This article provides a comprehensive review of currently available treatment options for infections due to carbapenem-resistant enterobacteriaceae (CRE).

Clostridioides difficile infection occurs when the bacterium produces toxin that causes diarrhea and inflammation of the colon. These guidelines indicate the preferred approach to the management of adults with C. difficile infection and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation process. In instances where the evidence was not appropriate for Grading of Recommendations Assessment, Development, and Evaluation but there was consensus of significant clinical merit, key concept statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not the only, approach to clinical scenarios.

We evaluated the impact of high (9.5 log 10 CFU/g) and moderate (5.5 log 10 CFU/g) inocula of methicillinsusceptible and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) on the activities of nafcillin, linezolid, vancomycin, and daptomycin, alone and in combination with gentamicin in an in vitro pharmacodynamic model with simulated endocardial vegetations over 72 h. Human therapeutic dosing regimens for nafcillin, daptomycin, vancomycin, linezolid, and gentamicin were simulated. At a moderate inoculum, nafcillin (MSSA only), vancomycin, and daptomycin demonstrated equivalent and significant (P < 0.01) bactericidal (99.9% kill) activities (decreases of 3.34 ؎ 1.1, 3.28 ؎ 0.4, and 3.34 ؎ 0.8 log 10 CFU/g, respectively). Bactericidal activity was demonstrated at 4 h for nafcillin and daptomycin and at 32 h for vancomycin. Linezolid demonstrated bacteriostatic activity over the course of the study period. At a high inoculum, daptomycin exhibited bactericidal activity against both MSSA and MRSA by 24 h (decrease of 5.51 to 6.31 ؎ 0.10 log 10 CFU/g). Nafcillin (versus MSSA), vancomycin, and linezolid (MSSA and MRSA) did not achieve bactericidal activity throughout the 72-h experiment. The addition of gentamicin increased the rate of 99.9% kill to 8 h for daptomycin (P < 0.01) and 48 h for nafcillin (MSSA only) (P ‫؍‬ 0.01). The addition of gentamicin did not improve the activity of vancomycin or linezolid for either isolate for the 72-h period. Overall, high-inoculum Staphylococcus aureus had a significant impact on the activities of nafcillin and vancomycin. In contrast, daptomycin was affected minimally and linezolid was not affected by inoculum.

For BSIs, mRDT was associated with significant decreases in mortality risk in the presence of a ASP, but not in its absence. mRDT also decreased the time to effective therapy and the length of stay. mRDT should be considered as part of the standard of care in patients with BSIs.

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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

Vancomycin (VAN) and daptomycin (DAP) are approved as a monotherapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. A regimen of daptomycin plus ceftaroline (DAP+CPT) has shown promise in published case series of MRSA salvage therapy, but no comparative data exist to compare up-front DAP+CPT head-to-head therapy versus standard monotherapy as an initial treatment.

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