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Background Risk factors and outcomes associated with carbapenem-resistant Enterobacteriaceae (CRE) acquisitions are derived primarily from cohorts consisting of carbapenemase-producing (CP) strains. Worldwide epidemiology of non-CP-CRE is evolving, but controlled epidemiological analyses are lacking. Methods A matched case-case-control investigation was conducted at Shamir (Assaf Harofeh) Medical Center, Israel, on November 2014–December 2016. Noncarbapenemase-producing CRE (as defined by the US Clinical and Laboratory Standards Institute Standards) carriers were matched to patients with non-CRE Enterobacterales and to uninfected controls (1:1:1 ratio). Matched and nonmatched multivariable regression models were constructed to analyze predictors for acquisition and the independent impact of carriage on multiple outcomes, respectively. Representative isolates were whole genome sequenced and analyzed for resistome and phylogeny. Results Noncarbapenemase-producing CRE carriers (n = 109) were matched to the 2 comparative groups (overall n = 327). Recent exposure to antibiotics (but not specifically to carbapenems), prior intensive care unit admission, and chronic skin ulcers were all independent predictors for non-CP-CRE acquisition. Acquisitions were almost exclusively associated with asymptomatic carriage (n = 104), and despite strong associations per univariable analyses, none were independently associated with worse outcomes. Genomic analyses of 13 representative isolates revealed polyclonality, confirmed the absence of carbapenemases, but confirmed the coexistence of multiple other genes contributing to carbapenem-resistance phenotype (multiple beta-lactamases and efflux pumps). Conclusions Noncarbapenemase-producing CRE acquisitions are primarily associated with asymptomatic carriage, specifically among prone populations with extensive recent exposures to antibiotics. The prevalent mode of acquisition is "emergence of resistance" (not "patient-to-patient transmission"), and therefore the role of stewardship interventions in reducing the spread of these therapeutically challenging pathogens should be further explored. [ABSTRACT FROM AUTHOR]

Background: Thiazide diuretics and angiotensin-converting enzyme inhibitors can cause excessive urinary zinc (Zn) loss and Zn depletion. Thiazides may also induce magnesium (Mg) deficiency, which may exacerbate hypertension. Data on the effects of angiotensin receptor blockers on Zn and Mg homeostasis are scarce. Methods: Seventeen hypertensive patients were studied (ten men and seven women, age 50 ± 3 years, blood pressure 158 ± 5 / 95 ± 3 mm Hg). Patients were treated with losartan 50 mg/day for 4 weeks followed by a fixed combination of 50 mg losartan and 12.5 mg hydrochlorothiazide for 4 weeks more. Blood and 24-h urine were collected at baseline and after each study period. Zinc and Mg levels were measured in serum, urine, and peripheral blood mononuclear cells. Nitric oxide metabolites were measured in urine. Results: Treatment with losartan resulted in a significant increase in the urinary Zn/creatinine ratio (from 0.020 ± 0.004 μg/mg to 0.034 ± 0.005 μg/mg, P = .02), which was further increased by the losartan/hydrochlorothiazide combination (from 0.034 ± 0.005 μg/mg to 0.053 ± 0.008 μg/mg, P = .03). Serum Zn levels were significantly decreased after losartan/hydrochlorothiazide (from 80.0 ± 4.0 μg/dL at baseline to 74.0 ± 3.0 μg/dL, P = .007). Peripheral blood mononuclear Zn concentrations were decreased also, but this was not statistically significant. Serum, urinary, and peripheral blood mononuclear Mg levels were not significantly affected by treatment. Nitric oxide urinary metabolites were unchanged throughout the study. Conclusions: Treatment with losartan causes an increase in urinary Zn excretion and induces Zn deficiency in patients with hypertension. The addition of hydrochlorothiazide has an additive effect. Magnesium and nitric oxide metabolism are not affected by either treatment. [Copyright &y& Elsevier]

Background In the era of widespread resistance, there are two events in the course of a hospitalized septic patient where the majority of empiric prescription errors occur: (1) infections upon admission (UA) due to multi-drug-resistant organisms (MDRO) and (2) nosocomial infections due to extensively drug-resistant organisms (XDRO). These errors seriously impact patient outcomes and the ecological burden of resistance. Our objective was to develop a tool, to calculate the probability of MDRO UA, and nosocomial XDRO infections, in order to reduce delays in initiating appropriate therapy to the "right population," i.e. with "resistant pathogens," while avoiding overuse of broader (frequently more toxicת less efficacious) therapeutics to the "wrong population," i.e. with "susceptible pathogens." Methods Retrospective case–control analyses were conducted for septic adults at Shamir Medical Center, Israel (2016). Logistic regression was used to develop models of risk factors. All parameters incorporated into the models were readily accessible at the point of