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      The Burden of the Serious and Difficult-to-Treat Infections and a New Antibiotic Available: Cefiderocol

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          Abstract

          Background: Infection is a disease that can occur due to the entrance of a virus, bacteria, and other infectious agents. Cefiderocol is innovative cephalosporin drug that belongs to a special class of antibiotics, sideromycins, which are taken up by bacterial cells through active transport. The unique cell entry and stability to β-lactamases allow cefiderocol to overcome the most common resistance mechanisms in Gram-negative bacteria.

          Objective: This article aims to highlight the therapeutic efficacy, safety and tolerability of cefiderocol, with a focus on the FDA label.

          Methods: The pharmacological properties of cefiderocol are also summarized. In this review, we conducted literature research on the PubMed database using the following keywords: “antimicrobial treatment”, “new antibiotic”, “cefiderocol”, “siderophore cephalosporin”; “multidrug-resistant”, “Gram-negative bacilli”, “critically ill patients”; “severe bacterial infections”.

          Results: There were identified the most relevant data about the pathophysiology of serious bacterial infections, antibacterial mechanism of action, microbiology, mechanisms of resistance, pharmacokinetic and pharmacodynamic properties of cefiderocol.

          Conclusion: The results highlighted there appeared to be clinical benefit from cefiderocol in the treatment of infections caused by Gram-negative aerobic microorganisms in adult patients with severe infections and limited treatment options.

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          Most cited references85

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          Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis

          Summary Background Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs). Methods We estimated the incidence of infections with 16 antibiotic resistance–bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011–12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature. Findings From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval [UI] 583 148–763 966) infections with antibiotic-resistant bacteria, of which 63·5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480–38 430) attributable deaths and 874 541 (768 837–989 068) DALYs. The burden for the EU and EEA was highest in infants (aged <1 year) and people aged 65 years or older, had increased since 2007, and was highest in Italy and Greece. Interpretation Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases. Funding European Centre for Disease Prevention and Control.
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            Combating antimicrobial resistance: policy recommendations to save lives.

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              Clinical and economic impact of antibiotic resistance in developing countries: A systematic review and meta-analysis

              Introduction Despite evidence of the high prevalence of antibiotic resistant infections in developing countries, studies on the clinical and economic impact of antibiotic resistance (ABR) to inform interventions to contain its emergence and spread are limited. The aim of this study was to analyze the published literature on the clinical and economic implications of ABR in developing countries. Methods A systematic search was carried out in Medline via PubMed and Web of Sciences and included studies published from January 01, 2000 to December 09, 2016. All papers were considered and a quality assessment was performed using the Newcastle-Ottawa quality assessment scale (NOS). Results Of 27 033 papers identified, 40 studies met the strict inclusion and exclusion criteria and were finally included in the qualitative and quantitative analysis. Mortality was associated with resistant bacteria, and statistical significance was evident with an odds ratio (OR) 2.828 (95%CI, 2.231–3.584; p = 0.000). ESKAPE pathogens was associated with the highest risk of mortality and with high statistical significance (OR 3.217; 95%CIs; 2.395–4.321; p = 0.001). Eight studies showed that ABR, and especially antibiotic-resistant ESKAPE bacteria significantly increased health care costs. Conclusion ABR is associated with a high mortality risk and increased economic costs with ESKAPE pathogens implicated as the main cause of increased mortality. Patients with non-communicable disease co-morbidities were identified as high-risk populations.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                14 January 2021
                2020
                : 11
                : 578823
                Affiliations
                [ 1 ]Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
                [ 2 ]Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
                [ 3 ]The Faculty of Science and Mathematics, University of Niš, Niš, Serbia
                [ 4 ]Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, United States
                [ 5 ]Department of Biobehavioral Nursing Science, College of Nursing, University of Florida, Gainesville, FL, United States
                [ 6 ]Department of Botany, University of Fort Hare, Alice, South Africa
                [ 7 ]Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, Craiova, Romania
                Author notes

                Edited by: Ileana Mardare, Carol Davila University of Medicine and Pharmacy, Romania

                Reviewed by: Kurt Neumann, Independent researcher, Hungary

                Brian Godman, University of Strathclyde, United Kingdom

                *Correspondence: Alfred Maroyi, amaroyi@ 123456ufh.ac.za ; Daniela Calina, calinadaniela@ 123456gmail.com

                This article was submitted to Pharmaceutical Medicine and Outcomes Research, a section of the journal Frontiers in Pharmacology

                Article
                578823
                10.3389/fphar.2020.578823
                7898678
                33628170
                05292018-4831-44d3-a879-130880bbe3f1
                Copyright © 2021 Taheri, Joković, Vitorović, Grundmann, Maroyi and Calina.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 09 July 2020
                : 23 October 2020
                Page count
                Pages: 0
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                antimicrobial treatment,new antibiotic,cefiderocol,siderophore cephalosporin,multi drug-resistant gram-negative bacilli,critically ill patients,bacterial severe infections

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