Risk factors for bloodstream infections due to carbapenem-resistant Enterobacterales: a nested case-control-control study.

Background: Carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) are a major threat to patients. To date, data on risk factors have been limited, with low internal and external validity. In this multicentre study, risk factors for CRE BSI were determined by comparison with two control groups: patients with carbapenem-susceptible Enterobacterales (CSE) BSI, and patients without Enterobacterales infection (uninfected patients).

International and regional spread of carbapenem-resistant Klebsiella pneumoniae in Europe.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) are of particular concern due to the spread of antibiotic resistance genes associated with mobile genetic elements. In this study, we collected 687 carbapenem-resistant strains recovered among clinical samples from 41 hospitals in nine Southern European countries (2016-2018). We identified 11 major clonal lineages, with most isolates belonging to the high-risk clones ST258/512, ST101, ST11, and ST307.

Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries.

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs.

Attributable mortality of infections caused by carbapenem-resistant Enterobacterales: results from a prospective, multinational case-control-control matched cohorts study (EURECA).

Objectives: To assess the mortality attributable to infections caused by carbapenem-resistant Enterobacterales (CRE) and to investigate the effect of clinical management on differences in observed outcomes in a multinational matched cohort study.

Methods: A prospective matched-cohorts study (NCT02709408) was performed in 50 European hospitals from March 2016 to November 2018. The main outcome was 30-day mortality with an active post-discharge follow-up when applied.

Patterns of antibiotic use, pathogens, and prediction of mortality in hospitalized neonates and young infants with sepsis: A global neonatal sepsis observational cohort study (NeoOBS).

Background: There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design.

Methods And Findings: Hospitalized infants <60 days with clinical sepsis were enrolled during 2018 to 2020 by 19 sites in 11 countries (mainly Asia and Africa).

Challenges in the Implementation of the NeoOBS Study, a Global Pragmatic Observational Cohort Study, to Investigate the Aetiology and Management of Neonatal Sepsis in the Hospital Setting.

Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that can feasibly be implemented in these settings. This paper provides an overview of the complexities faced by diverse research teams in different countries and regions, together with actions implemented to achieve pragmatic study management of a large multi-centre observational study of neonatal sepsis.

An analysis of existing national action plans for antimicrobial resistance-gaps and opportunities in strategies optimising antibiotic use in human populations.

At the 2015 World Health Assembly, UN member states adopted a resolution that committed to the development of national action plans (NAPs) for antimicrobial resistance (AMR). The political determination to commit to NAPs and the availability of robust governance structures to assure sustainable translation of the identified NAP objectives from policy to practice remain major barriers to progress. Inter-country variability in economic and political resilience and resource constraints could be fundamental barriers to progressing AMR NAPs.

Importance of antimicrobial stewardship in solid organ transplant recipients: An ESCMID perspective.

Background: In the last decades, solid organ transplantation (SOT) has emerged as an important method in the management of chronic kidney, liver, heart, and lung failure. Antimicrobial use has led to a significant reduction of morbidity and mortality due to infectious complications among patients with SOT; however, it can lead to adverse events and drive the development of antimicrobial resistance; thus, antimicrobial stewardship is of extreme importance. Even though there are ongoing efforts of transplant societies to implement principles of antimicrobial stewardship in everyday practice in SOT, there is still a lack of guidelines in this patient population.

Are antibiotic prescription practices in Eastern Uganda concordant with the national standard treatment guidelines? A cross-sectional retrospective study.

Objectives: This study aimed to evaluate the antibiotic prescription patterns of health workers in Eastern Uganda and more specifically whether they are in accordance with the Ugandan standard treatment guidelines and other indicators of appropriate antimicrobial prescription.

Methods: Patient data were obtained from the health management information system of the outpatient department registers of Soroti and Mbale Regional Referral Hospitals from 2016-2018.

Results: The prevalence of non-adherence to treatment guidelines when prescribing antibiotics was 82.

Indications for medical antibiotic prophylaxis and potential targets for antimicrobial stewardship intervention: a narrative review.

Background: Most of the antimicrobial stewardship (AMS) literature has focused on antimicrobial consumption for the treatment of infections, for the prophylaxis of surgical site infection and for the prevention of endocarditis. The role of AMS for medical antibiotic prophylaxis (AP) has not been adequately addressed.

Aims: To identify targets for AMS interventions for medical AP in adult patients.

COMBACTE LAB-Net: building a European laboratory network for clinical trials on anti-infectives.

LAB-Net, the laboratory network of COMBACTE, has established itself as an indispensable network for clinical trials in infectious diseases that plays a crucial part across 30 clinical studies not only within, but also outside the COMBACTE consortium. Since its official launch in January 2013, LAB-Net has expanded more than threefold and in Q4 2020 it encompasses 841 labs across 41 countries in Europe. In addition, LAB-Net has crossed the European borders and collaborates with more than 300 laboratories spread across the globe.

Phenotypic and molecular characterizations of carbapenem-resistant Acinetobacter baumannii isolates collected within the EURECA study.

Multi-drug-resistant Acinetobacter baumannii isolates are key pathogens that contribute to the global burden of antimicrobial resistance. This study aimed to investigate the phenotypic and molecular characteristics of carbapenem-resistant A. baumannii (CRAB) isolates from the EURECA clinical trial.

Experiences and views of healthcare professionals on the prescription of antibiotics in Eastern Uganda: A qualitative study.

