A proposal for a comprehensive approach to infections across the surgical pathway.

Despite evidence supporting the effectiveness of best practices in infection prevention and management, many healthcare workers fail to implement them and evidence-based practices tend to be underused in routine practice. Prevention and management of infections across the surgical pathway should always focus on collaboration among all healthcare workers sharing knowledge of best practices. To clarify key issues in the prevention and management of infections across the surgical pathway, a multidisciplinary task force of experts convened in Ancona, Italy, on May 31, 2019, for a national meeting. This document represents the executive summary of the final statements approved by the expert panel.

Different Cardiotoxicity of Palbociclib and Ribociclib in Breast Cancer: Gene Expression and Pharmacological Data Analyses, Biological Basis, and Therapeutic Implications.

Breast cancer is the most frequent tumor in women. The recent advent of cyclin-dependent kinase (CDK) 4/6 inhibitors palbociclib and ribociclib has represented a major step forward for patients with hormone receptor-positive breast cancer. These two agents have showed similar efficacy in terms of breast cancer outcome but different cardiotoxic effects. In particular, ribociclib, but not palbociclib, has been associated with QT interval prolongation, and the mechanisms underlying this event are still unclear. In order to clarify such difference, we matched the candidate genes associated with QT interval prolongation with genes whose expression is altered following palbociclib or ribociclib treatment. We also investigated whether pharmacokinetic and pharmacodynamic characteristics, such as IC50 (hERG) [concentration of drug producing 50% inhibition (human ether-à-go-go related gene)] and maximum concentration (Cmax), could justify the different effects on QT interval prolongation. Our results show that ribociclib, but not palbociclib, could act by down-regulating the expression of KCNH2 (encoding for potassium channel hERG) and up-regulating SCN5A and SNTA1 (encoding for sodium channels Nav1.5 and syntrophin-α1, respectively), three genes associated with long QT syndrome. Consistent with the cardiotoxicity induced by ribociclib, its IC50 (hERG)/free concentration (Cmax free) ratio is closer to the safety threshold than that of palbociclib. In summary, we hypothesize that the different cardiotoxicity associated with ribociclib and palbociclib could be due to the alteration of potassium and sodium channels induced by ribociclib. A better comprehension of the mechanisms of cardiac channelopathies and drug-induced QT interval prolongation will be fundamental to avoid serious and potentially lethal adverse events and, as a consequence, optimize the management of breast cancer patients.

Non-Restrictive Antimicrobial Stewardship Program in a General and Emergency Surgery Unit.

BACKGROUND: The goal of an antimicrobial stewardship program (ASP) is to prevent the emergence of antimicrobial drug resistance and reduce adverse drug events, optimizing the selection, dosing, and duration of therapy in individual patients. METHODS: This retrospective study evaluated changes in antimicrobial agent use associated with implementation of an ASP in a general and emergency unit. The pre-intervention and post-intervention periods were defined as July 1, 2013, to December 31, 2013 (pre-intervention) and January 1, 2014, to June 30, 2014 (post-intervention). RESULTS: The mean total monthly antimicrobial use decreased by 18.8%, from 1,074.9 defined daily doses (DDD) per 1,000 patient-days to 873.0 DDD per 1,000 patient-days after the intervention. There was a significant reduction in the use of piperacillin-tazobactam, by 33.7% (p < 0.05), in imipenem/cilastatin, by 63.9% (p < 0.05), in meropenem by 68.0% (p < 0.05), and in levofloxacin by 45.0% (p < 0.05) without any negative effect on patient susceptibility to infections. Indeed, patient outcomes, including deaths, length of stay in the hospital, and re-admission within 30 days were not affected. CONCLUSIONS: The implementation of an education-based ASP achieved a significant improvement in all antimicrobial agent prescriptions in the surgical unit and a reduction in antimicrobial drug consumption, even when no restrictive measures were implemented.