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Scope: These ESCMID guidelines address the targeted antibiotic treatment of third-generation cephalosporin-resistant Enterobacterales (3GCephRE) and carbapenem-resistant Gram-negative bacteria, focusing on the effectiveness of individual antibiotics and on combination versus monotherapy. Methods: An expert panel was convened by ESCMID. A systematic review was performed including randomized controlled trials and observational studies, examining different antibiotic treatment regimens for the targeted treatment of infections caused by the 3GCephRE, carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii. Treatments were classified as head-to-head comparisons between individual antibiotics and between monotherapy and combination therapy regimens, including defined monotherapy and combination regimens only. The primary outcome was all-cause mortality, preferably at 30 days and secondary outcomes included clinical failure, microbiological failure, development of resistance, relapse/recurrence, adverse events and length of hospital stay. The last search of all databases was conducted in December 2019, followed by a focused search for relevant studies up until ECCMID 2021. Data were summarized narratively. The certainty of the evidence for each comparison between antibiotics and between monotherapy and combination therapy regimens was classified by the GRADE recommendations. The strength of the recommendations for or against treatments was classified as strong or conditional (weak). Recommendations: The guideline panel reviewed the evidence per pathogen, preferably per site of infection, critically appraising the existing studies. Many of the comparisons were addressed in small observational studies at high risk of bias only. Notably, there was very little evidence on the effects of the new, recently approved, β-lactam/β-lactamase inhibitors on infections caused by carbapenem-resistant Gram-negative bacteria. Most recommendations are based on very-low- and low-certainty evidence. A high value was placed on antibiotic stewardship considerations in all recommendations, searching for carbapenem-sparing options for 3GCephRE and limiting the recommendations of the new antibiotics for severe infections, as defined by the sepsis-3 criteria. Research needs are addressed. © 2021 European Society of Clinical Microbiology and Infectious Diseases

OBJECTIVES: Optimal treatment of carbapenem-resistant Gram-negative (CR-GNB) infections is uncertain due to the lack of good-quality evidence and the limited effectiveness of available antibiotics. The aim of this survey was to investigate clinicians' prescribing strategies for treating CR-GNB infections worldwide. METHODS: A 36-items-questionnaire was developed addressing the following aspects of antibiotic prescribing: respondent's background, diagnostic and therapeutic availability, preferred antibiotic strategies and rationale for selecting combination therapy. Prescribers were recruited following the snowball-sampling approach, and a post-stratification correction with inverse proportional weights was used to adjust the sample's representativeness. RESULTS: 1012 respondents from 95 countries participated in the survey. Overall, 298 (30%) of respondents had local guidelines for treating CR-GNB at their facility and 702 (71%) had access to Infectious Diseases consultation, with significant discrepancies according to country economic status: 85% (390/502) in High-Income-Countries vs 59% (194/283) in Upper-Medium-Income-Countries and 30% (118/196) in Lower-Middle-Income-Countries/Lower-Income-Countries). Targeted regimens varied widely, ranging from 40 regimens for CR-Acinetobacter spp. to more than 100 regimens for CR-Enterobacteriaceae. Although the majority of respondents acknowledged the lack of evidence behind this choice, dual combination was the preferred treatment scheme and carbapenem-polymyxin was the most prescribed regimen, irrespective of pathogen and infection source. Respondents noticeably disagreed around the meaning of 'combination therapy' with 20% (150/783) indicating the simple addition of multiple compounds, 42% (321/783) requiring the presence of in vitro activity and 38% (290/783) of in vitro-synergism. CONCLUSIONS: Management of CR-GNB infections is far from being standardized. Strategic public health focussed randomised controlled trials are urgently required to inform evidence-based treatment guidelines.

Antimicrobial stewardship (AMS) and Infection prevention and control (IPC) are two key complementary strategies that combat development and spread of antimicrobial resistance. The ESGAP (ESCMID Study Group for AMS), EUCIC (European Committee on Infection Control) and TAE (Trainee Association of ESCMID) investigated how AMS and IPC activities and training are organized, if present, at national level in Europe. From February 2018 to May 2018, an internet-based cross-sectional survey was conducted through a 36-item questionnaire, involving up to three selected respondents per country, from 38 European countries in total (including Israel), belonging to the ESGAP/EUCIC/TAE networks. All 38 countries participated with at least one respondent, and a total of 81 respondents. Education and involvement in AMS programmes were mandatory during the postgraduate training of clinical microbiology and infectious diseases specialists in up to one-third of countries. IPC was acknowledged as a specialty in 32% of countries. Only 32% of countries had both guidance and national requirements regarding AMS programmes, in contrast to 61% for IPC. Formal national staffing standards for AMS and IPC hospital-based activities were present in 24% and 63% of countries, respectively. The backgrounds of professionals responsible for AMS and IPC programmes varied tremendously between countries. The organization and training of AMS and IPC in Europe are heterogeneous and national requirements for activities are frequently lacking., peer-reviewed

Infections are a major complication of solid organ transplants (SOTs). This study aimed to describe recipients’ characteristics, and the frequency and etiology of infections and transplant outcome in liver and lung SOTs, and to investigate exposures associated to infection and death in liver transplant recipients. The study population included recipients of SOTs performed in Italy during a 1-year period in ten Italian lung transplant units and eight liver transplant units. Data on comorbidities, infections, retransplantation, and death were prospectively collected using a web-based system, with a 6-month follow-up. The cumulative incidence of infection was 31.7% and 47.8% in liver and lung transplants, respectively, with most infections occurring within the first month after transplantation. Gram-negatives, which were primarily multidrug-resistant, were the most frequent cause of infection. Death rates were 0.42 per 1000 recipient-days in liver transplants and 1.41 per 1000 recipient-days in lung transplants. Infection after SOT in adult liver recipients is associated to an increased risk of death (OR = 13.25; p-value < 0.001). Given the frequency of infection caused by multidrug-resistant microorganisms in SOT recipients in Italy and the heavy impact of infections on the transplant outcome, the reinforcement of surveillance and control activities to prevent the transmission of multidrug-resistant microorganisms in SOT recipients represents a priority. The implementation of the study protocol in liver and lung transplant units and the sharing of results have increased the awareness about the threat due to antimicrobial resistance in the country.

The article aims to show how two drawings of the Metropolitan Museum in New York, recently published and attributed to Giorgio Vasari, should be dated instead to the mid-sixties of the sixteenth century and should be interpreted as preparatory sketches for the fountain of the Apennine in the Villa Medicea di Castello, made by the painter and architect from Arezzo with the collaboration of Bartolomeo Ammannati, between 1563 and 1565. The essay also analyzes the important changes made by Vasari in the Giunti edition of The Lives to one of the introductory chapters (How Rustic Fountains are made with Stalactites and Incrustations from Water, and how Cockle Shells and Conglomerations of vitrified Stone are built into the Stucco), precisely as a result of the role played by the artist in the arrangement of the Medici gardens., Opus Incertum, Vol 4 (2018)