Objectives: This study aimed to explore the experiences and views of healthcare professionals on antibiotic prescription in Eastern Uganda.

Methods: This was an exploratory qualitative study using semi-structured interviews. Participants included 16 healthcare professionals from Mbale and Soroti Regional Referral Hospitals.

Prevalence of antibiotic-resistant bacteria among patients in two tertiary hospitals in Eastern Uganda.

Objective: The aim of this study was to determine the prevalence and antibiotic resistance patterns of bacterial isolates from inpatients and outpatients in Mbale and Soroti regional referral hospitals in Eastern Uganda.

Methods: A retrospective analysis of culture and antibiotic sensitivity test results from the microbiology laboratories of the two tertiary hospitals was conducted for a 3-year period (January 2016-December 2018).

Results: Microbiology records of 3092 patients were reviewed and analysed, with 1305 (42.

Evaluation of a Loop-Mediated Isothermal Amplification Assay to Detect Carbapenemases Directly From Bronchoalveolar Lavage Fluid Spiked With spp.

Carbapenem-resistant spp. mainly are frequently causing nosocomial infections with high mortality. In this study, the efficacy of the Eazyplex SuperBug Complete A system, based on loop-mediated isothermal amplification (LAMP), to detect the presence of carbapenemases in spp.

White Paper: Bridging the gap between human and animal surveillance data, antibiotic policy and stewardship in the hospital sector-practical guidance from the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks.

Background: Antimicrobial surveillance and antimicrobial stewardship (AMS) are essential pillars in the fight against antimicrobial resistance (AMR), but practical guidance on how surveillance data should be linked to AMS activities is lacking. This issue is particularly complex in the hospital setting due to structural heterogeneity of hospital facilities and services. The JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks have joined efforts to formulate a set of target actions for linking surveillance data with AMS activities.

A one health framework to estimate the cost of antimicrobial resistance.

Objectives/purpose: The costs attributable to antimicrobial resistance (AMR) remain theoretical and largely unspecified. Current figures fail to capture the full health and economic burden caused by AMR across human, animal, and environmental health; historically many studies have considered only direct costs associated with human infection from a hospital perspective, primarily from high-income countries. The Global Antimicrobial Resistance Platform for ONE-Burden Estimates (GAP-ON€) network has developed a framework to help guide AMR costing exercises in any part of the world as a first step towards more comprehensive analyses for comparing AMR interventions at the local level as well as more harmonized analyses for quantifying the full economic burden attributable to AMR at the global level.

A comparative study between real-time PCR and loop-mediated isothermal amplification to detect carbapenemase and/or ESBL genes in Enterobacteriaceae directly from bronchoalveolar lavage fluid samples.

Objectives: To evaluate and compare the efficacy of real-time PCR (Xpert Carba-R) and loop-mediated isothermal amplification (Eazyplex® SuperBug CRE) for detecting carbapenemase carriage in Enterobacteriaceae directly from bronchoalveolar lavage (BAL).

Methods: Negative BAL samples were spiked with 21 well-characterized carbapenemase-producing Enterobacteriaceae strains to a final concentration of 102-104 cfu/mL. Xpert Carba-R (Cepheid, Sunnyvale, CA, USA), which detects five targets (blaKPC, blaNDM, blaVIM, blaOXA-48 and blaIMP-1), and the Eazyplex® SuperBug CRE system (Amplex-Diagnostics GmbH, Germany), which detects seven genes (blaKPC, blaNDM, blaVIM, blaOXA-48, blaOXA-181, blaCTXM-1 and blaCTXM-9), were evaluated for the detection of these genes directly from BAL samples.

Detection and prevalence of carbapenem-resistant Gram-negative bacteria among European laboratories in the COMBACTE network: a COMBACTE LAB-Net survey.

Antimicrobial resistance (AMR) represents a global public health threat that jeopardises the progress medicine has made over the last century. To confront AMR, the Innovative Medicines Initiative (IMI) has supported the development of a large network of hospitals and laboratories in Europe as part of the New Drugs for Bad Bugs (ND4BB) programme and the COMBACTE projects. COMBACTE LAB-Net conducted a pilot survey on distribution and usage of carbapenem resistance detection methods among laboratories in the COMBACTE network in two clinical trials as part of the COMBACTE-CARE project.

Management of bloodstream infections by infection specialists: an international ESCMID cross-sectional survey.

Bloodstream infections (BSIs) are common, however international guidelines are available only for methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia and candidaemia. This international ESCMID cross-sectional survey, open from December 2016 to February 2017, explored the management of BSIs by infection specialists. All infection specialists (senior or trainees) giving at least weekly advice on positive blood cultures could participate.

EUropean prospective cohort study on showing REsistance to CArbapenems (EURECA): a protocol of a European multicentre observational study.

Introduction: The rapid worldwide spread of carbapenem-resistant (CRE) constitutes a major challenge. The aim of the EUropean prospective cohort study on showing REsistance to CArbapenems (EURECA), which is part of the Innovative Medicines Initiative Joint Undertaking (IMI JU) funded COMBACTE-CARE project, is to investigate risk factors for and outcome determinants of CRE infections to inform randomised clinical trial designs and to provide a historical cohort that could eventually be used for future comparisons with new drugs targeting CRE.

Methods: A multicentre (50 sites), multinational (11 European countries), analytical observational project was designed, comprising 3 studies.