care. The performances of the development cohorts, and on 8 other validation cohorts, were assessed by the area under the receiver operating characteristic curve (ROC AUC). A web calculator (mobile modifiable) was generated. Results A total of 4,199 patients were enrolled: 2,472 with sepsis UA, and 1,727 with nosocomial sepsis. The "MDR UA score" included 10 parameters and with a cutoff of ≥22 points, had a ROC AUC of 0.85 (sensitivity 86%, NPV 98%). The "Nosocomial XDR score" included 7 parameters and with a cutoff of ≥36 points, had a ROC AUC of 0.88 (sensitivity 90%, NPV 96%). The median ROC AUC was 0.75 among the validation cohorts of the "MDR UA score," and 0.66 among the "Nosocomial XDR score." A free web tool was generated: https://assafharofe.azurewebsites.net/. Conclusion A simple electronic calculator was generated to aid in bedside empiric prescription practices. The tool is composed of two scores to assist in common scenarios where the majority of errors occur. Prospective interventional investigations, should trial the performances of this tool in improving patient outcomes and the ecological burden in the facility. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background. Background The World Health Organization has declared carbapenem-resistant Enterobacteriaceae (CRE) as a worldwide public health threat. Analyzing the epidemiology of CRE was derived from cohorts consisting primarily of Klebsiella pneumoniae isolates. The second most frequent CRE is Enterobacter (CREn), but its molecular and clinical epidemiology differ from that of K. pneumoniae , and it has not been analyzed while implementing updated methodological tools and design. Methods A matched case-case–control investigation was conducted at Shamir (Assaf Harofeh) Medical Center, Israel, for calendar years 2007–2017. Each CREn case was matched to a carbapenem-susceptible Enterobacter (CSEn) case and to an uninfected control (1:1:1 ratio). Logistic and Cox regression-matched analyses were conducted in order to study predictors and outcomes of CREn colonization and/or infection, respectively. Results The study included 216 cases (72 in each group). Numerous predictors were significantly associated with CREn as per bivariable analyses, but the only independent significant predictors were: (1) recent (3 months) exposure to fluoroquinolones (aOR=2.94, P = 0.04), (2) intensive care unit stay in current hospitalization prior to culture (aOR=3.56, P = 0.003), and (3) a rapidly fatal McCabe score (aOR=0.471, P = 0.01). Patients with CREn suffered from significant delays in instituting appropriate antimicrobials (P = 0.03), and for those who survived the hospitalization, were more frequently discharged to a long-term care facility after being admitted to the index hospitalization from home (aOR=3.3, P = 0.02). Conclusion This case-case–control-matched investigation of CREn epidemiology, revealed a unique modifiable predictor, i.e. recent fluoroquinolone exposure, which could represent a target for stewardship intervention. The case-case–control-matched design allowed for the control of numerous confounders previously reported to be associated with CREn but may represent a risk factor for Enterobacter infection in general. As with other CRE, CREn carriers suffer from significant delays in initiation of appropriate antimicrobials and from worse outcomes. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Health care–associated infection (HcAI) is a term frequently used to describe community-onset infections likely to be caused by multidrug-resistant organisms (MDROs). The most frequently used definition was developed at Duke University Medical Center in 2002 (Duke-2002). Although some professional societies have based management recommendations on Duke-2002 (or modifications thereof), neither Duke-2002 nor other variations have had their performance measured. Methods A case–control study was conducted at Assaf Harofeh Medical Center (AHMC) of consecutive adult bloodstream infections (BSIs). A multivariable model was used to develop a prediction score for HcAI, measured by the presence of MDRO infection on admission. The performances of this new score and previously developed definitions at predicting MDRO infection on admission were measured. Results Of the 504 BSI patients enrolled, 315 had a BSI on admission and 189 had a nosocomial BSI. Patients with MDRO-BSI on admission (n = 100) resembled patients with nosocomial infections (n = 189) in terms of epidemiological characteristics, illness acuity, and outcomes more than patients with non-MDRO-BSI on admission (n = 215). The performances of both the newly developed score and the Duke-2002 definition to predict MDRO infection on admission were suboptimal (area under the receiver operating characteric curve, 0.76 and 0.68, respectively). Conclusions Although the term HcAI is frequently used, its definition does not perform well at predicting MDRO infection present on admission to the hospital. A validated score that calculates the risk of MDRO infection on admission is still needed to guide daily practice and improve patient outcomes. [ABSTRACT FROM AUTHOR]