Enterococci, one of the most common causes of hospital-associated infections, are responsible for substantial morbidity and mortality. Enterococcus faecalis, the more common and virulent species, causes serious high-inoculum infections, namely infective endocarditis, that are associated with cardiac surgery and mortality rates that remained unchanged for the last 30 years. The best cures for these infections are observed with combination antibiotic therapy; however, optimal treatment has not been fully elucidated. It is the purpose of this review to highlight treatment options and their limitations, and provide direction for future investigative efforts to aid in the treatment of these severe infections. While ampicillin plus ceftriaxone has emerged as a preferred treatment option, mortality rates continue to be high, and from a safety standpoint, ceftriaxone, unlike other cephalosporins, promotes colonization with vancomycin resistant-enterococci due to high biliary concentrations. More research is needed to improve patient outcomes from this high-mortality disease.Keywords. Enterococcus faecalis; infective endocarditis; antimicrobials. , and ability to form biofilm at higher rates than E. faecium (87%-95% vs 16%-29%, respectively) [4,5], makes treatment of E. faecalis infections particularly challenging and may contribute to the unchanging mortality rates. Consequently, combination antimicrobial therapy is required for deep-seated E. faecalis infections, and with >50% of isolates expressing aminoglycoside resistance, treatment options are becoming limited [6]. It is the purpose of this review to highlight available treatment options and their limitations and to provide direction for investigation of future novel combination therapies, including ampicillin plus non-ceftriaxone β-lactams and daptomycin combination therapy, to further aid in the treatment of E. faecalis IE. METHODSStudies were identified by conducting PubMed and Embase searches using the following keywords in 1 or more combinations with "Enterococcus faecalis ": infective, endocarditis, bacteremia, bloodstream, infection, treatment, guideline, antibiotic, combination, synergy, resistant, biofilm, clinical, diagnosis, epidemiology, in vitro, in vivo, simulated endocardial vegetation, experimental, and β-lactamase. Manual searches of reference lists of relevant articles found from initial searches were also conducted. No limitation was placed on publication time period. Studies were selected based on authors' (M. B. and M. K. L.) judgment of relevance to topic. ORIGIN OF COMBINATION THERAPYFor serious E. faecalis infections, such as IE, bactericidal agents, often as combination therapy, are preferred [2]. β-Lactam antibiotics lack bactericidal activity against enterococci when used as monotherapy, making treatment of systemic infections

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) decreases the time to organism identification and improves clinical and financial outcomes. The purpose of this study was to evaluate the impact of MALDI-TOF MS alone versus MALDI-TOF MS combined with real-time, pharmacist-driven, antimicrobial stewardship (AMS) intervention on patient outcomes. This single-center, pre-post, quasiexperimental study evaluated hospitalized patients with positive blood cultures identified via MALDI-TOF MS combined with prospective AMS intervention compared to a control cohort with MALDI-TOF MS identification without AMS intervention. AMS intervention included: real-time MALDI-TOF MS pharmacist notification and prospective AMS provider feedback. The primary outcome was the time to optimal therapy (TTOT). A total of 252 blood cultures, 126 in each group, were included in the final analysis. MALDI-TOF MS plus AMS intervention significantly reduced the overall TTOT (75.17 versus 43.06 h; P Ͻ 0.001), the Gram-positive contaminant TTOT (48.21 versus 11.75 h; P Ͻ 0.001), the Gramnegative infection (GNI) TTOT (71.83 versus 35.98 h; P Ͻ 0.001), and the overall hospital length of stay (LOS; 15.03 versus 9.02 days; P ϭ 0.021). The TTOT for Grampositive infection (GPI) was improved (64.04 versus 41.61 h; P ϭ 0.082). For GPI, the hospital LOS (14.64 versus 10.31 days; P ϭ 0.002) and length of antimicrobial therapy 24.30 versus 18.97 days; P ϭ 0.018) were reduced. For GNI, the time to microbiologic clearance (51.13 versus 34.51 h; P Ͻ 0.001), the hospital LOS (15.40 versus 7.90 days; P ϭ 0.027), and the intensive care unit LOS (5.55 versus 1.19 days; P ϭ 0.035) were reduced. To achieve optimal outcomes, rapid identification with MALDI-TOF MS combined with real-time AMS intervention is more impactful than MALDI-TOF MS alone.KEYWORDS MALDI-TOF MS, antimicrobial stewardship, rapid molecular diagnostics D espite advances in antimicrobial therapy, bloodstream infections (BSIs) remain a threat to hospitalized patients. A significant proportion of health care-associated infections result from multidrug-resistant organisms (MDROs). These infection rates continue to uptrend, posing a substantial public health risk by driving providers to utilize broad-spectrum antimicrobials and potentiating the cycle that creates MDROs

IntroductionApproximately 30% of all outpatient antimicrobials are inappropriately prescribed. Currently, antimicrobial prescribing patterns in emergency departments (ED) are not well described. Determining inappropriate antimicrobial prescribing patterns and opportunities for interventions by antimicrobial stewardship programs (ASP) are needed.MethodsA retrospective chart review was performed among a random sample of non-admitted, adult patients who received an antimicrobial prescription in the ED from January 1 to December 31, 2015. Appropriateness was measured using the Medication Appropriateness Index, and was based on provider adherence to local guidelines. Additional information collected included patient characteristics, initial diagnoses, and other chronic medication use.ResultsOf 1579 ED antibiotic prescriptions in 2015, we reviewed a total of 159 (10.1%) prescription records. The most frequently prescribed antimicrobial classes included penicillins (22.6%), macrolides (20.8%), cephalosporins (17.6%), and fluoroquinolones (17.0%). The most common indications for antibiotics were bronchitis or upper respiratory tract infection (URTI) (35.1%), followed by skin and soft tissue infection (SSTI) (25.0%), both of which were the most common reason for unnecessary prescribing (28.9% of bronchitis/URTIs, 25.6% of SSTIs). Of the antimicrobial prescriptions reviewed, 39% met criteria for inappropriateness. Among 78 prescriptions with a consensus on appropriate indications, 13.8% had inappropriate dosing, duration, or expense.ConclusionConsistent with national outpatient prescribing, inappropriate antibiotic prescribing in the ED occurred in 39% of cases with the highest rates observed among patients with bronchitis, URTI, and SSTI. Antimicrobial stewardship programs may benefit by focusing on initiatives for these conditions among ED patients. Moreover, creation of local guideline pocketbooks for these and other conditions may serve to improve prescribing practices and meet the Core Elements of Outpatient Stewardship recommended by the Centers for Disease Control and Prevention.