6  3.7  <0.001    CRE  4.7  0  0.1    K. pneumoniae   K. oxytoca   P   Source        IVC  12.8  33.3  <0.001  UTI  34.9  24.1  0.1  Soft/tissue bone  8.7  11.1  0.6  Abdomen  21.3  14.8  0.4  Pneumonia  8.3  0  0.03  Antibiotics resistance  Cefazolin  28.6  20.4  0.1  Ceftriaxone  25.2  5.6  0.001  Ciprofloxacin  25.6  1.9  <0.001  Gentamicin  18.2  1.9  0.001  TMP/SMX  25.4  1.9  <0.001  ESBL 25.6  3.7  <0.001    CRE  4.7  0  0.1    K. pneumoniae   K. oxytoca   P   Source        IVC  12.8  33.3  <0.001  UTI  34.9  24.1  0.1  Soft/tissue bone  8.7  11.1  0.6  Abdomen  21.3  14.8  0.4  Pneumonia  8.3  0  0.03  Antibiotics resistance  Cefazolin  28.6  20.4  0.1  Ceftriaxone  25.2  5.6  0.001  Ciprofloxacin  25.6  1.9  <0.001  Gentamicin  18.2  1.9  0.001  TMP/SMX  25.4  1.9  <0.001  ESBL 25.6  3.7  <0.001    CRE  4.7  0  0.1  Conclusion KO and KP BSI differ in the type of host and source, suggesting different colonization dynamics. KO remains antibiotic-susceptible but might be cefazolin less susceptible. Prospective studies are needed to confirm differential cephalosporin susceptibility and delineate host–pathogen interactions. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Monitoring bloodstream infections provides updates of the microbiology and antibiotic susceptibility trends. We elected to examine GNB-BSI. Methods We retrospectively studied adults (≥18 years old) inpatients with gram-negative bacilli (GNB) bloodstream infection (BSI; January 1, 2010–December 31, 2017), determined the demographics, onset place, microbiology and source. The results were stratified to study year and evaluated by the extended Mantel–Haenszel chi square for linear trends. Results GNB were encountered in 4520/14314 (31.6%) positive blood culture (BC) accounting for 2811 BSI episodes (2291 patients) with a steadily increasing rate (table). The 3 most common organisms were Escherichia coli (EC; 44.4%), Klebsiella pneumoniae (KP; 19.2%) and Pseudomonas aeruginosa (PA; 9.6%). GNB-BSI rate increase was mainly in EC-BSI (P = 0.01). The rate of other GNB-BSI did not change. Source distribution of EC-BSI did not change and antibiotic resistance did not change. Conclusion GNB-BSI is rising, primarily due to EC, without changes in source distribution or antibiotic susceptibility. Prospective studies to look at EC lineage and virulence factors are needed to determine the reason for EC-BSI rise. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Current recommendations by Infectious diseases society of America (IDSA) endorse cefazolin for perioperative use. What is less known currently is the emergence of resistance in Gram-positive (GP) and Gram-negative (GN) prosthetic joint infections (PJIs) in the setting of perioperative use of antibiotics. Methods A retrospective multi-centric cohort was studied at three hospitals from January 2012 to December 2018. Patients with PJIs were identified using ICD codes. We reviewed electronic medical records and identified PJIs which followed primary arthroplasties. We included cases where perioperative antibiotics records were available. Results 66 infected PJIs with available preoperative records were included. 40 (61%) patients were females, and 42 (64%) were caucasians. Indications for undergoing arthroplasty were degenerative joint disease (DJD) in 52 (78%), trauma in 13 (20%) and avascular necrosis in 1 (1.5%). Sites for arthroplasty were knee in 33 (50%), hip 28 (42.5%), shoulder 4 (6%), and ankle in 1(1.5%). 43 (65%) had GP monomicrobial, 6 (9%) had GN monomicrobial and 17 (26%) had polymicrobial infections. 40 (60.5%) patients received cefazolin, 25 (38%) received vancomycin and 1 (1.5%) received ceftriaxone as perioperative prophylaxis. 7 (11%) PJIs among monomicrobial infections and 6 (35%) among polymicrobial infections had non-susceptible (NS) organisms (Figure 1 and 2). 8 (47%) polymicrobial PJIs had a mixed susceptibility profile with drug susceptible and resistant organisms. Conclusion In general, when monomicrobial GP pathogens are causative for PJI, current use of cefazolin as perioperative drug of choice is sound and we agree with the current perioperative recommendations. It should be recognized that in situations where the PJI is due to GN or is polymicrobial, resistance to perioperative antibiotics may be present at a greater rate. From this study we conclude that in cases where the pathogen is known to be GN or polymicrobial from a diagnostic aspiration, then a broader antibiotic selection may be of benefit perioperatively. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Diet is an important modifiable lifestyle factor related to dementia risk. Yet, the role of midlife dietary changes is unclear. The goal is to investigate whether midlife healthy dietary changes are associated with late-life dementia risk. Data were collected within the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) population-based cohort study (n = 2000) (mean baseline age = 56 years). Participants returned for two late-life re-examinations (mean age = 70 and 78 years). Self-reported midlife diet was measured in a sub-sample (n = 341) (mean total follow-up = 16.8 years). Changes in specific dietary components (fats, vegetables, sugar, salt) were measured in midlife. Dementia diagnoses were ascertained with detailed examinations. Analyses adjusted for potential confounders. Total midlife healthy dietary changes (improving quality of fats, increasing vegetables, decreasing sugar and salt) were associated with a reduced risk of dementia (fully adjusted odds ratio (OR) 0.41, 95% confidence interval (CI) = 0.20–0.85). In contrast, when each factor was assessed individually, associations were not significant. This study is the first to show that beneficial midlife dietary changes are associated with a reduced dementia risk later in life. The results highlight the importance of targeting dietary patterns, where various food items may have synergistic effects. [ABSTRACT FROM AUTHOR]